Hyperandrogenism In Polycystic Ovary Syndrome Research Articles

Differential Expression of miR-93 and miR-21 in Granulosa Cells and Follicular Fluid of Polycystic Ovary Syndrome Associating with Different Phenotypes

The heterogeneous and multifactorial essence of polycystic ovary syndrome (PCOS) renders a remarkable significance to microRNAs (miRNAs). Normo-androgenic (NA) and hyperandrogenic (HA) PCOS patients were compared with matched healthy women. Expression of miRNAs and TGFβ signaling genes was studied by qRT-PCR and western blotting. Effect of androgen on expression of miR-93 and miR-21 and involvement of androgen receptor were appraised. In granulosa cells (GCs), miR-93 and miR-21 showed significantly increased levels in HA patients compared to NA patients. On the contrary, follicular fluid (FF) levels of both miRNAs were significantly decreased in HA group compared to control women. No significant change in the expression of miRNAs in serum samples was detected. Furthermore, mRNA levels of SMAD7 and TGFBR2 were significantly downregulated in GCs of HA group compared to NA and control subjects. TGFBR2 protein level was significantly decreased in HA patients compared to controls. Free testosterone and free androgen index were positively correlated with expression of miR-93 and miR-21 in GCs of PCOS group. Our findings show distinct molecular signature of different subtypes of PCOS. Intermediary position of miRNAs as androgen responsive factors may play critical role in the pathogenesis of PCOS in hyperandrogenic condition.

Prevalence of dermatologic manifestations and metabolic biomarkers in women with polycystic ovary syndrome in north China.

Cutaneous features of hyperandrogenism in polycystic ovary syndrome (PCOS) include acne, hirsutism, seborrhea, androgenic alopecia (AGA), and acanthosis nigricans (AN). However, the relationships have not been well known broadly in terms of clinical hyperandrogenism and biochemical markers. The aim of this study was to investigate biochemical and metabolic parameters in relation to cutaneous characters women in with and without PCOS. This was a cross-sectional retrospective study including 186 women with PCOS and 113 age-matched without PCOS women. Acne grade, hirsutism, seborrhea, AGA, and AN were recorded. Hormonal and metabolic parameters were measured. The most common finding was acne, and AN was the least dermatological manifestations between PCOS and non-PCOS groups. The severity location and type of acne did not differ in PCOS women compared to non-PCOS women. Significant differences were found with respect to free androgen index (FAI) (P=.036), sex hormone-binding globulin (SHBG) (P=.023), and body mass index (BMI) (P=.001) between PCOS with acne and PCOS without acne groups. Overall, age (P=.005) was significantly decreased, while BMI (P=.004) was significantly higher in PCOS with hirsutism. The mean serum total testosterone (TT), dehydroepiandrosterone sulfate, and FAI were significantly elevated, but SHBG was decreased between PCOS with and without hirsutism groups. There were significantly different BMI (P=.018) and triglyceride (P=.024) except other hormonal parameter of without AGA group. This study indicated a strong correlation between hirsutism and metabolic abnormalities. Hirsutism is the most common cutaneous finding in PCOS women. Acne and AGA are associated with other manifestations of clinical hyperandrogenism, but not obvious markers of biochemical hyperandrogenemia and metabolic dysfunction.

Increased rates of complications in singleton pregnancies of women previously diagnosed with polycystic ovary syndrome predominantly in the hyperandrogenic phenotype

To study the presence of several maternal and neonatal complications in a cohort of women with hyperandrogenic as well as normoandrogenic polycystic ovary syndrome (PCOS) and women with PCOS who received different fertility treatments. Prospective multicenter cohort study. Hospitals and midwifery practices. One hundred and eighty-eight women with PCOS and singleton pregnancies (study group) and 2,889 women with a naturally conceived singleton pregnancy (reference group). Observational study. Maternal and neonatal pregnancy complications. Women with PCOS had a statistically significantly increased risk of developing gestational diabetes (adjusted odds ratio [AOR] 4.15; 95% confidence interval [CI], 2.07-8.33) compared with the reference group, and their infants were more often born small for gestational age (AOR 3.76; 95% CI, 1.69-8.35). In a subgroup analysis, maternal complications were statistically significantly more often present in women with hyperandrogenic (defined as a free androgen index >4.5) PCOS (n = 76; 40% of all PCOS women) compared with those with normoandrogenic PCOS (n = 97; 52% of all PCOS women) (45% vs. 24%; P=.003); no statistically significant differences were observed between these groups regarding neonatal complications. Women with PCOS have an increased risk of maternal and neonatal pregnancy complications, especially women with the hyperandrogenic phenotype. NCT00821379.

