Biochemistry, Genetics and Molecular Biology › Molecular Biology

Sexual Differentiation and Disorders

Works Count: 54442

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Description

This cluster of papers explores the molecular biology, biochemistry, and physiology of human steroidogenesis, focusing on disorders such as Congenital Adrenal Hyperplasia and Intersex Disorders. It delves into topics like androgen receptor gene mutations, prenatal hormone effects on sexual differentiation, digit ratio as a marker for prenatal hormone action, and the influence of fetal testosterone on gender identity and behavior.

Keywords

Congenital Adrenal Hyperplasia; Steroid 21-Hydroxylase Deficiency; Intersex Disorders; Androgen Receptor Gene Mutations; Prenatal Hormone Effects; Digit Ratio (2D:4D); Sexual Differentiation; Gender Identity; Fetal Testosterone; Genetic Variants

A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans

1999-06-01

John C. Achermann , Masafumi Ito , Mika Ito +2 more

Pathology and genetics of tumours of the urinary system and male genital organs

2004-01-01

John N. Eble

Handbook of sexual assault: Issues, theories, and treatment of the offender.

1990-01-01

William L. Marshall , D. Richard Laws , Howard E. Barbaree

Introduction: Issues in Sexual Assault W.L. Marshall, et al. The Nature and Extent of Sexual Assault G.G. Abel, J.L. Rouleau. Classifying Sexual Offenders: The Development and Corroboration of Taxonomic Models … Introduction: Issues in Sexual Assault W.L. Marshall, et al. The Nature and Extent of Sexual Assault G.G. Abel, J.L. Rouleau. Classifying Sexual Offenders: The Development and Corroboration of Taxonomic Models R.A. Knight, R.A. Prentky. Factors Influencing Sexual Assault: Sexual Aggression: Achieving Power Through Humiliation J.L. Darke. The Influence of Pornography on Sexual Crimes M.R. Murrin, D.R. Laws. Androgenic Hormones and Sexual Assault S.J. Hucker, J. Bain. Sexual Anomalies and the Brain R. Langevin. Stimulus Control of Sexual Arousal: Its Role in Sexual Assault H.E. Barbaree. Social and Cultural Factors in Sexual Assault L.E. Stermac, et al. The Role of Cognition in Sexual Assault Z.V. Segal, L.E. Stermac. Theories of Sexual Assault: Sex Offenders: A Feminist Perspective J.L. Herman. Court Disorder K. Freund. Treatment of the Offender: The Modification of Sexual Preferences V.L. Quinsey, C.M. Earls. The Antiandrogen and Hormonal Treatment of Sex Offenders J.M.W. Bradford. 8 additional articles. Index.

Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline

2010-09-01

Phyllis Speiser , Ricardo Azziz , Laurence S. Baskin +7 more

Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians … Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society’s CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing’s syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients’ quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

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SJOEGREN'S SYNDROME. A CLINICAL, PATHOLOGICAL, AND SEROLOGICAL STUDY OF SIXTY-TWO CASES.

1965-05-01

Kurt Bloch , W. W. Buchanan , Martin J. Wohl +1 more

Syndrome Characterized by Gynecomastia, Aspermatogenesis without A-Leydigism, and Increased Excretion of Follicle-Stimulating Hormone1

1942-11-01

Harry F. Klinefelter , Edward C. Reifenstein , Fuller Albright

The syndrome under discussion begins during 11 adolescence and is characterised by gynecomastia and a very specific type of hypogonadism. This latter is almost entirely in respect to the function … The syndrome under discussion begins during 11 adolescence and is characterised by gynecomastia and a very specific type of hypogonadism. This latter is almost entirely in respect to the function of the tubular tissue (germinal epithelium and Sertoli cells) while the function of the Leydig cells (growth of phallus and prostate and of sexual hair) remains relatively normal. Thus one finds bilateral gynecomastia, small testes, aspermatogenesis. evidence of normal to moderately reduced function of the Leydig cells, increased excretion of follicle-stimulating hormone (FSH), and usually a reduced excretion of 17-ketosteroids. During the last 4 years, 7 cases have been observed in the clinics of the Massachusetts General Hospital; studies on these patients and two additional private patients form the subject of this report. review of literature Although these cases are not uncommon, few reports are found in the literature, and to our knowledge, no author has grouped them together as a definite clinical entity.

Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I.

1992-08-01

Deepak S. Lala , Douglas Rice , K L Parker

We proposed that a cell-selective regulatory protein coordinately regulates the expression of three enzymes that are required for the biosynthesis of corticosteroids: cholesterol side chain cleavage enzyme, steroid 21-hydroxylase, and … We proposed that a cell-selective regulatory protein coordinately regulates the expression of three enzymes that are required for the biosynthesis of corticosteroids: cholesterol side chain cleavage enzyme, steroid 21-hydroxylase, and the aldosterone synthase isozyme of steroid 11 beta-hydroxylase. In this report, we identify a 53-kilodalton protein, termed steroidogenic factor 1 (SF-1), that interacts with the related promoter elements from these steroidogenic enzymes, and we isolate and characterize a cDNA that very likely encodes this protein. We first showed that nuclear extracts from bovine adrenal glands interact with the mouse steroidogenic regulatory elements, forming complexes indistinguishable from those produced by nuclear extracts from mouse Y1 adrenocortical cells. These bovine adrenal extracts were subjected to sequential ion exchange and affinity chromatography to yield a highly enriched preparation of SF-1. The predominant protein in the affinity-purified preparation comigrated with shift activity and had a mol wt of 53,000; UV cross-linking experiments demonstrated directly that this 53-kilodalton protein interacted with the steroidogenic regulatory element. Even with this marked enrichment, affinity-purified SF-1 bound six steroidogenic regulatory elements. These results support strongly the model that a steroidogenic cell-selective protein interacts with related promoter elements from three steroidogenic enzymes to regulate their coordinate expression. The recognition sequence of SF-1 closely resembles those of nuclear hormone receptor family members, suggesting that SF-1 may belong to this supergene family. By screening a Y1 cell cDNA library with the DNA-binding region of the H-2RIIBP nuclear hormone receptor cDNA, we isolated a cDNA that is selectively expressed in steroidogenic cells. When expressed as a glutathione S-transferase fusion protein in Escherichia. coli, the protein encoded by this cDNA interacts with all six related steroidogenic regulatory elements with a binding specificity indistinguishable from that of SF-1. Surprisingly, the sequence of the putative DNA-binding domain of this cDNA matches exactly the corresponding sequence of the mouse homolog of the Drosophila transcription factor fushi tarazu-factor I. The demonstration that a member of the nuclear hormone receptor family interacts with the steroidogenic regulatory elements provides intriguing insights into possible mechanisms by which these essential genes are regulated.

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Steroid 5α-Reductase Deficiency in Man: An Inherited Form of Male Pseudohermaphroditism

1974-12-27

Julianne Imperato‐McGinley , Luis Guerrero , Teófilo Gautier +1 more

In male pseudohermaphrodites born with ambiguity of the external genitalia but with marked virilization at puberty, biochemical evaluation reveals a marked decrease in plasma dihydrotestosterone secondary to a decrease in … In male pseudohermaphrodites born with ambiguity of the external genitalia but with marked virilization at puberty, biochemical evaluation reveals a marked decrease in plasma dihydrotestosterone secondary to a decrease in steroid 5alpha-reductase activity. In utero the decrease in dihydrotestosterone results in incomplete masculinization of the external genitalia. Inheritance is autosomal recessive.

