Effects of interleukin-1 receptor antagonism in women with polycystic ovary syndrome-the FertIL trial.

Introduction: Chronic low-grade inflammation might contribute to hyperandrogenemia and metabolic complications in polycystic ovary syndrome (PCOS). The proinflammatory cytokine interleukin (IL)-1 stimulates androgen production from ovarian cells, whereas blockade of the IL-1 pathway improves cardiometabolic health. We aimed to investigate whether blocking the IL-1 pathway ameliorates hyperandrogenemia in patients with PCOS. Methods: This is a prospective, interventional, single-arm, proof-of-concept trial performed at a tertiary hospital in Switzerland (August 2018 to July 2020) in 18 premenopausal women with a diagnosis of PCOS according to the Rotterdam criteria, total testosterone levels ≥ 1.7 nmol/L, and C-reactive protein (CRP) ≥ 1.0 mg/L. Patients received 100 mg/day of the IL-1-receptor antagonist anakinra for 28 days and underwent weekly blood sampling until 1 week after the end of treatment. The primary endpoint was the change in serum androstenedione levels on day 7 of treatment, assessed with liquid chromatography-tandem mass spectrometry. Seven of these women participated in a subsequent observational sub-study (May 2021 to December 2021). Results: Median [interquartile range (IQR)] androstenedione increased by 0.5 [-0.1, 1.6] nmol/L (p = 0.048) with anakinra and by 1.3 [0.08, 2.4] nmol/L [p = 0.38] without anakinra between baseline and day 7. Anakinra reduced CRP levels on days 7, 21, and 28 (p < 0.001) but did not lead to an absolute reduction in androgens. However, four of six patients (67%) had smaller areas under the curves for androstenedione and/or testosterone during the 28-day intervention with anakinra as compared to 28 days without treatment. Discussion: Our findings suggest that anakinra suppresses IL-1-mediated chronic low-grade inflammation in PCOS and might attenuate biochemical hyperandrogenemia.

Frequency of Phenotypes and their Clinical and Hormonal Characteristics of Polycystic Ovarian Syndrome.

OBJECTIVE: To determine the frequency of phenotypes of polycystic ovarian syndrome (PCOS) in patients presenting with sub-fertility, and to compare the clinical and hormonal characteristics among them. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Forest View Specialist Clinic, Peshawar, Pakistan, from August 2022 to January 2023. METHODOLOGY: The study included 662 female patients presenting with menstrual irregularities, hyperandrogenism, and infertility to the clinic. PCOS was diagnosed on the basis of the Rotterdam criterion and clinical features and classified into different phenotypes on the basis of the National Institute of Health (NIH) panel criteria. Data were entered and analysed by IBM SPSS VERSION 23.0. The frequency of four phenotypes was calculated and phenotypes were compared for age, weight, hormonal profiles, and history of miscarriages. A p <0.05 was considered statistically significant. RESULTS: Frequency of PCOS in patients with infertility was 59.76%. Phenotype A was seen in 58.2%, phenotype D in 23.3%, phenotype C in 16.9%, and phenotype B in 1.7% of cases. The LH/FSH ratio was statistically significant in phenotype A as compared to other phenotypes, while other parameters were non-significant. CONCLUSION: The frequency of PCOS is high in patients with infertility. Phenotype A is the most common variant and is associated with significant impairment of the LH/FSH ratio. KEY WORDS: Polycystic ovarian syndrome, Subfertility, Phenotypes of PCOS, Hyperandrogenism, Anovulation, R-C1.

The Role of 11-Oxygenated Androgens and Endocrine Disruptors in Androgen Excess Disorders in Women.

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis.

The association between female sexual function and metabolic features of the polycystic ovary syndrome in Turkish women of reproductive age.

OBJECTIVE: To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age. METHOD: This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls. RESULTS: Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls. CONCLUSION: PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.

The impact of androgen levels on serum metabolic profiles in patients with polycystic ovary syndrome.