Weight loss in obese girls with polycystic ovarian syndrome is associated with a decrease in Anti-Muellerian Hormone concentrations.

The Anti-Muellerian Hormone (AMH) has been reported as surrogate marker of antral follicles, which are the origins of hyperandrogenism in polycystic ovarian syndrome (PCOS). Therefore, AMH may be useful for the diagnosis of PCOS. The objective was to study the longitudinal changes in AMH concentrations in girls with and without PCOS. This is a longitudinal study of obese girls participating in a 1-year lifestyle intervention. Forty obese girls aged 13-16years (50% with PCOS) were included in the study. Girls with and without PCOS were matched to age, BMI and change in weight status. AMH, gonadotropins, androstenedione, testosterone, oestradiol and sex hormone-binding globulin (SHBG) were determined. Obese girls with PCOS demonstrated significantly (P<.001) higher AMH concentrations (5.8±3.1ng/mL) compared to obese girls without PCOS (2.4±1.4ng/mL). None of the girls without PCOS had AMH concentrations ≥6ng/mL and none of the PCOS girls showed AMH concentrations ≤3ng/mL. Weight loss in girls with PCOS was associated with a significant drop in AMH concentrations (-1.4±1.8ng/mL, P=.045). AMH was significantly related to testosterone (cross-sectional: b-coefficient 3.7±1.7, P=.001, longitudinal: b-coefficient 0.54±0.47, P=.026) and luteinizing hormone (LH) (cross-sectional: b-coefficient 0.05±0.04, P=.039, longitudinal: b-coefficient 0.005±0.004, P=.039), but not to any other analysed parameter in multiple linear regression analyses adjusted to multiple confounders. AMH was increased in adolescent girls with PCOS and normalized with weight loss. AMH was cross-sectionally and longitudinally related to hyperandrogenism.

Genetic susceptibility for adrenal hyperandrogenism in polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Using gonadotropin-releasing hormone agonist before frozen embryo transfer may improve ongoing pregnancy rates in hyperandrogenic polycystic ovary syndrome women

Polycystic ovary syndrome (PCOS), affecting more than 5–10% of woman at reproductive childbearing age, is characterized by anovulation and hyperandrogenism. Frozen-thawed embryo transfer (ET) has been widely used for PCOS women to minimize the risk of ovarian hyperstimulation syndrome. However, the hyperandrogenic status of PCOS women deteriorates endometrial function, which has subsequently increased miscarriage rates in PCOS women. Therefore, we conducted this retrospective study to compare the pregnancy outcomes of hyperandrogenic PCOS women with (n = 29) and without (n = 31, controls) pretreatment of gonadotropin-releasing hormone (GnRH) agonist before frozen-thawed ET. We found that pretreatment with GnRH agonist before frozen-thawed ETs could not significantly improve the clinical pregnancy rate in these hyperandrogenic PCOS women. However, the ongoing pregnancy rate was significantly increased in women with GnRH agonist pretreatment (odds ratio: 3.98, 95% confidence interval: 1.12–14.20, p = 0.033). We concluded that androgen deprivation status due to pretreatment with GnRH agonist might improve the ongoing pregnancy rate in hyperandrogenic PCOS women. Additional large, well-designed prospective studies are worthwhile and necessary.

