Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial.

Objective: Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women. We studied the effects of ospemifene on hormone levels, genital tract organs, climacteric symptoms, and quality of life.
Design: A double-blinded study in which 160 postmenopausal women were randomly allocated to receive either ospemifene at three different daily doses (30, 60, or 90 mg) or placebo for 3 months.
Results: No significant differences were observed among the study groups in clinical characteristics or parameters reflecting estrogen action at baseline. Ospemifene reduced follicle-stimulating hormone and insulin-like growth factor I levels, whereas estradiol failed to change at all, and luteinizing hormone was reduced only in the 90-mg group of ospemifene. In the vast majority of participants, the endometrium remained atrophic after 3 months of treatment with ospemifene. Although the rate of proliferative endometrium slightly increased in all groups, including placebo, no hyperplasia or bleeding occurred in any participant. Ospemifene had no effect on the appearance of proliferation marker Ki-67 in the endometrium as compared with placebo, and endometrial thickness increased by mean 0.4 to 0.6 mm (P < 0.01, P < 0.05 and P < 0.05 for 30, 60 and 90 mg ospemifene, respectively). Uterine volume slightly increased (8.4%-14.7%) in the ospemifene groups (P > 0.05), perhaps as a result of increased uterine blood flow. The most conspicuous finding was the significant estrogenic effect on vaginal epithelium, as evidenced by an increase in intermediate and superficial cells in repeat Pap smears. Ospemifene was not observed to aggravate climacteric symptoms or cause adverse events, nor did it suppress climacteric symptoms.
Conclusions: Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period. Such effects would be advantageous if ospemifene were found to be effective in the long-term prevention of osteoporosis.