Prolonged administration of letrozole induces polycystic ovary syndrome leading to osteoporosis in rats: model development and validation studies.

Polycystic ovary syndrome (PCOS) mainly affects women of reproductive age. Clinical studies suggest a link between PCOS and osteoporosis (OP). Our goal was to explore the correlation between the two. Seventy-two female rats were divided into four groups of 18 each. Control group received vehicle (0.5% solution of carboxymethyl cellulose/day). Rats in treatment groups 2, 3 and 4 received letrozole orally at 0.1, 0.5 or 1.0 mg/kg bodyweight daily, respectively for ten weeks. Their estrous cycle, hormonal and biochemical parameters were observed along with the histological changes in their ovaries and femur bones. Treatment groups were administered metformin (50 mg/kg daily) orally for three weeks after the administration of letrozole was stopped. Letrozole disrupted the estrous cycle and produced ovarian cysts. Its administration elevated luteinizing hormone and testosterone levels, and reduced estradiol and progesterone levels in a dose-dependent manner. Groups 3 and 4 showed increased porosity, thinning of trabeculae and expanded vascular cavities in femur on withdrawal of letrozole. Rats treated with 0.5 mg/kg of letrozole did not show resumption of estrous cycle or normalization of deranged hormonal levels on their own. Metformin administration was successful in regressing the ovarian cysts in these rats. The estrous cycle was also resumed within ten days of metformin administration. However, the ovarian cysts did not regress even with metformin in rats administered with 1.0 mg/kg of letrozole. It was thus concluded that prolonged PCOS induced by 0.5 mg/kg letrozole administration daily for ten weeks may have ultimately led to OP in rats.