Biochemical Hyperandrogenism Research Articles

Comparison of clinical, metabolic, and hormonal parameters in lean vs. obese women with polycystic ovary syndrome: a single-center study from Bangladesh

A bi‑directional relationship exists between obesity and polycystic ovary syndrome (PCOS). Although most of the patients with PCOS are obese, normal-weight patients still account for a certain proportion of PCOS who have lesser degrees of insulin resistance and fewer metabolic risk factors. This study was conducted to compare the clinical, metabolic, and endocrine parameters of the two categories of PCOS: lean and obese PCOS. We evaluated 523 women with PCOS attending the Endocrinology outpatient department of a tertiary hospital in Bangladesh. PCOS patients with body mass index (BMI) <23 kg/m2 were categorized as lean PCOS and those with BMI ≥23 kg/m2 as obese PCOS. Out of 523 women with PCOS studied, the frequencies of lean- and obese PCOS were 23.3% and 76.7%, respectively. Age, systolic blood pressure (BP), diastolic BP, fasting plasma glucose, plasma glucose 2-hour after oral glucose tolerance test, serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, total testosterone, and thyroid-stimulating hormone were higher in obese PCOS group; serum prolactin was higher in the lean PCOS group; modified Ferriman-Gallwey score and high-density lipoprotein cholesterol were similar in the two groups. Acanthosis nigricans (89.3% vs. 45.9%), prediabetes (24.4% vs. 13.1%), diabetes (6.7% vs. 1.6%), pre-hypertension (22.2% vs. 9.8%), hypertension (8.7% vs. 0.8%), metabolic syndrome (61.3% vs. 14.8%), and biochemical hyperandrogenism (27.7% vs. 11.5%) were more frequent in the obese group than the lean group. The two groups had similar frequencies of menstrual irregularity, hirsutism, a family member with type 2 diabetes, and dyslipidemia. Though metabolic abnormalities are more frequently observed when obesity is associated with PCOS, both lean and obese have adverse metabolic consequences. All patients with PCOS should be screened for metabolic abnormalities irrespective of BMI category.

Chronic Low Grade Inflammation in Pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

Psychological Issues and Sexual Function in Women with Different Infertility Causes: Focus on Polycystic Ovary Syndrome.

The objectives of this study are to assess the prevalence of psychological complaints and changes in sexual function in infertile PCOS women compared with patients with other infertility causes (tubal and male infertility factors) and to identify the predisposing factors. An observational study with three cohorts of infertile women was designed including 37 PCOS patients, 36 women with tubal factor, and 31 women with male factor. Clinical history and physical examination were carried out in all patients. All subjects completed the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, and the Female Sexual Function Index questionnaires. Women with infertility due to PCOS showed asignificantly higher prevalence of depressive (48.6 vs 19.4 and 12.9%, p < 0.01) and anxiety symptoms (21.6 vs 5.6 and 3.2%, p = 0.041) than respondents of reference groups. Sexual function in PCOS subjects was impaired in the areas orgasm and satisfaction (p < 0.01 for both) compared to patients of reference groups. Clinical, biochemical hyperandrogenism, and overweight were associated with ahigher incidence of depressive and anxiety symptoms in the infertile PCOS group (p < 0.01 for all). Besides, the severity of anxiety symptoms was associated with the number of medically assisted reproduction attempts (p = 0.014). Weight gain and age (p = 0.04 and p = 0.047) were associated with impaired sexual functioning. The relation between reduced sexuality and depressive/anxiety symptoms was found (p = 0.038 and p = 0.012, respectively). Infertile PCOS patients showed the highest prevalence of psychological complaints and some impairment in their sexual functioning. Mental health and sexual functioning need to be part of the routine clinical screening of every PCOS patient. The study was registered at clinicaltrials.gov (identifier: NCT03306459) https://clinicaltrials.gov/ct2/show/NCT03306459?cond=PCOS&cntry=ES&city=Barcelona&draw=2&rank=3.

Inflammation and reproductive function in women with polycystic ovary syndrome†.

Polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies, affecting 5-10% of women of reproductive age, and is characterized by the presence of ovarian cysts, oligo, or anovulation, and clinical or biochemical hyperandrogenism. Metabolic abnormalities such as hyperinsulinemia, insulin resistance, cardiovascular complications, dyslipidemia, and obesity are frequently present in PCOS women. Several key pathogenic pathways overlap between these metabolic abnormalities, notably chronic inflammation. The observation that this mechanism was shared led to the hypothesis that a chronic inflammatory state could contribute to the pathogenesis of PCOS. Moreover, while physiological inflammation is an essential feature of reproductive events such as ovulation, menstruation, implantation, and labor at term, the establishment of chronic inflammation may be a pivotal feature of the observed reproductive dysfunctions in PCOS women. Taken together, the present work aims to review the available evidence about inflammatory mediators and related mechanisms in women with PCOS, with an emphasis on reproductive function.

Cardiovascular, anthropometric, metabolic and hormonal profiling of normotensive women with polycystic ovary syndrome with and without biochemical hyperandrogenism

PurposeWomen with polycystic ovary syndrome (PCOS) present with or without biochemical hyperandrogenism (HAPCOS or non-HAPCOS, respectively). Cardiometabolic and hormonal abnormalities have been reported in women with PCOS, particularly those with hypertension. However, no direct comparison between normotensive (blood pressure <140/90 mmHg) patients with HAPCOS and non-HAPCOS has been made. This study compared different cardiovascular (CV), anthropometric, metabolic and hormonal features between normotensive patients with HAPCOS and non-HAPCOS and healthy women.MethodsWe consecutively recruited 249 normotensive patients with PCOS and 85 healthy eumenorrheic women to a case-control observational study. Based on blood androgen concentration, patients with PCOS were divided into HAPCOS (n = 69) or non-HAPCOS (n = 180) groups.ResultsAlthough within normal ranges, patients with HAPCOS had significantly (p < 0.05) higher peripheral and central systolic blood pressure and pulse pressure, C-reactive protein, low-density lipoprotein cholesterol, triglycerides, glucose, and insulin than subjects with non-HAPCOS, and healthy women. They also had lower N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration. In contrast, their body mass index (BMI) was higher of over 4 kg/m2 than patients with non-HAPCOS and nearly 6 kg/m2 than in healthy participants. Except for BMI, statistical differences in the cardiometabolic profile were of little clinical relevance.ConclusionsYoung normotensive women with HAPCOS have a worse cardiometabolic profile but lower NT-proBNP concentration than patients with non-HAPCOS. Features of this profile in both PCOS groups are within ranges typical for healthy women. Increased BMI is the only clinically relevant feature differentiating hyperandrogenic from non-hyperandrogenic patients with PCOS, and healthy women.

Clinical, biochemical, and radiological profile of polycystic ovary syndrome in adolescents attending an obesity clinic

Background: Paucity of data on adolescent polycystic ovary syndrome (PCOS) from South India. Objective: The objective of the study was to describe the clinical and biochemical profile of PCOS and its relationship to cardiometabolic risk in obese adolescent girls. Materials and Methods: A prospective observational study was conducted on adolescent girls attending obesity clinic over a 3-year period. Overweight and obese adolescent girls diagnosed as PCOS (based on Rotterdam criteria) were considered as Group I and without PCOS considered as Group II. A detailed history, physical examination, markers of hyperandrogenism, and metabolic profile were assessed and compared in two groups. Prevalence of metabolic syndrome and individual cardiometabolic risk factors was ascertained. All subjects were initiated on lifestyle measures and medications as clinically indicated. Results: Thirty-three girls with PCOS (Group I) and 33 without PCOS (Group II) were recruited. About 72.7% of subjects showing oligo or anovulatory cycles, 51.5% showed biochemical hyperandrogenism (mean testosterone level 36.76 ± 9.86 ng/dL), 69.7% showed clinical hyperandrogenism, and 84.5% showed radiological evidence of PCOS. The percentages of subjects fulfilling two and all three criteria of Rotterdam criteria for PCOS were 75.75% and 24.24%, respectively. Total 36% of the subjects had positive family history. Hirsutism was present in 54.54% (mean Ferriman-Gallwey score 8.6 ± 2.17). Percentage of subjects with individual metabolic abnormalities increased across the tertiles of BMI irrespective of the presence of PCOS. Conclusion: The profile of PCOS in obese South Indian adolescent girls is described. All overweight and obese adolescent girls should be screened for metabolic abnormalities, irrespective of the presence of PCOS.

