Medicine › Endocrinology, Diabetes and Metabolism

Hormonal and reproductive studies

Works Count: 80797

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This cluster of papers explores the long-term effects of testosterone levels and therapy on various aspects of men's health, including aging, metabolic syndrome, cardiovascular risk, and muscle strength. It also investigates the association between testosterone levels and conditions such as diabetes, androgen deficiency, and the use of anabolic steroids.

Keywords

Testosterone; Hormone Therapy; Aging Men; Metabolic Syndrome; Cardiovascular Risk; Androgen Deficiency; Muscle Strength; Diabetes; Elderly Men; Anabolic Steroids

The Conversion of Testosterone to 5α-Androstan-17β-ol-3-one by Rat Prostate in Vivo and in Vitro

1968-04-01

Nicholas Bruchovsky , Jean D. Wilson

The identity of the nonpolar transformation products of testosterone-1,2-3H, the time course of the appearance of these metabolites in various tissue compartments, and the subcellular distribution of testosterone and its … The identity of the nonpolar transformation products of testosterone-1,2-3H, the time course of the appearance of these metabolites in various tissue compartments, and the subcellular distribution of testosterone and its metabolites in prostate have been investigated following the intravenous administration of the hormone to normal and to functionally hepatectomized rats. Evidence has been obtained in both types of animals that within 1 min following its administration testosterone is taken up by the prostate, and at least 90% is converted to three products, androstandiol, dihydrotestosterone, and androsterone. From prostatic nuclei, however, only testosterone-3H and dihydrotestosterone-3H were recovered for as long as 2 hours following testosterone injection. Furthermore, it has been shown that in the presence of a NADPH2-generating system prostatic nuclei convert testosterone to dihydrotestosterone, whereas prostatic cytoplasm, in addition, reduces dihydrotestosterone to androstandiol. The nuclear enzyme which performs this reaction has been partially characterized and appears to be located within the chromatin. Finally, the tissue distribution of dihydrotestosterone-3H has been investigated at a short time interval following testosterone-1,2-3H injection; this metabolite was detected only in prostate, seminal vesicle, preputial gland, kidney, and plasma.

Prevalence of hypogonadism in males aged at least 45 years: the HIM study

2006-06-07

Thomas Mulligan , Madeleine Frick , Qing Zuraw +2 more

The Hypogonadism in Males study estimated the prevalence of hypogonadism [total testosterone (TT) < 300 ng/dl] in men aged > or = 45 years visiting primary care practices in the … The Hypogonadism in Males study estimated the prevalence of hypogonadism [total testosterone (TT) < 300 ng/dl] in men aged > or = 45 years visiting primary care practices in the United States. A blood sample was obtained between 8 am and noon and assayed for TT, free testosterone (FT) and bioavailable testosterone (BAT). Common symptoms of hypogonadism, comorbid conditions, demographics and reason for visit were recorded. Of 2162 patients, 836 were hypogonadal, with 80 receiving testosterone. Crude prevalence rate of hypogonadism was 38.7%. Similar trends were observed for FT and BAT. Among men not receiving testosterone, 756 (36.3%) were hypogonadal; odds ratios for having hypogonadism were significantly higher in men with hypertension (1.84), hyperlipidaemia (1.47), diabetes (2.09), obesity (2.38), prostate disease (1.29) and asthma or chronic obstructive pulmonary disease (1.40) than in men without these conditions. The prevalence of hypogonadism was 38.7% in men aged > or = 45 years presenting to primary care offices.

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Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism.

1996-12-01

Laurence Katznelson , Joel S. Finkelstein , David Schoenfeld +3 more

Acquired hypogonadism is being increasingly recognized in adult men. However, the effects of long term testosterone replacement on bone density and body composition are largely unknown. We investigated 36 adult … Acquired hypogonadism is being increasingly recognized in adult men. However, the effects of long term testosterone replacement on bone density and body composition are largely unknown. We investigated 36 adult men with acquired hypogonadism (age, 22-69 yr; median, 58 yr), including 29 men with central hypogonadism and 7 men with primary hypogonadism, and 44 age-matched eugonadal controls. Baseline evaluation included body composition analysis by bioimpedance, determination of site-specific adipose area by dual energy quantitative computed tomography scan (QCT) of the lumbar spine, and measurements of spinal bone mineral density (BMD) using dual energy x-ray absortiometry, spinal trabecular BMD with QCT, and radial BMD with single photon absorptiometry. Percent body fat was significantly greater in the hypogonadal men compared to eugonadal men (mean +/- SEM, 26.4 +/- 1.1% vs. 19.2 +/- 0.8%; P < 0.01). The mean trabecular BMD determined by QCT for the hypogonadal men was 115 +/- 6 mg K2HPO4/cc. Spinal BMD was significantly lower than that in eugonadal controls (1.006 +/- 0.024 vs. 1.109 +/- 0.028 g/cm2; P = 0.02, respectively). Radial BMD was similar in both groups. Testosterone enanthate therapy was initiated in 29 hypogonadal men at a dose of 100 mg/week, and the subjects were evaluated at 6-month intervals for 18 months. During testosterone therapy, the percent body fat decreased 14 +/- 4% (P < 0.001). There was a 13 +/- 4% decrease in subcutaneous fat (P < 0.01) and a 7 +/- 2% increase in lean muscle mass (P = 0.01) during testosterone therapy. Spinal BMD and trabecular BMD increased by 5 +/- 1% (P < 0.001) and 14 +/- 3% (P < 0.001), respectively. Radial BMD did not change. Serum bone-specific alkaline phosphatase and urinary deoxypyridinoline excretion, markers of bone formation and resorption, respectively, decreased significantly over the 18 months (P = 0.003 and P = 0.04, respectively). We conclude that testosterone therapy given to adult men with acquired hypogonadism decreases sc fat and increases lean muscle mass. In addition, testosterone therapy reduces bone remodeling and increases trabecular bone density. The beneficial effects of androgen administration on body composition and bone density may provide additional indications for testosterone therapy in hypogonadal men.

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Calculation of free and bound fractions of testosterone and estradiol-17β to human plasma proteins at body temperature

1982-06-01

R. Södergård , Torbjorn Bäckström , Vasant Shanbhag +1 more

Testosterone Replacement in Older Hypogonadal Men: A 12-Month Randomized Controlled Trial

1997-06-01

Rahmawati Sih , John E. Morley , Fran E. Kaiser +3 more

Abstract A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. … Abstract A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 ± 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65± 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone &lt;60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory. Testosterone improved bilateral grip strength (P &lt; 0.05 by ANOVA) and increased hemoglobin (P &lt; 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean ± sem: −2.0 ± 0.9 ng/dL vs. 0.8 ± 0.7 ng/dL; P &lt; 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.

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The Endocrinology of Aging

1997-10-17

Steven W. J. Lamberts , Annewieke W. van den Beld , Aart‐Jan van der Lely

Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of … Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.

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Plasma Testosterone and Progesterone Titers of Pregnant Rats, Their Male and Female Fetuses, and Neonatal Offspring*

1980-01-01

Judith Weisz , Ingeborg L. Ward

Testosterone and progesterone titers were determined by RIA in the plasma of pregnant rats and their male and female fetuses from day 17 of gestation through the day of birth … Testosterone and progesterone titers were determined by RIA in the plasma of pregnant rats and their male and female fetuses from day 17 of gestation through the day of birth and in male and female neonates on days 3 and 5 post partum. Males had significantly higher mean testosterone levels than females from day 18 of gestation through day 5 post partum. Sex differences in plasma testosterone concentrations were greatest in the fetuses on days 18 and 19 of gestation when testosterone levels peaked in the males. Instances in which female fetuses had testosterone titers equal to or greater than their male littermates were found on every day of gestation except day 18. Mean testosterone concentrations in plasma of female fetuses were high throughout gestation (>1000 pcg/ml). Testosterone concentrations decreased in both sexes after birth. Differences between the sexes remained significant, and although there was an overlap in the values for males and females, testosterone concentrations in females exceeded those of their male littermates in only one out of nine pairs of samples on day 5 and in none of seven pairs on day 3 post partum. There were no significant differences in progesterone levels in plasma of males and females, either pre- or postnatally. Progesterone titers changed as a function of days post conception in both the fetuses and their mothers. In the fetuses, progesterone levels declined progressively from day 18 post conception through the day of birth, while in the mother they rose from days 18 to 19 then declined between days 20 and 21 of pregnancy. Fetuses had lower progesterone titers than their mothers. From these data, we conclude that day 18 and possibly day 19 post conception represent a critical period during which the central nervous system of the male is primed by high levels of testosterone. Thereafter, the process of masculinization is completed by exposure to testosterone levels that are relatively low and need not be consistently higher than those of female littermates. (Endocrinology106: 306, 1980)

Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men*

1983-06-01

William J. Bremner , Michael V. Vitiello , Patricia N. Prinz

Journal Article Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men Get access William J. Bremner, William J. Bremner 1Departments of Medicine and Psychiatry and Behavioral … Journal Article Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men Get access William J. Bremner, William J. Bremner 1Departments of Medicine and Psychiatry and Behavioral Sciences, and Population Research Center, University of Washington School of Medicine; GRECC Program and Endocrinology Section, Veterans Administration Medical Centers, American Lake and Seattle, Washington 98108 Search for other works by this author on: Oxford Academic Google Scholar Michael V. Vitiello, Michael V. Vitiello 1Departments of Medicine and Psychiatry and Behavioral Sciences, and Population Research Center, University of Washington School of Medicine; GRECC Program and Endocrinology Section, Veterans Administration Medical Centers, American Lake and Seattle, Washington 98108 Search for other works by this author on: Oxford Academic Google Scholar Patricia N. Prinz Patricia N. Prinz 1Departments of Medicine and Psychiatry and Behavioral Sciences, and Population Research Center, University of Washington School of Medicine; GRECC Program and Endocrinology Section, Veterans Administration Medical Centers, American Lake and Seattle, Washington 98108 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 56, Issue 6, 1 June 1983, Pages 1278–1281, https://doi.org/10.1210/jcem-56-6-1278 Published: 01 June 1983 Article history Received: 30 September 1982 Published: 01 June 1983

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Biological Actions of Androgens

1987-02-01

A. D. Mooradian , John E. Morley , S. G. Korenman

WHILE the role of estrogens in women has received a great deal of scientific attention, the analogous questions regarding the role of androgens in men have received relatively little attention. … WHILE the role of estrogens in women has received a great deal of scientific attention, the analogous questions regarding the role of androgens in men have received relatively little attention. To date we do not know the frequency or extent to which men become androgen deprived as they age, the consequences for longevity, and the adverse effects of androgen deficiency on the quality of life. This review is designed to focus on the biological actions of androgens and on the consequences of a decline in androgen availability. The secretion and metabolism of androgens to biologically active products will be discussed briefly. We will not emphasize the developmental effects of androgens or elaborate on the molecular mechanism of transcriptional control. We will try to distinguish between physiological and pharmacological effects of the hormones and will attempt to identify the active product responsible for the action in the tissue of interest.

Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes

2006-03-14

Eric L. Ding , Yiqing Song , Vasanti Malik +1 more

Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in … Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in men.To systematically assess studies evaluating the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with risk of type 2 diabetes.Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords diabetes, testosterone, sex-hormone-binding-globulin, and estradiol; references of retrieved articles; and direct author contact.From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 women and 6427 men and presenting relative risks (RRs) or hormone levels for cases and controls.Information on study design, participant characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol.Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that testosterone level was significantly lower in men with type 2 diabetes (mean difference, -76.6 ng/dL; 95% confidence interval [CI], -99.4 to -53.6) and higher in women with type 2 diabetes compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that men with higher testosterone levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of type 2 diabetes (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that testosterone increased risk in women (P = .06 for sex difference). Cross-sectional and prospective studies both found that SHBG was more protective in women than in men (P< or =.01 for sex difference for both), with prospective studies indicating that women with higher SHBG levels (>60 vs < or =60 nmol/L) had an 80% lower risk of type 2 diabetes (RR, 0.20; 95% CI, 0.12 to 0.30), while men with higher SHBG levels (>28.3 vs < or =28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). Estradiol levels were elevated among men and postmenopausal women with diabetes compared with controls (P = .007).This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women. High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men; the inverse association of SHBG with risk was stronger in women than in men.

The Serum Transport of Steroid Hormones

1982-01-01

Pentti K. Siiteri , James T. Murai , WILLIAM J. RAYMOURE +3 more

Effects of Androgenic-Anabolic Steroids in Athletes

2004-01-01

Fred Hartgens , Harm Kuipers

Cloning of Human Androgen Receptor Complementary DNA and Localization to the X Chromosome

1988-04-15

Dennis B. Lubahn , D. Joseph , Patrick M. Sullivan +3 more

The androgen receptor (AR) mediates the actions of male sex steroids. Human AR genomic DNA was cloned from a flow-sorted human X chromosome library by using a consensus nucleotide sequence … The androgen receptor (AR) mediates the actions of male sex steroids. Human AR genomic DNA was cloned from a flow-sorted human X chromosome library by using a consensus nucleotide sequence from the DNA-binding domain of the family of nuclear receptors. The AR gene was localized on the human X chromosome between the centromere and q13. Cloned complementary DNA, selected with an AR-specific oligonucleotide probe, was expressed in monkey kidney (COS) cells and yielded a high-affinity androgen-binding protein with steroid-binding specificity corresponding to that of native AR. A predominant messenger RNA species of 9.6 kilobases was identified in human, rat, and mouse tissues known to contain AR and was undetectable in tissues lacking AR androgen-binding activity, including kidney and liver from androgen-insensitive mice. The deduced amino acid sequence of AR within the DNA-binding domain has highest sequence identity with the progesterone receptor.

SEX‐HORMONE‐BINDING GLOBULIN

1974-01-01

David C. Anderson

A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the … A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.

Age Changes and Sex Differences in Serum Dehydroepiandrosterone Sulfate Concentrations throughout Adulthood

1984-09-01

Norman Orentreich∥ , Joel Brind , Ronald L. Rizer +1 more

In a cross-sectional study, serum dehydroepiandrosterone sulfate (DS) concentrations were measured in 981 men and 481 women, aged 11-89, yr. The resulting data were asymetrically distributed and were normalized by … In a cross-sectional study, serum dehydroepiandrosterone sulfate (DS) concentrations were measured in 981 men and 481 women, aged 11-89, yr. The resulting data were asymetrically distributed and were normalized by logarithmic transformation and analyzed by 5-yr age grouping (e.g. 15-19 yr, 20-24 yr, etc.). The DS concentration peaked at age 20-24 yr in men (logarithmic mean, 3470 ng/ml) and at age 15-19 yr in women (log mean, 2470 ng/ml). Mean values then declined steadily in both sexes (log mean at greater than 70 yr of age, 670 ng/ml in men and 450 ng/ml in women) and were significantly higher in men than women at ages from 20-69 yr. Analysis of 517 randomly selected sera (from women) which had been stored frozen for 10-15 yr gave results indistinguishable from values obtained from fresh specimens. In a supplementary study, a longitudinal analysis of weekly specimens from 4 normal men, aged 36-59 yr, revealed individual variability (mean coefficient of variation, 19%) and failed to demonstrate any monthly, seasonal, or annual rhythmicity. Based on the above analyses, a table of normal serum DS ranges for adult men and women is presented for use as a clinical reference.

Adverse Events Associated With Testosterone Replacement in Middle-Aged and Older Men: A Meta-Analysis of Randomized, Placebo-Controlled Trials

2005-11-01

Olga M. Calof , Atam B. Singh , M. L. Lee +4 more

We performed a meta-analysis of randomized clinical trials to determine the risks of adverse events associated with testosterone replacement in older men.The MEDLINE database was searched from 1966 to April … We performed a meta-analysis of randomized clinical trials to determine the risks of adverse events associated with testosterone replacement in older men.The MEDLINE database was searched from 1966 to April 2004, using testosterone as the indexing term; limits included human, male, > or =45 years old, and randomized controlled trial. Of the 417 studies thus identified, 19 met the inclusion criteria: testosterone replacement for at least 90 days, men > or =45 years old with low or low-normal testosterone level, randomized controlled trial, and medically stable men. Odds ratios (ORs) were pooled using a random effects model, assuming heterogeneous results across studies, and were weighted for sample size.In the 19 studies that met eligibility criteria, 651 men were treated with testosterone and 433 with placebo. The combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (OR = 1.78, 95% confidence interval [CI], 1.07-2.95). Rates of prostate cancer, prostate-specific antigen (PSA) >4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between the groups were not individually statistically significant. Testosterone-treated men were nearly four times as likely to have hematocrit >50% as placebo-treated men (OR = 3.69, 95% CI, 1.82-7.51). The frequency of cardiovascular events, sleep apnea or death was not significantly different between the two groups.Testosterone replacement in older men was associated with a significantly higher risk of detection of prostate events and of hematocrit >50% than was placebo; hematocrit increase was the most frequent adverse event associated with testosterone replacement. These data reaffirm the need to monitor hematocrit, PSA, and digital examination of the prostate during testosterone replacement in older men.

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Age, Disease, and Changing Sex Hormone Levels in Middle-Aged Men: Results of the Massachusetts Male Aging Study*

1991-11-01

Anna Gray , Henry A. Feldman , John B. McKinlay +1 more

To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins … To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a populationbased cross-sectional survey of men aged 39–70 yr conducted in 1986–89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39–70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3α,17β-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5α-dihydrotestosterone remained essentially constant between ages 39–70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2–3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10–15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2. This study provides epidemiological evidence for some hormone age trends that were previously documented only in smaller, uncontrolled, or questionably representative samples. We found no significant difference between healthy men (group 1) and less healthy men (group 2) with respect to the percent rate of change of any of the serum hormone, metabolite, or protein concentrations measured. The 10–15% lower levels of testosterone, SHBG, and some androgen metabolites in the less healthy men, which were maintained between ages 39–70 yr, might be causes, effects, or mere correlates of disease.

Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension*

2005-01-20

Hans-Peter Brunner , John Cockcroft , John Deanfield +7 more

Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore held to be an early feature in atherogenesis. However, the mechanisms … Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore held to be an early feature in atherogenesis. However, the mechanisms by which endothelial dysfunction occurs in smoking, dyslipidaemia, hyperhomocysteinaemia, diabetes mellitus, arterial hypertension, cerebrovascular diseases, coronary artery disease and heart failure are complex and heterogeneous. Recent data indicate that endothelial dysfunction is often associated with erectile dysfunction, which can precede and predict cardiovascular disease in men. This paper will provide a concise overview of the mechanisms causing endothelial dysfunction in the different cardiovascular risk factors and disease conditions, and of the impact of the intervention measures and treatments.

Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies

2008-01-30

Endogenous Hormones

BackgroundSex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in … BackgroundSex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in a uniform manner and to provide more precise estimates of risks.

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Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men

2010-06-17

Frederick C. W. Wu , Abdelouahid Tajar , Jennifer M. Beynon +7 more

The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis … The association between aging-related testosterone deficiency and late-onset hypogonadism in men remains a controversial concept. We sought evidence-based criteria for identifying late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.