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

2008-03-12

Michelle Welsh , Philippa T. K. Saunders , M. Fisken +4 more

Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset … Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.

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European Association of Urology Guidelines on Male Infertility: The 2012 Update

2012-05-03

A. Jungwirth , Aleksander Giwercman , Herman Tournaye +4 more

Advances in Male Contraception

2008-04-24

Stephanie T. Page , John K. Amory , William J. Bremner

Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that … Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90-95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade.

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Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist

1995-06-01

William Kelce , Christy R. Stone , Susan Laws +3 more

2nd to 4th digit ratios, fetal testosterone and estradiol

2004-03-23

Svetlana Lutchmaya , Simon Baron‐Cohen , P R Raggatt +2 more

Sexual differentiation of the brain

1981-06-01

Bruce S. McEwen

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A Case of Human Intersexuality Having a Possible XXY Sex-Determining Mechanism

1959-01-01

Patricia A. Jacobs , J.A. Strong

The CAG repeat within the androgen receptor gene and its relationship to prostate cancer

1997-04-01

Edward L. Giovannucci , Meir J. Stampfer , Krishna Krithivas +5 more

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase … The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancer. We conducted a nested case-control study of 587 newly diagnosed cases of prostate cancer detected between 1982 and 1995, and 588 controls without prostate cancer, within the Physician’s Health Study. An association existed between fewer androgen receptor gene CAG repeats and higher risk of total prostate cancer [relative risk (RR) = 1.52; 95% confidence interval (CI) = 0.92–2.49; P trend = 0.04; for men with CAG repeat lengths ≤18 relative to ≥26 repeats]. In particular, a shorter CAG repeat sequence was associated with cancers characterized by extraprostatic extension or distant metastases (stage C or D) or high histologic grade (RR = 2.14; CI = 1.14–4.01; P trend = 0.001). This association was observed individually both for high stage (RR = 2.23) and high grade prostate cancer (RR = 1.89). Men with shorter repeats were at particularly high risk for distant metastatic and fatal prostate cancer. Variability in the CAG repeat length was not associated with low grade or low stage disease. These results demonstrate that a shorter CAG repeat sequence in the androgen receptor gene predicts higher grade and advanced stage of prostate cancer at diagnosis, and metastasis and mortality from the disease. The clinical implications of these results should be evaluated further.

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Role of Steroidogenic Acute Regulatory Protein in Adrenal and Gonadal Steroidogenesis

1995-03-24

Dong Lin , Teruo Sugawara , Jerome F. Strauss +5 more

Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with this disorder, steroidogenic … Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with this disorder, steroidogenic acute regulatory protein, which enhances the mitochondrial conversion of cholesterol into pregnenolone, was mutated and nonfunctional, providing genetic evidence that this protein is indispensable for normal adrenal and gonadal steroidogenesis.

PATTERN OF MALFORMATION IN OFFSPRING OF CHRONIC ALCOHOLIC MOTHERS

1973-06-01

KennethL. Jones , DavidW. Smith , ChristyN. Ulleland +1 more

Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism

1991-11-01

Stefan Andersson , David M. Berman , Elizabeth P. Jenkins +1 more

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How sexually dimorphic are we? Review and synthesis

2000-03-01

Melanie Blackless , Anthony Charuvastra , Amanda Derryck +3 more

The belief that Homo sapiens is absolutely dimorphic with the respect to sex chromosome composition, gonadal structure, hormone levels, and the structure of the internal genital duct systems and external … The belief that Homo sapiens is absolutely dimorphic with the respect to sex chromosome composition, gonadal structure, hormone levels, and the structure of the internal genital duct systems and external genitalia, derives from the platonic ideal that for each sex there is a single, universally correct developmental pathway and outcome. We surveyed the medical literature from 1955 to the present for studies of the frequency of deviation from the ideal male or female. We conclude that this frequency may be as high as 2% of live births. The frequency of individuals receiving "corrective" genital surgery, however, probably runs between 1 and 2 per 1,000 live births (0.1-0.2%). Am. J. Hum. Biol. 12:151-166, 2000. Copyright 2000 Wiley-Liss, Inc.

A SEX-CHROMOSOME ANOMALY IN A CASE OF GONADAL DYSGENESIS (TURNER'S SYNDROME)

1959-04-01

C. E. Ford

Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.

1993-08-01

Anice E. Thigpen , Richard I. Silver , Joseph M. Guileyardo +3 more

The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are … The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.

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Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood

2003-06-01

RM Sharpe , Chris McKinnell , C Kivlin +1 more

Disorders of testicular function may have their origins in fetal or early life as a result of abnormal development or proliferation of Sertoli cells. Failure of Sertoli cells to mature, … Disorders of testicular function may have their origins in fetal or early life as a result of abnormal development or proliferation of Sertoli cells. Failure of Sertoli cells to mature, with consequent inability to express functions capable of supporting spermatogenesis, is a prime example. In a similar way, failure of Sertoli cells to proliferate normally at the appropriate period in life will result in reduced production of spermatozoa in adulthood. This review focuses on the control of proliferation of Sertoli cells and functional maturation, and is motivated by concerns about 'testicular dysgenesis syndrome' in humans, a collection of common disorders (testicular germ-cell cancer, cryptorchidism, hypospadias and low sperm counts) which are hypothesized to have a common origin in fetal life and to reflect abnormal function of Sertoli (and Leydig) cells. The timing of proliferation of Sertoli cells in different species is reviewed, and the factors that govern the conversion of an immature, proliferating Sertoli cell to a mature, non-proliferating cell are discussed. Protein markers of maturity and immaturity of Sertoli cells in various species are reviewed and their usefulness in studies of human testicular pathology are discussed. These markers include anti-Mullerian hormone, aromatase, cytokeratin-18, GATA-1, laminin alpha5, M2A antigen, p27(kip1), sulphated glycoprotein 2, androgen receptor and Wilms' tumour gene. A scheme is presented for characterization of Sertoli-cell only tubules in the adult testis according to whether or not there is inherent failure of maturation of Sertoli cells or in which the Sertoli cells have matured but there is absence, or acquired loss, of germ cells. Functional 'de-differentiation' of Sertoli cells is considered. It is concluded that there is considerable evidence to indicate that disorders of maturation of Sertoli cells may be a common underlying cause of human male reproductive disorders that manifest at various life stages. This recognition emphasizes the important role that animal models must play to enable identification of the mechanisms via which failure of proliferation and maturation of Sertoli cells can arise, as this failure probably occurs in fetal life.

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Targeted Disruption of the Insl3 Gene Causes Bilateral Cryptorchidism

1999-05-01

Stephan Zimmermann , Gerd Steding , Judith M. A. Emmen +5 more

Abstract The sexual dimorphic position of the gonads in mammals is dependent on differential development of two ligaments, the cranial suspensory ligament (CSL) and the gubernaculum. During male embryogenesis, outgrowth … Abstract The sexual dimorphic position of the gonads in mammals is dependent on differential development of two ligaments, the cranial suspensory ligament (CSL) and the gubernaculum. During male embryogenesis, outgrowth of the gubernaculum and regression of the CSL result in transabdominal descent of the testes, whereas in the female, development of the CSL in conjunction with failure of the gubernaculum development holds the ovaries in a position lateral to the kidneys. Several lines of evidence suggest that regression of the CSL and induction of gubernaculum development are mediated by testosterone and a yet unidentified testicular factor, respectively. The Insl3 gene (orginally designated Ley I-L), a member of the insulin-like superfamily, is specifically expressed in Leydig cells of the fetal and postnatal testis and in theca cells of the postnatal ovary. Here we show that male mice homozygous for a targeted deletion of the Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital ducts. These malformations are due to failure of gubernaculum development during embryogenesis. In double-mutant male mice for Insl3 and androgen receptor genes, testes are positioned adjacent to the kidneys and steadied in the abdomen by the CSL. These findings demonstrate, that the Insl3 induces gubernaculum development in an androgen-independent way, while androgen-mediated regression of the CSL occurs independently from Insl3.

