Beginning in the middle of next year, women will have a new hormone replacement therapy available called Angeliq. Developed by Germany's Schering AG, the FDA sanctioned the drug at the end of September after a lengthy delay to carefully review potential safety issues. The agency's approval marked a sharp reversal of fortune for the HRT therapy. The FDA originally decided in 2002 that it couldn't approve the treatment, shortly after a new study indicated that Wyeth's hormone replacement therapy increased risks of stroke, cancer and heart disease. A year ago, when Angeliq was approved in Europe, U.S. regulators said that they needed more trial data before they could approve it here. But Schering persisted, noting that Angeliq was the only hormone therapy that contained the progestin drospirenone, also found in the contraceptive Yasmin, which reduces water and sodium retention caused by estrogen. Researchers also emphasize that the drug contains estradiol, an estrogen hormone that is produced in ovaries before menopause. "It is more important than ever for women to have a variety of hormone therapy options because one particular therapy will not be optimal for all women," says David Archer, M.D., director of clinical research at the Contraceptive Research and Development Program of Eastern Virginia Medical School in Norfolk and Angeliq's lead clinical investigator. "Estrogen is still the most effective way to manage the symptoms of menopause, but by combining estrogen with new and different progestins, each with unique biologic profiles, we better enable clinicians to tailor treatment for individual patients." Archer presented data on Angeliq at the 16th annual meeting of the North American Menopause Society in San Diego. The Women's Health Initiative has raised serious concerns about HRT. It suspended a study in 2002 after concluding that the risks outweighed the benefits of the therapy, which consisted of 625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate (HRT, estrogen plus progestin) in 1 tablet daily for an average of 5.2 years. The study suggested that long-term use—more than four years—of the hormone placement therapy raised the risk of heart disease and breast cancer. Schering AG is quick to acknowledge the study, noting that the WHI focused on women 65 and older and suggesting that doses of Angeliq should be kept to low levels and for as short a duration as practical. "The WHI did bring to the fore an increased need of the physician to counsel women about the risks and benefit and the need for lower doses of estrogen plus progestin," responds Archer. But it's important to note that one of the primary reasons why women have stopped using other HRT therapies is due to bleeding, he adds. With Angeliq, only about 18 percent of the patients in clinical trials experienced bleeding. Also, says Archer, women in the Angeliq trial experienced weight losses of 1.5 to 2 pounds, promoting an enhanced feeling of health among the group. And a subset of patients with mild hypertension also demonstrated a reduction in blood pressure. Archer also noted that as more women demand effective therapies to treat hot flashes and other menopausal symptoms, they'll be asking for treatments for longer periods than what many physicians are now recommending. "I think we're going to see a little more use than what can be construed from shortest use," says Archer, noting that there are indications that some of the incidents of breast cancer noted in the WHI appear to have been preexisting conditions. Once those women were weeded out of the study, he says, the elevated risks associated with HRT therapy has declined. Due to the fact that drospirenone may increase potassium levels in some patients, says Schering, women with liver disease, kidney disease, or adrenal disease, should not take Angeliq. And researchers add that patients taking drugs that could increase potassium should consult their health care professional before taking Angeliq. They also recommend that doctors consider testing serum potassium levels in the first treatment cycle for patients prescribed Angeliq. Financial analysts have cheered the FDA's action on the HRT therapy, estimating that annual sales of Angeliq should bring in $300 million a year in a high-margin payback now that it is being marketed in the United States.