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 coursework required 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 to determine 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 excessive androgen production and reproductive dysfunction is the most common reproductive disorder in women of reproductive age. The etiology of PCOS is unclear. However abnormal neuroendocrine function and hyperinsulinemia are considered primary candidates involved in the development in PCOS. Weight loss is regarded as the choice treatment of infertility in overweight women with the condition. However it is not known if reproductive function is improved as a result of improving insulin sensitivity and/or reducing body weight. Preliminary studies conducted by the PI indicate that exercise, independent of weight loss, induces menstrual cyclicity in women with PCOS. Since exercise did not cause weight loss, we now hypothesize that the observed increase in insulin sensitivity may mediate the improvement in reproductive function rather than weight loss. In support of this hypothesis, our 16-week aerobic exercise study reduced fasting insulin and increased insulin-stimulated glucose disposal during a hyperinsulinemic euglycemic clamp. Furthermore, treatment of PCOS patients with insulin sensitizers improves both androgen excess and ovulatory function without weight change. The proposed randomized controlled trial will provide data to indicate possible mechanisms by which lifestyle modification can influence reproductive function in women with PCOS. It is hoped that further studies will then lead to the development of evidence based treatment programs for infertility 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)
Project #
Application #
Study Section
Special Emphasis Panel (NSS)
Program Officer
Eisenberg, Esther
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Lsu Pennington Biomedical Research Center
Organized Research Units
Baton Rouge
United States
Zip Code
Heymsfield, S B; Gonzalez, M C C; Shen, W et al. (2014) Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev 15:310-21
Thomas, Diana M; Martin, Corby K; Redman, Leanne M et al. (2014) Effect of dietary adherence on the body weight plateau: a mathematical model incorporating intermittent compliance with energy intake prescription. Am J Clin Nutr 100:787-95
Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena et al. (2014) Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise. Biochimie :
Gilmore, L Anne; Ravussin, Eric; Bray, George A et al. (2014) An objective estimate of energy intake during weight gain using the intake-balance method. Am J Clin Nutr 100:806-12
Thomas, Diana M; Gonzalez, M Cristina; Pereira, Andrea Z et al. (2014) Time to correctly predict the amount of weight loss with dieting. J Acad Nutr Diet 114:857-61
Frost, Elizabeth A; Redman, Leanne M; de Jonge, Lilian et al. (2014) Interaction between dietary fat and exercise on excess postexercise oxygen consumption. Am J Physiol Endocrinol Metab 306:E1093-8
Tam, Charmaine S; Frost, Elizabeth A; Xie, Wenting et al. (2014) No effect of caloric restriction on salivary cortisol levels in overweight men and women. Metabolism 63:194-8
Johansson, Julia; Redman, Leanne; Veldhuis, Paula P et al. (2013) Acupuncture for ovulation induction in polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metab 304:E934-43
Tam, Charmaine S; Xie, Wenting; Johnson, William D et al. (2012) Defining insulin resistance from hyperinsulinemic-euglycemic clamps. Diabetes Care 35:1605-10
Tam, Charmaine S; Covington, Jeffrey D; Ravussin, Eric et al. (2012) Little evidence of systemic and adipose tissue inflammation in overweight individuals(ýýý). Front Genet 3:58