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Investigation, treatment and monitoring of late-onset hypogonadism in males

2008-10-27

Christina Wang , Eberhard Nieschlag , Ronald S. Swerdloff +7 more

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest … Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

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A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum

1999-10-01

Alex Vermeulen , L. Verdonck , Jean‐Marc Kaufman

Abstract The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of … Abstract The free and nonspecifically bound plasma hormone levels generally reflect the clinical situation more accurately than total plasma hormone levels. Hence, it is important to have reliable indexes of these fractions. The apparent free testosterone (T) concentration obtained by equilibrium dialysis (AFTC) as well as the fraction of serum T not precipitated by 50% ammonium sulfate concentration (non-SHBG-T; SHBG, sex hormone-binding globulin), often referred to as bioavailable T, appear to represent reliable indexes of biologically readily available T, but are not well suited for clinical routine, being too time consuming. Several other parameters have been used without complete validation, however: direct immunoassay of free T with a labeled T analog (aFT), calculation of free T (FT) from total T and immunoassayed SHBG concentrations (iSHBG), and the free androgen index (FAI = the ratio 100T/iSHBG). In the view of substantial discrepancies in the literature concerning the free or bioavailable T levels, we compared AFTC, FT, aFT, FAI, and non-SHBG-T levels in a large number of sera with SHBG capacities varying from low, as in hirsute women, to extremely high as in hyperthyroidism. All these indexes of bioavailable T correlated significantly with the AFTC concentration; AFTC and FT values were almost identical under all conditions studied, except during pregnancy. Values for aFT, however, were only a fraction of either AFTC or FT, the fraction varying as a function of SHBG levels. Also, the FAI/AFTC ratio varied as a function of the SHBG levels, and hence, neither aFT nor FAI is a reliable index of bioavailable T. The FT value, obtained by calculation from T and SHBG as determined by immunoassay, appears to be a rapid, simple, and reliable index of bioavailable T, comparable to AFTC and suitable for clinical routine, except in pregnancy. During pregnancy, estradiol occupies a substantial part of SHBG-binding sites, so that SHBG as determined by immunoassay overestimates the actual binding capacity, which in pregnancy sera results in calculated FT values that are lower than AFTC. The nonspecifically bound T, calculated from FT, correlated highly significantly with and was almost identical to the values of non-SHBG-T obtained by ammonium sulfate precipitation, testifying to the clinical value of FT calculated from iSHBG.

Effect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age1

1999-08-01

Peter J. Snyder , Helen Peachey , Peter Hannoush +7 more

As men age, serum testosterone concentrations decrease, the percentage of body mass that is fat increases, the percentage of lean body mass decreases, and muscle strength decreases. Because these changes … As men age, serum testosterone concentrations decrease, the percentage of body mass that is fat increases, the percentage of lean body mass decreases, and muscle strength decreases. Because these changes are similar to those that occur in hypogonadal men, we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass, increase their lean mass, and increase their muscle strength.

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Some Studies of the Protein-Binding of Steroids and Their Application to the Routine Micro and Ultramicro Measurement of Various Steroids in Body Fluids by Competitive Protein-Binding Radioassay1

1967-07-01

Beverley E. Pearson Murphy

A method utilizing the steroid-binding properties of corticosteroid-binding globulin (CBG, transcortin) was described in 1963 for the routine determination of corticoids in 1 ml of plasma (J Clin Endocr23: 293, … A method utilizing the steroid-binding properties of corticosteroid-binding globulin (CBG, transcortin) was described in 1963 for the routine determination of corticoids in 1 ml of plasma (J Clin Endocr23: 293, 1963) and later modified to reduce the time required (J Clin Endocr24: 919, 1964). A 100-fold increase in sensitivity has now been achieved by using tritiated steroids in place of 14C-labeled steroids, by utilizing the CBG's of species other than man, and by using adsorption in place of dialysis or gel filtration. The use of several insoluble adsorbing agents (Fuller's earth, Florisil, coated charcoal) to separate protein-bound and unbound steroids was investigated and their effects on specificity were studied. The use of these techniques in plasma, urine and cerebrospinal fluid was vindicated. With these methods, cortisol can be measured routinely in 0.01 ml of plasma or 0.1 ml of cerebrospinal fluid, and progesterone in 0.3 ml of plasma. Compound S (11-desoxycortisol), corticosterone, cortisone and 11-hydroxyprogesterone can also be measured by this means.

Testosterone dose-response relationships in healthy young men

2001-12-01

Shalender Bhasin , Linda J. Woodhouse , Richard Casaburi +7 more

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent … Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18–35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose ( P = 0.0001) and correlated with log testosterone concentrations ( r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications

2005-10-01

Jean‐Marc Kaufman , Alex Vermeulen

Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum … Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between "substitutive" and "pharmacological" androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.

Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men

1997-04-01

John E. Morley , Fran E. Kaiser , Horace M. Perry +6 more

Prospective Study of Sex Hormone Levels and Risk of Prostate Cancer

1996-08-21

Peter H. Gann , Charles H. Hennekens , Jing Ma +2 more

Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult … Sex steroids, particularly androgens, have been implicated in the pathogenesis of prostate cancer. Data from previous studies comparing circulating hormone levels in men with and without prostate cancer are difficult to interpret, since the studies were limited in size, hormone levels were analyzed in blood drawn after the diagnosis of cancer, nonrepresentative control subjects were used, and hormone and hormone-binding protein levels were not simultaneously adjusted. We conducted a prospective, nested case-control study to investigate whether plasma hormone and sex hormone-binding globulin (SHBG) levels in healthy men were related to the subsequent development of prostate cancer. Among participants in the Physicians' Health Study who provided plasma samples in 1982, we identified 222 men who developed prostate cancer by March 1992. Three hundred ninety control subjects, matched to the case patients on the bases of age, smoking status, and length of follow-up, were also identified. Immunoassays were used to measure the levels of total testosterone, dihydrotestosterone (DHT), 3α-androstanediol glucuronide (AAG), estradiol, SHBG, and prolactin in the stored (at −82 °C) plasma samples. Correlations between individual hormone levels and between hormone levels and SHBG in the plasma of control subjects were assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) and 95% confidence intervals (CIs) specifying the prostate cancer risk associated with quartile levels of individual hormones, before and after adjustment for other hormones and SHBG, were calculated by use of conditional logistic regression modeling. Reported P values are two-sided. No clear associations were found between the unadjusted levels of individual hormones or SHBG and the risk of prostate cancer. However, a strong correlation was observed between the levels of testosterone and SHBG (r = .55), and weaker correlations were detected between the levels of testosterone and the levels of both estradiol (r = .28) and DHT (r = .32) (all P<.001). When hormone and SHBG levels were adjusted simultaneously, a strong trend of increasing prostate cancer risk was observed with increasing levels of plasma testosterone (ORs by quartile = 1.00, 1.41, 1.98, and 2.60 [95% CI = 1.34–5.02]; P for trend = .004), an inverse trend in risk was seen with increasing levels of SHBG (ORs by quartile = 1.00, 0.93, 0.61, and 0.46 [95% CI = 0.24–0.89]; P for trend = .01), and a nonlinear inverse association was found with increasing levels of estradiol (ORs by quartile = 1.00, 0.53, 0.40, and 0.56 [95% CI = 0.32–0.98]; P for trend = .03). No associations were detected between the levels of DHT or prolactin and prostate cancer risk; for AAG, a marker of 5α-reductase activity, only suggestive evidence of a positive association was found. The results were essentially unchanged when case patients diagnosed within 4 years of plasma collection, case patients diagnosed with localized (i.e., nonaggressive) disease, or control subjects with elevated prostate serum antigen levels (>2.5 ng/mL) were excluded from the analyses. High levels of circulating testosterone and low levels of SHBG—both within normal endogenous ranges—are associated with increased risks of prostate cancer. Low levels of circulating estradiol may represent an additional risk factor. Circulating levels of DHT and AAG do not appear to be strongly related to prostate cancer risk. [J Natl Cancer Inst 1996;88:1118–26]

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Transdermal Testosterone Gel Improves Sexual Function, Mood, Muscle Strength, and Body Composition Parameters in Hypogonadal Men1

2000-08-01

Christina Wang , Ronald S. Swerdloff , Ali Iranmanesh +6 more

Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sexual function, increase in muscle mass and strength, and decrease in fat mass, … Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sexual function, increase in muscle mass and strength, and decrease in fat mass, with minimal adverse effects. We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range. We now report the effects of 180 days of treatment with this 1% T gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel, respectively) compared to those of a permeation-enhanced T patch (5 mg/day) on defined efficacy parameters in 227 hypogonadal men. In the T gel groups, the T dose was adjusted up or down to 75 mg/day (contained in 7.5 g gel) on day 90 if serum T concentrations were below or above the normal male range. No dose adjustment was made with the T patch group. Sexual function and mood changes were monitored by questionnaire, body composition was determined by dual energy x-ray absorptiometry, and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises. Sexual function and mood improved maximally on day 30 of treatment, without differences across groups, and showed no further improvement with continuation of treatment. Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment. Moderate increases were also observed in arm/chest muscle strength. At 90 days of treatment, lean body mass increased more in the 100 mg/day T gel group (2.74 ± 0.28 kg; P = 0.0002) than in the 50 mg/day T gel (1.28± 0.32 kg) and T patch groups (1.20 ± 0.26 kg). Fat mass and percent fat were not significantly decreased in the T patch group, but showed decreases in the T gel groups (50 mg/day, −0.90 ± 0.32 kg; 100 mg/day, −1.05 ± 0.22 kg). The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement. These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile. The increase in mean serum prostate-specific antigen levels (within the normal range) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group. Skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeation-enhanced T patch group. We conclude that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch.

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Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.

1994-06-01

Arlene J. Morales , John J. Nolan , J C Nelson +1 more

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) … Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

2013-11-05

Rebecca Vigen , Colin O’Donnell , Anna E. Barón +7 more

Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with … Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. At 3 years after coronary angiography, the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group,with an absolute risk difference of 5.8%(95%CI, -1.4%to 13.1%) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1% vs 11.3%; at 2 years, 15.4% vs 18.5%; and at 3 years, 19.9% vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.

Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men

2007-11-27

Kay‐Tee Khaw , Mitch Dowsett , Elizabeth Folkerd +5 more

Background— The relation between endogenous testosterone concentrations and health in men is controversial. Methods and Results— We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all … Background— The relation between endogenous testosterone concentrations and health in men is controversial. Methods and Results— We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively ( P <0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (≈1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P <0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.

Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men

2001-02-01

S. Mitchell Harman , E. Jeffrey Metter , Jordan D. Tobin +2 more

Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is … Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, age-invariant, longitudinal effects of age on both T and free T index (free T index = T/SHBG), with an average change of− 0.124 nmol/L·yr and −0.0049 nmol T/nmol SHBG·yr. T, but not free T index, also decreased with increasing body mass index. Use ofβ− blocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.

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Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

2010-06-01

Shalender Bhasin , Glenn R. Cunningham , Frances J. Hayes +4 more

Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006.

