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Roman physicians recognized as early as 200 AD that women often have benign tumors in the walls of their uterus. Today, experts estimate that by age 50, some 70 percent of white women and more than 80 percent of Black women have uterine fibroids. But scientists still have so many questions about them, including basics like why do they develop and what makes them grow.
Fibroids, technically called leiomyomas, are solid masses of smooth muscle cells and connective tissue that grow inside the uterine wall. These growths can severely impact a woman’s quality of life and fertility and are the most common reason for hysterectomies in the United States. A review of drugs used to treat fibroids published this month in Medical Science Monitor pointed to a “significant need for further research.”
“Research on fibroids is in its embryonic phase. We’re just starting to scratch the surface,” says Erica Marsh, chief of reproductive endocrinology and infertility at the University of Michigan Medical School, who spoke about fibroids at a National Academy of Medicine meeting on women’s health last spring.
Scientists still aren’t clear how fibroids form, why some grow to the size of a watermelon while others remain small, how they can be prevented, how fertility is impacted by some therapies, and other important issues.
With low levels of funding—at $17 million a year from the National Institutes of Health, fibroids rank toward the bottom of studied conditions—scientists have not even created a quality mouse model in which to study the disease, Marsh says.
Still, there have been some advances in recent years, including the introduction of a procedure that shrinks fibroids using radiofrequency energy and the identification of certain lifestyle interventions that seem to minimize recurrence.
A long road to diagnosis
On average, it takes four years after symptoms begin for women to get a diagnosis. Several more years often pass before treatment is initiated.
Tanika Gray Valbrun, a Black woman in Atlanta, was 25 when a doctor first diagnosed fibroids, after an ultrasound revealed why she periodically required blood transfusions for low red blood cell counts. That was a decade after Valbrun, now 46, first experienced what in retrospect were obvious fibroid symptoms: painful period cramps, frequent urination, and menstrual bleeding so heavy it caused the anemia and often confined her at home. Over time, her uterus distended to the size of a four-month pregnancy.
Valbrun says that she often hears doctors say, “If they’re not bothering you, don’t bother them” to describe when fibroid treatment should be initiated. “In hindsight, they were bothering me,” she says, “but I didn’t know that.”
Valbrun thought heavy menstrual bleeding and pain were normal because they started within a few years of her first period. Although she knew her mother suffered from fibroids—the condition has a known genetic component—no one around her talked about their periods.
It would be another nine years before Valbrun had her first of three fibroid surgeries, after she learned from a different physician that her distended uterus would prevent a successful pregnancy. (She is currently undergoing in vitro fertilization.)
Fibroids are the sole cause of infertility in about 3 percent of women, but they likely contribute to miscarriage and other pregnancy problems in many others. This is especially the case for fibroids inside the muscle wall (known as intramural fibroids) or those that bulge into the vaginal cavity (submucosal).
During Valbrun’s first operation, 27 fibroids, including one the size of a grapefruit, were removed. “I remember feeling like, Wow, those benign tumors have really run my life,” says Valbrun, who realized that it even affected her choice of clothing. She has since founded a patient education and advocacy organization called the White Dress Project, a nod to a color she and others with excessive menstrual bleeding from fibroids avoid.
Valbrun’s journey is representative in another way: Black women often have twice as many fibroids and more severe symptoms than whites. And Black women’s fibroids tend to develop at earlier ages.
Black women are also less likely to get treatment for fibroids, according to a study at the Department of Veterans Affairs. That research also found that when treatments were recommended, they often differed from those offered to white women. Marsh recently received funding to better understand these racial disparities.
Unique like snowflakes
About a decade ago scientists discovered a key mutation within the mediator complex subunit 12 gene, or MED12, that exists in more than 70 percent of fibroids.
Cells carrying this mutation, or others, can become fibroids years later after exposure to estrogen and progesterone during puberty. Contact with endocrine-disrupting environmental chemicals and other factors may also be involved. Fibroids can increase in size and quantity until menopause, although not all do.
(How everywhere chemicals help uterine fibroids grow)
Fibroid symptoms generally fall into four categories: excessive period bleeding; pelvic pressure, urinary frequency issues, and/or constipation resulting from a heavier or larger uterus, known as bulk symptoms; intensive cramps or pelvic pain during menstruation or sex; and infertility.
“Fibroids are unique and one of a kind, like a snowflake,” says Linda Bradley, a professor of obstetrics/gynecology and reproductive biology at the Cleveland Clinic in Ohio. This means treatments must be individualized for each person and for each fibroid.
