Introduction: Arzoxifene, a benzothiophene estrogen agonist/antagonist, is being developed for prevention and treatment of osteoporosis and for risk reduction of invasive breast cancer in postmenopausal women.
Methods: The effects of arzoxifene 20 mg/d on bone mineral density (BMD), uterine safety, and overall safety were studied in the FOUNDATION study, a 2-yr randomized, placebo-controlled trial including 331 postmenopausal women with normal to low bone mass.
Results: Compared to placebo, arzoxifene significantly increased lumbar spine (+2.9%) and total hip (+2.2%) BMD. Arzoxifene decreased biochemical markers of bone metabolism compared to placebo. Changes in breast density were neutral or slightly decreased in the arzoxifene vs. placebo group. There was no evidence of endometrial hyperplasia or carcinoma in the arzoxifene group as assessed by central review of baseline and follow-up endometrial biopsies. There was no significant change between the groups in endometrial thickness assessed by transvaginal ultrasound. The incidence of uterine polyps and vaginal bleeding was not significantly different between the groups. Vulvovaginal mycotic infection was the only adverse event significantly increased in the arzoxifene vs. placebo group. Hot flushes were not significantly different between the groups.
Conclusion: In postmenopausal women with normal to low bone mass, arzoxifene 20 mg/d increased BMD at the spine and hip and had a neutral effect on the uterus and endometrium.