scholarly journals Loss of anti-Müllerian hormone (AMH) immunoactivity due to a homozygous AMH gene variant rs10417628 in a woman with classical polycystic ovary syndrome (PCOS)

2020 ◽  
Vol 35 (10) ◽  
pp. 2294-2302 ◽  
Author(s):  
Luis R Hoyos ◽  
Jenny A Visser ◽  
Anke McLuskey ◽  
Gregorio D Chazenbalk ◽  
Tristan R Grogan ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Phenotypic Expression ◽  
Antral Follicle ◽  
Dehydroepiandrosterone Sulfate ◽  
Normal Weight ◽  
Sex Hormone Binding Globulin ◽  
Transvaginal Sonography ◽  
Ovary Syndrome

ABSTRACT Anti-Müllerian hormone (AMH) is produced by granulosa cells of pre-antral and small antral ovarian follicles. In polycystic ovary syndrome (PCOS), higher levels of serum AMH are usually encountered due to the ample presence of small antral follicles and a high AMH production per follicular unit which have led to the proposal of AMH as a serum diagnostic marker for PCOS or as a surrogate for polycystic ovarian morphology (PCOM). However, heterozygous coding mutations of the AMH gene with decreased in vitro bioactivity have been described in some women with PCOS. Such mutation carriers have a trend toward reduced serum AMH levels compared to noncarriers, although both types of women with PCOS have similar circulating gonadotropin and testosterone (T) levels. This report describes a normal-weight woman with PCOS by NIH criteria with severely reduced AMH levels (index woman with PCOS). Our objective was to examine the molecular basis for her reduced serum AMH levels and to compare her endocrine characteristics to similar-weight women with PCOS and detectable AMH levels. Twenty normoandrogenic ovulatory (control) and 13 age- and BMI-matched women with PCOS (19–35 years; 19–25 kg/m2) underwent transvaginal sonography and serum hormone measures including gonadotropins, sex hormone-binding globulin, total and free T, androstenedione, dehydroepiandrosterone sulfate, estrone, estradiol and AMH. The latter was measured by ELISA (Pico-AMH: Ansh Labs, Webster, TX, USA). Women with PCOS and detectable AMH had higher serum AMH (10.82 (6.74–13.40) ng/ml, median (interquartile range)), total and free T (total T: 55.5 (49.5–62.5) ng/dl; free T: 5.65 (4.75–6.6) pg/ml) levels and greater total antral follicle count (AFC) (46 (39–59) follicles) than controls (AMH: 4.03 (2.47–6.11) ng/ml; total T: 30 (24.5–34.5) ng/dl; free T: 2.2 (1.8–2.45) pg/ml; AFC 16 (14.5–21.5) follicles, P < 0.05, all values), along with a trend toward LH hypersecretion (P = 0.06). The index woman with PCOS had severely reduced serum AMH levels (∼0.1 ng/ml), although she also had a typical NIH-defined PCOS phenotype resembling that of the other women with PCOS and elevated AMH levels. All women with PCOS, including the index woman with PCOS, exhibited LH hypersecretion, hyperandrogenism, reduced serum estrogen/androgen ratios and PCOM. A homozygous Ala515Val variant (rs10417628) in the mature region of AMH was identified in the index woman with PCOS. Recombinant hAMH-515Val displayed normal processing and bioactivity, yet had severely reduced immunoactivity when measured by the commercial pico-AMH ELISA assay by Ansh Labs. In conclusion, homozygous AMH variant rs10417628 may severely impair serum AMH immunoactivity without affecting its bioactivity or PCOS phenotypic expression. Variants in AMH can interfere with serum AMH immunoactivity without affecting the phenotype in PCOS. This observation can be accompanied by discordance between AMH immunoactivity and bioactivity.

scholarly journals Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women

2021 ◽  
Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Normal Weight ◽  
Model Assessment ◽  
Metabolic Function ◽  
Ovary Syndrome ◽  
Intravenous Glucose

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.

scholarly journals Alarin/FSH Ratio Might Be A New Biological Marker in Polycystic Ovary Syndrome Women with Normal and Women with Obese

2019 ◽  
Vol 3 (5) ◽  
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Biological Marker ◽  
Dehydroepiandrosterone Sulfate ◽  
Normal Weight ◽  
Control Group ◽  
Total Testosterone ◽  
Ovary Syndrome