Features of Chronic Endometritis in Women of Reproductive Age with Polycystic Ovary Syndrome

Background. The prevalence of chronic endometritis among women of reproductive age reaches 68 % . Polycystic ovary syndrome (PCOS) is a common cause of reproductive disorders. Data on the characteristics of the manifestation of chronic endometritis in patients with PCOS are incredibly insufficient. PCOS is known as closely associated with metabolic syndrome and chronic systemic inflammation. However, there is no information on the role of chronic systemic inflammation in the pathogenesis of chronic endometritis in women with PCOS. The objective . Determination of the clinical and morphological features of chronic endometritis in women with polycystic ovary syndrome and to establish the role of systemic inflammation and hormones of the hypothalamic-pituitaryovarian axis in chronic endometritis associated with PCOS. Materials and methods . We performed a cross-sectional study from May 2017 to December 2019 and examined 198 women of reproductive age (33.71 ± 5.93 years) during annual preventive examinations. We used clinical, in strumental, and laboratory research methods, including hormonal, biochemical, immunohistochemical techniques, and statistical analysis. Results. Of the 198 women examined chronic endometritis was diagnosed in 76 patients, including 15 patients with PCOS. Chronic endometritis in PCOS is characterized by a relative decrease in the duration of the menstrual cycle and less pronounced lymphoid infiltration of endometrial tissue. The risk of chronic endometritis in women of reproductive age is not associated with changes in gonadotropins, prolactin, and manifestations of clinical and biochemical hyperandrogenism. Chronic endometritis is not accompanied by an increase in the concentration of C-reactive protein. At the same time, BMI, waist circumference, and leptin are considered «anti-risk» factors for chronic endometritis. Conclusion. The specific clinical manifestations of chronic endometritis in PCOS allows us to consider them as diagnostically significant. The revealed negative associations of chronic endometritis with BMI, waist circumference, and leptin require further investigation of the role of adipose tissue products in the control of local and systemic inflammation.

Association between biochemical hyperandrogenism parameters and modified Ferriman-Gallwey score in patients with hirsutism in Basrah (Southern Iraq).

IntroductionHyperandrogenemia is the most frequent endocrine disorder in women causing a variety of adverse metabolic disturbances. Establishing the diagnosis of androgen overproduction has significant implications for the follow-up and treatment of patients.AimTo investigate the severity of hirsutism and its correlation with serum androgen in women with hirsutism from Basrah (Southern Iraq).Material and methodsThis was a cross-sectional study of 300 hirsute women, mean age: 26.6 ±7.1 years with a modified Ferriman and Gallwey (mFG) score of 8 or higher. Assessment of hirsutism severity was performed and hormonal markers including total testosterone (TT), calculated free testosterone (FT) and dehydroepiandrosterone sulfate (DHEA-S), were measured.ResultsThere was a significant correlation between the severity of hirsutism using mFG score and FT, TT levels (p < 0.001 and p < 0.047, respectively), while no association was seen between mFG score and DHEA-S.ConclusionsOur data suggest that FT and, to a less extent, TT were important biochemical hyperandrogenism markers that correlate with severity of hirsutism. DHEA-S was not found to be beneficial.

Clinical, Metabolic and Hormonal Profiles of Bangladeshi Adolescents with Polycystic Ovary Syndrome.

Background: The features of polycystic ovary syndrome (PCOS) vary greatly among adolescent girls and adult women. Some of the features of PCOS may overlap with features of normal pubertal development in girls. Methods: This cross-sectional study was conducted among adolescents newly diagnosed with PCOS attending a tertiary hospital in Bangladesh. The relevant clinical, metabolic and hormonal profiles of 175 participants were evaluated. Results: The mean age of the study participants was 16.8 (±1.7) years. Oligomenorrhea was the predominant menstrual irregularity (88%). More than one-quarter of participants (27.4%) had a first-degree relative with PCOS, and 12% had a first-degree relative with type 2 diabetes. More than three-quarters (77.7%) had acanthosis nigricans. The majority (69.1%) were overweight (29.7%) or obese (39.4%), whereas 6.3% were underweight. A total of 65.7% had abdominal obesity. One-fifth (20%) of participants had pre-hypertension, and 3.4% were hypertensive. Around one-quarter (24%) had abnormal glucose tolerance (prediabetes 21.1%, diabetes 2.9%) and the majority (90.9%) had dyslipidaemia. The median Ferriman-Gallwey score was 12, 94.9% of participants had hirsutism and 33.7% had biochemical hyperandrogenism. Metabolic syndrome was present in 42.3% of participants. Higher body mass index and presence of hirsutism were associated with higher risks of metabolic syndrome. Conclusions: The clinical, metabolic and hormonal profiles of Bangladeshi adolescents with PCOS highlight risk factors and the need for clinical vigilance with respect to metabolic disease.