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A sex difference in the human brain and its relation to transsexuality

1995-11-01

Jiang‐Ning Zhou , Michel A. Hofman , Louis Gooren +1 more

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GST and its relatives do not measure differentiation

2008-08-05

Lou Jost

Abstract G ST and its relatives are often interpreted as measures of differentiation between subpopulations, with values near zero supposedly indicating low differentiation. However, G ST necessarily approaches zero when … Abstract G ST and its relatives are often interpreted as measures of differentiation between subpopulations, with values near zero supposedly indicating low differentiation. However, G ST necessarily approaches zero when gene diversity is high, even if subpopulations are completely differentiated, and it is not monotonic with increasing differentiation. Likewise, when diversity is equated with heterozygosity, standard similarity measures formed by taking the ratio of mean within‐subpopulation diversity to total diversity necessarily approach unity when diversity is high, even if the subpopulations are completely dissimilar (no shared alleles). None of these measures can be interpreted as measures of differentiation or similarity. The derivations of these measures contain two subtle misconceptions which cause their paradoxical behaviours. Conclusions about population differentiation, gene flow, relatedness, and conservation priority will often be wrong when based on these fixation indices or similarity measures. These are not statistical issues; the problems persist even when true population frequencies are used in the calculations. Recent advances in the mathematics of diversity identify the misconceptions, and yield mathematically consistent descriptive measures of population structure which eliminate the paradoxes produced by standard measures. These measures can be directly related to the migration and mutation rates of the finite‐island model.

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Secondary Sexual Characteristics and Menses in Young Girls Seen in Office Practice: A Study from the Pediatric Research in Office Settings Network

1997-04-01

Marcia E. Herman‐Giddens , Eric J. Slora , Richard C. Wasserman +4 more

Objective. To determine the current prevalence and mean ages of onset of pubertal characteristics in young girls seen in pediatric practices in the United States. Methods. A cross-sectional study was … Objective. To determine the current prevalence and mean ages of onset of pubertal characteristics in young girls seen in pediatric practices in the United States. Methods. A cross-sectional study was conducted by 225 clinicians in pediatric practices belonging to Pediatric Research in Office Settings, a practice-based research network. After standardized training in the assessment of pubertal maturation, practitioners rated the level of sexual maturation on girls 3 through 12 years who were undergoing complete physical examinations. Results. Data were analyzed for 17 077 girls, of whom 9.6% were African-American and 90.4% white. At age 3, 3% of African-American girls and 1% of white girls showed breast and/or pubic hair development, with proportions increasing to 27.2% and 6.7%, respectively, at 7 years of age. At age 8, 48.3% of African-American girls and 14.7% of white girls had begun development. At every age for each characteristic, African-American girls were more advanced than white girls. The mean ages of onset of breast development for African-American and white girls were 8.87 years (SD, 1.93) and 9.96 years (SD, 1.82), respectively; and for pubic hair development, 8.78 years (SD, 2.00) and 10.51 years (SD, 1.67), respectively. Menses occurred at 12.16 years (SD, 1.21) in African-American girls and 12.88 years (SD, 1.20) of age in white girls. Conclusions. These data suggest that girls seen in a sample of pediatric practices from across the United States are developing pubertal characteristics at younger ages than currently used norms. Practitioners may need to revise their criteria for referral of girls with precocious puberty, with attention to racial differences.

Sexual dimorphism of body composition

2007-09-01

Jonathan C. K. Wells

Androgen Receptor Defects: Historical, Clinical, and Molecular Perspectives*

1995-06-01

Charmian A. Quigley , Alessandra De Bellis , Keith B. Marschke +3 more

IN 1953 lohn Morris, an obstetrician at Yale University, reported a series of 82 individuals (80 cases collated from the literature and two cases of his own) who had a … IN 1953 lohn Morris, an obstetrician at Yale University, reported a series of 82 individuals (80 cases collated from the literature and two cases of his own) who had a female phenotype despite the presence of bilateral testes (1). Since his initial description, studies of the endocrinology, pathophysiology, biochemistry, and molecular biology of the androgen insensitivity syndrome (AIS) have provided insights into the role of androgens in male sex differentiation, the mechanisms of androgen action, and aspects of the structure/function relationships of the androgen receptor. AIS is an archetypal example of a hormone resistance disorder. Androgens are secreted by the testes of these 46,XY individuals in normal or increased amounts; however, due to defective androgen receptor (AR1) function, there is loss of target organ response to the hormone, and the effects of androgens are reduced or absent. Clinical disorders of the AR are reported far more commonly than resistance disorders of other members of the steroid receptor family and, in fact, more mutations have been reported in the AR gene than in that of any other transcription factor (2). This is, in part, due to the fact that the AR is encoded by a single copy X-chromosomal gene (it is the only X-chromosomal steroid receptor gene).

Sexual dimorphism of brain developmental trajectories during childhood and adolescence

2007-04-07

Rhoshel Lenroot , Nitin Gogtay , Deanna Greenstein +7 more

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Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens.

1995-12-01

A Morishima , Melvin M. Grumbach , E R Simpson +2 more

The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human … The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been isolated; tissue-specific regulation is controlled in part by alternative promoters in a tissue-specific manner. We report a novel mutation in the CYP19 gene in a sister and brother. The 28-yr-old XX proband, followed since infancy, exhibited the cardinal features of the aromatase deficiency syndrome as recently defined. She had nonadrenal female pseudohermaphrodism at birth and underwent repair of the external genitalia, including a clitorectomy. At the age of puberty, she developed progressive signs of virilization, pubertal failure with no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries on pelvic sonography, and tall stature. The basal concentrations of plasma testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, whereas plasma estradiol was low. Cyst fluid from the polycystic ovaries had a strikingly abnormal ratio of androstenedione and testosterone to estradiol and estrone. Hormone replacement therapy led to breast development, menses, resolution of ovarian cysts, and suppression of the elevated FSH and LH values. Her adult height is 177.6 cm (+2.5 SD). Her only sibling, an XY male, was studied at 24 yr of age. During both pregnancies, the mother exhibited signs of progressive virilization that regressed postpartum. The height of the brother was 204 cm (+3.7 SD) with eunuchoid skeletal proportions, and the weight was 135.1 kg (+2.1 SD). He was sexually fully mature and had macroorchidism. The plasma concentrations of testosterone (2015 ng/dL), 5 alpha-dihydrotestosterone (125 ng/dL), and androstenedione (335 ng/dL) were elevated; estradiol and estrone levels were less than 7 pg/mL. Plasma FSH and LH concentrations were more than 3 times the mean value. Plasma PRL was low; serum insulin-like growth factor I and GH-binding protein were normal. The bone age was 14 yr at a chronological age of 24 3/12 yr. Striking osteopenia was noted at the wrist. Bone mineral densitometric indexes of the lumbar spine (cancellous bone) and distal radius (cortical bone) were consistent with osteoporosis; the distal radius was -4.7 SD below the mean value for age- and sex-matched normal men; indexes of bone turnover were increased. Hyperinsulinemia, increased serum total and low density lipoprotein cholesterol, and triglycerides and decreased high density lipoprotein cholesterol were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Molecular Biology of Steroid Hormone Synthesis*