Neuropeptides coordinate and regulate physiological processes in all animals. Alarin is a 25 amino acid neuropeptide which promotes the secretion of luteinizing hormone (LH). It has been known that serum luteinizing hormone levels are increased in women with polycystic ovary syndrome. Therefore, purpose of this was to examine the association of circulating gonadotropin secretions, and alarin with women with polycystic ovary syndrome, and to compare these findings with those of control subjects in an effort to better understand the pathophysiology of PCOS. 28 participants with a diagnosis of PCOS with normal weight and 28 participants with a diagnosis of PCOS with obese and 28 control group participants were included in this case-control study. Hormone profiles of the participants (alarin, insulin, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-SO4 ), lipid profiles total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol) and fasting blood sugar (FBS) values were measured. Results: Serum androgens were elevated in the PCOS. Blood LH was also elevated (P < 0.05) but was higher in PCOS than Control. Patients with PCOS had an increased alarin compared with controls. LH/FSH ratio and Alarin /FSH ratio were greater than 2.1, 2.4, respectively. The blood alarin levels were significantly correlated with the serum LH levels (r=0.492, p=0.002) and the LH/FSH ratios (r=0.450, p<0.001) and Alarin/ FSH ratios. The FSH/LH and alarin /FSH ratio were elevated in the PCOS. Based on these results, the FSH/LH and Alarin /FSH ratio appears to be a useful marker of PCOS.

scholarly journals Predicting the outcome of different protocols of in vitro fertilization with anti-Muüllerian hormone levels in patients with polycystic ovary syndrome

2017 ◽  
Vol 45 (3) ◽  
pp. 1138-1147 ◽  
Author(s):  
Ya Chen ◽  
Bilv Ye ◽  
Xiaojing Yang ◽  
Jiujia Zheng ◽  
Jinju Lin ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
Ivf Outcomes ◽  
Basal Serum

Objective This study evaluated associations of basal serum and follicular fluid (FF) anti-Muüllerian hormone (AMH) levels with in vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients. Methods This prospective study included 179 consecutive women undergoing IVF, including 59 with PCOS and non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF outcomes were assessed. Results Median serum and FF AMH levels, antral follicle count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and retrieved oocyte numbers were higher in PCOS patients than in controls (all P < 0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS patients than in controls (P < 0.01), but both groups had similar fertilization, implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH-ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels were correlated with AFC in PCOS patients ( P < 0.01). Peak E2 and FF AMH levels were independent predictors of oocyte number. Peak E2 predicted the fertilization rate. Conclusion Serum basal AMH levels are predictive of oocyte quantity, but not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar among protocols.

scholarly journals Influence of body mass index on in vitro fertilization outcome in women with polycystic ovary syndrome

2016 ◽  
Vol 69 (7-8) ◽  
pp. 230-236
Author(s):  
Milan Trenkic ◽  
Jasmina Popovic ◽  
Artur Bjelica ◽  
Vesna Kopitovic ◽  
Marija Trenkic-Bozinovic ◽  
...  
Keyword(s):  
Body Mass Index ◽  
In Vitro Fertilization ◽  
Polycystic Ovary Syndrome ◽  
Body Mass ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
Gonadotrophin Releasing Hormone

Introduction. The purpose of this study was to investigate the influence of the body mass index on the outcome of in vitro fertilization in patients with polycystic ovary syndrome. Material and Methods. The study sample consisted of 123 patients with polycystic ovary syndrome who completed their in vitro fertilization treatment at the Department of Gynecology and Obstetrics, Clinical Center Nis, Republic of Serbia, and they were retrospectively analyzed. The patients were divided by body mass index into two groups for the comparison of the findings. One group (normal weight) consisted of women with body mass index ? 25 kg/m2 (mean 22.08?1.90), and the other group (overweight) included women with body mass index > 25 kg/m2 (mean 27.65?1.47). The patients underwent either the standard long gonadotrophin-releasing hormone agonist protocol or flexible multidose gonadotrophin-releasing hormone antagonist protocol. Results. The normal-weight patients had a higher number of mature oocytes, significantly higher fertilization rate (p<0.001) and significantly higher number of the obtained embryos class I (p<0.01) than the overweight patients. However, the implantation rate and clinical pregnancy rate were the same in both groups. Conclusion. In the group of overweight women the numbers of mature oocytes and good quality embryos were lower. However, since this study dealt with the patients with polycystic ovary syndrome who generally had a higher number of the obtained oocytes and embryos, this shortfall did not affect clinical pregnancy rates, which were the same in both groups. Certainly, before starting the in vitro fertilization, each infertile patient should be informed about the possible negative effect of her high body mass index on the treatment outcome.

scholarly journals The Effect of Androgen Blockade on Granulosa Cell Estradiol Production after Follicle-Stimulating Hormone Stimulation in Women with Polycystic Ovary Syndrome

