The objective of this K99/R00 award is to complete further training in female reproductive endocrinology,particularly translational studies in primary cell muscle cultures from women with polycystic ovary syndrome(PCOS), analyze, publish and present data collected during 2 pilot studies and complete the courseworkrequired for the Masters of Science in Clinical Research program at Tulane University. During the R00(independent phase) the PI will conduct a randomized controlled trial in obese women with PCOS todetermine the effect of: a) exercise training, b) 25% dietary restriction c) metformin and d) no intervention(control group) on neuroendocrine function (pulsatile LH secretion), reproductive function (ovulation rate),ovarian morphology/function and insulin sensitivity. PCOS, an endocrinopathy characterized by excessiveandrogen production and reproductive dysfunction is the most common reproductive disorder in women ofreproductive age. The etiology of PCOS is unclear. However abnormal neuroendocrine function andhyperinsulinemia are considered primary candidates involved in the development in PCOS. Weight loss isregarded as the choice treatment of infertility in overweight women with the condition. However it is notknown if reproductive function is improved as a result of improving insulin sensitivity and/or reducing bodyweight. Preliminary studies conducted by the PI indicate that exercise, independent of weight loss, inducesmenstrual cyclicity in women with PCOS. Since exercise did not cause weight loss, we now hypothesize thatthe observed increase in insulin sensitivity may mediate the improvement in reproductive function rather thanweight loss. In support of this hypothesis, our 16-week aerobic exercise study reduced fasting insulin andincreased insulin-stimulated glucose disposal during a hyperinsulinemic euglycemic clamp. Furthermore,treatment of PCOS patients with insulin sensitizers improves both androgen excess and ovulatory functionwithout weight change. The proposed randomized controlled trial will provide data to indicate possiblemechanisms by which lifestyle modification can influence reproductive function in women with PCOS. It ishoped that further studies will then lead to the development of evidence based treatment programs forinfertility in overweight women with PCOS.

Public Health Relevance

Polycystic ovary syndrome (PCOS) is the most common reproductive abnormality in premenopausal women. The prevalence of PCOS in the community is increasing in parallel with the rise in obesity. Weight loss by regular exercise and dieting is currently recommended in the treatment of the syndrome. The ability of these treatments to restore menstrual function and fertility in some women is not known.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Eisenberg, Esther
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Lsu Pennington Biomedical Research Center
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Baton Rouge
United States
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