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| |  Bazedoxifene Prevents Osteoporosis in Postmenopausal Women: Presented at ASRM By Crina Frincu-Mallos, PhD WASHINGTON, DC -- October 24, 2007 -- An optimal selective oestrogen receptor modulator (SERM) would display agonistic activity in bone and on serum lipids, with minimal or antagonistic activity in breast and endometrial tissue. A novel SERM, bazedoxifene, appears to have oestrogen antagonistic potential in both the breast and endometrium, according to a study presented here at the 63rd Annual Meeting of the American Society for Reproductive Medicine (ASRM). JoAnn V. Pinkerton, MD, Medical Director, Midlife Health Center, and Professor, Department of Obstetrics and Gynecology, University of Virginia Health System, Charlottesville, Virginia, United States, discussed the results in an interview here on October 15. Prior to this study, tamoxifen was used for the treatment and prevention of oestrogen receptor-positive breast cancers, Dr. Pinkerton said. But this agent is known to increase the risk of uterine cancer, she added. Raloxifene prevents breast cancer and does not increase the risk of uterine cancer, she added. However, researchers showed that raloxifene in combination with systemic oestrogen results in an increase in hyperplasia, she said. "Bazedoxifene, in the preclinical work, protected against endometrial stimulation. And what we found in this study is that, using bazedoxifene alone, there is no increased risk of the endometrial stimulation, and no ovarian stimulation," she said. Dr. Pinkerton presented the results of her 2-year randomised, double-blind, phase 3 clinical trial, conducted at 101 sites in Canada, Europe, and the United States. A total of 1,583 healthy, postmenopausal women with a mean age of 57.6 years were treated with one of the following five treatment regimens: bazedoxifene (10 mg, 20 mg, or 40 mg); raloxifene 60 mg (active comparator); placebo. A total of 1,116 (70.5%) women had an intact uterus and were evaluable for endometrial safety; 1,387 (87.6%) had not undergone prior oophorectomy and were therefore evaluable for ovarian safety. The women were evaluated by endometrial biopsy and transvaginal ultrasound. Statistical analysis of endometrial thickness data was performed by analysis of covariance method, with baseline endometrial thickness as the covariate. The Fisher exact test was used for comparison between the different treatment groups, looking at changes from baseline in ovarian volume, incidence of ovarian cysts, and incidence of endometrial hyperplasia. The results show that for subjects in the bazedoxifene treatment groups, endometrial thickness remained stable, with no statistically significant changes from baseline after 2 years of therapy, according to the researchers. Incidences of endometrial polyps after 2 years were similar for bazedoxifene 10 mg, 20 mg, and 40 mg (2.2%, 3.4%, and 2.3%, respectively) and similar to placebo-treated patients (3.5%). A relatively higher incidence of polyps occurred in the raloxifene group (4.7%). Interestingly, hyperplastic polyps occurred only in the raloxifene and placebo treatment groups. There were no significant differences between treatment groups when analysing for incidence of gynaecological adverse events (AEs). The most common AE was breast pain, which occurred in 3.7% of women treated with 10 mg bazedoxifene, in 3.4% of women treated with 20 mg bazedoxifene, in 2.8% of women on 40 mg bazedoxifene, in 2.6% of women on 60 mg raloxifene, and in 2.6% of women on placebo. "Looking at the bone density data, bazedoxifene was shown to have oestrogen agonist activity in the bone, with improvement in bone density in the vertebral spine and hip," explained Dr. Pinkerton, adding that the therapy "significantly decreased the risk for vertebral fracture in postmenopausal women with osteoporosis." "The suggestion is that bazedoxifene has a unique effect on the endometrium. So now, ongoing multicentre trials are evaluating the combination of bazedoxifene and conjugated oestrogens for efficacy at preventing bone loss and safety with regards to the breast and endometrium, to see if it can relieve hot flushes, prevent bone loss, without stimulating the breast or the uterus," concluded Dr. Pinkerton. The study was funded by Wyeth Research Inc.
[Presentation title: Endometrial and Ovarian Safety of Bazedoxifene in the Prevention of Postmenopausal Osteoporosis. Abstract P-407]
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