Hyperandrogenic Conditions Research Articles

Test With Oral Administration of Clomiphene May Add to Differential Diagnosis of Severe Hyperandrogenism in Postmenopausal Women - A Case Report

A 62-year-old female patient, in menopause since the age of 47, presented with severe and virilizing hyperandrogenism condition that had been progressing for 10 years, with plasma testosterone levels above 500 ng/dL. Medical history included Cushing 's disease in remission since hypophysectomy in 2014 and obesity. On imaging tests, there was an adenoma in the left adrenal gland with normal ovaries. Serum DHEA-sulfate concentrations, however, were normal and pelvic ultrasound and magnetic resonance imaging showed no ovarian lesions. Given the etiological doubt of hyperandrogenism, ovarian or adrenal, an additional test was necessary. However, serum gonadotropin concentrations were low, preventing testing with a GnRH analogue. A test was carried out with Clomiphene - a selective estrogen receptor modulator that stimulates the secretion of gonadotropins - at a dose of 50 mg/day orally for 5 days. Serum testosterone concentrations increased from 670 ng/dL, pre-use, to 893 ng/dL post-use, suggesting ovarian origin. The patient underwent bilateral oophorectomy and a Leydig cell tumor was confirmed. Therefore, we suggest that in women with hyperandrogenism of undefined origin, with suppressed concentrations of plasma gonadotropins, a clomiphene administration test be performed. The significant increase in plasma testosterone concentrations is indicative of the ovarian origin of the condition.

Modern view on the etiology and pathogenesis of hyperandrogenic conditions in women of reproductive age against the background of normal levels of male steroid hormones

Modern view on the etiology and pathogenesis of hyperandrogenic conditions in women of reproductive age against the background of normal levels of male steroid hormones

A comparison of obstetric and neonatal outcomes in polycystic ovary syndrome and congenital adrenal hyperplasia: a retrospective analysis of a population database

To investigate potential differences in pregnancy, delivery, and neonatal outcomes between 2 hyperandrogenic conditions in reproductive-aged women: polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH). Retrospective population-based study with data from the Health Care Cost and Utilization Project-Nationwide Inpatient Sample Database from 2004-2014. Not applicable. A total of 14,881 women with PCOS and 298 women with CAH. Not applicable. Gestational diabetes mellitus, placenta previa, pregnancy-induced hypertension (HTN), gestational HTN, preeclampsia, eclampsia, preeclampsia and eclampsia superimposed on HTN, preterm birth, preterm premature rupture of membrane, abruptio placenta, chorioamnionitis, mode of delivery, maternal infection, hysterectomy, blood transfusion, venous thromboembolism (deep vein thrombosis and pulmonary embolism during pregnancy, intrapartum, or postpartum), maternal death, chorioamnionitis, septicemia during labor, postpartum endometritis, septic pelvic, peritonitis, small for gestational age, congenital anomalies, and intrauterine fetal demise. After adjusting for potential confounders, we found that women with PCOS were at increased risk of developing pregnancy-induced HTN (adjusted odds ratio [OR] = 1.76; 95% confidence interval [CI]: 1.12-2.77) and gestational diabetes (adjusted OR = 1.68; 95% CI: 1.12-2.52) when compared with women with CAH. Contrary women with CAH were at increased risk for delivery via cesarean section (adjusted OR = 0.59; 95% CI: 0.44-0.80) and small for gestational age neonates (adjusted OR = 0.32; 95% CI: 0.20-0.52). To our knowledge, this study is the first to directly compare obstetric and neonatal outcomes between patients with PCOS and CAH. Despite the similar phenotypes and some common hormonal and biochemical profiles, such as insulin resistance, hyperinsulinemia, and hyperandrogenism, our results suggest the existence of additional metabolic pathways implicated in the pathogenesis of pregnancy complications.

Expression and localization of apelin and apelin receptor protein in the oviduct of letrozole-induced hyperandrogenized mice.

