Manufacturer seeking FDA approval: ultralow-dose estradiol patch boosts bone mineral density.(News)

PHILADELPHIA -- A quarter of the standard, hormone-therapy estradiol dose was safe and effective for boosting bone mineral density in women aged 60-80 years in a controlled study with 417 women.

Two years of treatment of postmenopausal women with an unopposed, ultralow dose of estradiol delivered through a transdermal patch led to a significant rise in bone mineral density (BMD) compared with placebo, with virtually no adverse effects on the endometrium or breast and no vaginal bleeding. Dr. Bruce Ettinger reported at the annual meeting of the American College of Obstetricians and Gynecologists.

"This is very promising and important, but we need to know what happens with 3 or 5 years of treatment," commented Dr. Isaac Schiff, chief of the ob.gyn. service at Massachusetts General Hospital in Boston.

This month, the Food and Drug Administration is expected to announce whether it will approve the new patch with an indication for preventing osteoporosis in postmenopausal women, said a spokeswoman for Berlex, the company that makes the patch and sponsored this study.

This is the first study to look at the efficacy of an unopposed estradiol patch in women with an intact uterus, said Dr. Ettinger, a clinical professor of medicine at the University of California, San Francisco. A prior study examined the safety and efficacy of an ultralow dose of unopposed, oral estradiol in postmenopausal women (JAMA 290[8]:1042-48, 2003).

The concept originated with results from epidemiologic studies showing that postmenopausal women with serum estradiol levels higher than 5 pg/mL seemed to be protected against developing osteoporosis, while those with serum levels of 5 pg/mL or lower had the biggest problem with lost BMD. The ultralow-dose patch formulation was designed to boost a woman's serum estradiol level by about 5 pg/mL.

The study enrolled 417 women at nine centers in the United States. Each woman had an intact uterus and normal BMD for her age. The average age of the women was about 67 years, and their average body mass index was 28 kg/[m.sup.2]. About 15% of the women had osteoporosis; at baseline, their median level of plasma estradiol was about 5.3 pg/mL.