2006 ◽  
Vol 91 (9) ◽  
pp. 3503-3506 ◽  
Author(s):  
Rinku V. Mehta ◽  
Pamela J. Malcom ◽  
R. Jeffrey Chang
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cell ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Dehydroepiandrosterone Sulfate ◽  
Ovary Syndrome ◽  
Before And After ◽  
Normal Women ◽  
17 Hydroxyprogesterone

Abstract Context: Previously, we have shown that women with polycystic ovary syndrome (PCOS) exhibit an exaggerated serum estradiol (E2) response to recombinant human FSH (rhFSH) (150 IU) compared with similarly treated normal women. This enhanced granulosa cell responsiveness is consistent with excessive follicular development after gonadotropin therapy and the corresponding risk of ovarian hyperstimulation syndrome. In vitro studies have shown that granulosa cells treated with androgens display greater FSH-induced E2 production than untreated cells, suggesting a role for androgens in granulosa cell responsiveness. Main Objective: This study was conducted to determine whether blockade of androgen action in PCOS women by administration of the antiandrogen flutamide would alter E2 responses to rhFSH. Design: We conducted a prospective cohort study. Subjects and Setting: We studied 11 women with PCOS at an institutional general clinical research center. Intervention: On study d 1, each subject received 150 IU rhFSH iv. Frequent blood samples were obtained over 24 h. After completion of rhFSH stimulation, each subject was treated with flutamide, 125 mg, twice daily, for 6 wk. Thereafter, the rhFSH stimulation test was repeated. Main Outcome Measures: Baseline and stimulated E2 levels before and after treatment were assayed. Results: Mean baseline and maximally stimulated E2, integrated E2 response, and fold change in E2 were not different before and after treatment. Levels of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, estrone, and SHBG before and after treatment were unchanged. Baseline dehydroepiandrosterone sulfate levels declined significantly after flutamide therapy. Conclusion: These findings indicate that in women with PCOS, the E2 hyperresponsiveness to FSH may not be attributable to increased circulating androgens.

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome

2017 ◽  
Vol 71 (3-4) ◽  
pp. 224-233 ◽  
Author(s):  
Scheila K. Graff ◽  
Fernanda M. Mario ◽  
Jose A. Magalhães ◽  
Ruy S. Moraes ◽  
Poli Mara Spritzer
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Polycystic Ovary Syndrome ◽  
Dietary Intake ◽  
Fruits And Vegetables ◽  
Polycystic Ovary ◽  
Dehydroepiandrosterone Sulfate ◽  
Sex Hormone Binding Globulin ◽  
Calorie Intake ◽  
Ovary Syndrome

Background/Aims: There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). Methods: Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). Results: Body mass index (p = 0.041), blood pressure (p < 0.01), and HOMA-IR (p = 0.003) were higher in PCOS vs. controls. PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake <8.5%. PCOS women with SFA <8.5% consumed more beans, fruits, and vegetables and had better frequency and time domain HRV indices. No differences in HRV were detected between SFA categories in controls. In PCOS, age and SFA intake were independent predictors of HRV. Conclusions: Lower SFA intake is related to improved cardiovascular autonomic function in PCOS.

scholarly journals OR20-03 Transcriptional Changes in Lipid Metabolism of Adipocytes Derived from Subcutaneous Abdominal Adipose Stem Cells of Normal-Weight Polycystic Ovary Syndrome Women

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Karen Lynn Leung ◽  
Smriti Sanchita ◽  
Phillip Dumesic ◽  
Xiangming Ding ◽  
Xinmin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Beta Oxidation ◽  
Ovary Syndrome ◽  
Time Points ◽  
Upstream Regulator ◽  
Regulator Genes