Apelin and its receptor (APJ) are expressed in the reproductive organs of some mammalian females. The function of oviduct has also been suggested to be compromised in the hyperandrogenism condition. However, expression of apelin and APJ has not been shown in the oviduct of hyperandrogenized mice. Thus, the present study has investigated the localization and expression of apelin and APJ in the letrozole-induced hyperandrogenized mice oviduct. Histomorphometric analysis showed decreased lumen of oviduct in the hyperandrogenized mice. Our results showed elevated expression of APJ and decreased abundance of apelin in the hyperandrogenized mice oviduct. This finding suggests impaired apelin signaling in the oviduct of hyperandrogenized mice. The expression of androgen receptor was upregulated while estrogen receptors were downregulated in the hyperandrogenized mice. The expression of HSP70 was also downregulated along with increased expression of active caspase 3 and BAX and decreased expression of BCL2 in hyperandrogenized mice. Furthermore, the phosphorylation of phospho-Ser473-Akt and phospho-Thr308-Akt also showed differential levels in the oviduct of hyperandrogenized mice. Whether this differential phosphorylation of Akt was solely due to impaired apelin signaling in the oviduct, remains unclear. Moreover, increased androgen signaling and suppressed estrogen signaling coincides with elevated apoptosis. In conclusion, hyperandrogenized conditions could also impair the gamete transport and fertilization process due to apoptosis in the oviduct. However, further study would be required to unravel the exact role of apelin signaling in the oviduct in relation to apoptosis.

Reproductive Profile of Neuronal Androgen Receptor Knockout Female Mice With a Low Dose of DHT.

Hyperandrogenism and polycystic ovarian syndrome result from the imbalance or increase of androgen levels in females. Androgen receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron-specific AR knockout (KO) mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone, and estradiol were comparable between the control and the SynARKO mice. There were no differences in cyclicity and fertility between the control and SynARKO mice, with similar impairment in both groups on DHT treatment. Neuronal AR KO, as in this SynARKO mouse model, did not alleviate the infertility associated with DHT treatment. These studies suggest that neuronal AR KO neither altered reproductive function under physiological androgen levels, nor restored fertility under hyperandrogenic conditions.

Correlation of hyperprolactinemia, Subclinical hypothyroidism with Polycystic Ovary Syndrome and infertility

Background: Polycystic ovarian syndrome (PCOS) is a hyperandrogenic condition characterized by polycystic ovarian morphology and chronic oligo-anovulation. When it is combines with hypothyroidism and hyperprolactinemia, this condition can have severe consequences, may even lead to infertility.
 Case Presentation: This case study illustrates the complexity of PCOS and the significance of a multidisciplinary approach to its diagnosis and therapy. The patient is a 24-year-old non diabetic nonsmoker female with PCOS who has been attempting to conceive for seven years. The patient presented to the hospital with irregular menstrual cycles and a desire to become pregnant. The patient had previously been unsuccessfully treated with Clomid and letrozole. The patient's BMI was determined to be 23. 3 and a pelvic scan indicated PCO ovaries. Laboratory results revealed hyperprolactinemia (53 ng/ml) and subclinical hypothyroidism (TSH 12.6 uIU/ml, T4 0.54 ng/dL- TPO antibodies:187 IU/mL, Anti thyroglobulin antibodies 235 IU/mL), but a pituitary gland MRI was normal. Thyroid US features going with Hashimoto thyroiditis. The patient's PCOS symptoms were initially managed with metformin and Duphaston, and then Cabergoline was introduced to address hyperprolactinemia. The patient became pregnant shortly following hyperprolactinemia medication. Prenatal screenings revealed elevated fasting glucose levels and gestational diabetes. The patient's blood sugar was initially controlled by Metformin, but she later required multiple insulin doses to maintain control. The patient was scheduled for induction of labor at 38 weeks, but a lower segment emergency cesarean surgery was performed due to fetal distress.
 Conclusion: Regular monitoring and management of both PCOS and related conditions such as hypothyroidism and hyperprolactinemia are crucial to ensure the best outcome for the patient. Additionally, we suggest Metformin, Duphaston, Cabergoline to treat PCOS patient having subclinical hypothyroidism and hyperprolactinemia.
 Keywords: Polycystic ovarian syndrome, subclinical hypothyroidism, hyperprolactinemia, gestational diabetes.

Elevated Maternal Testosterone Levels Alter PFOA Elimination and Tissue Distribution in Pregnant Rats.

