Dataset Information

Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome.

ABSTRACT: OBJECTIVE:To determine the degree to which E2 hyperresponsiveness to FSH and antimüllerian hormone (AMH) overproduction in normal-weight women with polycystic ovary syndrome (PCOS) correlate with increased antral follicle number (AFN), hyperandrogenism, and/or metabolic dysfunction. DESIGN:Prospective cohort study. SETTING:Academic medical center. PATIENT(S):Seven normal-weight women with PCOS (1990 National Institutes of Health criteria) ages 20-34 years and 13 age- and body mass index- (BMI-; 18.5-25 kg/m2) matched normoandrogenic ovulatory women were studied. INTERVENTION(S):All women underwent basal serum hormone and metabolic measurements, FSH stimulation testing with transvaginal ovarian sonography, frequently sampled IV glucose tolerance testing, and whole-body dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURE(S):Serum hormone/metabolite levels, 24-hour serum E2 response to 150 IU recombinant human (rh) FSH infusion, AFN, insulin sensitivity, and body mass measurements. RESULT(S):Serum E2 responsiveness to rhFSH and AMH levels were greater in women with PCOS than in BMI- and age-matched control women, as were serum androgen levels, AFN, and abdominal fat mass. In all women combined, serum E2 responsiveness to rhFSH was associated with AFN. Serum AMH levels, however, positively correlated with AFN but remained positively correlated with serum LH and free T levels and negatively correlated with total body fat and percent body fat, adjusting for AFN. CONCLUSION(S):In normal-weight women with PCOS, serum E2 hyperresponsiveness to rhFSH represents increased AFN, while elevated serum AMH levels reflect opposing effects of stimulatory reproductive (hyperandrogenism and increased AFN) versus inhibitory metabolic (body fat) factors. Given the small number of subjects reported, additional follow-up studies are required to confirm these data.

SUBMITTER: Guedikian AA

PROVIDER: S-EPMC5812340 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome.

Guedikian Annie A AA Lee Alexandria Y AY Grogan Tristan R TR Abbott David H DH Largaespada Karla K Chazenbalk Gregorio D GD Dumesic Daniel A DA

Fertility and sterility 20180207 3

<h4>Objective</h4>To determine the degree to which E<sub>2</sub> hyperresponsiveness to FSH and antimüllerian hormone (AMH) overproduction in normal-weight women with polycystic ovary syndrome (PCOS) correlate with increased antral follicle number (AFN), hyperandrogenism, and/or metabolic dysfunction.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>Academic medical center.<h4>Patient(s)</h4>Seven normal-weight women with PCOS (1990 National Institutes of Health criteria) ages 20-34 years ...[more]

PMID: 29428312

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Project description:ContextOvarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.ObjectivesTo compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.DesignProspective, cross-sectional, cohort study.SettingAcademic medical center.PatientsTwenty normal-weight women with PCOS and 20 body mass index-/age-matched controls.InterventionsBlood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry.Main outcome measuresClinical characteristics, hormonal concentrations, and body fat distribution.ResultsWomen with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens P < .001; android/gynoid fat mass ratio, P = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined (P < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass (P = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls (P = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity.ConclusionReduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.

Dataset Information

Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome.

Publications

Reproductive and metabolic determinants of granulosa cell dysfunction in normal-weight women with polycystic ovary syndrome.

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