OBJECTIVE: This study aimed to investigate the impact of serum androgen levels on metabolic profiles in patients with polycystic ovary syndrome (PCOS). METHODS: We included 216 patients with PCOS and 216 healthy individuals selected as the control group. According to the measured serum androgen levels, patients with PCOS were divided into the hyperandrogenism group and non-hyperandrogenism group. Clinical metabolic indicators were assessed and compared between the two groups. Additionally, we assessed the correlation between androgen levels and clinical metabolic indicators. RESULTS: The body mass index, waist-to-hip ratio, mF-G score, and acne score, as well as T, LH, LSH/FSH, FPG, Cr, UA, TG, TC, and LDL-C levels were significantly higher in the PCOS group than in the control group. The incidence of hyperandrogenism and clinical hyperandrogenism in the PCOS group was significantly higher than that in the control group. Regarding clinical hyperandrogenism, hirsutism, acne, and acanthosis nigricans were significantly more common in the PCOS group than in the control group. Serum androgen levels were significantly correlated with the mF-G score, acne score, FSH, glucose concentration at 30 min, glucose concentration at 60 min, glucose concentration at 120 min, FINS, N120, HOMA-IR, HbA1c, AUCG, UA, TG, and hHDL-Clevels. CONCLUSION: Elevated serum androgen levels are commonly observed in patients with PCOS and are associated with multiple metabolic abnormalities. Therefore, it is recommended to regularly monitor glucose and lipid metabolism-related indicators in patients with PCOS who have elevated androgen levels.

Alterations in nonesterified free fatty acid trafficking rather than hyperandrogenism contribute to metabolic health in obese women with polycystic ovary syndrome.

OBJECTIVE: To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS). DESIGN: Prospective cross-sectional study. SETTING: Tertiary-care academic center. PATIENTS: One hundred twenty-five obese women with PCOS. INTERVENTION: Consecutive obese (body mass index [BMI] ≥ 30 kg/m2) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics. MAIN OUTCOME MEASURES: Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir], the time it took for NEFA levels to reach nadir [TIMEnadir], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFAsupp]); peak lipolysis rate (SNEFA) and peak rate of NEFA disposal from plasma pool (KNEFA); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels). RESULTS: A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA, and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFAsupp) and greater TIMEnadir, NEFAnadir, and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and SNEFA. Women with MUO-PCOS had a higher homeostasis model of assessment-ß% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFAnadir, weakly and negatively with TIMEnadir, and positively with KNEFA and %NEFAsupp, in women with MUO-PCOS only. CONCLUSION: Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.

Is There a Difference in Hirsutism Score in Adolescents with Polycystic Ovary Syndrome on the Basis of Ethnicity and Race?

BACKGROUND: The complex correlation between ethnicity and race, clinical hyperandrogenism as signified by hirsutism, and biochemical androgen concentrations in polycystic ovary syndrome (PCOS) is poorly understood. STUDY OBJECTIVE: The aim of this study was to define the correlation between ethnicity/race and hirsutism score in patients with PCOS. METHODS: We conducted a retrospective chart review of a total of 251 patients with PCOS at the time of diagnosis. Patients were categorized by their ethnicity and race into 5 main groups: Asian (n = 19, 7.6%), Black or African American (n = 11, 4.4%), Hispanic or Latino (n = 26, 10.3%), White (n = 177, 70.5), and others (n = 18, 7.2%). A general linear model was applied using BlueSky software. RESULTS: For the entire study population, the mean age at diagnosis was 15.6 ± 1.7, the mean body mass index (BMI) was 30.6 ± 9.8, the mean hirsutism score using the modified Ferriman-Gallwey score chart was 6.2 ± 3.8, and the mean total testosterone was 40.1 ± 20. The hirsutism score was the highest in the Asian population (mean = 9.1, P = .002) and Hispanic or Latino population (mean = 7.8, P = .02), followed by others (mean = 7.4, P = .04) and the Black or African American population (mean = 7.1, P = .2), compared with the White population (mean = 5.4). This correlation remained significant despite accounting for BMI and androgen levels (P < .001). CONCLUSION: There are factors likely related to hair follicle sensitivity or endogenous response to circulating free androgens that differ between ethnicities and races, such that similar biochemical concentrations lead to differing severity of hirsutism, despite accounting for differences in BMI and androgen levels. More research is needed in this realm to understand the pathophysiologic basis of this interaction.

Recent Advances in the Clinical Application of Adrenal Vein Sampling.