Perfluorooctanoic acid (PFOA) is an enduring synthetic chemical that harms human health. Recent studies indicate heightened bioaccumulation of PFOA, particularly in pregnant women experiencing preeclampsia. Since plasma testosterone levels are elevated in pregnant women with preeclampsia, we hypothesized that hyperandrogenic conditions during pregnancy may hinder PFOA elimination and contribute to their higher body burden. Pregnant Sprague-Dawley rats were s/c injected with vehicle or testosterone propionate from gestational day (GD) 15 to 20 to increase plasma testosterone levels by 2-fold, similar to levels in preeclampsia. On GD 16, [14C]-PFOA (9.4 pmol/kg) was given intravenously, and subsequently, 14C radioactivity was measured in maternal blood, urine, feces, and tissues. PFOA was primarily eliminated through urine; however, less PFOA was excreted in urine of pregnant rats with elevated testosterone levels than controls. Fecal excretion of PFOA was minimal and did not significantly differ between groups. The total elimination of PFOA (urine plus feces) was significantly reduced by 12% in pregnant rats with elevated testosterone levels. In controls, PFOA distribution was highest in placenta, followed by the kidneys, liver, brain, heart, lungs, and spleen. Pregnant rats with elevated testosterone levels displayed 12% higher concentrations of PFOA in these tissues than controls. Furthermore, the renal expression of Oat2 and Oat3 was significantly decreased, while Oatp1 and Oat-k expression was significantly increased in pregnant rats with elevated testosterone levels than controls. In conclusion, elevated maternal testosterone levels decrease urinary elimination of PFOA, possibly through altered expression of renal transporters leading to increased tissue concentrations of PFOA in pregnant rats.

Phytochemical Characterization of Vitex negundo Leaves: a Potent Antiandrogenic and Antioxidant Agent

This study was conducted to characterise phytochemicals and to explore the biological activities of Vitex negundo leaves. The washed, course powder of V. negundo leaves were extracted with different solvents of increasing polarity. All the extracts were characterized and biological activities were compared. The results revealed that the ethanolic and cold water extracts showed the presence of all phytochemicals studied except protein compared to other extracts. Further, the quantitative estimation of phytochemicals showed that the ethanolic extract had highest yield and maximum amount of total polyphenols, flavonoids, and alkaloids with the least amount of tannins compared to other extracts studied. Furthermore, the highest total polyphenol content corresponds with the potent biological activities. Indeed, in vitro antioxidant and antisteroidogenic activities were highest in the ethanolic extract than others. To conclude, the present study is the first to report the characterization and antiandrogenic property of V. negundo leaf extracts. The ethanolic extract of V. negundo leaves can be used as an antioxidant and antiandrogenic agent. Hence, it can be considered for the treatment of hyperandrogenic conditions like polycystic ovary syndrome, etc.

Curcumin Inhibits Hyperandrogen-Induced IRE1α-XBP1 Pathway Activation by Activating the PI3K/AKT Signaling in Ovarian Granulosa Cells of PCOS Model Rats.

Background Hyperandrogenism is a common characteristic of polycystic ovary syndrome (PCOS). Long-term, continuous exposure to hyperandrogenic environments may cause excessive endoplasmic reticulum (ER) stress in ovarian granulosa cells (GCs). Curcumin is a polyphenol extracted from turmeric rhizomes which has several pharmacological effects that may benefit patients with PCOS. To explore whether curcumin can inhibit hyperandrogen-induced ER stress in ovarian GCs of PCOS rats and to elucidate the possible underlying mechanisms. Methods We developed PCOS model rats by exposure to hyperandrogenic conditions and divided the rats into control, PCOS, and PCOS+curcumin (200 mg/kg, for 8 weeks) groups. The levels of ER stress-related proteins and PI3K/AKT phosphorylation were measured in the ovarian tissue of all experimental groups by real-time quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence. Subsequent in vitro analysis on primary cultured GCs was performed to confirm the influence of curcumin on ER stress inhibition by immunofluorescence and western blotting. Results Curcumin protects GCs from hyperandrogen-induced apoptosis in PCOS model rats by inhibiting the ER stress-related IRE1α-XBP1 pathway and activating the PI3K/AKT signaling pathway. Conclusions These observations indicate that curcumin might be a safe and useful supplement for PCOS patients.

Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice.

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS.