1988-08-01

Walter L. Miller

STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal … STEROID hormones are familiar clinically and physiologically as regulators of physiological processes. Five groups of steroid hormones are generally recognized according to their physiological behavior: mineralocorticoids, which instruct the renal tubules to retain sodium; glucocorticoids, which are named for their carbohydratemobilizing properties but have many other effects as well; estrogens, which induce female secondary sexual characteristics; progestins, which are essential for reproduction; and androgens, which induce male secondary sexual characteristics. These classes of steroid hormones are structurally similar and arise from a common series of pathways. They are distinguished by their actions on one or more specific steroid hormone receptors. The hormone/receptor complexes function as tissue-specific transcriptional regulators of distinct domains of genes and, consequently, exert their broad array of physiological effects. (For reviews, see Refs. 1 and 2.) The pathways by which these steroid hormones are produced from cholesterol were initially studied by studying the structures of the steroids themselves. Over the past 30 yr, studies of enzyme kinetics and of steroidal precursorproduct relationships have led to the widely held belief that a very large number of distinct enzymes are involved in the conversion of cholesterol and its esters to active steroid hormones. The application of modern protein chemistry and molecular biology to these questions has radically changed this view.

Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency*

2000-06-01

Perrin C. White , Phyllis Speiser

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California Medical Center, San Francisco. Taken from transcriptions, they are prepared by Drs. Martin … These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California Medical Center, San Francisco. Taken from transcriptions, they are prepared by Drs. Martin J. Cline and Hibbard E. Williams, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine.

Consensus Statement on Management of Intersex Disorders

2006-08-01

Peter A. Lee , Christopher P. Houk , S. Faisal Ahmed +1 more

The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding … The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

Androgen Excess in Women: Experience with Over 1000 Consecutive Patients

2004-02-01

Ricardo Azziz , Luis A. Sánchez , Eric S. Knochenhauer +5 more

The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of … The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients.

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The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen

1998-11-01

John T. Manning , Diane Scutt , J. Wilson +1 more

The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility … The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility that patterns of digit formation may relate to spermatogenesis and hormonal concentrations. This work was concerned with the ratio between the length of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in right and left hands has a sexually dimorphic pattern; in males mean 2D:4D = 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal length. The dimorphism is present from at least age 2 years and 2D:4D is probably established in utero; (ii) high 2D:4D ratio in right hands was associated with germ cell failure in men (P = 0.04); (iii) sperm number was negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men testosterone concentrations were negatively related to right hand 2D:4D and in women and men LH (right hand), oestrogen (right and left hands) and prolactin (right hand) concentrations were positively correlated with 2D:4D ratio and (v) 2D:4D ratio in right hands remained positively related to luteinizing hormone and oestrogen after controlling for sex, age, height and weight.

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Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion

2001-05-01

N E Skakkebæk , Ewa Rajpert‐De Meyts , Katharina M. Main

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high … Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

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Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

2015-11-19

Niels E. Skakkebæk , Ewa Rajpert‐De Meyts , Germaine M. Buck Louis +7 more

It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per … It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

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Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care

2016-01-01

Peter A. Lee , Anna Nordenström , Christopher P. Houk +7 more

The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the 2005 Consensus … The goal of this update regarding the diagnosis and care of persons with disorders of sex development (DSDs) is to address changes in the clinical approach since the 2005 Consensus Conference, since knowledge and viewpoints change. An effort was made to include representatives from a broad perspective including support and advocacy groups. The goal of patient care is focused upon the best possible quality of life (QoL). The field of DSD is continuously developing. An update on the clinical evaluation of infants and older individuals with ambiguous genitalia including perceptions regarding male or female assignment is discussed. Topics include biochemical and genetic assessment, the risk of germ cell tumor development, approaches to psychosocial and psychosexual well-being and an update on support groups. Open and on-going communication with patients and parents must involve full disclosure, with the recognition that, while DSD conditions are life-long, enhancement of the best possible outcome improves QoL. The evolution of diagnosis and care continues, while it is still impossible to predict gender development in an individual case with certainty. Such decisions and decisions regarding surgery during infancy that alters external genital anatomy or removes germ cells continue to carry risk.

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Effect of Testosterone and Estradiol in a Man with Aromatase Deficiency

1997-07-10

Cesare Carani , Kenan Qin , Manuela Simoni +5 more

Recent reports of disruptive mutations of the genes for the estrogen receptor or for cytochrome P-450 aromatase1–6 have shed new light on the role of estrogen. In females the lack … Recent reports of disruptive mutations of the genes for the estrogen receptor or for cytochrome P-450 aromatase1–6 have shed new light on the role of estrogen. In females the lack of estrogen due to aromatase deficiency leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal. In members of both sexes epiphyseal closure is delayed, resulting in a eunuchoid habitus, and osteopenia is present.6 These findings suggest a crucial role of estrogen in skeletal maturation.1–6 We describe the responses to androgen and estrogen in a man with a novel, homozygous inactivating mutation of . . .

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Precocious Puberty

2008-05-28

Jean‐Claude Carel , Juliane Léger

The parents of a 6-year-old girl bring her to a pediatrician because of breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports … The parents of a 6-year-old girl bring her to a pediatrician because of breast development. Her medical history is unremarkable. The parents are of average height, and the mother reports first menstruating when she was 11 years old. On physical examination, the girl is 125 cm tall (in the 97th percentile for her age), weighs 28 kg, and has a body-mass index of 17.9 (90th percentile for her age). Her breast development is classified as Tanner stage 3, and she has Tanner stage 2 pubic hair. Review of her previous growth data indicates that she has grown 8 cm during the past year. How should her condition be evaluated and managed?

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline

2017-09-13

Wylie C. Hembree , Peggy T. Cohen‐Kettenis , Louis Gooren +7 more

To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009.The participants include an Endocrine Society-appointed task force of nine … To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009.The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer.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.Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines.Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

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Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline

2018-09-27

Phyllis Speiser , Wiebke Arlt , Richard J. Auchus +7 more

To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. The writing committee presents updated best practice guidelines for … To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.

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Congenital Adrenal Hyperplasia

2003-08-20

Phyllis Speiser , Perrin C. White

Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most frequent … Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90 percent of cases. This article discusses the molecular mechanisms, diagnosis, and management of this disease and highlights new developments, including genotype–phenotype correlations, gene-specific prenatal diagnosis, and prenatal therapy.