Utility, Limitations, and Pitfalls in Measuring Testosterone: An Endocrine Society Position Statement

2006-11-07

William Rosner , Richard J. Auchus , Ricardo Azziz +2 more

The objective of the study was to evaluate the current state of clinical assays for total and free testosterone.The five participants were appointed by the Council of The Endocrine Society … The objective of the study was to evaluate the current state of clinical assays for total and free testosterone.The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion.Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants.The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations.Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration.

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Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

2006-05-25

Dheeraj Kapoor , Erica Goodwin , Kevin S. Channer +1 more

Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on … Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes.This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes.Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone.Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed.Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.

Low Serum Testosterone and Mortality in Older Men

2007-10-03

Gail A. Laughlin , Elizabeth Barrett‐Connor , Jaclyn Bergstrom

Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few.The … Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few.The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men.This was a prospective, population-based study of 794 men, aged 50-91 (median 73.6) yr who had serum testosterone measurements at baseline (1984-1987) and were followed for mortality through July 2004.All-cause mortality by serum testosterone level was measured.During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14-1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle. Additional adjustment for health status markers, lipids, lipoproteins, blood pressure, glycemia, adipocytokines, and estradiol levels had minimal effect on results. The low testosterone-mortality association was also independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein. In cause-specific analyses, low testosterone predicted increased risk of cardiovascular (HR 1.38; 95% CI 1.02-1.85) and respiratory disease (HR 2.29; 95% CI 1.25-4.20) mortality but was not significantly related to cancer death (HR 1.34; 95% CI 0.89-2.00). Results were similar for bioavailable testosterone.Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.

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StAR Protein and the Regulation of Steroid Hormone Biosynthesis

2001-03-01

Douglas M. Stocco

▪ Abstract Steroid hormone biosynthesis is acutely regulated by pituitary trophic hormones and other steroidogenic stimuli. This regulation requires the synthesis of a protein whose function is to translocate cholesterol … ▪ Abstract Steroid hormone biosynthesis is acutely regulated by pituitary trophic hormones and other steroidogenic stimuli. This regulation requires the synthesis of a protein whose function is to translocate cholesterol from the outer to the inner mitochondrial membrane in steroidogenic cells, the rate-limiting step in steroid hormone formation. The steroidogenic acute regulatory (StAR) protein is an indispensable component in this process and is the best candidate to fill the role of the putative regulator. StAR is expressed in steroidogenic tissues in response to agents that stimulate steroid production, and mutations in the StAR gene result in the disease congenital lipoid adrenal hyperplasia, in which steroid hormone biosynthesis is severely compromised. The StAR null mouse has a phenotype that is essentially identical to the human disease. The positive and negative expression of StAR is sensitive to agents that increase and inhibit steroid biosynthesis respectively. The mechanism by which StAR mediates cholesterol transfer in the mitochondria has not been fully characterized. However, the tertiary structure of the START domain of a StAR homolog has been solved, and identification of a cholesterol-binding hydrophobic tunnel within this domain raises the possibility that StAR acts as a cholesterol-shuttling protein.

Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Linked to Age and Modifiable Risk Factors: The European Male Aging Study

2008-02-13

Frederick C. W. Wu , Abdelouahid Tajar , Stephen R. Pye +7 more

Abstract Context: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. Objective: The objective of the study was to investigate the relationships … Abstract Context: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. Objective: The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men. Design: This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40–79 yr from a prospective cohort study in eight European countries. Results: Four predictors were associated with distinct modes of altered function: 1) age: lower free T (FT; −3.12 pmol/liter·yr, P &lt; 0.001) with raised LH, suggesting impaired testicular function; 2) obesity: lower total T (TT; −2.32 nmol/liter) and FT (−17.60 pmol/liter) for body mass index (BMI; ≥ 25 to &lt; 30 kg/m2) and lower TT (−5.09 nmol/liter) and FT (−53.72 pmol/liter) for BMI 30 kg/m2 or greater (P &lt; 0.001–0.01, referent: BMI &lt; 25 kg/m2) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction; 3) comorbidity: lower TT (−0.80 nmol/liter, P &lt; 0.01) with unchanged LH in younger men but higher LH in older men; and 4) smoking: higher SHBG (5.96 nmol/liter, P &lt; 0.001) and LH (0.77 U/liter, P &lt; 0.01) with increased TT (1.31 nmol/liter, P &lt; 0.001) but not FT, compatible with a resetting of T-LH-negative feedback due to elevated SHBG. Conclusions: Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men.

Adverse Events Associated with Testosterone Administration

2010-06-30

Shehzad Basaria , Andrea D. Coviello , Thomas G. Travison +7 more

Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility … Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.

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Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy

2005-07-01

Sonia L. Davison , Robin J. Bell , Susan Donath +2 more

Abstract Context: Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established. Objective: The objective of this … Abstract Context: Changes in androgen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established. Objective: The objective of this study was to document the effects of age on androgen levels in healthy women and to explore the effects of natural and surgical menopause. Design, Setting, and Participants: A cross-sectional study was conducted of 1423 non-healthcare-seeking women, aged 18–75 yr, randomly recruited from the community over 15 months. Main Outcome Measures: Serum levels by age of total testosterone (T), calculated free T, dehydroepiandrosterone sulfate, and androstenedione in a reference group of women free of confounding factors. Women in the reference group had no usage of exogenous steroid therapy; no history of tubal ligation, hysterectomy, or bilateral oophorectomy; and no hyperprolactinemia or polycystic ovarian syndrome. The effects of natural and surgical menopause on sex steroid levels were also examined. Results: In the reference population (n = 595), total T, calculated free T, dehydroepiandrosterone sulfate, and androstenedione declined steeply with age (P &lt; 0.001), with the decline of each being greater in the earlier than the later decades. Examination of serum androgen levels by year in women aged 45–54 yr showed no independent effect of menopausal status on androgen levels. In women aged 55 yr or older, those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group. Conclusions: We report that serum androgen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production. These significant variations in androgens with age must be taken into account when normal ranges are reported and in studies of the role of androgens in women.

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study

2002-02-01

Henry A. Feldman , Christopher Longcope , Carol A. Derby +5 more

We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level … We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally. Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10-15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends. The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.

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Transport of Steroid Hormones: Binding of 21 Endogenous Steroids to Both Testosterone-Binding Globulin and Corticosteroid-Binding Globulin in Human Plasma

1981-07-01

James F. Dunn , BRUCE C. NISULA , David Rodbard

This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under … This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under equilibrium conditions using a solid phase method at physiological pH and temperature. A computer program was used to solve the complex equilibrium interactions between these steroids and TeBG, CBG, and albumin. In this manner, we calculated the plasma distribution of each steroid into TeBG-bound, CBG-bound, albumin-bound, and unbound fractions in normal men, normal women during both the follicular and luteal phases of the ovarian cycle, and women during the third trimester of a normal pregnancy.

Testosterone and Sex Hormone–Binding Globulin Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men

2004-05-01

David E. Laaksonen , Leo Niskanen , Kari Punnonen +5 more

In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. … In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men.Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome.After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone.Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.

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Effects of Testosterone Treatment in Older Men

2016-02-17

Peter J. Snyder , Shalender Bhasin , Glenn R. Cunningham +7 more

Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.

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Transdermal Testosterone Treatment in Women with Impaired Sexual Function after Oophorectomy

2000-09-07

Jan Shifren , Glenn D. Braunstein , James A. Simon +7 more

The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone … The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause.

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Testosterone Therapy in Men With Hypogonadism: An Endocrine Society* Clinical Practice Guideline

2018-03-17

Shalender Bhasin , Juan P. Brito , Glenn R. Cunningham +7 more

To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.The participants include an Endocrine Society-appointed task force of 10 medical content experts and a clinical … To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.The participants include an Endocrine Society-appointed task force of 10 medical content experts and a clinical practice guideline methodologist.This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.One group meeting, several conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline.We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone-binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.

Cardiovascular Risks Associated with Gender and Aging

2019-04-27

Jennifer L. Rodgers , Jarrod Jones , Samuel Ignatious Bolleddu +5 more

The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional … The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional factors, including frailty, obesity, and diabetes. These factors are known to complicate and enhance cardiac risk factors that are associated with the onset of advanced age. Sex is another potential risk factor in aging adults, given that older females are reported to be at a greater risk for CVD than age-matched men. However, in both men and women, the risks associated with CVD increase with age, and these correspond to an overall decline in sex hormones, primarily of estrogen and testosterone. Despite this, hormone replacement therapies are largely shown to not improve outcomes in older patients and may also increase the risks of cardiac events in older adults. This review discusses current findings regarding the impacts of age and gender on heart disease.

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Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline

2006-05-23

Shalender Bhasin , Glenn R. Cunningham , Frances J. Hayes +4 more

The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men.The Task Force was composed of a chair, selected by the Clinical Guidelines … The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men.The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration.The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group.Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes.We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.

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The Deadly Quartet

1989-07-01

Norman M. Kaplan

• The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, … • The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, and hypertriglyceridemia even in the absence of significant overall obesity. This article examines the evidence that upper-body obesity, as usually induced by caloric excess in the presence of androgens, mediates these problems by way of hyperinsulinemia. Because of these interrelationships, there is a need to identify and prevent upper-body obesity or, failing that, to provide therapies that will control the associated problems without aggravating hyperinsulinemia. (Arch Intern Med. 1989;149:1514-1520)

Testosterone pellet surface area relates to effectiveness more than dose

2025-06-24

Charles Virden , Maron B. Calderwood Mays | The Aging Male

Hypogonadism, while common, can be devastating with long-term ramifications. There are multiple treatment options, but most are burdensome leading to poor compliance. Administration of testosterone (T) pellets offers consistent blood … Hypogonadism, while common, can be devastating with long-term ramifications. There are multiple treatment options, but most are burdensome leading to poor compliance. Administration of testosterone (T) pellets offers consistent blood levels based on the implantation of pellets that dissolve over months. Guidelines for pellet dosing has been absent and often men are overdosed with T. The goal of the study was to evaluate the effect of pellet dose versus surface area on blood levels over 3 months in healthy men. One group of men were administered small individual pellets that resulted in higher surface than the other group, but at a lower dose. Within 2 weeks the T levels had risen over two times the baseline level in both groups, but the cohort administered the lowest T dose (but highest surface area) had the greatest response whether calculated as peak change or when analyzed according to age-adjusted values. Increasing the pellet surface area resulted in fewer extrusions, no adverse events, and higher serum T levels compared to subjects that received a higher dose with a lower surface area. Presently there appears to be no negative consequences of administering T pellets using methods that maximize the total pellet surface area.

