Female Hyperandrogenism in Elite Sports and the Athletic Triad

2021 ◽  
Author(s):  
Angelica Lindén Hirschberg
Keyword(s):  
Female Athletes ◽  
Polycystic Ovary ◽  
Disorders Of Sex Development ◽  
Normal Female ◽  
Menstrual Disorders ◽  
Mineral Density ◽  
Energy Deficiency ◽  
Sex Development ◽  
Endocrine Disturbances ◽  
Increased Risk

AbstractEssential hyperandrogenism seems to be overrepresented in female elite athletes. This applies to mild forms such as polycystic ovary syndrome, as well as rare differences/disorders of sex development (DSD). The reason is likely a selection bias since there is increasing evidence that androgens are beneficial for athletic performance by potent anabolic effects on muscle mass and bone mass, and stimulation of erythropoiesis. XY DSD may cause a greatly increased production of testosterone in the male range, that is, 10 to 20 times higher than the normal female range. The established regulations concerning the eligibility of female athletes with severe hyperandrogenism to compete in the female classification remain controversial. The most common cause of menstrual disorders in female athletes, however, is probably an acquired functional hypothalamic disturbance due to energy deficiency in relation to energy expenditure, which could lead to low bone mineral density and increased risk of injury. This condition is particularly common in endurance and esthetic sports, where a lean body composition is considered an advantage for physical performance. It is important to carefully evaluate endocrine disturbances and menstrual disorders in athletes since the management should be specific according to the underlying cause.

scholarly journals Female hyperandrogenism and elite sport

2020 ◽  
Vol 9 (4) ◽  
pp. R81-R92 ◽  
Author(s):  
Angelica Lindén Hirschberg
Keyword(s):  
Muscle Mass ◽  
Athletic Performance ◽  
Female Athletes ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Disorders Of Sex Development ◽  
Sport Performance ◽  
Aerobic Performance ◽  
Normal Female ◽  
Testosterone Levels

Emerging evidence indicates that testosterone, which can increase muscle mass and strength, stimulates erythropoiesis, promotes competitive behaviour, and enhances the physical performance of women. Indeed, the levels of testosterone within the normal female range are related to muscle mass and athletic performance in female athletes. Furthermore, among these athletes, the prevalence of hyperandrogenic conditions, including both polycystic ovary syndrome and rare differences/disorders of sex development (DSD), which may greatly increase testosterone production, are elevated. Thus, if the androgen receptors of an individual with XY DSD are functional, her muscle mass will develop like that of a man. These findings have led to the proposal that essential hyperandrogenism is beneficial for athletic performance and plays a role in the choice by women to compete in athletic activities. Moreover, a recent randomized controlled trial demonstrated a significant increase in the lean mass and aerobic performance by young exercising women when their testosterone levels were enhanced moderately. Circulating testosterone is considered the strongest factor to explain the male advantage in sport performance, ranging between 10 and 20%. It appears to be unfair to allow female athletes with endogenous testosterone levels in the male range (i.e. 10–20 times higher than normal) to compete against those with normal female androgen levels. In 2012, this consideration led international organizations to establish eligibility regulations for the female classification in order to ensure fair and meaningful competition, but the regulations are controversial and have been challenged in court.

Low energy availability surrogates correlate with health and performance consequences of Relative Energy Deficiency in Sport

2018 ◽  
Vol 53 (10) ◽  
pp. 628-633 ◽  
Author(s):  
Kathryn E Ackerman ◽  
Bryan Holtzman ◽  
Katherine M Cooper ◽  
Erin F Flynn ◽  
Georgie Bruinvels ◽  
...  
Keyword(s):  
Female Athletes ◽  
Relative Energy ◽  
Low Energy ◽  
Clinical Population ◽  
Energy Availability ◽  
Energy Deficiency ◽  
Increased Risk ◽  
Performance Consequences ◽  
And Performance ◽  
Low Energy Availability

Low energy availability (EA) is suspected to be the underlying cause of both the Female Athlete Triad and the more recently defined syndrome, Relative Energy Deficiency in Sport (RED-S). The International Olympic Committee (IOC) defined RED-S as a syndrome of health and performance impairments resulting from an energy deficit. While the importance of adequate EA is generally accepted, few studies have attempted to understand whether low EA is associated with the health and performance consequences posited by the IOC.ObjectiveThe purpose of this cross-sectional study was to examine the association of low EA with RED-S health and performance consequences in a large clinical population of female athletes.MethodsOne thousand female athletes (15–30 years) completed an online questionnaire and were classified as having low or adequate EA. The associations between low EA and the health and performance factors listed in the RED-S models were evaluated using chi-squared test and the odds ratios were evaluated using binomial logistic regression (p<0.05).ResultsAthletes with low EA were more likely to be classified as having increased risk of menstrual dysfunction, poor bone health, metabolic issues, haematological detriments, psychological disorders, cardiovascular impairment and gastrointestinal dysfunction than those with adequate EA. Performance variables associated with low EA included decreased training response, impaired judgement, decreased coordination, decreased concentration, irritability, depression and decreased endurance performance.ConclusionThese findings demonstrate that low EA measured using self-report questionnaires is strongly associated with many health and performance consequences proposed by the RED-S models.

WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease

2021 ◽  
pp. 1-9
Author(s):  
Maria T.M. Ferrari ◽  
Andreia Watanabe ◽  
Thatiane E. da Silva ◽  
Nathalia L. Gomes ◽  
Rafael L. Batista ◽  
...  
Keyword(s):  
Kidney Development ◽  
Wilms Tumor ◽  
Genetic Diagnosis ◽  
Germ Cell Tumors ◽  
Disorders Of Sex Development ◽  
Medical Attention ◽  
Primary Amenorrhea ◽  
Normal Female ◽  
Sex Development ◽  
Pathogenic Variants

Wilms’ tumor suppressor gene 1 (<i>WT1</i>) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of <i>WT1</i> have been classically associated with Denys–Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between <i>WT1</i> disorders has been frequently observed. New <i>WT1</i> variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic <i>WT1</i> variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of <i>WT1</i> between exons 9 and 10. Two pathogenic missense <i>WT1</i> variants were identified in two 46,XY individuals with Wilms’ tumors; both patients were &#x3c;1 year of age at the time of diagnosis. A novel <i>WT1</i> variant<i>,</i> c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with <i>WT1</i> variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.

scholarly journals Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology

2019 ◽  
Vol 20 (20) ◽  
pp. 5017 ◽  
Author(s):  
Leendert H. J. Looijenga ◽  
Chia-Sui Kao ◽  
Muhammad T. Idrees
Keyword(s):  
Germ Cell ◽  
Y Chromosome ◽  
Association Studies ◽  
Cell Cancer ◽  
Disorders Of Sex Development ◽  
Germ Cell Cancer ◽  
Genome Wide Association Studies ◽  
Sex Development ◽  
Stage Of Development ◽  
Increased Risk

The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients.

scholarly journals Serum Androgen Levels in Elite Female Athletes

2014 ◽  
Vol 99 (11) ◽  
pp. 4328-4335 ◽  
Author(s):  
Stéphane Bermon ◽  
Pierre Yves Garnier ◽  
Angelica Lindén Hirschberg ◽  
Neil Robinson ◽  
Sylvain Giraud ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Contraceptive Use ◽  
Female Athletes ◽  
Large Population ◽  
Disorders Of Sex Development ◽  
Sex Development ◽  
Biological Passport ◽  
Androgen Sensitivity ◽  
High Level ◽  
Androgen Levels

Objective: Prior to the implementation of the blood steroidal module of the Athlete Biological Passport, we measured the serum androgen levels among a large population of high-level female athletes as well as the prevalence of biochemical hyperandrogenism and some disorders of sex development (DSD). Methods and Results: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate, androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography-mass spectrometry high resolution or immunoassay. Free T was calculated. The sampling hour, age, and type of athletic event only had a small influence on T concentration, whereas ethnicity had not. Among the 85.5% that did not use oral contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral contraceptive users showed the lowest serum androgen and gonadotrophin and the highest SHBG concentrations. After having removed five doped athletes and five DSD women from our population, median T and free T values were close to those reported in sedentary young women. The 99th percentile for T concentration was calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for competition eligibility of hyperandrogenic women with normal androgen sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population is approximately 7 per 1000, which is 140 times higher than expected in the general population. Conclusion: This is the first study to establish normative serum androgens values in elite female athletes, while taking into account the possible influence of menstrual status, oral contraceptive use, type of athletic event, and ethnicity. These findings should help to develop the blood steroidal module of the Athlete Biological Passport and to refine more evidence-based fair policies and recommendations concerning hyperandrogenism in female athletes.

scholarly journals Comprehensive Transcriptome Analysis of Hypothalamus Reveals Genes Associated With Disorders of Sex Development in Pigs

2020 ◽  
Author(s):  
Shuwen Tan ◽  
Yi Zhou ◽  
Haiquan Zhao ◽  
Jinhua Wu ◽  
Hui Yu ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Rna Isolation ◽  
Functional Enrichment ◽  
Regulation Mechanism ◽  
Normal Female ◽  
Sex Development ◽  
Mirna Expression Profiles ◽  
Hormone Biosynthesis