Congenital adrenal hyperplasia

2017-05-31

Diala El‐Maouche , Wiebke Arlt , Deborah P. Merke

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Sexual Selection and Animal Genitalia

1985-12-31

William G. Eberhard

Consensus statement on management of intersex disorders

2005-06-14

Ieuan A. Hughes

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Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

2000-06-01

Perrin C. White

Sertoli Hücrelerinin Testis Fonksiyonu, Terapötik Potansiyeli ve Belirteçleri: Tarihsel Perspektif ve Fonksiyonel Değerlendirme

2025-06-24

Oya Korkmaz | Özgür Yayınları eBooks

Sertoli hücreleri, memeli testislerinde germ hücreleriyle doğrudan etkileşim içinde bulunan somatik hücrelerdir. Çeşitli fonksiyonlara sahip olan bu hücreler, spermatojenik hücrelerin spermatozoaya dönüşümünü ve olgunlaşmasını destekleyerek spermatogenez sürecinin düzenlenmesinde önemli bir … Sertoli hücreleri, memeli testislerinde germ hücreleriyle doğrudan etkileşim içinde bulunan somatik hücrelerdir. Çeşitli fonksiyonlara sahip olan bu hücreler, spermatojenik hücrelerin spermatozoaya dönüşümünü ve olgunlaşmasını destekleyerek spermatogenez sürecinin düzenlenmesinde önemli bir rol oynamaktadır. Bu hücrelerin en önemli işlevleri arasında, germ hücrelerine besin sağlamak, puberte öncesi testiste peritübüler miyoid hücrelerin gelişimini desteklemek, testiküler vaskülarizasyonun işlevselliğini sürdürmek ve testis somatik hücrelerinin düzenleyici mekanizmalarında rol almak sayılabilir. Ayrıca, Sertoli hücreleri testiste bağışıklık sisteminin düzenlenmesinde önemli bir rol oynamaktadır ve gelişmekte olan germ hücreleri için immünolojik özel bir mikroçevre sağlamaktadır. Bu hücrelerin immünolojik bir mikroçevre oluşturma yeteneği, çeşitli hastalıkların tedavisinde potansiyel kullanım alanlarının araştırılmasına yol açmıştır. Yapılan çok sayıda çalışma, Sertoli hücrelerinin diyabet, nörodejeneratif bozukluklar ve spermatogenezin restorasyonu gibi alanlarda terapötik potansiyel taşıdığını ortaya koymaktadır. Erkek üreme hücreleri için önemli bir işlev görmeleri nedeniyle, Sertoli hücrelerinde meydana gelen değişiklikler fertilite üzerinde olumsuz etkilere yol açabilir. Mevcut veriler, Sertoli hücrelerinin proliferasyonu ve/veya fonksiyonel olgunlaşmasındaki bozuklukların erkek üreme bozukluklarına yol açabileceğini göstermektedir. Bu bağlamda, testiste Sertoli hücrelerinin gelişimsel, proliferatif ve olgunlaşma durumunun yalnızca fetal dönem, prepuberte, puberte veya yetişkinlik döneminde tanımlanması için değil, aynı zamanda spermatojenik disfonksiyonun altında yatan mekanizmaların teşhis edilmesi amacıyla da uygun bir Sertoli hücresi belirtecinin seçilmesinin büyük önem taşıdığı anlaşılmaktadır. Bu bölümde, Sertoli hücrelerinin keşfi, biyolojik özellikleri, belirteçleri, testisteki spesifik rolleri ve terapötik uygulamaları mevcut bilgiler ışığında özetlenmekte ve kapsamlı bir bakış açısı sunulmaktadır.

Gonadal function in pediatric female post-Allo-HSCT: a real-life prospective study from China

2025-06-24

Huina Su , H. J. Yang , Lin Pei +7 more | Gynecological Endocrinology

While advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) have improved survival rates, the impact on reproductive function in Chinese female pediatric survivors remains underexplored. This study evaluated the incidence … While advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) have improved survival rates, the impact on reproductive function in Chinese female pediatric survivors remains underexplored. This study evaluated the incidence and factors influencing ovarian function impairment in these survivors. A prospective study was conducted on 104 children who survived allo-HSCT between 2018 and 2021 at Beijing Children's Hospital. Data on hematologic disease, age, and ovarian function were collected. Statistical analyses assessed changes in sex hormone levels and identified factors linked to gonadal damage. Post-transplant, follicle-stimulating hormone levels rose significantly (p = 0.013 for girls ≥10 years old), while anti-Müllerian hormone levels decreased (p < 0.001). The incidence of premature ovarian insufficiency (POI) was 26.92% at 1 year, 47.44% at 2 years, and 70.18% at 3 years post-transplant. Risk factors for POI included transplantation age ≥10 years, weight >20 kg at transplantation, myeloablative conditioning, and total body irradiation (OR = 6.76, p = 0.005; OR = 6.63, p = 0.003; OR = 17, p = 0.017; OR = 15.03, p = 0.026). Only 3.85% of patients received ovarian function protection before transplantation. Among patients aged ≥12 years at follow-up, 86.36% developed POI, with 26.32% receiving oral estrogen replacement therapy. Hypogonadal function significantly declines in pediatric patients after allo-HSCT. Fertility protection and hormone replacement therapy were rarely used.

Aménorrhée chez l’adolescente

2025-06-24

Claire Bouvattier | EMC - Gynécologie

The rising role of genetics in andrology research and clinical practice

2025-06-22

Maris Laan , Kenneth I. Aston , Donald F. Conrad | Andrology

Complete Androgen Insensitivity Syndrome in a Phenotypic Female: The Role of Frozen Section in Assisting Diagnosis

2025-06-20

Vijaya Raj Bhatt , Reena Tomar , Nikita Sharma +2 more | Cureus

Tubular ectasia of the epididymis

2025-06-20

Ammar Ashraf | Radiopaedia.org

Reply: The AUA/SUFU/AUGS Guideline on Genitourinary Syndrome of Menopause

2025-06-19

Melissa R. Kaufman , Una Lee | The Journal of Urology

Comparison of 2D:4D digit ratios in patients with Hashimoto's and Graves' diseases: A systematic review

2025-06-18

Tuba Güner Emül , Emine Kaplan Serin , Özlem Elvan | Early Human Development

Clinical Characteristics and Molecular Aetiology of Cytochrome P450 Oxidoreductase Deficiency Diagnosed in 46,XX Patients

2025-06-18

Duoduo Zhang , Lihua Ding , Shan Deng +1 more | Reproductive Sciences

Editorial: Androgen receptors in male and female reproduction

2025-06-18

Federica Barbagallo , Settimio D’Andrea | Frontiers in Endocrinology

Growth Assessment and Nutritional Status in Children with Congenital Adrenal Hyperplasia—A Cross-Sectional Study from a Vietnamese Tertiary Pediatric Center

2025-06-16

Thi Thuy Hong Nguyen , Khanh Le , Thi Anh Thuong Tran +5 more | Diagnostics

Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, … Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, and associated factors among children with CAH treated in a Vietnamese tertiary pediatric center. Methods: We assessed 201 children aged 1.1-16.5 years in a tertiary pediatric center in Vietnam for anthropometric parameters, biochemical markers (calcium, phosphate, 25-hydroxyvitamin D), and clinical features. Growth status was evaluated using WHO standards, and bone age was assessed radiographically. Statistical analyses explored associations between growth outcomes and clinical, biochemical, and treatment-related factors. Results: Stunting was present in 16.4% of children, while 53.3% were overweight or obese. Bone age advancement occurred in 51.7% of cases. Vitamin D insufficiency or deficiency was detected in 85.6% of patients, and hypocalcemia was present in 85.1%. Overweight/obesity, vitamin D deficiency, and bone age advancement were associated with older age, prolonged corticosteroid therapy, higher androgen levels, and clinical features of treatment imbalance (e.g., Cushingoid appearance, hyperpigmentation). Female sex was significantly associated with higher rates of stunting. Conclusions: Growth impairment, nutritional deficiencies, and skeletal maturation disturbances are prevalent among children with CAH in Vietnam. Early identification of risk factors and the implementation of tailored management strategies that address both endocrine and nutritional health are crucial for optimizing long-term outcomes.

