Endocrine and Metabolic Effects of Rosiglitazone in Non-obese Women with Polycystic Ovary Disease

Abstract

Abstract. We hypothesized that the administration of rosiglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Forty women with PCOS and impaired glucose tolerance test (IGT) were randomly assigned to the 8-month treatment with rosiglitazone at either 2 mg/day or 4 mg/day. We compared changes in ovulatory function, hirsutism, hormonal levels (total and free testosterone, estradiol, estrone, androstenedione, LH and FSH), and measures of glycemic parameters (fasting and post-challenge levels of glucose and insulin, HOMA-IR, hemoglobin A1c), between the study groups. The patients' baseline characteristics were similar across all treatment arms. Fifteen of 20 women in the 2 mg group and 19 of 20 women in the 4 mg group achieved normal glucose tolerance; 14 of 20 women in the 2 mg group and 17 of 20 women in the 4 mg group achieved ovulatory menses at the end of the study period. The decreases of free testosterone levels were better in the 4 mg group than the 2 mg rosiglitazone group (-1.89 ± 0.35 pg/ml vs. -2.21 ± 0.39 pg/ml; P<0.01). There were neither any serious adverse events nor any liver enzyme elevations in our study patients during the treatment period. This study demonstrated that rosiglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with minimal adverse effects. This drug may be a good choice for lifetime treatment of patients with PCOS, especially for the ones who failed to show satisfactory results in metformin therapy.

Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome

“…Clinical trials of TZDs in PCOS demonstrated improvement in ovulatory dysfunction, hirsutism, and hyperandrogenemia (27). Acting as PPARG agonists, they have been shown to decrease mean serum testosterone levels when administered to both obese and non-obese PCOS women, and even men (28)(29)(30)(31)(32). Therefore, it is plausible that a genetic polymorphism affecting PPARγ activity can influence testosterone production in our control women.…”

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

“…Various studies have reported clinical efficacy of these agents in hirsutism, in the form of diminished hair growth and biochemically in the form of reduced free serum testosterone and androstenedione levels. Dereli et al [19] reported significant reduction in Ferriman-Gallwey scoring of hirsutism after 8 months of therapy with rosiglitazone (2 or 4 mg/day). Similarly, Yilmaz et al [109] treated 80 obese and nonobese women with PCOS and hirsutism, divided in two equal groups for 12 weeks with rosiglitazone 4 mg/day or metformin 850 mg/day.…”

Insulin sensitizing agent improves clinical pregnancy rate and insulin resistant parameters in polycystic ovarian syndrome patients with acanthosis nigricans: a randomized controlled study

“…In addition; this drug may be a good choice for patients with PCOS, especially for the ones who failed to show satisfactory results in metformin therapy. 27 It was noticed that the gastrointestinal side effects of metformin were dramatically improved when the patients used them during meals as recommended by previous studies. 28 This improvement enabled us to continue using metformin with CC for three successive months.…”