We reviewed clinical research investigating the applications of adrenal vein sampling (AVS). AVS could be applied not only to primary aldosteronism (PA) but also to other endocrine diseases, such as adrenocorticotropic hormone (ACTH) independent Cushing syndrome (AICS) and hyperandrogenemia (HA). However, the AVS protocol requires improvements to increase its success rate. Using the computed tomography image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing (CCF) technique could improve the success rate of catheterization in AVS for PA. ACTH loading could be considered in medical centers with a low selectivity of AVS for PA but is not essential in those with mature AVS technology. The continuous infusion method should be recommended for ACTH stimulation in AVS for PA to reduce adverse events. AVS has not been routinely recommended before management decisions in AICS, but several studies verified that AVS was useful in finding out the source of excess cortisol, especially for distinguishing unilateral from bilateral disease. However, it is necessary to reassess the results of AVS in AICS with the use of reference hormones to fully normalize cortisol levels. In addition, it is essential to determine the optimal model that combines AVS results and mass size to guide the selection of surgical plans, including identifying the dominant gland and presenting the option of staged adrenalectomy, to minimize the impact of bilateral resection. For HA, AVS combined with ovarian intravenous sampling to locate excess androgens could be considered when imaging results are equivocal.

Elevated plasma pentraxin-3 in polycystic ovary syndrome is associated with hyperandrogenism: a case-control study.

BACKGROUND: Pentraxin 3 (PTX3) - a crucial humoral innate immunity component - is related to obesity and cardiovascular complications in women who suffer from polycystic ovary syndrome (PCOS). However, the circulating PTX3 level in PCOS is still debated. In this study, we aimed to evaluate PTX3 plasma levels in PCOS women of childbearing age, and find possible endocrine/metabolic factors that could affect this level. METHODS: A total of 360 women were enrolled: 120 PCOS women and 240 body mass index (BMI) matched normally ovulating women. Blood samples were collected on the third day of natural menstrual cycle or from the bleeding after progesterone withdrawal. The PTX3 concentration was measured by immunoassay. RESULTS: The PTX3 plasma level was significantly higher in PCOS women compared to controls. There was a positive correlation between PTX3 plasma level and PCOS diagnosis, overweight, cycle length, serum LH to FSH ratio, estradiol, total testosterone (TT) on the third day of menstrual cycle, antral follicle count (AFC), as well as uric acid. Multivariant linear regression analysis indicated that participants' serum PTX3 levels were proportional to the circulating TT level, existence of PCOS, basal estradiol level and AFC. CONCLUSIONS: Overall, the circulating PTX3 level was elevated in PCOS women and significantly associated with the presence of hyperandrogenism. This study provided the basis for further in-depth researches regarding PTX3 role in PCOS pathophysiology.

Hyperandrogenism? Increased 17, 20-Lyase Activity? A Metanalysis and Systematic Review of Altered Androgens in Boys and Girls with Autism.

Introduction: There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. Methods: An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Results: Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. Conclusions: We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.

Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome.

OBJECTIVE: To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 533 women with PCOS and 292 control women were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells. RESULT(S): The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels <75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells. CONCLUSION(S): Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α in vitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.

Progranulin and tumor necrosis factor-alpha in lean polycystic ovary syndrome patients.

OBJECTIVE: In this study, levels of progranulin (PGRN) and tumor necrosis factor-alpha (TNF-α) were measured to detect the presence of inflammation in lean polycystic ovary (PCOS) patients. METHODS: 40 lean PCOS patients were assessed by Rotterdam criteria. Forty healthy women with regular menstrual cycles and without biochemical and clinical hyperandrogenism were involved in our study. Blood samples were taken from the patient and control groups for the measurement of progranulin (PGRN), tumor necrosis factor-alpha (TNF-α), lipid parameters, glucose, insulin, and other hormones. RESULTS: Serum PGRN and TNF-α levels were significantly higher in patients with lean PCOS, compared with the control group (p = .037, p = .041). PGRN levels were positively correlated with TNF-α levels in lean PCOS patients. CONCLUSION: PGRN is known as a ligand for the TNF-α receptor. PGRN level increase in lean PCOS patients may be due to inhibiting the inflammatory effects of TNF-α. To observe the PGRN and TNF-α connection in obesity, further study is needed in obese PCOS patients and obese control groups.

Cardiometabolic consequences of maternal hyperandrogenemia in male offspring.

