The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome

Andrea Dunaif*, Denise Scott, Diane Finegood, Benjamin Quintana, Randall Whitcomb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

520 Scopus citations

Abstract

We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose lead insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone- binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose lead (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydroepiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.

Original languageEnglish (US)
Pages (from-to)3299-3306
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume81
Issue number9
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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