Keep calm but do not carry on: ethical issues with the recommendations made by the Cass Review (2024)

2025-06-15

Simona Giordano | Journal of Medical Ethics

This paper discusses some of the ethical and legal issues that the recommendations contained in the Cass Review raise. It focuses, in particular, on the recommendation that hormonal treatment in … This paper discusses some of the ethical and legal issues that the recommendations contained in the Cass Review raise. It focuses, in particular, on the recommendation that hormonal treatment in the form of puberty blockers be made available only within a clinical trial. This paper explains why a clinical trial is highly unlikely to expand the evidence base in the way stated in the Review, and that other kinds of research, such as observational and longitudinal studies, are much more likely to be useful in this context. Those other kinds of research, however, are considered by Cass to provide low quality of evidence. In addition to the feasibility of clinical trials in this context, there are important ethical issues, which relate to consent and its voluntariness.

THE EFFECTS OF OVERWEIGHT AND OBESITY ON THE STATE THE ORAL CAVITY IN CHILDREN AND ADOLESCENTS

2025-06-15

A. I. Maksymenko , Ольга Вікторівна Шешукова , Anastasiya Onyshchenko +5 more | PROBLEMS OF ENDOCRINE PATHOLOGY

The relevance of the problem of overweight is beyond doubt. Obesity in children is not only a medical but also a social and psychological problem of our time. Our country … The relevance of the problem of overweight is beyond doubt. Obesity in children is not only a medical but also a social and psychological problem of our time. Our country is among the European leaders in terms of obesity prevalence. The results of scientific research show that obesity causes many diseases, including dental ones. Dental health depends on oral hygiene, the intensity of dental caries and its complications, the impact of various orthodontic problems, the peculiarities of inflammatory processes in periodontal tissues, as well as the presence of concomitant general somatic diseases in the child's body. Dental health often depends on what a person eats. It has been established that obese children who overconsume cakes, sweets, bakery products, and carbohydrate foods have a strong intensity of caries, as well as impaired saliva mineralization, which indicates an extensive activity of the caries process. The frequency of consumption of sugar products directly affects the intensity of caries development. It has been established that dental caries, together with overweight, is a multifactorial disease that affects the health and psychosocial development of a child. In recent decades, it has been determined that obesity plays a significant role in the predisposition to periodontal disease and negatively affects the severity of gingivitis and periodontitis. The adverse effect of obesity on periodontal disease may be due to a state of chronic systemic inflammation. Proinflammatory cytokines such as interleukins (IL-6, TNF-α), adipokines (adiponectins and leptins) and other biologically active substances can have a direct impact on the condition of periodontal tissues. Metabolic disorders play an important role in the pathogenesis of periodontitis. It has been found that in obesity and metabolic syndrome, the structure of the microbiocenosis of periodontal pockets is characterized by a decrease in the number of saprophytic microflora and a significant contamination with periodontopathogenic microorganisms. Many researchers suggest that overweight patients also suffer from osteoporosis. The problem of osteoporosis is also of interest to paediatric dentists, as it directly affects the bone component of the periodontium. Many studies have shown an inverse correlation between the degree of mineralization and the severity of generalized periodontitis. Therefore, the analysis of scientific papers confirms the presence of significant pathological changes in the oral cavity in overweight children. Interdisciplinary collaboration between paediatricians, endocrinologists and paediatric dentists will allow for a deeper investigation of the common causes and mechanisms of the pathogenesis of periodontal diseases in obese children, which will further substantiate an integrated approach to the diagnosis, treatment and prevention of major dental diseases. Systematic literature research was carried out in the following databases: Scopus, PubMed, Web of Science, Embase, The Cochrane Library, MedLine.

Which trigger digit is the most common?

2025-06-14

Daniel A. Portney , Jacob M. Johnson , Alan H. Daniels +2 more | Journal of Hand Surgery (European Volume)

A national database was queried to determine the frequency of trigger finger diagnoses by digit and the frequency of multiple digit involvement. The middle finger was the most diagnosed digit, … A national database was queried to determine the frequency of trigger finger diagnoses by digit and the frequency of multiple digit involvement. The middle finger was the most diagnosed digit, with 33% of patients having multiple digit involvement. Level of evidence: III

Predicting Treatment Outcome in Congenital Adrenal Hyperplasia Using Urine Steroidomics and Machine Learning

2025-06-14

Ozair Abawi , Grit Sommer , Michael Größl +7 more | European Journal of Endocrinology

Abstract Objective Treatment monitoring of individuals with congenital adrenal hyperplasia (CAH) remains unsatisfactory. Comprehensive 24h urine steroid profiling provides detailed insight into adrenal steroid pathways. We investigated whether 24h urine … Abstract Objective Treatment monitoring of individuals with congenital adrenal hyperplasia (CAH) remains unsatisfactory. Comprehensive 24h urine steroid profiling provides detailed insight into adrenal steroid pathways. We investigated whether 24h urine steroid profiling can predict treatment control in children and adolescents with CAH using machine learning (ML). Design Prospective observational cohort study Methods This study included children with 21-hydroxylase deficiency. On 24h urines of 2 consecutive visits 40 steroids were measured by gas chromatography-mass spectrometry. Treatment outcome was clinically classified as undertreated, optimally treated or overtreated. We used sparse partial least-squares discriminant analysis (sPLS-DA) to investigate prediction of treatment outcome. We computed area under the ROC-curve (AUC) of two sPLS-DA models: (1) using only 24h urine metabolites, (2) adding clinical variables. Results We included 112 visits (68 optimal, 44 undertreatment) from 59 patients: 27 (46%) girls, 46 (78%) classic CAH, 19 (32%) prepubertal. Mean age at first visit was 11.9 ± 4.0 years and mean BMI SDS 0.6 ± 1.1. SPLS-DA using 24h urine metabolites showed clear clustering of optimally treated patients on two components, while undertreated patients were more heterogenous (AUC 0.88). The model selected pregnanetriol and 17α-hydroxypregnanolone contributing to excluding optimal treatment and 5 metabolites contributing to excluding undertreatment: 17β-estradiol, cortisone, tetrahydroaldosterone, androstenetriol, and etiocholanolone. Addition of clinical variables marginally improved classification (AUC 0.90). Conclusions Using ML on 24h urine steroid profiling predicted treatment outcome in children with CAH, even in the absence of clinical data, suggesting that routine comprehensive 24h urine steroid profiling could improve treatment monitoring in CAH.

An Unusual and Late Presentation of 46, XY Ovotesticular Difference of Sex Development

2025-06-13

Uthara Elsa Mathew , Arun S. Menon , Victor George +2 more | JCEM Case Reports

Abstract Ovotesticular difference of sex development (OT-DSD) is a rare condition encompassing a broad spectrum of phenotypic variations. We describe a 67-year-old man who presented with complaints of poor urinary … Abstract Ovotesticular difference of sex development (OT-DSD) is a rare condition encompassing a broad spectrum of phenotypic variations. We describe a 67-year-old man who presented with complaints of poor urinary stream and hesitancy for the past 6 months. He had normal pubertal development, libido, and erection, but has been experiencing sexual dysfunction and reduced energy over the last 2 years. Physical examination revealed bilateral cryptorchidism with no other genital ambiguities. Laboratory evaluation showed a 46, XY karyotype with hypergonadotropic hypogonadism, and imaging revealed müllerian structures with abdominal gonads and a large pelvic mass arising from the right gonad, abutting the bladder. He underwent laparoscopic right gonadectomy and biopsy of the left gonad, which revealed bilateral ovotestes and a serous cystadenofibroma arising from the right ovotestis. Given the low risk of malignancy in OT-DSD, early distinction from other differences of sex development could facilitate the preservation of the gonads, allowing for spontaneous puberty and sustained sexual function.

