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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Transition Award (R00)
Project #
5R00HD060762-04
Application #
8337618
Study Section
Special Emphasis Panel (NSS)
Program Officer
Eisenberg, Esther
Project Start
2011-09-26
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$235,071
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
None
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Shumilov, Dmytro; Heymsfield, Steven B; Redman, Leanne M et al. (2016) New compartment model analysis of lean-mass and fat-mass growth with overfeeding. Nutrition 32:590-600
Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena et al. (2016) Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise. Biochimie 124:27-33
Gilmore, L Anne; Butte, Nancy F; Ravussin, Eric et al. (2016) Energy Intake and Energy Expenditure for Determining Excess Weight Gain in Pregnant Women. Obstet Gynecol 127:884-92
Harrison, Cheryce L; Brown, Wendy J; Hayman, Melanie et al. (2016) The Role of Physical Activity in Preconception, Pregnancy and Postpartum Health. Semin Reprod Med 34:e28-37
Peterson, Courtney M; Lecoultre, Virgile; Frost, Elizabeth A et al. (2016) The thermogenic responses to overfeeding and cold are differentially regulated. Obesity (Silver Spring) 24:96-101
Covington, Jeffrey D; Bajpeyi, Sudip; Moro, Cedric et al. (2015) Potential effects of aerobic exercise on the expression of perilipin 3 in the adipose tissue of women with polycystic ovary syndrome: a pilot study. Eur J Endocrinol 172:47-58
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
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
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

Showing the most recent 10 out of 30 publications