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Submitted on July 14, 2004
Accepted on September 24, 2004
Department of Obstetrics & Gynecology, Division of Reproductive Endocrinology & Infertility, University of Texas Medical Branch, Galveston, Texas
* To whom correspondence should be addressed.
MANUBAI NAGAMANI, E-mail: mnagaman{at}utmb.edu
Our objective was to evaluate the effectiveness of the insulin-sensitizing agent rosiglitazone in obese women with polycystic ovary syndrome (PCOS) and severe insulin resistance. Twelve obese women with PCOS were recruited. All were hirsute and anovulatory with acanthosis nigricans indicating severe insulin resistance. All women were treated with 4 mg of rosiglitazone daily for 6 months. A standard 75 g oral glucose tolerance test (OGTT) with insulin levels was performed before and after the women were treated with rosiglitazone. Glucose and insulin area under the curve (AUC) were calculated. Serum levels of total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), LH (LH), and 17 hydroxy progesterone (17 OH-P) were also measured before and after treatment. The body mass index (BMI) was determined before and after treatment. There was a highly significant (r = 0.881, P < 0.0001) positive correlation between insulin response during OGTT and basal total testosterone levels. After treatment with rosiglitazone, there were significant decreases in fasting insulin levels (46.0 ± 6.5 vs. 16.9 ± 2.0 µU/mL; P < 0.001), insulin AUC (749.3 ± 136.3 vs. 225.0 ± 15.7 µU/mL; P = 0.003), fasting glucose levels (90.8 ± 3.0 vs. 81.8 ± 1.9 mg/dL; P = 0.003), and glucose AUC (437.9 ± 25.0 vs. 322.5 ± 14.7; P < 0.001). Both total testosterone (96.3 ± 17.3 vs. 56.1 ± 5.8 ng/dL; P = 0.01) and free testosterone (5.8 ± 0.6 vs. 3.4 ± 0.5 pg/mL; P < 0.001) decreased significantly after treatment, even though there was no significant change in LH levels. Levels of sex hormone-binding globulin increased significantly (18.3 ± 3.4 vs. 25.8 ± 6.6 nmol/L; P = 0.009) after treatment, and DHEA-S levels decreased significantly (P = 0.04). There was no significant change in BMI (40.4 ± 2.4 vs. 41.1 ± 2.7 kg/m2). Eleven of the women reverted to regular ovulatory cycles during the treatment period. We conclude that 1) rosiglitazone therapy improves insulin resistance and glucose tolerance in obese women with PCOS; 2) rosiglitazone decreases ovarian androgen production, which appears to be independent of any changes in LH levels; 3) hyperinsulinemia appears to play a key role in the overproduction of ovarian androgens in these women as attenuation of insulin levels is associated with decreased testosterone levels; and 4) short-term rosiglitazone therapy helps restore spontaneous ovulation.
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