Wallenberg Syndrome Following Anabolic-Androgenic Steroid Use: A Case Report

2025-06-23

Daniel Vidrio Carrizales , Manuel Villegas , Lizeth Nayeli Gutierrez Góme +3 more | International Journal of Medical Science and Clinical Research Studies

Background: Wallenberg syndrome is a rare ischemic stroke syndrome resulting from infarction in the posterior inferior cerebellar artery (PICA) territory. Anabolic-androgenic steroids (AAS), used frequently in athletic settings, are associated … Background: Wallenberg syndrome is a rare ischemic stroke syndrome resulting from infarction in the posterior inferior cerebellar artery (PICA) territory. Anabolic-androgenic steroids (AAS), used frequently in athletic settings, are associated with prothrombotic and vasospastic phenomena that may increase the risk of cerebrovascular events. Case presentation: We report a case of a 39-year-old male strength coach with no prior medical history, who presented with acute onset of vomiting, singultus, ataxia, and ipsilateral facial hypoesthesia. He had a history of self-administered AAS cycles since the age of 19. MRI revealed a left cerebellar hemisphere infarct, and CT angiography hypoplasia of the left vertebral artery with occlusion of distal segments V3 and V4. Cardioembolic, infectious, and autoimmune etiologies were excluded. Conclusion: Although causality cannot be definitively established, this case highlights the possible association between chronic anabolic steroid use and posterior circulation ischemic stroke. AAS may induce cerebrovascular risk via vascular remodeling, vasospasm, or thrombosis.

Delayed Puberty and Incidental Hypertension in a 14-year-old Girl

2025-06-23

| American Academy of Pediatrics eBooks

test submission

2025-06-21

Test hotmail | European Journal of Business Management and Research

this is a test submission this is a test submission

Quantification of Endogenous Steroids and Hormonal Contraceptives in Human Plasma via Surrogate Calibration and UHPLC-MS/MS

2025-06-20

Min Su , Bernhard Drotleff , Tamara Janker +4 more | Analytical Chemistry

Quantifying endogenous and exogenous steroids at low concentrations in biological matrices remains a major analytical challenge. Immunoassay-based diagnostics are limited by cross-reactivity, particularly at low levels, prompting a shift toward … Quantifying endogenous and exogenous steroids at low concentrations in biological matrices remains a major analytical challenge. Immunoassay-based diagnostics are limited by cross-reactivity, particularly at low levels, prompting a shift toward (ultra)high-performance liquid chromatography-tandem mass spectrometry ((U)HPLC-MS/MS) for clinical applications. A key limitation for endogenous hormone quantification is the absence of a true blank matrix for external calibration. To address this, we developed a surrogate calibration method employing 1,2-dimethylimidazole-5-sulfonyl chloride (DMIS) derivatization for estrogens, enabling sensitive and selective quantification alongside nonderivatized steroids. Stable isotope-labeled surrogate calibrants and internal standards were used to achieve matrix-matched quantification within a clinically relevant range. Parallelism between analytes and surrogate calibrants was systematically verified in plasma across multiple calibration levels. The method was further optimized through the use of narrow-bore UHPLC columns and refined chromatographic conditions to enhance sensitivity and resolution for a broad analyte panel. Combined with efficient protein precipitation and 96-well plate-based solid-phase extraction, the developed assay achieves pg/mL-level quantification in human plasma with high precision and accuracy. This integrated approach uniquely combines surrogate calibration for endogenous steroids with external calibration for exogenous contraceptives, including sensitive DMIS-based derivatization for estrogens, enabling comprehensive hormonal profiling in a single run. Beyond its analytical scope, the method outlines a structured validation strategy, which is aligned with regulatory principles, and may therefore serve as a practical reference for future LC-MS/MS assays employing surrogate calibration.

Hydroxychloroquine modulates the progression of experimentally induced benign prostatic hyperplasia in rats via targeting EGFR/ERK/STAT3 and AR/FOXO1/TRAIL pathways: computational and in vivo studies

2025-06-20

Walaa H. El-Maadawy , Ehab Hafiz , Samer A. Tadros +4 more | Scientific Reports

Abstract Benign prostatic hyperplasia (BPH) is a prevalent progressive age-related disorder in men, yet its etiopathophysiology remains poorly understood. Current treatments like finasteride (Fin) have limited long-term efficacy, necessitating alternative … Abstract Benign prostatic hyperplasia (BPH) is a prevalent progressive age-related disorder in men, yet its etiopathophysiology remains poorly understood. Current treatments like finasteride (Fin) have limited long-term efficacy, necessitating alternative therapies. Hydroxychloroquine (HCQ), a safe antimalarial agent, possesses anti-inflammatory, immunomodulatory, and antiproliferative activities, however, its therapeutic effect in BPH has not been investigated. Accordingly, we examined its therapeutic potential and underlying mechanisms, alone or combined with Fin, in testosterone-induced BPH in rats. In BPH-induced rats, HCQ markedly reduced prostate weight and index, and PSA, testosterone, dihydrotestosterone, pro-inflammatory cytokines (TNF-α, κ and IL-6), and the transcription factor “NF-κB” levels, while improving histological abnormalities in epithelial and stromal tissues. HCQ reduced the mRNA expression of AR and ERK1/2, and decreased the protein levels of EGFR and STAT3. Additionally, HCQ increased the mRNA expression of FOXO1 and promoted apoptosis through both intrinsic and TRAIL-mediated pathways. This was evidenced by the upregulation of pro-apoptotic Bax and the downregulation of anti-apoptotic Bcl-2 and Bcl-XL levels in the intrinsic pathway, as well as the reduction in mRNA expression of DR4 and DR5 in the TRAIL-mediated pathway. Notably, combining HCQ with Fin enhanced these effects. Molecular docking revealed HCQ’s strong interactions with androgen receptor (AR), EGFR, ERK1/2, FOXO, and TRAIL death receptors (DR4/DR5), comparable to Fin except for STAT3. Our findings suggest that HCQ modulates BPH progression by targeting STAT3/FOXO1/TRAIL and EGFR/ERK/AR pathways, offering a promising therapeutic strategy for BPH, either alone or in combination with Fin.

Sudden cardiac testosterone-related death involving a young bodybuilder: autopsy, histopathological and toxicological findings

2025-06-20

Donato Morena , Alessandro Bonsignore , Alessandro Santurro +2 more | Egyptian Journal of Forensic Sciences

Abstract Background Anabolic androgenic steroids (AASs) comprise a large group of synthetic derivatives of testosterone, designed to enhance anabolic properties while minimizing androgenic effects. In addition to their therapeutic applications, … Abstract Background Anabolic androgenic steroids (AASs) comprise a large group of synthetic derivatives of testosterone, designed to enhance anabolic properties while minimizing androgenic effects. In addition to their therapeutic applications, AASs are frequently abused by athletes, particularly bodybuilders, to enhance performance, promote muscle growth, and increase lean body mass due to their significant anabolic effects. Prolonged misuse and abuse of AASs can lead to multiple adverse effects, some of which may be fatal, particularly in the cardiovascular system. Case presentation This report presents a case of sudden cardiac death (SCD) in a 28-year-old, apparently healthy male bodybuilder with a history of chronic AAS abuse. A complete autopsy, along with histological and toxicological analyses, was performed. The autopsy findings included pronounced muscle hypertrophy and hepatomegaly. Macroscopically, the left and right coronary arteries exhibited 75–80% luminal narrowing, and there was a moderate increase in left ventricular wall thickness. Histological examination of myocardial tissue revealed multifocal myocardial necrosis, areas of myocyte disarray with a star-like arrangement, focal colliquative myocytolysis (grade 1), small foci of mild interstitial and perivascular fibrosis in the myocardium of the left ventricular wall, and peliosis hepatis. Toxicological analysis demonstrated a urinary testosterone-to-epitestosterone (T/E) ratio of 38.7, confirming exogenous testosterone administration. In this case, the combined effects of vigorous physical training and intramuscular testosterone administration likely led to sympathetic nervous system activation, predisposing the individual to myocardial damage and subsequent SCD. Conclusions In cases of sudden death among apparently healthy bodybuilders, a thorough circumstantial investigation, along with comprehensive autopsy, histological, and toxicological analyses, is essential to confirm AAS abuse and identify the cardiac pathologies associated with these substances, which play a critical role in such fatalities.

Unveiling therapeutic targets and preventive components for kidney insufficiency and blood stasis-type BPH: bridging metabolomics, network pharmacology and reverse screening

2025-06-19

Xiangpeng Kong , Haiqin Ren , Ke Pei +7 more | Frontiers in Pharmacology

Benign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine … Benign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine mainly adopts symptomatic treatments such as 5-alpha reductase inhibitors and alpha1 adrenergic receptor blockers. However, due to the complex pathogenesis of BPH, these drugs can only partially alleviate symptoms and have shortcomings such as high treatment costs and significant side effects. BPH is similar to the descriptions of “Jīng Lóng” and “Lóng Bì” in traditional Chinese medicine (TCM), and its onset is closely related to liver and kidney dysfunction. Kidney insufficiency and blood stasis are common clinical syndromes of BPH. Compared with modern medicine, treatment based on syndrome differentiation of TCM can achieve good results in treating this subtype of BPH. Therefore, guided by the holistic view of TCM, adopting a holistic and systematic research approach to explore therapeutic targets and potential therapeutic components for BPH with a specific syndrome can provide new ideas for the clinical treatment of BPH. This study integrated clinical metabolomics and network pharmacology to identify therapeutic targets for kidney insufficiency and blood stasis-type BPH. Serum analysis of BPH patients and healthy controls for testosterone, estradiol, SRD5α2, NF-κB p65, and TGF-β levels, alongside metabolomics and network pharmacology, revealed hormonal imbalance, increased inflammatory/fibrotic markers, and 58 differential metabolites in BPH. Pathway enrichment analysis identified 6 key metabolic pathways, while network pharmacology constructed four compound-reaction-enzyme-gene networks and pinpointed 178 potential targets, including 23 core targets. Reverse screening against the Yaozh Database-Natural Product AI Engine Platform matched 11 druggable targets with 49 interacting components, and target-component fitting analysis confirmed the reliability of 8 core targets. This combined approach validated the findings of hormonal imbalance and significant metabolic pathway changes and provided valuable insights for BPH treatment and drug development.