Prostate Specific Antigen as Predictive Factor for Androgenemia in Women

Background: Sex hormones of steroid origin - androgens, play an important role in the life of thebody. They are involved in the regulation of bone maturation, gonadotropin secretion and the synthesisof high-density lipids, the production of β-endorphins. Along with the anabolic effect, androgensregulate libido and sexual potency, stimulate the function of the sebaceous glands and hair follicles.At physiological concentrations, androgens participate in the regression mechanism of the follicle inthe ovaries and provide pubic hair and inguinal hair growth .The present study was conducted withthe aim the possibility of using PSA for the diagnosis of hyper androgenic conditions in women. Thestudy included 105 girls aged 17–26 were examined. The concentration in the peripheral blood ofPSA and a androgens, testosterone and DHEA-S, were determined. In addition, the concentration ofthe transport proteins of androgens SHBG and albumin was investigated. The calculation of (FT) and(BT) was carried out according to special computer programs. The aim of this work was diagnostics ofhyperandrogenic conditions in women. The result shows that the concentration of PSA increases withan increase in T peripheral blood, the concentration of PSA increases with an increase in DHEA-S inperipheral blood and the concentration of PSA increases with an decrease in SHBG in peripheral blood.In conclusion, we found that there is a relationship between androgen levels and PSA concentration inperipheral blood, and PSA is a valuable marker in the diagnosis of hyperandrogenism in women.

Intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome via activating macrophage-angiogenesis-related androgen signaling

The development of polycystic ovary syndrome (PCOS) is closely related to the chronic inflammatory and obese. Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling, but the underlying mechanisms have not been clarified. In this study, we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate liposome. Then, the offspring rat macrophage phenotype in offspring female rat adipose tissue, and levels of testosterone, angiogenic factors (PDGF and VEGF) and inflammatory factors (TNF-α and MCP-1) were investigated. By coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells (ECs), the mobility of adipocytes, and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide, NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996. It was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity, increased size and reduced number of subcutaneous and intra-abdominal adipocytes, and increased secretion of TNF-α and MCP-1 in female rats in the offspring. Eliminating macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen, and reduced TNF-α and MCP-1. Macrophages promoted mobility of adipocytes, and inhibited proliferation, migration, tube formation of ECs under hyperandrogenic condition, which were significantly inhibited by Apalutamide, JSH-23 and LY3214996. Thus, intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.

Association of Angiotensin-Converting Enzyme gene polymorphism in Pakistani women with the atypical steroidogenesis in Polycystic ovarian syndrome: A case-control study.

BackgroundPolymorphism in the angiotensin-converting enzyme gene (ACE) is responsible for elevated ACE concentrations in plasma. High ACE levels induce insulin resistance and hyperandrogenism, which are the main attributes of polycystic ovary syndrome (PCOS). Therefore, it was hypothesized that I/D polymorphism plays a role in the pathogenesis of PCOS.ObjectiveA case-control study was designed to investigate the association of I/D polymorphism of the ACE gene with PCOS in Pakistani women of reproductive age.MethodsACE I/D polymorphism was assessed in 252 women of age group 16–40 years. For genotypic analysis, PCR amplification of genomic DNA was carried out. Statistical analysis was performed to interpret the results using SPSS software.ResultsOur study showed that PCOS women were more likely to have a high body mass index and waist circumferences. Most PCOS patients had menstrual irregularities 99.3%, hirsutism 75.2% and cysts in ovaries 66.6%, along with other hyperandrogenic conditions (P-value = 0.001). The genotypic and allelic frequencies were significantly different between patients and controls. There was a significant association of three genotypes with the ratio of LH: FSH among PCOS patients (P = 0.05). Anthropometric characters, comorbidities, clinical symptoms, and PCOS conditions showed no statistical significance with ACE polymorphism.ConclusionsACE I/D polymorphism was not found associated with clinical conditions of PCOS in women of reproductive age. However, it was associated with atypical steroidogenesis. So, it indicates that ACE I/D polymorphism aggravates the pathogenesis of PCOS.

Hyperandrogenic Milieu Dysregulates the Expression of Insulin Signaling Factors and Glucose Transporters in the Endometrium of Patients With Polycystic Ovary Syndrome

