Abstract

Evidence suggests that insulin resistance accompanied by compensatory hyperinsulinemia is a common feature of polycystic ovary syndrome (PCOS), and that hyperinsulinemia is responsible in part for the hyperandrogenism of the disorder. In this project, the hypothesis that hyperinsulinemia plays a pathogenetic role in the hyperandrogenism and anovulation of both lean and obese women with PCOS will be tested. Separate effects of hyperinsulinemia will be tested in three clinical protocols in vivo. Protocol I will examine the effects of hyperinsulinemia on ovarian androgen production (namely P450c17( activity), serum androgens and the serum sex hormone-binding globulin concentration in lean women with PCOS. Protocol II will examine insulin effects on gonadotropin (LH)) secretory dynamics in both obese and lean women with PCOS. The last protocol will examine the effects of insulin-sensitizing agents on spontaneous ovulatory function and clomiphene responsiveness in obese women with PCOS. If these studies confirm an important role of hyperinsulinemia in the pathogenesis of PCOS, then a possible first-line treatment for hyperandrogenism and / or anovulation would be measures aimed at improving insulin sensitivity and reducing serum insulin-- be that diet and weight loss or the use of """"""""insulin-sensitizing"""""""" agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD035629-01
Application #
2383563
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Gupta, Anshu; Jakubowicz, Daniela; Nestler, John E (2016) Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome. Metab Syndr Relat Disord 14:391-396
Randeva, Harpal S; Tan, Bee K; Weickert, Martin O et al. (2012) Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev 33:812-41
Nestler, John E; Reilly, Elizabeth R; Cheang, Kai I et al. (2012) A pilot study: effects of decreasing serum insulin with diazoxide on vitamin D levels in obese women with polycystic ovary syndrome. Trans Am Clin Climatol Assoc 123:209-19; discussion 219-20
Wickham 3rd, Edmond P; Cheang, Kai I; Clore, John N et al. (2011) Total and high-molecular weight adiponectin in women with the polycystic ovary syndrome. Metabolism 60:366-72
Baillargeon, Jean-Patrice; Iuorno, Maria J; Apridonidze, Teimuraz et al. (2010) Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome. Metab Syndr Relat Disord 8:127-36
Baillargeon, Jean-Patrice; Nestler, John E; Ostlund, Richard E et al. (2008) Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum Reprod 23:1439-46
Nestler, John E (2008) Metformin in the treatment of infertility in polycystic ovarian syndrome: an alternative perspective. Fertil Steril 90:14-6
Cheang, Kai I; Baillargeon, Jean-Patrice; Essah, Paulina A et al. (2008) Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metabolism 57:1390-7
Nestler, John E (2008) Metformin for the treatment of the polycystic ovary syndrome. N Engl J Med 358:47-54
Baillargeon, Jean-Patrice; Diamanti-Kandarakis, Evanthia; Ostlund Jr, Richard E et al. (2006) Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 29:300-5

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