Dietary patterns and the phenotype of polycystic ovary syndrome: the chance of ongoing pregnancy

Polycystic ovary syndrome (PCOS) is generally considered a complex disorder caused by interactions between genetic and environmental factors. In a sub-cohort of women with PCOS visiting the preconception outpatient clinic of a tertiary hospital with follow-up in a periconception cohort, we identified specific dietary patterns and adherence in patients with PCOS with and without hyperandrogenism and the chance of ongoing pregnancy. Food frequency questionnaires were available from 55 patients diagnosed with PCOS during follow-up in routine clinical practice, including 25 with hyperandrogenism and 30 without hyperandrogenism. Strong adherence to the healthy dietary pattern was inversely associated with the hyperandrogenic PCOS phenotype (Adjusted OR 0.27; 95% CI 0.07 to 0.99). In women with PCOS overall, a strong adherence to the healthy dietary pattern showed a three-fold higher chance of ongoing pregnancy (adjusted OR 3.38; 95% CI 1.01 to 11.36) and an association with anti-Müllerian hormone concentration (β −0.569 µg/L; 95% CI −0.97 to −0.17). The effect of this dietary pattern on the chance of ongoing pregnancy and AMH suggests causality, which needs further investigation in prospective studies in the general population.

Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients.

AKTs have a pivotal role in the granulosa-lutein cell (GC) proliferation and folliculogenesis, and there is a reciprocal feedback between AKT with androgen. Therefore, we aimed to evaluate the role of AKTs in GCs of hyperandrogenic (+HA) PCOS cases. There were three groups: control, +HA PCOS and -HA (non-hyperandrogenic) PCOS. All groups were subjected to GnRH antagonist protocol for stimulation of ovulation. Follicular fluid was aspirated from large follicles, and GCs were isolated using cell strainer method. AKT1, AKT2, AKT3, and androgen receptor (AR) mRNA expressions were analyzed with quantitative real-time PCR (qRT-PCR), and total-AKT and p-AKT (Ser473 & Thr308) were investigated using western blotting. There were high levels of AKT1, AKT2, and AR mRNA expressions and high levels of p-AKT protein expression in the +HA PCOS group (p ≤ 0.05). There was a direct positive correlation between free testosterone (FT) and total testosterone (TT) with the levels of AKT1, AKT2, and p-AKT (Ser473), and also between FT with the levels of AR. High expressions of AKT1 and AKT2 through possible relation with androgen may cause GCs dysfunction in the +HA PCOS patients.

Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is a common cause of reproductive and metabolic dysfunction. We hypothesized that serum prostate-specific antigen (PSA) may constitute a new biomarker for hyperandrogenism in PCOS. We conducted a cross-sectional study of 45 women with PCOS and 40 controls. Serum from these women was analyzed for androgenic steroids and for complexed PSA (cPSA) and free PSA (fPSA) with a novel fifth- generation assay with a sensitivity of ~10 fg/mL for cPSA and 140 fg/mL for fPSA. cPSA and fPSA levels were about three times higher in PCOS compared to controls. However, in PCOS, cPSA and fPSA did not differ according to waist-to-hip ratio, Ferriman-Gallwey score, or degree of hyperandrogenemia or oligo-ovulation. In PCOS and control women, serum cPSA and fPSA levels were highly correlated with each other, and with free and total testosterone levels, but not with other hormones. Adjusting for age, body mass index (BMI) and race, cPSA was significantly associated with PCOS, with an odds ratio (OR) of 5.67 (95% confidence interval [CI]: 1.86, 22.0). The OR of PCOS for fPSA was 7.04 (95% CI: 1.65, 40.4). A multivariate model that included age, BMI, race and cPSA yielded an area-under-the-receiver-operating-characteristic curve of 0.89. Serum cPSA and fPSA are novel biomarkers for hyperandrogenism in PCOS and may have value for disease diagnosis.

Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Case-control study. Not applicable. In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30-39, and >39years). None. Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.

The Ovarian Renin-Angiotensin System (OVRAS): A Major Factor in Ovarian Function and Disease.