Polycystic ovary syndrome (PCOS) in women is characterized by hyperandrogenemia, obesity, and oligo- or anovulation. In addition, women with PCOS are often obese, with insulin resistance, hyperlipidemia, and elevated blood pressure. The cardiometabolic consequences for the male offspring of maternal hyperandrogenemia are unclear. The present studies tested the hypothesis that male offspring of a rat model of PCOS would develop cardiometabolic disease as adults. Female Sprague-Dawley rats (hyperandrogenemic females (HAF)) were implanted with dihydrotestosterone or placebo pellets (controls) at 4 weeks of age, and were mated at 10-12 weeks and allowed to lactate their offspring after birth. Body weights in male HAF offspring were lower at birth than in controls until postnatal day 4, but body weights remained similar between male control and HAF offspring from 2 to 8 weeks of age. However, at 16 weeks of age, body weight was lower in HAF male offspring, but there were no differences in fat mass or lean mass factored for body weight in HAF males, compared to controls. Plasma total cholesterol and HDL and proteinuria were higher and nitrate/nitrite excretion was lower in male HAF offspring than in controls. Baseline blood pressure was similar between HAF male offspring and controls, but HAF offspring had an exaggerated pressor response to angiotensin II infusion. These data suggest that adult sons of PCOS mothers may be at increased risk of cardiometabolic disease.

The comparative effectiveness of 55 interventions in obese patients with polycystic ovary syndrome: A network meta-analysis of 101 randomized trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-age females. The prevalence of obesity in PCOS patients reaches up to 80%, which is 2-fold higher than the general population. OBJECTIVE: The present study aimed to compare the effectiveness of 55 pharmacological interventions across 17 different outcomes in overweight/obese PCOS patients with hyperandrogenism manifestations for both short- and long-term follow-ups. A comprehensive literature search was performed on PubMed, Scopus, Embase, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials comparing any conventional pharmacological intervention as a monotherapy or a combination in overweight/obese patients with polycystic ovary syndrome and hyperandrogenism manifestations. Extracted data included three main parameters; I. Anthropometric parameters (BMI, Waist and Hip circumferences, and Waist/HIP ratio), II. Hormonal parameters (FSH, LH, FSG, SHBG, Estradiol, Total Testosterone, Free testosterone, DHEAS, Androstenedione), and III. Metabolic parameters (Total Cholesterol, LDL-C, HDL-C, Triglycerides, Fasting glucose, Fasting glucose, HOMA-IR). Critical appraisal and risk of bias assessments were performed using the modified Jadad scale, and the overall quality of this network meta-analysis was evaluated according to the CINeMA framework. We performed both a pairwise meta-analysis and a network meta-analysis to evaluate the effect sizes with 95% CI, and we calculated the surface under the cumulative ranking curve (SUCRA) for each intervention. RESULTS: Our final search on May 15th 2021 retrieved 23,305 unique citations from searching six electronic databases. Eventually, 101 RCTs of 108 reports with a total of 8,765 patients were included in our systematic review and multi-treatments meta-analysis. 55 different interventions were included: 22 monotherapies, and 33 combinations. The two-dimensional cluster ranking of the average SUCRA values for metabolic and hormonal parameters with significant estimates revealed flutamide (77.5%, 70%; respectively) as the highest and rosiglitazone (38.2%, 26.3%; respectively) as the lowest, in terms of the overall efficacy in reducing weight and hyperandrogenism. However, cyproterone-acetate+ethinylestradiol exhibited a higher ranking in improving hormonal parameters (71.1%), but even a lower-ranking regarding metabolic parameters (34.5%). CONCLUSIONS AND RELEVANCE: Current evidence demonstrated the superiority of flutamide in improving both metabolic and hormonal parameters, and the higher efficacy of cyproterone-acetate+ethinylestradiol only in improving hormonal parameters. Nearly all interventions were comparable in female hormones, FGS, HDL, glucose, and insulin levels improvements.

