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

Estradiol hyperresponsiveness to follicle-stimulating hormone in polycystic ovary syndrome represents increased antral follicle number (AFN), while antimullerian hormone overproduction represents opposing effects of hyperandrogenism and increased AFN versus increased adiposity.

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Volume 109, Issue 3, Pages 508–515

Authors:

Annie A. Guedikian, B.S., Alexandria Y. Lee, Tristan R. Grogan, M.S., David H. Abbott, Ph.D., Karla Largaespada, B.S., Gregorio D. Chazenbalk, Ph.D., Daniel A. Dumesic, M.D.

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.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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