Tratamiento Médico y Farmacológico de la Hiperplasia Prostática Benigna

2025-06-19

Juan Carlos Luigi | Revista venezolana de urología/Revista Venezolana de Urología

El crecimiento benigno de las células glandulares y estromales de la zona de transición prostática se conoce como Hiperplasia prostática benigna (HPB)1. Es casi omnipresente en el hombre mayor y … El crecimiento benigno de las células glandulares y estromales de la zona de transición prostática se conoce como Hiperplasia prostática benigna (HPB)1. Es casi omnipresente en el hombre mayor y su prevalencia histológica alrededor del mundo, demostrada por autopsias, aumenta a partir de los 40-45 años. Esta puede ocasionar un agrandamiento de la próstata denominado crecimiento prostático benigno (CPB).

Frequent use of methylphenidate causes reduction in sperm production and sperm quality in adult balb/c mice

2025-06-17

Grasielle Avelar Vieira Rodrigues , Fernanda Carolina Ribeiro Dias , Elizabeth Lopes de Oliveira +2 more | Reproductive Biology

Association between serum testosterone and measures of cardiovascular health among transgender individuals using gender-affirming testosterone therapy: a cross-sectional study

2025-06-17

Badal S B Pattar , Tyrone G. Harrison , Nathalie Saad +7 more | Biology of Sex Differences

Abstract Background Gender-affirming testosterone therapy (GATT) use may be associated with increased systolic blood pressure (SBP). The association between serum testosterone and cardiovascular health in individuals using GATT is unknown. … Abstract Background Gender-affirming testosterone therapy (GATT) use may be associated with increased systolic blood pressure (SBP). The association between serum testosterone and cardiovascular health in individuals using GATT is unknown. The objective of this study was to estimate the association between serum testosterone and validated measures of cardiovascular health, including SBP and arterial stiffness, in persons assigned female sex at birth using GATT. Methods Healthy participants assigned female sex at birth on a stable GATT regimen for ≥ 4 months were recruited to this community-partnered exploratory cross-sectional study. Exposures of interest were total and free serum testosterone concentration. As our primary outcome, SBP was measured by an automated sphygmomanometer, and carotid-radial pulse wave velocity (PWVcr) and aortic augmentation index (AIx) were used to measure arterial stiffness via applanation tonometry. Results Participants (n = 18, median age 28 years, range: 18, 50) who predominantly self-identified as white (94%) and had been using GATT for a median of 48 months (range: 5, 84) were studied. Resting SBP, PWVcr, and AIx were 113 mmHg (range: 102, 129), 7 m/s (range: 4, 9), and 9% (range: − 10, 23), respectively. Total and free serum testosterone were not significantly associated with SBP or PWVcr. Free, but not total, serum testosterone was positively associated with AIx (p = 0.03). Sensitivity analyses did not modify any results. Conclusions In healthy transgender individuals, serum testosterone concentrations may not be associated with measures of cardiovascular health. However, these results need to be interpreted with caution given the limited sample size.

Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry

2025-06-17

Serena Correnti , Giuseppina Fanelli , Mariaimmacolata Preianò +7 more | Frontiers in Molecular Biosciences

Teratozoospermia, a qualitative sperm disorder characterized by abnormal sperm morphology, represents one of the causes of male infertility worldwide. The metabolic analysis of human seminal plasma (SP), can provide insights … Teratozoospermia, a qualitative sperm disorder characterized by abnormal sperm morphology, represents one of the causes of male infertility worldwide. The metabolic analysis of human seminal plasma (SP), can provide insights into the underlying molecular mechanisms of this condition, identifying novel biomarkers and facilitating the development of diagnostic tests. In this study, an untargeted High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) approach was performed to explore SP metabolic alterations associated with teratozoospermia. SP samples from 15 teratozoospermic (TZ) vs. 20 normozoospermic (NZ) subjects were analyzed to identify metabolic pathways linked to sperm morphology dysfunction. Multivariate statistical analysis, including Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA, revealed a distinct separation between TZ and NZ, highlighting 14 significantly altered metabolites. Based on Variable Importance in Projection scores, O-acetyl-L-serine showed the highest score. Main findings include alterations in Creatine, Histidine, Adenine, Allantoin and Deoxyuridine levels, suggesting perturbations in inflammation, oxidative stress and sperm DNA damage in teratozoospermia. Correlation and Receiver Operating Characteristic (ROC) analyses identified potential biomarkers, including O-acetyl-L-serine, Creatine, and Histidine, with robust discriminatory power (AUC &gt;0.7). These findings highlight potential metabolic pathways implicated in the pathophysiology of teratozoospermia and provide a foundation for enabling personalized patient management with precision treatment.

Testosterone Suppression with or without Testicular Preservation: Impact on Mouse Behavior, Including Emotional State, Locomotor Activity, Social Interaction, Cognitive Function, and Sexual Behavior

2025-06-16

Yaxin Zang , Liuxia Lin , Ye Lu +7 more | Biochemical and Biophysical Research Communications

A comparative analysis of blood groups and testosterone levels in infertile men in Yenagoa, South-South Nigeria.

2025-06-16

Enebrayi Nelson Onitsha , Okutu Jackson Borobuebi , Ectors Francis +4 more | Sokoto Journal of Medical Laboratory Science

Infertility remains a very common global issue that is often associated with several factors such as hormonal, cervical, uterine, immunological or psychological influences. Aside from these factors, there are instances … Infertility remains a very common global issue that is often associated with several factors such as hormonal, cervical, uterine, immunological or psychological influences. Aside from these factors, there are instances where infertility remains inexplicable. Therefore, further research is required to identify the underlying causes of unexplained infertility. This study assessed the nexus between blood groups and male infertility by evaluating the serum testosterone levels. The study utilized a cross-sectional study design. A total of 200 male within the ages of 18 to 40 years attending fertility clinic at the Federal Medical Centre Yenagoa, Family Care Hospital, Yenagoa, and Tobis Clinic and Consultant between the period of February 2023 and August 2024 were recruited for the study. The subjects consist of 120 known infertile male patients, and 60 apparently healthy fertile males, which served as the control group. Five milliliters of blood was collected following standard procedures and used for the determination of blood groups and testosterone levels using Slide Haem-agglutination technique and Enzyme linked immunosorbent assay (ELISA) technique respectively. Special Package for Social Science version 23.0 was used to perform the statistical analysis, and p-value less than 0.05 was considered statistically significant. The result revealed that the distribution of blood groups in the studied population was 61.7%, 21.7%, 11.7%, and 5.0% for blood groups O, B, A and AB respectively. The Rhesus blood group distribution in the infertile males was 95.0% and 5.0% for Rhesus D positive and negative respectively. The mean values of testosterone in blood group O males were slightly higher than group A, AB and B, but not statistically significant (p>0 . 05) . Furthermore, the mean values of testosterone levels in Rhesus D positive infertile males were insignificantly (p>0.05) higher than Rhesus D negative patients. The study indicated that the incidence of male infertility among individuals with blood group O is consistently higher as compared with other blood groups, suggesting a strong connection between blood group O and male infertility. However, no correlation was found between ABO and Rhesus blood groups and male infertility hormone. But the elevated testosterone levels observed in men with blood group O could represent a possible connection between blood groups and male infertility.

Associations of plasma sex‐related hormone and protein levels and alcohol dependence

2025-06-16

Ada Man‐Choi Ho , Jennifer R. Geske , Vanessa Pazdernik +4 more | Addiction

Abstract Background and Aims Sex‐related hormones and proteins may underlie sex differences in alcohol use disorder characteristics and consequences. Previous reports suggest steroid sex hormones may influence alcohol consumption behaviors … Abstract Background and Aims Sex‐related hormones and proteins may underlie sex differences in alcohol use disorder characteristics and consequences. Previous reports suggest steroid sex hormones may influence alcohol consumption behaviors while proteins that regulate their circulation levels are rarely investigated. Following up on our earlier study of individual sex‐related hormones' associations with alcohol dependence (AD), this study measured the associations between the combinations of sex‐related hormones and proteins and AD in a larger sample. Design Sex‐stratified case‐control comparison and clustering of plasma sex‐related hormone and protein levels, plus a genome‐wide association study on the AD‐associated hormone and protein combinations. Setting Addiction treatment programs in the United States. Participants Four hundred treatment‐seeking recently abstained AD patients (median = 24.5 days) and 388 age‐and‐sex‐matched controls from a community biobank (male:female ≈ 2:1). Measurements Plasma levels of total testosterone, estrone (E1), estradiol (E2), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin (SHBG) and albumin. Findings In males, we found higher E2 [ β = 0.13, P unadjusted < 0.001, false discovery rate (FDR) = 0.005], progesterone ( β = 0.01, P unadjusted = 0.025, FDR = 0.054), LH ( β = 0.12, P unadjusted = 0.017, FDR = 0.044) and albumin ( β = 0.09, P unadjusted < 0.001, FDR = 0.005) in AD patients than controls; in females, we observed lower E1 ( β = −0.24, P unadjusted = 0.024, FDR = 0.113) and progesterone ( β = −1.86, P unadjusted = 0.026, FDR = 0.113) and higher albumin ( β = 0.18, P unadjusted < 0.001, FDR = 0.001) in AD patients than controls. Three principal components (PCs), reflecting hormone signatures, were statistically significantly associated with AD in each sex: PC1 (TT, E2 and SHBG; β = −0.15, P = 0.016), PC3 (E1, progesterone and albumin; β = 0.28, P = 0.007) and PC4 (SHBG and albumin; β = 0.34, P = 0.001) in males; PC3 (progesterone and albumin; β = −0.38, P = 0.009), PC4 (TT and albumin; β = −0.49, P = 0.001) and PC5 (TT and progesterone; β = 0.54, P = 0.004) in females. Statistically significant SNP × group associations were found in females between PC4 and polymorphisms in RP51004I9.1 (top SNP: rs6082693; P = 5.41E‐12) and in males between PC3 and a genomic locus that contained SLC35E4 , DUSP18 and OSBP2 (top SNP: rs13053277; P = 1.77E‐07). Conclusions Three sex‐related hormone and protein signatures appear to be associated with alcohol dependence in each sex. Peripheral levels of sex‐related hormones and proteins, as well as their combinations, could be altered in people with alcohol dependence who have abstained for a few weeks compared with controls, and such differences may be sex‐specific.