The association between 24-hour ambulatory blood pressure measurement and selected biochemical and anthropometric parameters in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorders, which may contribute to the development of cardiovascular diseases. The aim of our study was to evaluate the association between of 24-hour ambulatory blood pressure measurement (ABPM) and selected biochemical and anthropometric parameters in women with PCOS. PATIENTS AND METHODS: The study involved 153 Polish, Caucasian women with PCOS hospitalized in the Department of Endocrinology Gynecology from January 2018 to March 2020. All women had stable body mass during the 3-month period. ABPM was performed using a portable lightweight device with oscillometric technology accepted by International Protocol of European Society of Hypertension (ABPM, HolCARD CR-07, Poland). RESULTS: The first factor taken into consideration was the variability phenotypic subgroups of PCOS on the values of 24-hour ABPM. We revealed that the daytime and night-time systolic and diastolic blood pressure values were significantly higher in phenotype A subgroup than in other subgroups. Moreover, daytime and night-time systolic and diastolic blood pressure value as well as day-time heart ratio value were significantly higher in subgroup with than without hyperandrogenemia. The obese women with PCOS were characterized of the highest value of all night-time measurements among women with PCOS and normal weight, overweight or obesity. In addition, insulin resistance in the PCOS subgroup was associated with lower value of systolic, diastolic blood pressure and both at daytime and night-time heart rate value than in insulin sensitive PCOS subgroup. CONCLUSIONS: Hyperandrogenemia and obesity were the crucial influencing factors on 24-hour ABPM in the group of women with PCOS. In addition, hypertension, apart from visceral obesity, hyperinsulinemia and insulin resistance, could be considered as component of metabolic syndrome in women with PCOS.

PCOS Features and Steroid Profiles Among Young Adult Women with a History of Premature Adrenarche.

CONTEXT: Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS). OBJECTIVE: To study features of PCOS in young adult women with a history of PA. METHODS: Thirty PA and 42 control females were followed from prepuberty to young adulthood (median age 18.1 years). The main outcome measures were ovarian function, the use of contraceptives, and clinical and biochemical indicators of hyperandrogenism. RESULTS: We found no differences in the use of hormonal contraceptives (50 vs 50%, PA vs controls, respectively; P > .999), indication for using contraceptives (P = .193), or in the history of oligo- (17 vs 26%, P = .392) and amenorrhea (0 vs 0%, P > .999). Among women not using hormonal contraceptives, those with a history of PA had a higher prevalence of hirsutism (27 vs 0%, P = .023) but not acne (87 vs 67%, P = .252). Steroid profiles were broadly comparable between the groups, but PA women had lower sex hormone-binding globulin (SHBG) concentrations (30.1 vs 62.4 nmol/L, P < .001) resulting in higher free androgen index (3.94 vs 2.14, P < .001). The difference in SHBG levels persisted through body mass index adjustment. SHBG correlated negatively with the homeostasis model assessment for insulin resistance (r -0.498, P = .003). Anti-Müllerian hormone concentrations were comparable between the groups (39.3 vs 32.1 pmol/L, P = .619). CONCLUSION: PA was not associated with evident ovarian dysfunction in young adult women. However, women with a history of PA had decreased SHBG levels and thus, increased bioavailability of circulating androgens.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

Differential Effects of Various Androgens on Polycystic Ovary Syndrome.

The hyperandrogenism in polycystic ovary syndrome (PCOS) is associated with the risk for the future development of the cardiovascular disease. The objective of the study is to verify whether different androgens have the same harmful effect. This cross-sectional study enrolled 823 women with PCOS: 627 (76.2%) with biochemical hyperandrogenism and 196 (23.8%) with normal androgen levels. The role of individual androgen was evaluated using univariate and multivariate logistic regression. In normoandrogenemic PCOS (NA-PCOS), free androgen index (FAI) predicted significant abnormality in visceral adipose index (VAI, OR=9.2, p=0.002) and dehydroepiandrosterone (DHEA) predicted against alteration in ß-cell function (OR=0.5, p=0.007). In hyperandrogenemic PCOS (HA-PCOS), FAI predicted derangements in waist triglyceride index (WTI), VAI, and lipid accumulation product (LAP) (OR ranging from 1.6 to 5.8, p<0.05). DHEA weakly predicted against VAI (OR 0.7, p=0.018), dehydroepiandrosterone sulfate (DHEAS) tended to predict against the conicity index (OR=0.7, p=0.037). After multiple regression, FAI retained significant strength to predict various anthropometric and metabolic abnormalities (OR ranging from 1.1 to 3.0, p<0.01), DHEA was kept as a protector factor against WTI, LAP, and VAI (OR ranging from 0.6 to 0.9; p<0.01) and DHEAS against the conicity index (OR=0.5, p<0.001). In conclusion, the free androgen index was the most powerful predictor of anthropometric and metabolic abnormalities of polycystic ovary syndrome. Conversely, DHEA and DHEAS demonstrated protective effects against disorders in some markers of obesity and abnormal metabolism.