This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Legro, R. S. Articles by Ghazzi, M. N. Search for Related Content PubMed PubMed Citation Articles by Legro, R. S. Articles by Ghazzi, M. N.

Minimal Response of Circulating Lipids in Women with Polycystic Ovary Syndrome to Improvement in Insulin Sensitivity with Troglitazone

Department of Obstetrics and Gynecology, Pennsylvania State University (R.S.L.), Hershey, Pennsylvania 17033; Department of Obstetrics and Gynecology, Cedars Sinai Hospital (R.A.), Los Angeles, California 90048; Department of Medicine, University of Chicago Medical Center (D.E.), Chicago, Illinois 60637; and Pfizer Pharmaceutical Research (A.G.F., M.O., M.N.G.), Ann Arbor, Michigan 48105

Address all correspondence and requests for reprints to: Richard S. Legro, M.D., C3608, Department of Obstetrics and Gynecology, H103, Pennsylvania State University College of Medicine, M. S. Hershey Medical Center, 500 University Drive, Hershey, Pennsylvania 17033. E-mail: rsl1{at}psu.edu.

We hypothesized that the administration of troglitazone (TGZ), an insulin-sensitizing agent of the thiazolidinedione class, would improve dyslipidemia associated with insulin resistance in polycystic ovary syndrome (PCOS). Three hundred and ninety-eight women with PCOS in a multicenter, double-blind trial were randomly assigned to 44 wk of treatment with: placebo or troglitazone (150, 300, or 600 mg/d). We examined the responses of circulating lipid and lipoproteins [total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and triglycerides (TTG)] by treatment arm, and the influence of glycemic parameters on baseline levels and response to treatment. There was a high prevalence of abnormal baseline lipid parameters, as defined by National Cholesterol Education Program guidelines [total cholesterol, 200 mg/dl (35%); LDL-C, 130 mg/dl (31%); HDL-C, <35 mg/dl (15%); TTG, >200 mg/dl (16%)]. Baseline models showed that parameters of insulin action had poor predictive power on lipid parameters. There was no significant response of any of the circulating lipids to treatment with either placebo or one of the troglitazone arms (after correction for multiple analyses). There were favorable, but nonsignificant, trends in HDL-C (increase) and LDL-C (decrease) and a trend toward decreased circulating TTG in the 300- and 600-mg TGZ dose treatment arms, both in an intention to treat analysis (n = 375) and in study completers (44 wk; n = 152). There also was a minimal treatment effect noted when only subjects with abnormal baseline levels were examined, and responders differed little from nonresponders in terms of indices of insulin action. There is a substantial prevalence of clinically recognized dyslipidemia in the population of women with unrecognized PCOS without type 2 diabetes. Treatment with an insulin-sensitizing agent may have minimal impact on circulating lipids. Further surveillance and treatment of abnormal lipid levels may be necessary in these women.

This work was supported by a grant from Parke-Davis Pharmaceutical Research, Inc.

* In addition to the authors the following investigators participated in the PCOS/Troglitazone Study Group: Stephen Aronoff (Dallas, TX), Richard Bernstein (Greenbrae, CA), Donald Bodenner (Rochester, NY), Susan Braithwaite (Chicago, IL), Joshua Cohen (Washington, D.C.), David DePaolo (Boulder, CO), Daniel Einhorn (San Diego, CA), Jennifer Hone (Arvada, CO), Anne Kenshole (Toronto, Canada), Charles Kilo (St. Louis, MO), Siri Linda Kjos (Los Angeles, CA), Mary Korytkowski (Pittsburgh, PA), Diane Koster (Albuquerque, NM), Rebecca Lau (Indianapolis, IN), Rogerio Lobo (New York, NY), Jean Lucas (Atlanta, GA), Kathryn Martin (Boston, MA), William Meyer (Chapel Hill, NC), Sumer Pek (Ann Arbor, MI), Samantha Pfeifer (Philadelphia, PA), Robert Rebar (Cincinnati, OH), Geoffrey Redmond (Cleveland, OH), Roger Rittmaster (Halifax, Canada), Peter Ross (Fairfax, VA), Sherwyn Schwartz (San Antonio, TX), Robert Wild (Oklahoma City, OK), and Samuel Yen (La Jolla, CA).

Abbreviations: AUC, Area under the curve; CI, confidence interval; HDL-C, high density lipoprotein cholesterol; ITT, intent to treat; LDL-C, low density lipoprotein cholesterol; NCEP, National Cholesterol Education Program; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; TGZ, troglitazone; TTG, triglycerides.

This article has been cited by other articles:

				S. Palomba, A. Falbo, T. Russo, F. Manguso, A. Tolino, F. Zullo, P. De Feo, and F. Orio Jr. Insulin Sensitivity after Metformin Suspension in Normal-Weight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3128 - 3135. [Abstract] [Full Text] [PDF]

				S. Sam, R. S. Legro, P. A. Essah, T. Apridonidze, and A. Dunaif Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome PNAS, May 2, 2006; 103(18): 7030 - 7035. [Abstract] [Full Text] [PDF]

				L. R. Harborne, N. Sattar, J. E. Norman, and R. Fleming Metformin and Weight Loss in Obese Women with Polycystic Ovary Syndrome: Comparison of Doses J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4593 - 4598. [Abstract] [Full Text] [PDF]

				E. Frohlich, F. Machicao, and R. Wahl Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture Endocr. Relat. Cancer, June 1, 2005; 12(2): 291 - 303. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann, K. Kasza, R. Azziz, R. S. Legro, M. N. Ghazzi, and for the PCOS/Troglitazone Study Group Effects of Race and Family History of Type 2 Diabetes on Metabolic Status of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 66 - 71. [Abstract] [Full Text] [PDF]