Purpose: Subfertility associated with polycystic ovary syndrome (PCOS) mainly originates from oligoovulation/anovulation. Although insulin resistance and androgen excess are known to cause PCOS-associated implantation failure, the consequences of PCOS on endometrial homeostasis and pathophysiology have not been comprehensively understood. In this study, we examined whether the pathophysiologic milieu of PCOS intrinsically affects expression profiles of genes related to insulin signaling and facilitative glucose transporters (GLUTs) in the human endometrium and/or during in vitro decidualization. Study Design: Seven healthy women with regular menstrual cycles and 13 patients with PCOS were recruited for this study. To mimic the hyperandrogenic or hyperinsulinemic milieu in the endometrium of patient with PCOS (PCOSE) in vitro, human endometrial stromal cells (hESCs) were treated with dihydrotestosterone (DHT) or insulin, respectively. Results: In PCOSE, messenger RNA (mRNA) levels of insulin receptor (IR), IR substrate (IRS) 1, and IRS2 were significantly increased. Furthermore, GLUT1 and GLUT12 were aberrantly increased. Chronic exposure to insulin or DHT aberrantly increased IRS1/IRS2 phosphorylation and protein levels of GLUT1 and GLUT12 in hESCs, suggesting that not only hyperinsulinemic but also hyperandrogenic conditions affect insulin signaling and glucose metabolism. The mRNA microarrays demonstrated that DHT dysregulates various gene sets, including cell cycle and glucose metabolism, in hESCs. Furthermore, DHT suppressed the expression of GLUT1 and GLUT12 as well as decidualization markers, IGFBP1 and prolactin, during in vitro decidualization. Conclusions: The hyperandrogenic milieu affects gene expression profiles, including gene sets associated with insulin signaling, cell cycle, glucose metabolism, and/or glucose transport, in human endometrium and during in vitro decidualization.

Effects of metformin alone and in combination with spironolactone on hyperandrogenism in polycystic ovarian syndrome

Objective To evaluate the efficacy of combined therapy with metformin and low-dose spironolactone as compared with metformin alone on the clinical and endocrine-metabolic alterations of patients with polycystic ovarian syndrome (PCOS). Background PCOS is the most common endocrinological disorder in reproductive-age women. Thus, at least theoretically, metformin plus spironolactone therapy may be an effective and safe combination for PCOS. Patients and methods A prospective randomized comparative study was carried out on 48 patients with the PCOS in Obstetrics and Gynecology Department, Menoufia University Hospital, and Al-Shohadaa Hospital, Egypt, from the period of May 2016 till January 2018. Detailed history, laboratory investigations, obstetric examination, and follow-up were done. Results Mean hirsutism score and BMI (kg/m2) were 10.8 ± 3.9 and 26.8 ± 2.2, respectively, before treatment, which decreased significantly to 7.6 ± 2.4 and 22.10 ± 1.92, respectively, after 6 months of treatment. Luteinizing hormone, follicle-stimulating hormone, free testosterone, dehydroepiandrosterone sulfate, fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance were decreased significantly after 6 months of treatment as compared with before treatment among women who received metformin + hypocaloric diet and received metformin + spironolactone + hypocaloric diet before treatment. Free testosterone was decreased in group B (58.2 ± 9.1) more than group A (73.6 ± 12. 9). Conclusion The results confirm the beneficial effects of metformin in patients with PCOS. It also proves that the addition of low-dose spironolactone induces a more marked reduction of clinical and biochemical hyperandrogenism in patients with PCOS present with hyperandrogenic conditions.

Female hyperandrogenism and elite sport.

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.

Пренатальне застосування порогової дози ендокринного дизраптора дибутилфталату викликає передчасну вікову інволюцію органів репродуктивної системи самців щурів

Мета — виявити морфологічні кореляти гіперандрогенного стану молодих статевозрілих самців щурів, матері яких зазнали експозиції до порогової дози дибутилфталату протягом останнього тижня вагітності, а також дослідити морфофункціональний стан органів репродуктивної системи цих тварин у процесі старіння. Матеріал і методи. Дибутилфталат (ДБФ) вводили самицям щурів Вістар перорально в щоденній дозі 100 мг/кг м.т. упродовж 15-21-го днів вагітності. У 6- та 18-місячних нащадків чоловічої статі визначали масу та гістологічну будову органів репродуктивної системи, кількість сперматозоїдів в епідидимісах і вміст тестостерону в плазмі крові. Результати. У 6-місячних тварин дослідної групи маса органів статевої системи та гістологічна будова простати й сперматогенного епітелію сім’яників не відрізнялись від контролю. Морфологічні ознаки клітин Лейдіга в сім’яниках цих тварин свідчили про їх функціональне напруження, що корелювало з підвищеним удвічі рівнем тестостерону. Натомість у 18-місячнихдослідних тварин порівняно з контролем відповідного віку маса додаткових статевих залоз, епідидимісів і кількість сперматозоїдів вірогідно зменшувались, більше ніж дворазове зниження вмісту тестостерону було на межі вірогідності. Морфологічна будова простати та сім’яників свідчила про посилення вікових інволютивних змін цих органів, кількість мікролейдігом в інтерстиціальному просторі збільшувалась удвічі. Висновок. Гіперандрогенний стан у молодих самців щурів, які зазнали пренатального впливу низьких доз ДБФ протягом критичного періоду статевої диференціації мозку, характеризується морфологічними ознаками функціональної активації клітин Лейдіга. У старіючих піддослідних щурів відбувається передчасна інволюція гормональної та генеративної функцій гонад.