Диагностика и тактика ведения пациенток с гиперандрогенией в раннем репродуктивном возрасте

Hyperandrogenism is characterized by the presence of clinical symptoms and / or biochemical parameters of high androgen levels. Dermopathy and particularly acne and hirsutism are regarded as the main clinical markers of hyperandrogenism. Cosmetic problems associated with hyperandrogenism are often the reason for young woman to seek medical attention. Body hair growth in atypical areas, acne and trophic skin changes have a significant effect on the emotional state, provoke a sense of imperfection and loss of attractiveness, and reduce the quality of life. Concomitant menstrual disorders (up to 50–75%) complicate the patient’s state and determine an increased risk of gynecological disorders in the future. The causes of hyperandrogenism in early reproductive age can be varied: from more common physiological hyperandrogenism in adolescence, idiopathic hyperandrogenism, polycystic ovary syndrome (PCOS) and the atypical form of congenital adrenal hyperplasia to less common hyperthecosis, acromegaly, hyperprolactinemia, hypothyroidism, Cushing’s disease, and androgen-secreting tumors. The diagnostic search should begin with assessing complaints and clinical symptoms, and a complete physical examination. To confirm biochemical hyperandrogenism, total and free testosterone, and free androgen index are evaluated. Additional methods of examination are used to clarify the diagnosis. Treatment is prescribed in accordance with the established diagnosis. Androgen-secreting tumors require surgical intervention. Other causes of hyperandrogenism are usually treated with medication. According to current recommendations, combined oral contraceptives are the first-line therapy for the most common conditions accompanied by hyperandrogenism (hirsutism, acne vulgaris, PCOS) in early reproductive age. A clinical solution may be a combined administration of microdoses of ethinylestradiol (20 μg) and drospirenone (3 mg), progestagen with antiandrogenic property in the mode 24 + 4 (for instance: Dimia). This article presents clinical cases of diagnosis and management tactics for patients of early reproductive age with hyperandrogenism. Conclusion. The differential diagnosis of physiological and pathological conditions accompanied by hyperandrogenism is one of the current challenges for obstetrician-gynecologist. A properly developed algorithm of examination, interpretation of its results, therapy and prevention of complications are of great importance. Key words: acne, alopecia acreata, congenital adrenal hyperplasia, hyperandrogenism, hirsutism, girls, drospirenone, combined oral contraceptives, contraception, adolescents, early reproductive age, polycystic ovary syndrome, ethinylestradiol

Letrozole versus clomiphene and tamoxifen in ovulation induction in clomiphene-resistant polycystic ovary syndrome cases

Objective The aim of this study was to make a comparison between the effects of letrozole and a combination of clomiphene citrate and tamoxifen in ovulation induction in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). Background PCOS is the most common endocrine disorder affecting ~ 6–15% of women of reproductive age causing several medical problems mainly infertility. Ovulation induction can be achieved by administration of an oral drug or a combination of drugs such as clomiphene citrate, tamoxifen, and letrozole, which are considered the first-line treatment for anovulatory PCOS. Patients and methods This prospective comparative study has been performed at the outpatient clinic of Obstetrics and Gynecology of both Menoufia University Hospital and Quesna Central Hospital during the period from December 2018 to March 2020. A total of 100 patients with PCOS (resistant to clomiphene citrate) were selected according to 'Rotterdam criteria,' including biochemical hyperandrogenism. Results There were no statistically significant differences between group A (40 cases) and group B (39 cases) regarding age, BMI, and duration of infertility. The results of both groups regarding ovulation rate were comparable, with no significant difference between the two groups. Conclusion The results of the present study are comparable to previous reported studies, revealing that clomiphene citrate, tamoxifen, and letrozole are effective in the treatment of infertility in patients with PCOS. Addition of tamoxifen to clomiphene citrate enhances its effect and gives better results.