Abstract Normal-weight polycystic ovary syndrome (PCOS) women exhibit increased adipose insulin resistance in vivo (1) accompanying enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with greater lipid accumulation per cell in vitro (2). To determine whether this phenomenon is associated with abnormal adipogenic gene transcription during ASC differentiation into adipocytes, SC abdominal ASCs isolated from three non-Hispanic Caucasian normal-weight PCOS women and three age- and BMI-matched controls were cultured in adipogenic differentiation medium for 3–12 days. After RNA isolation, gene expression levels were determined by RNA sequencing at days 3, 7, and 12. Differentially expressed genes were filtered for significance (padj&lt;0.05) and fold change (&gt;2-fold); upstream regulator genes and gene ontology (GO) functions were determined using Ingenuity Pathway Analysis. Gene set enrichment analysis (GSEA) also was used to identify enriched cellular processes (3). Differentially expressed genes in PCOS vs. control cells were either upregulated (466, 768 and 441 genes on days 3, 7 and 12, respectively) or downregulated (742, 974 and 605 genes on days 3, 7 and 12, respectively) over time, with critical genes governing adipocyte cell differentiation in PCOS cells increased 2–6 fold at days 3, 7 and 12 (PPARγ, CEBPα, ADIPOQ, AGPAT2, FABP4, LPL, PLIN1). The predicted upstream regulator genes TGFβ1 (an adipogenic inhibitor) and TNF (a pro-inflammatory adipokine) were significantly reduced in PCOS relative to control cells at all time points. The GO functions lipid oxidation and free fatty acid (FFA) beta-oxidation were enriched amongst upregulated genes in PCOS cells across all time points, while acylglycerol synthesis was increased at days 7 and 12 alone (z&gt;2, p&lt;0.05, all GO functions). In parallel, GSEA showed in PCOS cells significantly increased transcripts related to oxidative phosphorylation, peroxisome activity and adipogenesis at all time points (p&lt;0.05). Thus, adipocytes derived from SC abdominal ASCs of normal-weight PCOS women exhibit early activation of adipogenic genes, potentially underlying their exaggerated lipid accumulation in vitro, as previously described (2). These PCOS-related changes in gene expression involve an increase in both oxidative phosphorylation and FFA beta oxidation, which could disrupt the balance between energy production and lipid storage, particularly when caloric intake exceeds energy utilization. References: (1) Dumesic DA, et al JCEM 2019;104(6):2171–83; (2) Leung KL, et al. JES 2019;3:Supplement 1, SUN-107 (3) Subhramanian A, et al. PNAS 2005;102:43

scholarly journals Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Daniel A. Dumesic ◽  
Vasantha Padmanabhan ◽  
Gregorio D. Chazenbalk ◽  
David H. Abbott
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Abdominal Fat ◽  
Normal Weight ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Fetal Life ◽  
Ovary Syndrome

AbstractAs a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.

scholarly journals Serum Parathyroid Hormone Concentrations Are Increased in Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 51 (9) ◽  
pp. 1691-1697 ◽  
Author(s):  
Dimitrios Panidis ◽  
Christos Balaris ◽  
Dimitrios Farmakiotis ◽  
David Rousso ◽  
Anargyros Kourtis ◽  
...  
Keyword(s):  
Vitamin D ◽  
Body Weight ◽  
Parathyroid Hormone ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Sex Hormone Binding Globulin ◽  
Serum Parathyroid Hormone ◽  
Ovary Syndrome ◽  
25 Oh Vitamin D

Abstract Background: The present study was designed to investigate the effects of polycystic ovary syndrome (PCOS) and of obesity on serum parathyroid hormone (ΡΤΗ), 25-hydroxyvitamin D (25-OH-vitamin D), and 1,25-dihydroxyvitamin D [1,25-(OH)2-vitamin D] concentrations and the possible associations of the above calciotropic hormones with the hormonal and metabolic characteristics of the syndrome. Methods: We studied 58 obese [body mass index (BMI) &gt;30 kg/m2] women with PCOS, 64 overweight (ΒΜI, 25–30 kg/m2) women with the syndrome, 169 normal-weight (BMI &lt;25 kg/m2) women with PCOS, 29 obese controls (ovulatory women without clinical or biochemical hyperandrogenemia), 14 overweight controls, and 70 normal-weight controls. Blood samples were collected (at 0900 after an overnight fast) between the 3rd and 6th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups. Circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone, Δ4-androstenedione, 17α-hydroxyprogesterone, sex-hormone–binding globulin (SHBG), insulin, glucose, PTH, 25-OH-vitamin D, and 1,25-(OH)2-vitamin D were measured. Results: Both PCOS and increased body weight had a significant positive effect on serum PTH values. PTH concentrations were significantly correlated with age, BMI, glucose, PRL, SHBG, and testosterone. Only the correlations with testosterone and PRL were BMI-independent. The effect of PCOS on PTH concentrations remained significant after adjustment for BMI, but not after adjustment for testosterone concentration. Increased body weight also had a significant negative effect on 25-OH- and 1,25-(OH)2-vitamin D concentrations, but no association with the syndrome was observed. Conclusions: The results of the present study are in agreement with previous data supporting an association of increased PTH and decreased vitamin D metabolite concentrations with obesity. Moreover, the present findings indicate, for the first time, that PTH probably is also linked to PCOS-associated hyperandrogenism.

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