BENEFÍCIOS E MALEFÍCIOS DO USO DE ESTEROIDES E ANABOLIZANTES: REVISÃO DE LITERATURA

2025-06-16

Adroaldo De Miranda Rocha Neto , Demetryus Vieira Simeão , Pedro Simão da Silva Azevedo | Revista fisio&terapia.

FUNCTIONAL STATE OF TESTICLES AND VITAMIN D LEVELS IN THE BLOOD OF YOUNG MEN WITH PROSTATE DISEASES AND INFERTILITY

2025-06-15

Vоlodymyr Bondarenko , Ye. M. Korenieva , E. I. Skornyakov +4 more | PROBLEMS OF ENDOCRINE PATHOLOGY

Background. There is data indicating that the blood content of vitamin D able to influence on the level of androgenization and spermogram parameters in men. Nevertheless, how these indicators change … Background. There is data indicating that the blood content of vitamin D able to influence on the level of androgenization and spermogram parameters in men. Nevertheless, how these indicators change in young men with infertility and prostatopathy depending on the presence or absence of D-hypovitaminosis is unknown. The purpose of the work: To study the features of changes in spermatogenic and endocrine functions of the testes in men with infertility against the background of chronic prostatitis and benign prostatic hyperplasia depending on the blood level of vitamin D. Materials and methods. The level of testosterone (T) and estradiol (E2) in the blood were analyzed by enzyme immunoassay method in 63 men aged 24-45 years with infertility and prostatopathy depending on the level of vitamin D in the blood: more or less than 30,0 ng/mL, and spermogram parameters were also determined according to WHO recommendations. Among the examined of 32 persons had characteristics of chronic prostatitis (CP) and 31 patients had benign prostatic hyperplasia (BPH). Similarly, the hormonal status and spermogram parameters were analyzed in 27 practically healthy men of the same age, who made up the control group. The material was statistically processed by calculating the arithmetic average indica-tors and its deviations (X̅±Sx̅), χ2 values and Pearson correlation coefficients. Results. Infertile men with both CP and BPH in the presence of D-hypovitaminosis had significantly reduced averange levels T and T/E2 values compared to individuals whose blood vitamin D levels exceeded 30.0 ng/mL. At the same time low blood levels of vitamin D in patients with BPH are associated with moderate androgen deficiency, when the content of T in the blood is less than 2.0 nmol/L, but exceeds 9.2 nmol/L, or the limit below which the hypogonadal androgen level is determined. (χ2 =4.68; p < 0.05). These changes in androgenization were accompanied by a more significant decrease in the number of motile sperm forms in both groups of patients with D-hypovitaminosis. There is no correlation between the content of vitamin D and blood levels of T, as well as between the level of vitamin D and the number of sperm and their motile forms. Conclusions. In infertile men with chronic prostatitis or signs of benign prostatic hyperplasia, under conditions of D-hypovitaminosis, there is a significant decrease in androgenization levels compared to patients in whom the content of vitamin D in the blood is normal. The presence of D-hypovitaminosis in infertile men with chronic prostatitis and benign prostatic hyperplasia significantly affects sperm motility and does not change them. In infertility in men with chronic prostatitis or benign prostatic hyperplasia, there is no correlation between the level of vitamin D and the content of testosterone in the blood, nor with sperm concentration and motility.

Effect of androgen in peyronie plaque induction rats

2025-06-15

Gülsün Öz , Mustafa Ozan Ataçer , Gökhan Çevik +3 more | The Aging Male

Peyronie's disease and hypogonadism are believed to have a linear association; however, research has yielded conflicting results. This is the first histopathological study on this topic. This study randomly assigned … Peyronie's disease and hypogonadism are believed to have a linear association; however, research has yielded conflicting results. This is the first histopathological study on this topic. This study randomly assigned 40 three-month-old male Sprague-Dawley rats to five groups. We established Peyronie's model by injecting intratunical TGF-beta and 3% disodium phosphate dihydrate into four groups. One group received intratunical saline. The control group for the Peyronie's disease model was one group. In the other groups, the first had castration orchiectomy. The second group was the Peyronie's disease model control. The third group received intratunical saline injections. The fourth group received intraperitoneal testosterone injections, while the fifth received 0.5 mg of 5-alpha reductase inhibitor orally daily. We excised penile tissue for histopathology after a 30-day follow-up. Masson's trichrome staining found collagen and smooth muscle, picro-sirius staining found collagen III and collagen I, and hematoxylin and eosin staining found fibrosis. Histopathological examination revealed significant differences in fibrosis, smooth muscle/collagen ratios, and collagen III/collagen I ratios. Comparing groupings without a control group revealed no statistically significant differences. This study explored testosterone's effect on Peyronie's disease in rats. Fibrosis was analyzed, but no significant changes were observed.

Impacto do uso de contraceptivos hormonais na performance esportiva em mulheres

2025-06-14

Ana Cristina de Castro Pereira Santos , Bianca Santos Andrade , Luiza Augusto de Morais | Research Society and Development

O corpo feminino passa por inúmeras variações durante o mês e a vida. Além disso, fatores externos podem impactar no cotidiano feminino como, por exemplo, a escolha do método contraceptivo. … O corpo feminino passa por inúmeras variações durante o mês e a vida. Além disso, fatores externos podem impactar no cotidiano feminino como, por exemplo, a escolha do método contraceptivo. Logo, uma análise das consequências desse uso faz-se necessária para uma boa qualidade de vida desse público. O objetivo primário deste artigo foi compreender as alterações hormonais causadas pelo uso de contraceptivos hormonais e como isso pode influenciar o desempenho do exercício em mulheres. Trata-se de um estudo de revisão bibliográfica, na qual foram analisados artigos científicos, revistas científicas, documentos legais e censo demográfico, publicados entre 2002 e 2025, com uma leitura minuciosa de resumos, gráficos, tabelas, pesquisas e artigos na íntegra, as bases de dados utilizadas foram SCIELO, PUBMED, OMS, IBGE. Nesta revisão, foram encontradas alterações cerebrais, capazes influenciar na adesão de treinos e dietas, mudanças com relação no nível de inflamação em mulheres que utilizavam métodos contraceptivos hormonais, além da utilização de substratos energéticos de forma diferenciada de acordo com o momento do ciclo menstrual ou fase do método contraceptivo.

Alterations in the Morphology of the Testis and Epididymis Caused by the Consumption of Hyperlipidic Diets in Wistar Rats

2025-06-14

R. Castellanos , Mario Delgado , Lorena Ruiz Valderrama +7 more | Life

Obesity is considered a metabolic disease, in which leptin is used as an indicator of energy in the body. This hormone, in turn, is related to the neuroendocrine regulation of … Obesity is considered a metabolic disease, in which leptin is used as an indicator of energy in the body. This hormone, in turn, is related to the neuroendocrine regulation of the reproductive axis. However, leptin excess secretion due to obesity can have a negative effect on reproduction. Overweight and obesity were induced through high-calorie diets. Lee and gonadosomatic indices were determined to characterize the model and degree of reproductive development in the testis and epididymis. Sperm quality was analyzed using spermatobioscopy. Morphometry was analyzed through histological analysis. The changes described affect testicular function in hormone and sperm production. Exposure of 3-month-old male rats to diets with different fat contents (10% and 60%) induced both overweight and obesity. The animals showed morphological alterations, both testicular and epididymal, the latter being more sensitive to dietary changes by modifying the epididymal index, morphometric parameters (in both organs), and a decrease in cilia length. These changes induced a reduction in sperm viability, as well as an increase in malformed spermatozoa. In conclusion, both overweight and obesity have effects on male reproduction by modifying the morphology and physiology of reproductive organs.

1675-P: Study of Thyroid Dysfunction in Patients with Type 2 Diabetes Mellitus

2025-06-13

Darshankumar Manubhai Raval , Vaishnavi M Rathod , ZACH MINER +2 more | Diabetes

Introduction and Objective: Thyroid dysfunction is frequently observed in patients with type 2 diabetes mellitus (T2DM). Hypothyroidism can exacerbate microvascular complications and increase the risk of cardiovascular disease in diabetic … Introduction and Objective: Thyroid dysfunction is frequently observed in patients with type 2 diabetes mellitus (T2DM). Hypothyroidism can exacerbate microvascular complications and increase the risk of cardiovascular disease in diabetic patients. Early screening and management of thyroid dysfunction in T2DM patients could mitigate these risks and improve outcomes. The objective is to evaluate the prevalence of thyroid dysfunction in T2DM patients and assess its association with diabetic complications. Methods: This cross-sectional study was conducted at the Department of Medicine, PSH, Vadodara, from January 2022 to April 2024. A total of 100 T2DM patients attending the outpatient department, with no prior history of thyroid disease, were included. All participants were screened for diabetic complications, including nephropathy, neuropathy, retinopathy, and cardiovascular disease. Thyroid function tests were conducted using chemiluminescent immunoassay. Results: Thyroid dysfunction was observed in 17% of participants, with hypothyroidism in 14% and hyperthyroidism in 3%. Thyroid dysfunction was more prevalent in females than males. No significant correlation was found between thyroid dysfunction and diabetic complications. Patients with long-standing diabetes showed a higher prevalence of thyroid abnormalities. Conclusion: The prevalence of thyroid dysfunction among T2DM patients was 17%, with a higher occurrence in females and those with a longer duration of diabetes. However, thyroid dysfunction was not significantly associated with diabetic complications. These findings underscore the importance of routine thyroid screening in T2DM patients for early detection and management of thyroid disorders. Disclosure D. Raval: None. V.M. Rathod: None. Z. Miner: None. K.R. Rana: None. A. Bhattacharya: None.