Hyperandrogenism by Liquid Chromatography Tandem Mass Spectrometry in PCOS: Focus on Testosterone and Androstenedione.

The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography in tandem with mass spectrometry (LC/MS-MS), in the diagnosis of PCOS. We evaluated 131 patients referred for suspected PCOS. Fourteen patients in total were excluded, some because of other diagnosis (n = 7) or incomplete diagnostic workup (n = 7). We measured T and A both by IA and LC-MS/MS in the 117 subjects included. We calculated free T (fT) by the Vermeulen formula and recorded clinical and metabolic data. 73 healthy females served as controls to derive immunoassays (IA) and LC-MS/MS reference intervals for T, fT and A. PCOS was confirmed in 90 subjects by IA and in 93 (+3.3%) by LC-MS/MS. The prevalence of biochemical hyperandrogenism in PCOS by LC-MS/MS increased from 81.7% to 89.2% if A was also considered. The most frequently elevated androgens were fT (73.1%) and A (64.5%) and they had similar levels of accuracy in differentiating PCOS and controls (0.34 ng/dL, Sn 91% Sp 89%; 1.16 ng/mL, Sn 91% Sp 88%, respectively). Free testosterone correlated with body mass index (BMI), homeostatic model assessment (HOMA)-index, glycated hemoglobin (HbA1c), and sex-binding globulin (SHBG). The results confirm that LC-MS/MS is slightly more sensitive than IA in the diagnosis of PCOS with LC-MS/MS detecting higher levels of fT and A. Moreover, assessment of fT and A by LC-MS/MS had a similar level of accuracy in discriminating between PCOs and control subjects. Lastly, fT by LC-MS/MS correlates with adverse metabolic parameters.

Testosterone or Dehydroepiandrosterone Sulfate as a Biomarker for Hirsutism in Women with Polycystic Ovary Syndrome

Background:Hirsutism is a distressing medical problem for women. Most of hirsutism in women is associated with excess androgen, and most cases have PCOS as an underlying cause.Which androgen to be used to evaluate clinical or biochemical hyperandrogenism in women with PCOS is still debated.There are a small number of studies that evaluated androgens in women with PCOS having hirsutism with conflicting results. The Objective of this study was to determine which androgen predict hirsutism in women with polycystic ovary syndrome (PCOS). Patients and Methods:A case-control study was done in Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq. A total of 130 women with PCOS (based on Rotterdam criteria) and 70 healthy controls of comparable age (16-40 years) were investigated for androgens (total testosterone, free testosterone, DHEA-S) using Electrochemiluminescence technology assay; excess hair was examined according to the modified Ferriman-Gallwey (mFG) score and a cut-off value of 8 defined hirsutism. Results: In the three groups of women, the first (n=100) included PCOS with hirsutism, the second (n=30) PCOS without hirsutism, and the third (n=70) women without PCOS or hirsutism as healthy control, hirsutism was seen in about 77 % of PCOS women mostly of moderate severity; High TT, FT, DHEA-S, and overall androgens were seen in 69%, 76%, 37%, and 99% respectively of our PCOS women with hirsutism. No correlation was found between TT, FT, and DHEA-S and the mFG score. Conclusions: This study provides evidence that presence of hirsutism in women with PCOS was associated with a higher level of biochemical hyperandrogenism than seen in PCOS without hirsutism; however, there was no correlation between the studied androgens and mFG score.

