Finding Suggests Strategies for New Treatments
October 15, 2004
A new study suggests that the conventional hormone therapies used to treat fibroid tumors are unlikely to produce much improvement and at best will only temporarily relieve symptoms. However, the study findings also suggest a strategy for developing a new, non-surgical treatment.
Fibroid tumors—the sometimes painful uterine growths affecting many American women—are made up largely of abnormal collagen, a protein that doesn't respond to reproductive hormones, according to the study, which was conducted by researchers at the National Institute of Child Health and Human Development of the National Institutes of Health.
"This finding is an important step in understanding the nature of fibroids and offers a potential strategy for treating them without surgery," said Duane Alexander, M.D., Director of the NICHD. "NICHD researchers are preparing a study of drug treatments that may prevent fibroids from forming or dissolve them after they have formed."
The study appears in the October 2004 issue of Fertility and Sterility and was supported by NICHD and the National Naval Medical Center in Bethesda, MD.
Fibroids, or leiomyomas, are noncancerous growths that develop in the myoemetrium, the smooth muscle tissue of the uterus, explained the study's first author, Phyllis Leppert, M.D., Ph.D., Chief of NICHD's Reproductive Science Branch.
Women with fibroids may have painful menstrual periods, pain during sexual intercourse, infertility, urinary and fecal incontinence, and bowel obstruction, Dr. Leppert said. They are also more likely to go into labor prematurely and to experience a miscarriage.
It is not known how many U.S. women have fibroids. In many cases, fibroids do not cause symptoms, making it difficult to detect them. However, some studies indicate that, in the United States, from 25 to 40 percent of all U.S. women experience symptoms from fibroids. Fibroids disproportionately affect African Americans, with one study estimating that 80 percent of African American women are affected by the growths by age 60.
For women who experience severe symptoms, treatment often involves surgery. In one form of surgery, myomectomy, the fibroids are removed from the wall of the uterus. In many cases, the fibroids return after surgery or their removal results in the formation of painful scar tissue. In other cases, the number of fibroids is so great that hysterectomy (removal of the uterus) must be performed. Uterine fibroid embolization, an experimental treatment, involves using a catheter threaded through an artery to shut off the flow of blood supplying the fibroid. The experimental therapy carries the risk of damaging surrounding areas of the uterus.
According to the Centers for Disease Control and Prevention, fibroids account for 68 percent of hysterectomies among black women, 33 percent in white women, and 45 percent of women of other races.
In some cases, fibroids are treated with a leuprolide, a drug that halts production of reproductive hormones and brings on a temporary menopause. In other instances, physicians have attempted to treat fibroids with a combination of estrogen and progestin, the principal ingredients in oral contraceptives and menopausal hormone therapy.
In the current study, Dr. Leppert and her colleagues performed a microscopic analysis of fibroid tumors and normal uterine tissue collected from 5 women who had undergone hysterectomy for fibroids.
Dr. Leppert explained that collagen fibrils—the miniscule "threads" of collagen visible under an electron microscope—are normally arrange in a neat, orderly pattern, parallel to each other. In the fibroids, however, the collagen fibrils were arranged in large tangles, and were very loosely packed together. The tangled collagen masses constituted most of the fibroid tumors, and they contained little other uterine tissue. Fibroid tumors also appear to secrete substances that promote the formation of abnormal collagen mats outside the tumors.
Dr. Leppert noted that, unlike normal uterine tissue, these abnormal collagen fibrils are not affected by reproductive hormones. For this reason, attempting to influence fibroids by halting the production of reproductive hormones may shrink fibroids slightly, but will have little other effect.
"Hormone therapy is not enough," Dr. Leppert said. "It can shrink fibroids somewhat, but it won't make them go away."
Dr. Leppert and her colleagues are planning a study that would test the ability of two drug treatments for uterine fibroids. One drug would block the formation of collagen, in an attempt to keep existing fibroids from growing larger. The second drug acts to break apart collagen fibrils, and would be given in an attempt to shrink existing fibroids. The study is being planned by Dr. Leppert's coauthor on the current paper, James Segars, M.D., of NICHD's Pediatric and Reproductive Endocrinology Branch and the Uniformed Services University of the Health Sciences' Department of Obstetrics and Gynecology.
Women interested in volunteering for the new study may call Dr. Segars at 301-496-5800; FAX number 301-402-0884.
Additional information about fibroids is available from the NICHD publication, Uterine Fibroids. This publication, along with other NICHD publications, is available on the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; e-mail NICHDInformationResourceCenter@mail.nih.gov.
The NICHD is part of the National Institutes of Health (NIH), the biomedical research arm of the federal government. NIH is an agency of the U.S. Department of Health and Human Services.