This contribution summarizes the pivotal role of the ovarian renin-angiotensin system (OVRAS) in ovarian physiology and disease, with particular emphasis on human clinical implications and established translational applications. The presence of a complete OVRAS in all studied species has been known for decades. The OVRAS has major effects on follicle development/atresia and ovulation and steroid hormone secretion, that is, it is necessary for normal reproduction. It is well established that OVRAS activity is regulated by gonadotropins and depends on activation of proteases in the area of growing follicles. Angiotensin and angiotensin receptors are widely distributed in the ovarian follicle, preovulatory theca and granulosa cells, and postovulatory mural granulosa-lutein cells and regulate steroidogenesis. Molecular blockade of the OVRAS inhibits oocyte maturation and ovulation. Pathologically abnormal OVRAS function has been associated with infertility, polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), and ovarian cancer. Both hyperandrogenism in PCOS and third space fluid accumulation in OHSS have been convincingly linked to overexpression of renin and angiotensin. Blockade of angiotensin receptors is under study for the treatment of gynecologic cancer, OHSS, and PCOS. However, a full understanding of the OVRAS and translational applications is lacking. In part, this is due to the discovery in recent years of previously unknown renin-angiotensin system (RAS) components and novel functions of "classical" RAS components that remain to be integrated into translational studies; newer, more specific agents to block RAS components are available only now for such research and treatment. The need for further studies is evident.

The Relationship Between Hearing Thresholds and Hyperandrogenism in Polycystic Ovary Syndrome

BackgroundThe purpose of our study was to investigate the association between polycystic ovary syndrome (PCOS) and hearing thresholds.Material/MethodsForty women diagnosed with PCOS (mean age, 24.33±6.38 years) and 40 healthy women controls (mean age, 26.38±6.75 years) were included in prospective study. Each case was tested with low (250, 500, 1000, and 2000 Hz), high (4000, 6000, and 8000 Hz) and extended high (EH) (9000–20000 Hz) frequency audiometry. The fasting plasma glucose, insulin, FSH, LH, total testosterone, and sex hormone-binding globulin were measured in all patients.ResultsThe mean hearing thresholds at EH frequencies were statistically significantly higher in the PCOS group than in the control group (p=0.001 right ear and p=0.015 left ear). There were significant positive correlations among free testosterone index (FTI) values and hirsutism scores with EH frequency hearing thresholds.ConclusionsAt pure-tone audiometry (PTA) EH frequencies, we detected significantly higher hearing thresholds in PCOS patients than in controls. We also determined that elevated FTI and hirsutism score were positively correlated with elevated hearing thresholds in EH frequencies. These findings support that hyperandrogenism can play a role in the elevation of hearing thresholds in PCOS.

Advances in the Diagnosis and Treatment of PCOS.

While the Rotterdam criteria look simple and easy to follow, in clinical practice diagnosis of PCOS may be problematic because of the use of inaccurate commercial androgen assays. Progresses in ovarian ultrasound and in AMH measurement have modified the way to make the diagnosis of PCOS and an update of Rotterdam criteria may be necessary. In classic severe form of PCOS, ovarian follicle count is a very reliable diagnostic criterion but AMH measurement may also present high diagnostic specificity and sensitivity. This finding is particularly important when no clinical signs of androgen excess are present and only commercial assays for androgen measurement are available. At the contrary, in mild PCOS phenotypes, sensitivity of AMH measurement is too low whileFNPO count maintains a high diagnostic sensitivity. However, at least in ovulatory hyperandrogenic PCOS phenotype, increased AMH values in association with enlarged ovarian size permit the diagnosis of ovulatory PCOS in 85% of these patients. Treatment of PCOS women has to be directed to get fertility or in patients not seeking fertility to solve or attenuate the psychological implications of androgen excess and of irregular menses and the risk of endometrial hyperplasia. The therapeutic protocols that are used in our department are presented.

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

ObjectiveTo study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.DesignCross-sectional comparison of serum biomarkers.SettingUniversity Medical Center Utrecht.PatientsHyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6–8 years), and a paedriatic reference population (n = 30).Main Outcome Measure(s)Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100).ResultsThe cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.ConclusionIn this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.

Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess: a prospective study.

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome (PCOS). There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index (BMI), total testosterone (TT), modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin (SHBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index (FAI) between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyperandrogenism had significantly higher BMI (P < 0.05), but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong predictor of hyperandrogenism in PCOS.