Serum free testosterone levels in polycystic ovarian syndrome patients and its correlation with clinical hyperandrogenism in Pakistan

Background: Polycystic ovary syndrome (PCOS) is the most frequent pathology among women of reproductive age characterized by menstrual irregularities, hyperandrogenism and polycystic ovaries on ultrasound. Evidence suggests that high androgen levels are the fundamental factor in the pathogenesis of PCOS. The objectives of the present study was to determine serum free testosterone levels in polycystic ovarian syndrome patients, and observe its correlation with clinical hyperandrogenism.&#x0D; Patients and methods: This cross-sectional study was conducted at Jinnah Allama Iqbal Institute of Diabetes and Endocrinology Lahore, Pakistan from 15th May 2019 to 15th November 2019. The study included 140 patients of PCOS diagnosed as per Rotterdam criteria. Serum testosterone levels were determined in these patients by ELISA method. Ferriman-Gallwey (FG) score was used to assess severity of clinical hyperandrogenism in the form of hirsutism. Patients were categorized into three groups, mild (FG score 8-15), moderate (FG score 15-25) and severe (FG score &gt;25). Correlation between clinical (hirsutism) and biochemical hyperandrogenism (serum free testosterone levels) was assessed using Fisher exact test. Data was analyzed using SPSS version 25.&#x0D; Results: Biochemical hyperandrogenism in the form of raised free testosterone levels was present in 46 (32.9%) PCOS patients. Out of 12 patients having Ferriman Gallwey score &gt;25, 10 (83.3%) had biochemical hyperandrogenism. Out of 70 patients having Ferriman Gallwey score 15-25, 22 (31.4%) had biochemical hyperandrogenism whereas out of 58 patients having Ferriman Gallwey score 8-15, only 14 (24.1%) patients had biochemical hyperandrogenism.&#x0D; Conclusion: Prevalence of biochemical hyperandrogenism in PCOS patients in our studied population was significantly low when compared to the population studied worldwide making it less reliable as diagnostic tool in this part of the world. Also there was significant positive correlation between free testosterone levels and degree of hirsutism which means that diagnostic accuracy of free testosterone in PCOS patients is considerably high in those having clinical hyperandrogenism.

In utero exposure to maternal stressful life events and risk of polycystic ovary syndrome in the offspring: The Raine Study

BackgroundPCOS is the most common endocrine disorder in reproductive age women. The origins of PCOS are unknown but experimental and limited human evidence suggests that greater prenatal exposure to androgens may predispose to PCOS. Experimental evidence suggests that maternal stressors may affect reproductive function in the offspring via changes in prenatal androgen exposure. In this present study, we aim to investigate whether maternal stressful life events during pregnancy are associated with polycystic ovary morphology (PCOM) or polycystic ovary syndrome (PCOS) in adolescent offspring. MethodIn a large population-based pregnancy cohort study (The Raine Study) continuously followed from prenatal life through to adolescence we examined the association between maternal stressful life events during pregnancy in both early and late gestation, and subsequent circulating concentrations of ovarian and adrenal androgens, PCOM and PCOS in the normal menstrual cycle of offspring age 14–16 years. Maternal stressful life events were prospectively recorded during pregnancy at 18 and 34 weeks using a 10-point questionnaire. Female offspring (n = 223) completed a questionnaire about their menstrual cycles, underwent a clinical examination for hirsutism (Ferriman-Gallwey score) and transabdominal pelvic ultrasound examination to determine ovarian morphology according to standardized criteria for classification of PCOM. Plasma samples were obtained at day 2–6 of the normal menstrual cycle for measurement of androgens. PCOM was defined according to the international consensus definition, 2003 and the evidence-based guideline for the assessment and management of PCOS, 2018. PCOS was diagnosed according to Rotterdam criteria and National Institute of Health (NIH) criteria. Multivariate linear and logistic regression analyses were used to examine the associations between maternal stressful life event exposure and ovarian morphology (PCOM), circulating ovarian and adrenal androgens (clinical and biochemical hyperandrogenism (hirsutism)) and presence of PCOS. ResultsOf 223 recruited adolescent girls, 78 (35.9%) and 68 (31.3%) had PCOM by the 2003 and 2018 criteria respectively, while 66 (29.6%) and 37 (16.6%) had PCOS, using Rotterdam and NIH criteria, respectively. Most girls (141/223, 63.2%) were exposed to at least one stressful life event in early gestation and around half (121/223, 54.3%) were exposed to at least one stressful life event in late gestation. Maternal stressful life events in early gestation were associated with a statistically significant lower prevalence of PCOM when applying the 2003 criteria [adjusted odds ratio [aOR] and 95% confidence intervals (CI): 0.74 (95% CI: 0.55; 0.99)], and a similar association was detected when applying the 2018 PCOM criteria (aOR, 0.69, 95% CI: 0.50; 0.95)]. Maternal stressful life events in early gestation were also associated with lower circulating concentrations of testosterone (β = −0.05, 95% CI: −0.09; −0.004) and androstenedione (β = −0.05, 95% CI: −0.10; −0.002) in the offspring. No similar effects for PCOM or circulating androgens were detected in late gestation. No statistically significant associations between maternal stressful life events in early or late gestation with PCOS (neither Rotterdam nor NIH criteria) in adolescence were detected. The prospective collection of maternal stressful life events during both early and late gestation and direct measurement of PCOM, PCOS and circulating androgens in adolescence and key co-variates implies minimal possibility of recall, information bias and selection bias. ConclusionMaternal exposure to stressful life events in early gestation is associated with significantly reduced circulating ovarian and adrenal androgen concentrations in adolescence (testosterone and androstenedione), and an indication of fewer cases of polycystic ovary morphology (PCOM) defined by the 2003 international consensus definition and by the 2018 international evidence-based guideline, but has no effect on polycystic ovary syndrome (PCOS), diagnosed using either Rotterdam or NIH criteria.

Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome.

BACKGROUNDPolycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking.AIMTo investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia.METHODSWe conducted an observational routine screening program by means of transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD was defined as CAP ≥ 288 decibels per meter. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement ≥ 8.0 kilopascals. Elevated alanine aminotransferase (ALT) was defined as ALT > 24 IU/L, as per upper limit of normal reported in South Asian women. Biochemical hyperandrogenism was defined as free androgen index > 5. Predictors of NAFLD were determined by logistic regression analysis.RESULTS101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance, independent predictors of NAFLD were higher body mass index [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI): 1.13-1.52], hyperandrogenism (aOR: 5.32, 95%CI: 1.56-18.17) and elevated ALT (aOR: 3.54, 95%CI: 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31 ± 0.11 vs 0.26 ± 0.13).CONCLUSIONDespite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.

Is There Any Association Between Clinical and Biochemical Hyperandrogenism in Women With Female Pattern Hair Loss?

BackgroundThe exact association between clinical and biochemical hyperandrogenism (HA) is heterogeneous and cannot be ascertained, especially in normoandrogenic women.ObjectivesEvaluate any association between clinical phenotypes and biochemical parameters of HA in premenopausal women with female pattern hair loss (FPHL).Materials and methodsA cross-sectional observational study on 362 women, who were assessed for general characteristics, the different FPHL severities by Sinclair's score, hirsutism by modified Ferriman-Gallwey (mFG) score. Evaluation for biochemical HA included total, calculated free and bioavailable testosterone (TT), free testosterone (FT), and bioavailable testosterone (BT), respectively, and dehydroepiandrosterone sulfate. The variables of clinical HA were FPHL, hirsutism, and acne.ResultsThe enrolled young premenopausal women's age range was (14-47 years). Around 78% were overweight or obese women. Eighty-percent of women had a mild FPHL, with a median of three years, where 2/3 of women had a duration <3 years with no significant relationship to FPHL severity. About 73% of women had either a mild to moderate hirsutism, and around 16% had acne. The biochemical HA was confirmed in around 52% of women (n=188), who show high levels of calculated FT. The calculated BT is high in 78.5% of women (n=284). The means of HA's biochemical indicators were in their reference ranges or slightly above, with no specific change pattern with the corresponding FPHL severity. None of these parameters had a significant relationship with the severity of FPHL. The FPHL duration was not affected by any presumed variable of clinical or biochemical HA.ConclusionsFPHL severity was associated with other clinical HA signs like hirsutism and acne, but not to HA's biochemical parameter. Other parameters, like sex hormone-binding globulin (SHBG), and BMI, had no significant relation to the FPHL severity.

