New drugs are coming to treat uterine fibroids, one of the most common reasons for hospitalization of women.
Other than childbirth and severe depression, uterine fibroids are the next most common reason women in the United States are admitted to the hospital. This is according to a new book entitled Care of Women in U.S. Hospitals, 2000, put out by the Agency for Healthcare Research and Quality.
In 2000, 139,000 women in the United States were hospitalized for uterine fibroids. Estimates suggest that as many as 20% to 40% of American women older than 35 years and 50% of African-American women have uterine fibroids that are large in size.
Last month, the Uterine Fibroid Research & Education Act of 2003 was introduced in Congress. If passed, the act would double fibroid research funding, bringing it to $10 million per year for the next five years, and would educate researchers, women, and physicians about alternatives to hysterectomies.
Fibroids of the uterus are the most common nonmalignant uterine tumors. They usually occur during a woman's reproductive years, and, often, multiple fibroids are present in the same woman. These benign tumors can cause heavy menstrual bleeding, unbearable pelvic pain and pressure, urinary frequency, and pain during sexual intercourse. They may also result in the uterus' becoming unusually large.
Although what causes uterine fibroids is unknown, the tumors do seem to be hormonally sensitive. "Fibroid tissues contain an abnormally large number of estrogen and progesterone receptors," said Anna Marie Daniels, founder and COO of Balance Pharmaceuticals, a company committed to finding pharmacologic treatments for fibroids. "The distribution of these receptors varies from woman to woman and even from fibroid to fibroid within the same woman. Some fibroids are estrogen-dominant, while others are progesterone-dominant."
Historically, the gold standard for treating fibroids has been hysterectomy. In fact, fibroids are the most common indication for hysterectomy in premenopausal women. While hysterectomy may be lifesaving in the case of a malignant cancer, it may not be the most reasonable choice for treating benign fibroids. Anthony Scialli, M.D., an obstetrician/gynecologist at Georgetown University Medical Center who sees hundreds of patients with fibroids each year, said, "Virtually all women can be kept out of the operating room." But many women don't know about other options that are less invasive than hysterectomy and that treat the fibroids. Some women can successfully treat the symptoms of fibroids with drug therapy.
Currently, the most commonly used hormonal therapy is the gonadotropin-releasing hormone (GnRH) agonist leuprolide. GnRH agonists have a long history of use in gynecological disorders. At first glance, the mechanism of GnRH agonists in managing uterine fibroids is counterintuitive since early on, there is actually a surge in hormone production. However, with time, the drugs actually decrease estrogen and progesterone levels, which in turn decrease fibroid growth and bothersome symptoms.
Leuprolide's indication for management of uterine fibroids is actually quite specific. It is approved for concomitant use with iron therapy for the preoperative hematologic improvement in patients with anemia caused by uterine fibroids.
Daniels told Drug Topics that a product in development by her company would be the first drug approved for treatment of uterine fibroids. Currently, Balance Pharmaceuticals is negotiating phase III clinical trials for evaluating a combination deslorelin/17-ß-estradiol product. Like leuprolide, deslorelin is a GnRH agonist with a long history of use in Europe. Unlike leuprolide, deslorelin can be delivered daily in the form of a nonirritating nasal spray. The advantages of this dosing include no more intramuscular injections and the fact that the product can be stopped immediately if side effects become too bothersome.
"The biggest drawback to using long-term GnRH agonist therapy is that it makes you menopausal," Daniels noted. To minimize menopausal-like side effects, 17-ß-estradiol, the predominant endogenous estrogen in premenopausal women, will be codelivered intranasally with deslorelin, as an "add-back" therapy. Balance has just completed dose-response studies with 17-ß-estradiol with, he said, "the goal of finding the dose of estrogen sufficient to maintain efficacy of the GnRH agonist while minimizing menopausal side effects."
Elena Umland, Pharm.D., assistant professor of clinical pharmacy at the University of the Sciences in Philadelphia, said, "Historically, there haven't been a lot of options [to treat fibroids]. However, in the past decade, we've seen a shift toward more localized surgeries, which is wonderful. But more drug therapies are needed." She said she is encouraged to see research moving forward and to see more drugs in the pipeline.
Kelly Karpa. Hysterectomy isn't only recourse for uterine fibroids. Drug Topics Jun. 16, 2003;147:HSE16.