Is prenatal testosterone-estrogen balance related to enchondroma?

2025-06-12

Semih Yaş , Asım Ahmadov , İbrahim Kaya +4 more | Early Human Development

Hyperplasie congénitale des surrénales : formes précoces

2025-06-12

L. Levaillant , Natacha Bouhours‐Nouet , S. Rouleau +4 more | EMC - Pédiatrie - Maladies infectieuses

A novel variant in the MAP3K1 genomic locus reveals abnormal cell apoptosis as a potential pathogenic mechanism in 46, XY disorders of sex development

2025-06-05

Yufu Lu , Sijia Wei , Shuang Wang +5 more | Molecular Medicine Reports

Disorders of sex development (DSDs) are characterized by discrepancies among karyotype, the gonadal phenotype and gonadal anatomy following birth. Among these, 46, XY DSD is the most complex sub‑type and … Disorders of sex development (DSDs) are characterized by discrepancies among karyotype, the gonadal phenotype and gonadal anatomy following birth. Among these, 46, XY DSD is the most complex sub‑type and a major cause of birth defects associated with sexual development. However, due to the considerable heterogeneity in pathogenic genes, numerous cases remain genetically undiagnosed. In the present study, a novel gain‑of‑function variant was identified in the mitogen‑activated protein 3 kinase 1 (MAP3K1) gene, contributing to 46, XY DSD through the induction of abnormal cell apoptosis. Genetic analysis of a pediatric male patient and his family revealed a heterozygous MAP3K1 c.4445 G>A variant, resulting in an arginine‑to‑glutamine substitution. The variant site is highly conserved across species and the amino acid transition induced structural changes in the MAP3K1 protein. In vitro experiments demonstrated that the MAP3K1 c.4445 G>A variant markedly increased apoptotic signaling, leading to abnormal cell apoptosis, disruption of the cell cycle and reduced cell viability. Moreover, the variant exhibited increased levels of ERK1/2 and p38 phosphorylation, indicative of a gain‑of‑function effect. Subsequent analysis revealed increased expression of the testis‑determining gene, SOX9 and reduced expression of the ovary‑determining gene, FOXL2. Notably, alterations in gene expression were associated with the MAP3K1 c.4445 G>A variant, providing a mechanistic basis for the pathogenesis of 46, XY DSD. Collectively, these findings offer novel insights into the anti‑apoptotic role of MAP3K1, advancing genetic diagnosis and pre‑natal screening for individuals with DSDs.

Altered regional gray matter in Congenital Adrenal Hyperplasia (CAH)

2025-06-04

Eileen Lüders , Debra Spencer , Christian Gaser +6 more | Hormones and Behavior

Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers

2025-06-03

Joanna Hubska , Zuzanna Roszkowska , Małgorzata Bobrowicz +3 more | Frontiers in Endocrinology

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has … Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalance, prolonged glucocorticoid treatment, and associated metabolic disorders. We also discuss in vivo methods for assessing endothelial function alongside the potential utility of novel biomarkers, which may facilitate earlier identification of vascular dysfunction and stratification of cardiovascular risk. By summarizing emerging concepts in this field, we aim to highlight areas for future research and opportunities for improving long-term cardiovascular outcomes in individuals with 21OHD.

Problems and Prospects of Molecular Psychogenetics in the Study of Transsexsualism

2025-06-01

A. O. Zhukovskii , S. A. Kremenitskaya , N. V. Solovieva +2 more | Molecular Biology

FSH Receptor Variant: An Unusual Cause of Secondary Amenorrhea

2025-06-01

Oluwatosin Cooper , Elisabeth H. Quint , Yolanda R. Smith +1 more | Journal of Pediatric and Adolescent Gynecology

Gonadectomy in individuals with a difference of sex development – for whom, when, why, and why not?

2025-06-01

Sabine E Hannema , Michele A. O’Connell | Best Practice & Research Clinical Endocrinology & Metabolism

SELINEXOR IN COMBINATION WITH R‐EPOCH FOR PATIENTS WITH PREVIOUSLY UNTREATED HIV‐ASSOCIATED DLBCL: A SINGLE‐CENTER, PROSPECTIVE, SINGLE‐ARM TRIAL

2025-06-01

Cui Wang , Qi Xiao , Xin Zhang +2 more | Hematological Oncology

Case Report: When Glucocorticoid Challenge Gender Identity: A Case of Congenital Adrenal Hyperplasia With Connective Tissue Disease

2025-06-01

Deying Huang , Yanhong Li , Sheyu Li +2 more | International Journal of Rheumatic Diseases

Help-seeking Behavior of Disorders of Sex Development Patients in Palembang, Indonesia

2025-06-01

Tyas Citra Khairunnisa , Ziske Maritska , Septi Purnamasari +2 more | Biomedical Journal of Indonesia

Introduction. Disorders of Sex Development (DSD) is a congenital disorder in which there is atypical chromosomal, gonadal, or anatomical sex development. Children with DSD are often brought to the hospital … Introduction. Disorders of Sex Development (DSD) is a congenital disorder in which there is atypical chromosomal, gonadal, or anatomical sex development. Children with DSD are often brought to the hospital too late for care due to limited knowledge about this condition among medical practitioners. Early diagnosis is important to improve prognosis and minimize complications and comorbidities of DSD patients. Methods. This study is a descriptive observational study with a cross-sectional approach through interviews and data collection from medical records of Dr. Mohammad Hoesin Palembang Hospital in 2020 - 2023. Results. In this study, it was found that the infancy age group (28 days - 1 year) was the most common age of arrival of patients to the hospital (29%) and the most common main complaint was clitoral enlargement (19.4%). Conclusion. This study found a wide variation in patients’ chief complaints, which makes the age of arrival of DSD patients to the hospital still quite late.

ABS0409 IMPACT OF CROSS-HORMONE THERAPY ON BONE MINERAL DENSITY IN TRANS WOMEN: AN UPDATED META-ANALYSIS

2025-06-01

T. Beirão , Catarina Rua , Clóvis A. Silva +7 more | Annals of the Rheumatic Diseases

POS1478-HPR GENETIC LIABILITY TO URATE LEVELS IN RELATION TO CARDIOVASCULAR DISEASES: A MENDELIAN RANDOMISATION STUDY

2025-06-01

Yanxing Yang , Wen Qi Zhang , Jing Wang +4 more | Annals of the Rheumatic Diseases

POLICISTINIO KIAUŠIDŽIŲ SINDROMO KLINIKINIAI POŽYMIAI IR DIAGNOSTIKA

2025-06-01

Akvilė Drachnerytė , Roberta Naujalytė | Health Sciences

Policistinis kiaušidžių sindromas – tai endokrininė reprodukcinio amžiaus moterų liga, susijusi su hiperandrogenemija, disfunkcinėmis kiaušidėmis ir insulino rezistencija. Šis sindromas laikomas dažniausia moterų anovuliacinio nevaisingumo priežastimi. Diagnostikai svarbu išsami anamnezė, … Policistinis kiaušidžių sindromas – tai endokrininė reprodukcinio amžiaus moterų liga, susijusi su hiperandrogenemija, disfunkcinėmis kiaušidėmis ir insulino rezistencija. Šis sindromas laikomas dažniausia moterų anovuliacinio nevaisingumo priežastimi. Diagnostikai svarbu išsami anamnezė, klinikinė apžiūra, laboratoriniai kraujo tyrimai bei ultragarsinis tyrimas. Ištyrus šiuos aspektus, dažniausiai naudojami Roterdamo diagnostikos kriterijai, kurie padeda diagnozuoti policistinį kiaušidžių sindromą, atmetus kitas priežastis, galinčias sukelti šiuos požymius.