Clinicopathological features of polycystic ovarian syndrome in adolescence

<strong>Objectives: </strong>To evaluate the clinicopathological features of adolescence diagnosed with polycystic ovarian syndrome. <strong>Methods: </strong>This is a descriptive study conducted at the Gynecology Clinics of University Obstetric Unit, Teaching Hospital-Jaffna to evaluate the clinicopathological features of adolescence diagnosed with polycystic ovarian syndrome (PCOS) over a period of 3 years. A total of 56 adolescent girls were diagnosed with PCOS during this period with the currently accepted diagnostic criteria recommended by the Pediatric Endocrine Society and all of them were included in the study. Clinicopathological features at the time of diagnosis of PCOS obtained from medical records were analyzed and descriptive statistics were calculated. <strong> </strong> <strong>Discussion: </strong>Emphasizing the importance of early detection of PCOS in women especially during the adolescent periods, its diagnosis should be based on the presence of clinical and/or biochemical hyperandrogenism and irregular menses for at least 1 year as recommended. Our results suggest that the commonest feature of clinical hyperandrogenism being moderate hirsuitism (89.3%) and the commonest type of abnormal uterine bleeding being oligomenorrhea (54%). An obvious rising trend in the number of diagnosed patients with age was also observed. Though the prevalence anovulatory pattern of bleeding among adolescence diagnosed with PCOS consistent with larger studies in Caucasian population, commonest manifestation of clinical hyperandrogenism was moderate hirsutism which was significantly higher compared to other studies. This could be explained by its variation across ethnicities especially with a higher prevalence of hirsuitism among South Asian population. In the absence of any published data on clinicopathological features of adolescence diagnosed with PCOS in Sri Lanka, our series highlights its pattern at the time of diagnosis.

Protocolo diagnóstico del síndrome de ovario poliquístico en mujeres adultas y en adolescentes

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine-metabolic disease in childbearing age women. Patients are diagnosed with PCOS if they have two of the following three criteria: a) oligo-ovulation, b) clinical or biochemical hyperandrogenism, c) polycystic ovarian morphology (transvaginal ultrasound). Diagnosis requires the exclusion of similar, mimicking disorders, such as hyperprolactinemia, non-classical congenital adrenal hyperplasia, thyroid dysfunction, hypercortisolism, acromegaly or virilizing adrenal or ovarian tumors. Due to the immaturity of the reproductive axis, ovulatory dysfunction may be normal in first pubescent year; being highest the physiological presence of ovarian follicles in these ages, ultrasound criteria are not recommended. Coexisting metabolic complications screening, including: impaired glucose metabolism, dyslipidemia, hepatic steatosis, and high blood pressure, is recommended during diagnosis.

Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study.

IntroductionThe prevalence of polycystic ovary syndrome (PCOS) is 10–15% in women of reproductive age. Its characteristics are (i) clinical or biochemical hyperandrogenism, (ii) oligomenorrhea or amenorrhea, and (iii) polycystic ovaries on ultrasound. PCOS is associated with lower quality of life, depression, anxiety, diabetes, and cardiovascular disease. Treatment commonly entails oral contraceptive use to lower endogenous androgen levels. Androgen levels and comorbidities may affect sexual function. Previous studies have addressed a limited range of possible contributing factors. We will assess sexual function as well as genital and self-reported sexual arousal in a laboratory setting in women with PCOS compared to an age-matched healthy control group. Modulation by biopsychosocial factors mentioned will be studied.MethodsThis is a multicenter prospective case control study. The study population includes healthy women with and without PCOS, aged 18–40 years, in a stable heterosexual relationship for at least 6 months. Power is calculated at 67 participants in each group. Anticipating a drop out of 10%, 150 participants will be recruited.Main outcome measuresThe main outcomes measured are sexual function using the Female Sexual Function Index, Sexual Desire Inventory, and Female Sexual Distress Scale-Revised; genital sexual arousal measured as vaginal pulse amplitude; and self-reported sexual arousal in response to erotic stimuli in a laboratory setting. The mediators that will be investigated include testosterone, free androgen levels, oral contraceptive use, sensitivity to androgens (using CAG repeat length), body mass index, body image, mental health, and self-esteem.ConclusionStrengths of this study are the inclusion of a broad range of biopsychosocial outcome measures including DNA analysis, a healthy control group, and standardized assessment of genital and self-reported sexual arousal in a laboratory setting. With the design of this study we aim to provide an insight into which biopsychosocial factors associated with PCOS are related to sexual function, and how sexual function may be affected by treatment. These new insights may help to improve clinical management of PCOS while improving the quality of life.Pastoor H, Both S, Timman R, et al. Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study. Sex Med 2020;8:718–729.