Abstract Background Disorders of sex development (DSD) is a chronic autoimmune disease characterized by systemic inflammation, pathological osteogenesis, and endocrine abnormality. However, its genetic etiology remains mostly unknown. In addition, little research focuses on the regulation mechanism from the view of transcriptomics in the hypothalamic-pituitary-gonadal axis (HPGA). The hypothalamus is the integrated center of the HPGA mediating neural, hormonal, and environmental stimulus to sex development. Methods Three XX-DSD (SRY-negative) pig (DSD) and three NF pigs (five months old, 40 kg ± 5 kg) were selected by external genitalia observation and sex determining region Y gene (SRY) detection. The hypothalamus were sampled for RNA isolation, and the mRNA, lncRNA and miRNA expression profiles were analyzed by sequencing. Results A total of 1,258 lncRNAs, 1,086 mRNAs, and 61 microRNAs were found to differentially express in XX-DSD pigs compared with normal female pigs. Many genes in hormone biosynthesis and secretion pathway are significantly up-regulated, and the up-regulation of GNRH1, KISS1 and AVP may be the candidate genes leading the abnormal secretion of GnRH. Next, we predicted the lncRNA-miRNA-mRNA co-expression triplets and constructed three competing endogenous RNA (ceRNA) potentially associated with DSD. Functional enrichment suggested TCONS_00340886, TCONS_00000204 and miR-181a were related to GnRH secretion. Conclusions Our research revealed the first transcriptomic profile in the hypothalamus of XX-DSD pigs and provided new insight in coding and non-coding RNAs that may be associated with DSD in pigs.

scholarly journals Isolated 17,20-Lyase Deficiency in a CYB5A Mutated Female With Normal Sexual Development and Fertility

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Mei Tik Leung ◽  
Hoi Ning Cheung ◽  
Yan Ping Iu ◽  
Cheung Hei Choi ◽  
Sau Cheung Tiu ◽  
...  
Keyword(s):  
Pubertal Development ◽  
Cytochrome B5 ◽  
Disorders Of Sex Development ◽  
Normal Female ◽  
Lyase Deficiency ◽  
Sex Development ◽  
Spontaneous Pregnancy ◽  
Healthy Female ◽  
Cytochrome P450 Oxidoreductase ◽  
Microsomal Cytochrome B5

Abstract Isolated 17,20-lyase deficiency may be caused by mutations in the CYP17A1 (coding for cytochrome P450c17), POR (coding for cytochrome P450 oxidoreductase) and CYB5A (coding for microsomal cytochrome b5) genes. Of these, mutations in the CYB5A gene have thus far only been described in genetic males who presented with methemoglobinemia and 46,XY disorders of sex development (DSD) due to 17,20-lyase deficiency. A 24-year-old Chinese woman presented to the hematology outpatient clinic with purplish discoloration of fingers, toes, and lips since childhood. Investigations confirmed methemoglobinemia. A homozygous c.105C&gt;G (p.Tyr35Ter) nonsense mutation was detected in the CYB5A gene. Hormonal studies showed isolated 17,20-lyase deficiency. Interestingly, she had a completely normal female phenotype with no DSD, normal pubertal development, and spontaneous pregnancy giving birth uneventfully to a healthy female infant. The sex hormone-related features of genetic females with 17,20-lyase deficiency due to cytochrome b5 gene mutation appear to differ from that of females with 17,20-lyase deficiency caused by other genetic defects who presented with hypergonadotropic hypogonadism and infertility and differ from genetic males with the same mutation.

scholarly journals Disordered Eating and Eating Disorders in Aquatic Sports

2014 ◽  
Vol 24 (4) ◽  
pp. 450-459 ◽  
Author(s):  
Anna Melin ◽  
Monica Klungland Torstveit ◽  
Louise Burke ◽  
Saul Marks ◽  
Jorunn Sundgot-Borgen
Keyword(s):  
Eating Disorders ◽  
Disordered Eating ◽  
Eating Behavior ◽  
Female Athletes ◽  
Reproductive Function ◽  
Functional Impairments ◽  
Physical And Mental Health ◽  
Energy Deficiency ◽  
Impaired Performance ◽  
Increased Risk

Disordered eating behavior (DE) and eating disorders (EDs) are of great concern because of their associations with physical and mental health risks and, in the case of athletes, impaired performance. The syndrome originally known as the Female Athlete Triad, which focused on the interaction of energy availability, reproductive function, and bone health in female athletes, has recently been expanded to recognize that Relative Energy Deficiency in Sport (RED-S) has a broader range of negative effects on body systems with functional impairments in both male and female athletes. Athletes in leanness-demanding sports have an increased risk for RED-S and for developing EDs/DE. Special risk factors in aquatic sports related to weight and body composition management include the wearing of skimpy and tight-fitting bathing suits, and in the case of diving and synchronized swimming, the involvement of subjective judgments of performance. The reported prevalence of DE and EDs in athletic populations, including athletes from aquatic sports, ranges from 18 to 45% in female athletes and from 0 to 28% in male athletes. To prevent EDs, aquatic athletes should practice healthy eating behavior at all periods of development pathway, and coaches and members of the athletes’ health care team should be able to recognize early symptoms indicating risk for energy deficiency, DE, and EDs. Coaches and leaders must accept that DE/EDs can be a problem in aquatic disciplines and that openness regarding this challenge is important.

Sign in / Sign up

Export Citation Format

Share Document