Studies Show Drug Treats Uterine Fibroids Without Adverse Effects That Mimic Menopause

New research shows that ulipristal acetate, a selective progesterone-receptor modulator, alleviates uterine fibroid symptoms without causing the same menopause-like adverse effects as a current treatment. (Image: JAMA, ©AMA)

Two new studies show that women may find relief from excessive bleeding and other symptoms of uterine fibroids with a drug that doesn’t cause the menopause-like symptoms of leuprolide acetate, which currently is used to treat fibroids.

Leuprolide acetate, a gonadotropin-releasing hormone agonist used to treat hormone-sensitive cancers and other hormonal conditions, was approved in 1995 by the US Food and Drug Administration (FDA) to treat uterine fibroids when given with iron, typically before surgery to remove these growths. Because it suppresses estrogen secretion from the ovaries, common adverse effects include menopausal symptoms, including hot flashes, breast tenderness, and vaginal dryness. Over time, leuprolide acetate can weaken bones.

But ulipristal acetate, a selective progesterone-receptor modulator marketed as the emergency contraceptive ella, stops ovulation by acting on progesterone receptors in uterine tissue. Small studies have suggested that selective progesterone-receptor modulators may be effective in treating fibroids without causing hot flashes, but they haven’t gained FDA approval for that indication.

In the first study, researchers determined that ulipristal acetate was effective in controlling excessive bleeding and shrinking fibroids in women planning to have surgery to remove the growths. Findings showed that after 13 weeks, ulipristal acetate controlled uterine bleeding in 91% of 96 women who received 5 mg per day and in 92% of 98 who took 10 mg per day, compared with 19% of 48 who received a placebo. Fibroid volume shrank by 21% in the 5-mg group and by 12% in the 10-mg group but increased by 3% in the placebo group.

In the second study, investigators examined bleeding control and adverse effects of ulipristal acetate compared with leuprolide acetate. They randomly assigned 307 women to receive a daily dose of 5 mg or 10 mg of ulipristal acetate or monthly injections of leuprolide acetate. After 3 months, uterine bleeding was controlled in 90% of patients taking the 5-mg dose of ulipristal acetate, in 98% who received the 10-mg dose, and in 89% taking leuprolide acetate. But 11% in the 5-mg group and 10% in the 10-mg group reported having moderate or severe hot flashes, compared with 40% in the leuprolide acetate group.

Both studies appear in today’s New England Journal of Medicine. Although ulipristal acetate caused benign endometrial changes, researchers said those changes had resolved within 6 months. They also noted that fibroids stayed smaller for longer periods of time with ulipristal acetate, making it a good candidate for women with fibroids who are approaching menopause and want to avoid surgery. Reduced estrogen levels after menopause often shrink fibroids, alleviating symptoms.

In an editorial, Elizabeth Stewart, MD, of the Mayo Clinic in Rochester, Minn, said no major safety concerns emerged from these short-term studies. “There remains substantial need for effective medical therapy,” she wrote. “The present studies represent an important step in that direction.”

Categories: Adverse Effects, Drug Therapy, Gynecology, Women's Health