description): The immediate goals of the PI are to expand the focus of his research from familial forms of polycystic ovary syndrome (PCOS), and genetic influences on the development of the syndrome into areas with even greater clinical impact. Specifically the goals of this application are to 1) identify other unrecognized morbidity that results from insulin resistance in PCOS and in the long term. 2) expand the clinical trials of improving insulin sensitivity as a primary treatment modality in PCOS. Another long-term goal is to develop within the medical center a cadre of investigators interested in PCOS patient-oriented research. The overall hypothesis of this proposal is that insulin resistance is the fundamental pathophysiologic defect in women with PCOS, that its effects can be protean and unrecognized, and that metabolic abnormalities worsen with age. Our preliminary studies suggest that insulin resistance is major contributor to both the etiology of PCOS and its association with sleep apnea. We propose further studies to clarify the role of insulin resistance in both PCOS and control female populations on sleep disorders. We theorize that there is enhanced steroidogenesis in endometrial glandular and stromal cells from women with PCOS and this is further stimulated by hyperinsulinemia. We intend to study these hypotheses in endometrial tissue form PCOS women and appropriate controls. Our preliminary experience suggests that insulin resistance over time will lead to a worsening of glucose tolerance and other metabolic markers in PCOS women with an improvement in reproductive abnormalities such as anovulation and hyperandrogenemia. We propose to identify clinical interventions in PCOS women that will improve insulin sensitivity and manifestations of the syndrome. Improving insulin action through diet and exercise, with and without weight loss, will result in lowered circulating insulin levels, lowered androgens and increased ovulatory frequency rate in PCOS women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HD001476-02
Application #
6520650
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Parrott, Estella C
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
2
Fiscal Year
2002
Total Cost
$135,027
Indirect Cost
Name
Pennsylvania State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Dmitrovic, R; Kunselman, A R; Legro, R S (2013) Sildenafil citrate in the treatment of pain in primary dysmenorrhea: a randomized controlled trial. Hum Reprod 28:2958-65
Dmitrovic, Romana; Kunselman, Allen R; Legro, Richard S (2012) Continuous compared with cyclic oral contraceptives for the treatment of primary dysmenorrhea: a randomized controlled trial. Obstet Gynecol 119:1143-50
Raja-Khan, Nazia; Shuja, Showieb A; Kunselman, Allen R et al. (2011) Brachial artery conductance during reactive hyperemia is increased in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 155:49-53
Taylor, Mary C; Reema Kar, A; Kunselman, Allen R et al. (2011) Evidence for increased cardiovascular events in the fathers but not mothers of women with polycystic ovary syndrome. Hum Reprod 26:2226-31
Legro, Richard S; Roller, Rebecca L; Dodson, William C et al. (2010) Associations of birthweight and gestational age with reproductive and metabolic phenotypes in women with polycystic ovarian syndrome and their first-degree relatives. J Clin Endocrinol Metab 95:789-99
Trussell, J C; Kunselman, Allen R; Legro, Richard S (2010) Epinephrine is associated with both erectile dysfunction and lower urinary tract symptoms. Fertil Steril 93:837-42
Katcher, Heather I; Kunselman, Allen R; Dmitrovic, Romana et al. (2009) Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome. Fertil Steril 91:1175-82
Katcher, Heather I; Legro, Richard S; Kunselman, Allen R et al. (2008) The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr 87:79-90
Legro, Richard S; Pauli, Jaimey G; Kunselman, Allen R et al. (2008) Effects of continuous versus cyclical oral contraception: a randomized controlled trial. J Clin Endocrinol Metab 93:420-9
Kent, Sarah C; Gnatuk, Carol L; Kunselman, Allen R et al. (2008) Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 93:1662-9

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