62-PUB: The Mechanism of IGF2-IGF2R Signaling in Regulating Testosterone Synthesis in Testicular Leydig Cells

2025-06-13

Weiwei Gui , CAIPING ZHOU , Dingting Wu +1 more | Diabetes

Introduction and Objective: This study aims to explore how the IGF2 signal affects testosterone synthesis in Leydig cells and to further investigate its mechanism in male hypogonadism and obesity. Methods: … Introduction and Objective: This study aims to explore how the IGF2 signal affects testosterone synthesis in Leydig cells and to further investigate its mechanism in male hypogonadism and obesity. Methods: A model of obese male mice was created by combining bilateral orchiectomy with a high-fat diet, and compared with sham surgery high-fat and normal chow groups for weight gain, serum hormone levels, and metabolic indicators.IGF2R expression in Leydig cells was detected. The distribution of cholesterol esters in Leydig cells was detected by confocal microscopy. ELISA was utilized to measure testosterone levels. QPCR and Western Blot were used to analyze HSD17B3 and CYP7A1 levels. Finally, IGF2 supplementation therapy was employed. Results: Compared to sham surgery, orchiectomy-induced obese mice showed faster weight gain under high-fat diets, with reduced serum testosterone, DHT, estradiol, and IGF2 levels. Igf2 was mainly expressed in Leydig cells, with Igf2r similarly expressed. IGF2 and IGF2R expression in Leydig cells correlated with key enzymes in testosterone synthesis. Cellular experiments confirmed that IGF2R knockout reduced testosterone synthesis, while overexpression enhanced it. IGF2 supplementation activated AMPK, promoting lipophagy and increasing free cholesterol, which was converted to testosterone precursors. This improved testosterone synthesis and mitigated obesity in orchiectomy-induced mice. Conclusion: The IGF2 signal has a positive regulatory effect on testosterone synthesis in Leydig cells. IGF2 activates AMPK through the IGF2R signal, promotes lipophagy in Leydig cells, enhances cholesterol uptake and metabolism, and ultimately promotes testosterone synthesis. In the obese state, the weakening of the IGF2-IGF2R signal may lead to reduced testosterone synthesis, which may be associated with obesity-related hypogonadism. Disclosure W. Gui: None. C. Zhou: None. D. Wu: None. X. Lin: None. Funding National Natural Science Foundation of China (82200638)

2171-LB: A Low-Dose, Portal Dihydrotestosterone Implant Has a Sustained Effect to Improve Glycemic Control and Provides Cardiovascular and Renal Protection in a Large Animal Model of Type 2 Diabetes

2025-06-13

Charles-Henri Malbert , Mohamed Allouche , Michael Horowitz +1 more | Diabetes

Introduction and Objective: In a large animal model of type 2 diabetes (T2D), we have shown that portal, GLP-1-dependent, glucose sensing is impaired and a low-dose dihydrotestosterone (DHT) implant inserted … Introduction and Objective: In a large animal model of type 2 diabetes (T2D), we have shown that portal, GLP-1-dependent, glucose sensing is impaired and a low-dose dihydrotestosterone (DHT) implant inserted into the area of the portal sensor normalizes glucose metabolism acutely. We evaluated the capacity of portal DHT to achieve sustained remission of diabetes and its impact on cardiovascular and renal function. Methods: Three groups of six minipigs (aged 3yr) were used. In two groups, diabetes was induced (obesogenic diet plus streptozotocin 80 mg/kg, IV). In half of these, a silicon implant delivering 100μg/24H DHT was inserted laparoscopically in the region of the GLP-1r (DHT); the other half received a sham implant (Sham). The third group was fed a non-obesogenic diet (Lean). One year following implant insertion, daily glucose (CGM), fasting plasma insulin, insulin sensitivity (euglycemic hyperinsulinemic clamp), cardiovascular function (HF oscillometry, Doppler ultrasound, and gated 18 FDG PET) and glomerular filtration rate (68 Ga DOTA PET), were measured. Results: Data are presented in the table. Conclusion: In a large animal model of T2D, low-dose, portal DHT administration has sustained effects to improve both glycemic control and insulin sensitivity, and preserves cardiovascular and renal function. Disclosure C. Malbert: None. M.R. Allouche: None. M. Horowitz: None. K.L. Jones: None.

51-PUB: Prescription of Thyroid Hormone Replacement Therapy in Individuals with Diabetes in Spain—Differences by Sex, Age, and Temporal Trends (2018–2023)

2025-06-13

Jessica Ares Blanco , Edelmiro Menéndez Torre | Diabetes

Introduction and Objective: Diabetes mellitus (DM) is a chronic condition characterized by elevated blood glucose levels due to insufficient insulin production or ineffective utilization. DM often coexists with thyroid diseases, … Introduction and Objective: Diabetes mellitus (DM) is a chronic condition characterized by elevated blood glucose levels due to insufficient insulin production or ineffective utilization. DM often coexists with thyroid diseases, particularly hypothyroidism, which can impact glycemic control and increase the risk of complications. Thyroid replacement therapy, typically with levothyroxine, is crucial for managing hypothyroidism in diabetic patients. This study analyzes the prescription trends of thyroid replacement therapy in the diabetic population in Spain from 2018 to 2023 Methods: A retrospective analysis of thyroid replacement therapy prescriptions in diabetic individuals was conducted using data from BDCAP (Primary Care Clinical DataBase), categorized by gender and age groups (00-14, 15-34, 35-54, 65 and above). The total number of cases and the rate per thousand individuals treated were calculated Results: Data reveals a steady increase in thyroid replacement therapy prescriptions over the five-year period. In 2018, the prescription rates were notably higher in females compared to males, a trend that continued through 2023. Women, particularly those aged 65 and above, consistently showed the highest prescription rates throughout the study period. This trend highlights a significant gender and age disparity in the prescription of thyroid replacement therapy among diabetic patients Conclusion: The prescription of thyroid replacement therapy in the diabetic population has significantly increased over the last 5 years, with a higher prevalence in women aged 65 and above. These findings suggest a growing trend towards thyroid treatment in diabetes management. Further prospective studies are recommended to evaluate the efficacy and safety of this practice. Disclosure J. Ares: None. E. Menéndez-Torre: Speaker's Bureau; Abbott Diagnostics, Sanofi. Advisory Panel; Insulocloud.

1671-P: Higher Levels of Testosterone Are Associated with Insulin Resistance (Hyperinsulinemia) in Men with Type 2 Diabetes Mellitus

2025-06-13

Peter Paul Mwinsanga Dapare | Diabetes

Introduction and Objective: Insulin resistance and the consequent hyperinsulinemia, is often associated with several adverse outcomes of type 2 diabetes mellitus, including hypogonadism and sexual dysfunction. The aim of this … Introduction and Objective: Insulin resistance and the consequent hyperinsulinemia, is often associated with several adverse outcomes of type 2 diabetes mellitus, including hypogonadism and sexual dysfunction. The aim of this study was to assess the levels of testosterone and its derivatives, in type 2 diabetes men with apparent insulin resistance. Methods: One hundred twenty-one (121) men with type 2 diabetes mellitus participated in this cross-sectional study, in Tamale, Ghana, Africa. A questionnaire was used to obtain sociodemographic and clinical information. Blood was collected for fasting insulin, fasting blood glucose, testosterone and sex hormone binding globulin levels. Free testosterone was calculated using the Vermeulen (1999) equation and bioavailable testosterone was calculated as 23.43 x Free testosterone. HOMA-IR was computed from the fasting glucose and insulin values and a HOMA-IR ≥2 was deemed as insulin resistance. Data was analysed using GraphPad Prism and Medalc Statistical Software and presented as medians (Q1-Q3). Data was compared using the Mann-Whitney test, Spearman correlation was done to assess associations and the Receiver Operator Characteristics for AUCs. Results: About 40% (48/121) of the studied population had HOMA-IR ≥2. Concentrations of testosterone (ng/dL) [48.0(24.0-119.0) vs 20.0(8.5-54.0)], free testosterone (ng/dL) [1.81(1.04-4.68) vs 0.66(0.27-47.7)] and bioavailable testosterone (ng/dL) [38.6(22.80-102.0) vs 15.8(6.03-47.65)] were significantly higher in men with HOMA-IR≥2. There was a significant direct correlation between testosterone and insulin levels (r=0.26, p=0.004). At a cut-off &gt;0.90ng/dL, free testosterone significantly predicted men with HOMA-IR ≥2 (AUC=0.650, p=0.004). Conclusion: High concentrations of testosterone and its derivates are associated with hyperinsulinemia consequent to insulin resistance in men with type 2 diabetes Disclosure P.M. Dapare: None.

Astaxanthin mitigates radiation-induced erectile dysfunction: protective effects on corpus cavernosum in a rat model

2025-06-13

Günal Özgür , Bahadır Şahin , Beste M. Atasoy +7 more | International Journal of Impotence Research

Sex-Specific Impact of 17β-Estradiol and Testosterone Levels on Inflammation and Injury in Acute Myocardial Infarction—Preliminary Results

2025-06-13

Niya E Semerdzhieva , Adelina Tsakova , Vesela Lozanova | Biomedicines

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for … Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk.

Erectile function and quality of life among undergraduate university students in Almaty, Kazakhstan

2025-06-13

Malik Safargaliyev , Denis Vinnikov | Journal of Health Research

Pathogenetic significance of oxidative stress in canine prostatic hyperplasia

2025-06-12

V. І. Koshevoy , A. SyniahovskaK , Naumenko S.V. +1 more | Bulletin Veterinary biotechnology

Canine prostatic hyperplasia is a common disease, mainly in older males, which is registered in animals regardless of breed, fatness and other factors. The pathogenesis of this disease in dogs … Canine prostatic hyperplasia is a common disease, mainly in older males, which is registered in animals regardless of breed, fatness and other factors. The pathogenesis of this disease in dogs is not well studied. One of its components – hormonal changes, has been studied in more depth, as a result of which it is known that the development of prostatic hyperplasia occurs due to impaired androgenesis, changes in the testosterone-estradiol ratio. On the contrary, data on the redox balance in prostate tissue during hyperplastic changes are scarce.