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D-chiro-inositol (INS-1) enhances ovulatory rate in hyperandrogenemic, oligomenorrheic women with the polycystic ovary syndrome.

2001; Elsevier BV; Volume: 76; Issue: 3 Linguagem: Inglês

10.1016/s0015-0282(01)02325-1

1556-5653

John E. Nestler, Ronald D. Gunn, Susie A Bates, Justin M. Gregory, W. Jacobson, Alan D. Rogol,

Reproductive Biology and Fertility

Objective: Polycystic ovary syndrome (PCOS) is an oligo-ovulatory syndrome with wide variation in circulating androgen levels and insulin resistance. We sought to confirm our previously published exploratory, single site, 2 month study (N Engl J Med 1999;340:1314–20) in which INS-1, a biochemical precursor to a membrane-bound inositolphosphoglycan putative insulin mediator, 1200 mg/day, as a single oral dose, markedly increased the ovulatory rate in hyperandrogenemic, hyperinsulinemic oligo-ovulatory women. Design: In a randomized, double-blind, placebo-controlled, dose-ranging two month trial preceded by a 4 week placebo run-in at 17 US clinical sites, we assessed the effects of INS-1, 300 to 1200 mg/day or placebo on ovulatory rate and circulating total testosterone (T) and free T levels in 223 women who were oligomenorrheic and obese. Weekly serum progesterone levels were obtained to confirm ovulation (≥4 ng/mL) over the course of the study. Materials/Methods: (see above). Results: No study drug-related serious adverse events were reported. The adverse event profile was similar in both placebo and INS-1 groups. 71 women were determined to be hyperandrogenemic based on both elevated free and total T levels. 67 of these women completed at least one month of study drug administration. The ovulatory rates during the two months of treatment were: placebo, 18%, 300 mg, 6%, 600 mg, 32%, 1200 mg, 44% (p ≤ 0.05). In those women who ovulated while receiving INS-1 there was a 22% decrease in free T concentration (from 1.61 to 1.25 ng/dL) and a 20% decrease in T level (from 71 to 57 ng/dL; both p ≤ 0.05). In those women who did not ovulate while receiving INS-1 there were only small, non-significant, decreases in free and total T concentrations. Conclusions: We conclude that 32% of the women who entered our trial were hyperandrogenemic based on the criteria of both elevated T and free T levels. There was a statistically significant decrease in androgen levels in those women who ovulated while receiving INS-1. Longer-term, dose-ranging studies are underway to further assess the utility of INS-1 therapy in hyperandrogenemic women with PCOS. Supported By: Insmed Incorporated. Richmond, Virginia.