NEW YORK (Reuters Health) – Gynecologic side effects of the third-generation selective estrogen receptor modulator lasofoxifene are generally acceptable, researchers report, and “contribute to an overall favorable benefit-risk profile for the treatment of osteoporosis.”

The efficacy of lasofoxifene for osteoporosis in the PEARL trial was reported earlier this year in the New England Journal of Medicine (see Reuters Health February 24, 2010: “Lasofoxifene cuts fractures, breast CA, ischemic events — but still has a down side”), and the drug is awaiting FDA approval. The current study, in an August 3rd online issue of Menopause, looks at gynecologic safety using the PEARL data.

Dr. Steven R. Goldstein of New York University School of Medicine, New York, and colleagues note that 8,556 women aged 59 to 80 years with osteoporosis were randomized to receive lasofoxifene 0.25 mg/day or 0.5 mg/day, or placebo, for 5 years.

After 5 years, there were two cases of endometrial cancer in each lasofoxifene group and three in the placebo group. The incidence of ovarian cancer and ovarian cysts also were not significantly different in the three groups.

A small increase in endometrial thickness occurred with lasofoxifene treatment, the researcher found.

“Five cases of endometrial hyperplasia were confirmed by the gynecological external adjudication committee: three women in the lasofoxifene 0.25 mg/day group (two cases of simple hyperplasia and one case of atypical hyperplasia) and two women in the lasofoxifene 0.5 mg/day group (both were simple hyperplasia), corresponding to an absolute annual incidence rate in lasofoxifene-treated women of 0.24 per 1,000 patient-years,” the team reports.

Compared to placebo, lasofoxifene did increase rates of endometrial polyps, fibroids, vaginal bleeding, candidiasis and discharge. For example, the incidence of polyps observed by ultrasound was 8.8% for lasofoxifene 0.25 mg/d, 5.5% with lasofoxifene 0.5 mg/d, and 3.3% in the placebo group.

Pelvic floor effects were similar in all three groups, with approximately 3% of each experiencing an increase in uterine prolapse score.

“These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women,” Dr. Goldstein and colleagues conclude.

Pfizer sponsored the study and provided support to seven of the eleven authors.


Postmenopausal Evaluation and Risk Reduction With Lasofoxifene trial: 5-year gynecological outcomes

Menopause 2010;18.