Evaluation of Phenotypic Markers of Hyperandrogenism in Patients with Preeclampsia With Severe Features [10B

INTRODUCTION: Studies have shown an association between polycystic ovarian syndrome (PCOS), a hyperandrogenic condition, and increased risk of pre-eclampsia (PEC). Certain phenotypes, such as the ratio of the length of the second and fourth digits of the hand (2D:4D) have been suggested markers of elevated prenatal androgen exposure. This study seeks to evaluate the relationship between 2D:4D ratio, earlobe crease, feet type, and risk of developing PEC with severe features (PEC-S). METHODS: This is a case control study including women in the immediate post-partum period. Patients with diagnosis of PEC-S were examined in the postpartum unit, and the following were recorded: measured length of the 2D and 4D of the right hand, presence/absence of an earlobe crease, and feet type. Descriptive statistical analysis was used. RESULTS: 150 participants were included in the study (51 cases and 99 controls). The mean 2D:4D ratio was similar in both groups 0.96 (p=0.552). There was a marginally significant relationship between presence of earlobe crease and PEC-S, with 19.6% cases having an earlobe crease compared to only 9.1% of controls (p=0.075). Concerning feet type, cases had 68.6% Egyptian, 32.5% Greek, and 7.8% Roman compared to controls 54.5%, 39.4%, 6.1% respectively (p=0.149). CONCLUSION: There is no significant association between the 2D:4D ratio or feet type and PEC-S. Thus, we concluded that these are not valid phenotypic markers for early identification of preeclampsia. There was a marginal association between presence of earlobe crease and PEC-S. We recommend this, and other phenotypes of hyperandrogenism be investigated further.

Female hyperandrogenism and elite sport

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.

Hyperandrogenic Milieu Dysregulates the Expression of Insulin Signaling Factors and Glucose Transporters in the Endometrium of Patients With Polycystic Ovary Syndrome.

Subfertility associated with polycystic ovary syndrome (PCOS) mainly originates from oligoovulation/anovulation. Although insulin resistance and androgen excess are known to cause PCOS-associated implantation failure, the consequences of PCOS on endometrial homeostasis and pathophysiology have not been comprehensively understood. In this study, we examined whether the pathophysiologic milieu of PCOS intrinsically affects expression profiles of genes related to insulin signaling and facilitative glucose transporters (GLUTs) in the human endometrium and/or during in vitro decidualization. Seven healthy women with regular menstrual cycles and 13 patients with PCOS were recruited for this study. To mimic the hyperandrogenic or hyperinsulinemic milieu in the endometrium of patient with PCOS (PCOSE) in vitro, human endometrial stromal cells (hESCs) were treated with dihydrotestosterone (DHT) or insulin, respectively. In PCOSE, messenger RNA (mRNA) levels of insulin receptor (IR), IR substrate (IRS) 1, and IRS2 were significantly increased. Furthermore, GLUT1 and GLUT12 were aberrantly increased. Chronic exposure to insulin or DHT aberrantly increased IRS1/IRS2 phosphorylation and protein levels of GLUT1 and GLUT12 in hESCs, suggesting that not only hyperinsulinemic but also hyperandrogenic conditions affect insulin signaling and glucose metabolism. The mRNA microarrays demonstrated that DHT dysregulates various gene sets, including cell cycle and glucose metabolism, in hESCs. Furthermore, DHT suppressed the expression of GLUT1 and GLUT12 as well as decidualization markers, IGFBP1 and prolactin, during in vitro decidualization. The hyperandrogenic milieu affects gene expression profiles, including gene sets associated with insulin signaling, cell cycle, glucose metabolism, and/or glucose transport, in human endometrium and during in vitro decidualization.