Serum lipid profile in non-polycystic ovary syndrome and polycystic ovary syndrome women: a comparative and correlational study

Background: Polycystic ovary syndrome (PCOS), in addition to impaired ovulation, also affects metabolic pathways. Dyslipidemia, occurring in PCOS women leads to cardiovascular diseases in them. The purpose of the present study was to compare lipid profile and its correlation with biochemical and hormonal parameters in PCOS and non PCOS women, to analyse the correlation of lipid profile with hirsutism and body mass index (BMI) in PCOS women. Methods: The present study includes 68 women divided into non PCOS groups (n=30) and PCOS (n=38) as defined by Rotterdam criteria. PCOS group further divided into overweight / obese (n=23) and normal weight subgroups (n=15). Lipid profile, fasting blood glucose and hormonal profile were done in all the groups. Results: TG and TC/HDL ratio were significantly high in PCOS group. Hirsute patients had raised LDL levels as compared to non-hirsute. LDL showed positive significant correlation with insulin, HOMA, testosterone in PCOS group. TC was significantly positively correlated with insulin and HOMA in PCOS group. In both normal weight and overweight / obese PCOS subgroups, LDL had positive and significant correlation with testosterone. TC showed positive and significant correlation with HOMA in overweight/obese subgroup. HDL showed positive and highly significant correlation with FSH in normal weight PCOS. Conclusions: Hyperandrogenism in PCOS may be additionally marked by raised LDL. Overweight/obese PCOS subgroup may be prone to dyslipidemia as well as deranged glucose homeostasis, thereby making it an important therapeutic target.

Surface electromyography and ultrasound evaluation of pelvic floor muscles in hyperandrogenic women.

High levels of androgens increase muscle mass. Due to the characteristics of hyperandrogenism in polycystic ovary syndrome (PCOS), it is plausible that women with PCOS may have increased pelvic floor muscle (PFM) thickness and neuromuscular activity levels compared with controls. The aim of this study was to assess PFM thickness and neuromuscular activity among hyperandrogenic women with PCOS and controls. This was an observational, cross-sectional, case-control study evaluating PFM by ultrasound (US) and surface electromyography (sEMG) in nonobese women with and without PCOS. Seventy-two women were divided into two groups: PCOS (n = 33) and controls (n = 39). PFM thickness during contraction was assessed by US (Vingmed CFM 800). Pelvic floor muscle activity was assessed by sEMG (MyoTrac Infinit) during contractions at different time lengths: quick, and 8 and 60 s. Descriptive analysis, analysis of variance (ANOVA), and Student's t test were used for statistical analyses. There were no significant differences in PFM sEMG activity between PCOS and controls in any of the contractions: quick contraction (73.23 mV/ 71.56 mV; p = 0.62), 8 s (55.77 mV/ 54.17 mV; p = 0.74), and 60 s (49.26 mV/ 47.32 mV; p = 0.68), respectively. There was no difference in PFM thickness during contractions evaluated by US between PCOS and controls (12.78 mm/ 13.43 mm; p = .48). This study did not find statistically significant differences in pelvic floor muscle thickness or in muscle activity between PCOS women and controls.

Decanoic acid inhibits androgen production in vitro and in vivo by regulating HSD3B2: a promising drug candidate for the management of hyperandrogenism in polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Paracrine Regulation of Steroidogenesis in Theca Cells by Granulosa Cells Derived from Mouse Preantral Follicles.

Interaction partners of follicular cells play a significant role in steroidogenesis, follicular formation, and development. Androgen secreted by theca cells (TCs) can initiate follicle development and ovulation and provide precursor materials for estrogen synthesis. Therefore, studies on ovarian microenvironment will not only lead to better understanding of the steroidogenesis but also have clinical significance for ovarian endocrine abnormalities such as hyperandrogenism in polycystic ovary syndrome (PCOS). This study applied the Transwell coculture model to investigate if the interaction between granulosa and theca cells may affect androgen production in theca cells. Concentrations of testosterone and androstenedione in the spent medium were measured by radioimmunoassay and enzyme linked immunosorbent assay, respectively. The results show that the coculture with granulosa cells (GCs) increases steroidogenesis in TCs. In addition, testosterone and androstenedione productions in response to LH stimulation were also increased in the coculture model. Significantly increased mRNA expressions of steroidogenic enzymes (Star, Cyp11a1, Cyp17a1, and Hsd3b2) were observed in the cocultured TCs. Thus, GCs were capable of promoting steroidogenesis and LH responsiveness in TCs. This study provided a basis for further exploration of ovarian endocrine mechanism and pathologies.

Cardiovascular risk factors and events in women with androgen excess.

Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.