Therapy often starts with medications prescribed by a primary care physician or gynecologist to reduce monthly bleeding. This may involve birth control pills or other drugs, or a hormonal intrauterine device. Gonadotropin-releasing hormone (GnRH) medicines may be used to shrink fibroids, but because they trigger menopause-like side effects and reduce bone-mineral density, the American College of Obstetricians and Gynecologists recommends limiting their use for less than two years.
Another common treatment is to starve fibroids of their blood supply through uterine fibroid embolism (UFE, also called UAE), a procedure performed by an interventional radiologist. Although the research is inconclusive, UFE is generally not recommended for people who want to preserve fertility.
“There’s an underlying concern that because we are embolizing the vasculature of the uterus, in some patients that could also affect the vasculature of the ovaries,” says Sarah Allen, director of the Fibroid Treatment Center at the University of Pittsburgh Medical Center’s McGee-Womens Hospital. Allen is a minimally invasive gynecologic surgeon (MIGS), who specializes in non-cancerous gynecological conditions like fibroids and endometriosis.
(Endometriosis is common, incredibly painful—and often misdiagnosed)
Another non-surgical technique
A newer intervention is laparoscopic radiofrequency ablation, generally performed by MIGS surgeons, which uses heat to shrink fibroids. A study of 26 women in one clinical practice found significantly reduced menstrual bleeding three months after the procedure.
Radiofrequency ablation is best for women with up to five medium-sized intramural fibroids causing bulk symptoms and/or heavy bleeding and can work well for Black women with severe symptoms, Bradley says. Her study of 74 ethnically diverse women undergoing the procedure found that while before treatment Black women had twice as many fibroids as white women, three years later both groups saw similar improvements in size and bleeding reductions.
Physicians can also remove fibroids surgically, a procedure known as myomectomy. While gynecologists are well trained to perform this, women with large fibroids should be referred to MIGS physicians. “Gynecologists often do open abdominal surgery with large fibroids, whereas we specialize in treating complex cases minimally invasively,” Allen says.
This concern was shared by several MIGS surgeons from major universities in a paper published in Health Equity last year. They noted that 90 percent of myomectomies could be done laparoscopically, even as many gynecologists don’t. The MIGS surgeons admonished physicians who don’t discuss all options with patients (medical, radiological, and/or surgical) because of financial incentives or a lack of training as well as those who perform fertility-impacting procedures on women who may still want to bear children.
In the years following each of these treatments, fibroids often return. People who are younger, have multiple masses or an enlarged uterus, or have other pelvic diseases are at highest risk for recurrence.
The only definitive treatment is hysterectomy, which removes both the fibroids and the uterus that houses them. The lack of other permanent treatments is likely why 8 percent of women who had a myomectomy, and 18 percent who’d undergone UFE, in the prior six years eventually went back for a hysterectomy, according to a study by Kaiser Permanente.
Deciding on a treatment should be a thoughtful and deliberative process.
“Fibroids are never an emergency,” Bradley says. She advises patients to consider step therapy where they try medicine or an IUD before moving to a more invasive procedure. Comprehensive fibroid treatment centers located in academic medical facilities, which employ experts in all treatment methods who collaborate with one another, are a good option for complicated cases.
Lifestyle changes can help
A new line of early-stage research examines how lifestyle changes might prevent, or at least delay, the return of fibroids after treatment. Especially promising is Vitamin D, since preliminary studies correlate low levels with uterine fibroid prevalence. Another intriguing supplement is the polyphenol epigallocatechin gallate, or EGCG, found in green tea, which in lab cultures and animal studies inhibits fibroid cell growth.
Other lifestyle factors also likely impact fibroid development, says Somayeh Vafaei, a researcher in Iran who, while at the University of Chicago, helped develop a comprehensive anti-fibroid lifestyle program. Elements include eating a vegetable-based diet; reducing alcohol consumption; exercising vigorously at least four hours each week; and minimizing exposure to phthalate chemicals found in food packaging, certain cosmetics, and flexible plastic products, among other things.
Larger studies are needed to confirm the benefits for fibroid prevention, Vafaei says, but she notes these lifestyle changes “are helpful for cardiovascular and other diseases as well.”
Marsh envisions a day when fibroid research receives funding commensurate with its harms. She wants to see additional research on how fibroids develop and on other ways to treat them. She also wants scientists to better understand how the disease so devastatingly impacts women’s lives.
“All of those,” Marsh says, “are important questions we need to answer.”
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