97 - Does size matter? Functional and sexual outcomes in patients treated with Trans Perineal Laser Ablation (TPLA) with large prostate (>80 ml)

2025-06-01

Giulio Raffaele Resta , Paolo Polverino , Corso Caneschi +7 more | Continence

Genotype–Phenotype Correlation in Children With Congenital Adrenal Hyperplasia due to 21‐Hydroxylase Deficiency Using Next Generation Sequencing

2025-06-01

Nurgül Ataş , Murat Karaoğlan , Gülper Nacarkahya | Molecular Genetics & Genomic Medicine

Although there a well-known correlation in genotype and phenotype, patients with 21-OHD caused by severe pathogenic variants have better correlation, whereas inconsistencies are more common in the presence of milder … Although there a well-known correlation in genotype and phenotype, patients with 21-OHD caused by severe pathogenic variants have better correlation, whereas inconsistencies are more common in the presence of milder variants. This study aimed to evaluate CYP21A2 genotyping and reveal the genotype-phenotype correlation in children diagnosed with 21-OHD in the South-eastern Anatolia region, where ethnic diversity and consanguineous marriage rates are high. The patients were divided into three groups: salt wasting (SW), simple virilizing (SV) and non-classical (NC). Pathogenic variants of the CYP21A2 gene were classified into six groups based on predicted 21-hydroxylase activity: null-A-B-C-D-E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes. The overall genotype-phenotype concordance was found to be 73.1% (68/93). The expected concordance with the SW form of the null (n = 12) and A (n = 51) groups is 91.6% and 88.2%, respectively. While the percentage of the expected clinical form of SV in patients in group B (n = 5) was 80%, the concordance for the expected clinical form of NC for group C (n = 25) was not strong enough (32%). This study demonstrates that children with 21-hydroxylase deficiency show a good correlation between severe pathogenic variants and predicted clinical phenotypes; however, the correlation is not strong enough between milder variants. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.

A novel androgen resistance gene mutation (p.G590W) in complete androgen insensitivity syndrome: Emphasizing the need for early gonadectomy and integrated patient care

2025-06-01

Haiyan Sun , Xu Wang , Lixian Wang +1 more | Journal of International Medical Research

Complete androgen insensitivity syndrome is a rare 46,XY disorder of sex development caused by mutations in the androgen receptor gene, resulting in androgen resistance despite a normal male karyotype. Individuals … Complete androgen insensitivity syndrome is a rare 46,XY disorder of sex development caused by mutations in the androgen receptor gene, resulting in androgen resistance despite a normal male karyotype. Individuals with complete androgen insensitivity syndrome typically present with female external genitalia, primary amenorrhea, and a heightened risk of gonadal germ cell tumors. Herein, we report the case of a 30-year-old woman who was diagnosed with complete androgen insensitivity syndrome at 18 years of age during evaluation for primary amenorrhea. Chromosomal analysis revealed a 46,XY karyotype, and imaging confirmed the absence of a uterus and ovaries. Despite medical advice for prophylactic gonadectomy, the patient delayed surgery and later presented with a palpable abdominal mass. Genetic analysis identified a novel hemizygous germline missense mutation, c.1768G>T (p.G590W), in exon 2 of the androgen receptor gene, which was classified as potentially pathogenic based on the American College of Medical Genetics and Genomics criteria. The patient underwent tumor resection followed by four cycles of bleomycin, etoposide, cisplatin chemotherapy regimen for advanced seminoma and has remained disease-free during follow-up. This case underscores the importance of genetic analysis, early prophylactic gonadectomy, and multidisciplinary care in managing complete androgen insensitivity syndrome to mitigate tumor risk and optimize outcomes.

The Influence of Fetal Programming due to Maternal Obesity and Periodontitis on the Extensor Digitorum Longus Muscle of Wistar Rats

2025-06-01

G. Lopes Cappellaro , Thayná Nathally Petry de Paula , Maggie A. Kuhn +4 more | Muscles Ligaments and Tendons Journal

Menopoz Öncesi Adet/ Menstrüasyon Sorunları Yaşayan Kadının İddeti

2025-05-31

Süleyman Şahin | Ankara Üniversitesi İlahiyat Fakültesi Dergisi

İslam hukuku, aile birlikteliğinin sona erme aşamasında taraflara belirli sorumluluklar yüklemektedir. Nikah bağının sona ermesi veya nikah şüphesinin ortaya çıkması durumunda kadın için söz konusu olan iddet, bu görevlerden biridir. … İslam hukuku, aile birlikteliğinin sona erme aşamasında taraflara belirli sorumluluklar yüklemektedir. Nikah bağının sona ermesi veya nikah şüphesinin ortaya çıkması durumunda kadın için söz konusu olan iddet, bu görevlerden biridir. İddet, nikahın sona ermesine neden olan hususlar ve kadının fizyolojik durumu doğrultusunda beklenmesi gereken süreyi ifade ederken iddetin sebepleri arasında ölüm ile talâk, fesih ve benzeri işlemler yer alır. Bu makalede, menopoz öncesi adet sorunları yaşayan kadınların iddeti incelenmiştir. Adet sorunları yaşayan kadından, adet görmeye başladıktan sonra bilinen veya bilinmeyen nedenlerle hayız görmeyenlerle sürekli istiḥāḍa kanı gören ve hayız kanını bundan ayırt edemeyen kimseler kastedilmektedir. Kur’an ve Sünnet’te bu durumu doğrudan açıklayan bir nas bulunmamakla birlikte literatürde konuyla alakalı farklı yaklaşımlar mevcuttur. Hususen 65/eṭ-Ṭalāḳ suresinin 4. ayetindeki "irtebtum/şüphe ederseniz" ifadesi etrafında bazı yorumlar bu konuyla irtibatlandırılmıştır. Ayrıca, hayız görmeye başladıktan sonra bir daha adet görmeyen kadının iddeti, sahabe döneminde yaşanan olaylar etrafında ihtilaflara konu olmuş ve mezhepler arasındaki görüş ayrılıklarının temelini bu ihtilaflar oluşturmuştur. Makalede tümevarım yöntemi esas alınmış, kategorik detaylandırma ve yorumlama unsurlarından istifade ile ayet, sahabe uygulaması ve mezheplerin görüşleri tahlil edilmiştir. Meselenin aktüel yönüne dikkat çekmek üzere günümüzde İslam hukuku çerçevesinde oluşturulan aile hukuku kanunlarına da atıfta bulunulmuştur. Elde edilen bulgulara göre tıbben adete dair durumun süreklilik arz ettiğini ortaya koyma şartıyla hayız görmeyen kadın ile musteḥāḍanın iddetinin üç ay olarak takdir edilmesi hem maslahatın temini hem de zararın izalesi açısından daha isabetli bulunmuştur.