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In 2022, two colleagues from Johns Hopkins University School of Medicine, Bhuchitra Singh, MD, MPH, MS, MBA, and James Segars, Jr, MD, reviewed the available literature to evaluate the effectiveness of newer minimally invasive therapies in reducing bleeding and improving the quality of life and control of symptoms linked to uterine fibroids.
Their goal, according to Segars, a professor of obstetrics and gynecology and director of the Division of Women’s Health Research at Johns Hopkins, was to help guide clinicians and patients in making decisions about the use of the newer therapies, including radiofrequency ablation and ultrasound-guided removal of lesions.
But he and Singh, the director of clinical research at the Howard W. and Georgeanna Seegar Jones Laboratory of Reproductive Sciences and Women’s Health Research, were surprised by their findings. “The outcomes were relatively the same,” Segars said. “All of the modalities lead to significant reduction in bleeding and other fibroid-related symptoms.”
The data on long-term complications and risk for recurrence are sparse for some of the newer approaches, and not enough high-quality long-term studies have been conducted for the US Food and Drug Administration (FDA) to approve them as fertility-sparing treatments.
But perhaps, the biggest challenge now is to ensure that women can take advantage of these newer therapies, with large gaps in both the diagnosis of fibroids and geographic access to minimally invasive treatments.
A Widespread Condition Widely Underdiagnosed
Uterine fibroids occur in most women (the incidence rises with age) and can be found in up to 70% of women by the time they reach menopause. Risk factors include family history, increasing interval since last birth, hypertension, and obesity. Increasing parity and use of oral contraceptives are protective.
But as many as 50% of cases go undiagnosed, and one reason for this is the failure of clinicians to dig deeply enough into women’s menstrual histories to diagnose fibroids.
“The most common cause of anemia is heavy menstrual bleeding,” said Shannon Laughlin-Tommaso, MD, MPH, a professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota. She frequently sees patients who have already undergone colonoscopy to work-up the source of their anemia before anyone suspects that fibroids are the culprit.
“When women tell us about their periods, what they’ve been told is normal [bleeding] — or what they’ve always had and considered normal — is actually kind of on the heavier spectrum,” she said.
Ideally, treatment for uterine fibroids would fix abnormally prolonged or heavy menstrual bleeding, relieve pain, and ameliorate symptoms associated with an enlarged uterus, such as pelvic pressure, urinary frequency, and constipation. And the fibroids would never recur.
By those measures, hysterectomy fits the bill: Success rates in relieving symptoms are high, and the risk for recurrence is zero. But the procedure carries significant drawbacks: short-term complications of surgery, including infection, bleeding, and injury to the bowels and bladder along with potential long-term risks for cardiovascular disease, cancer, ovarian failure and premature menopause, depression, and decline in cognitive function. Those factors loom even larger for women who still hope to have children.
For that reason, the American College of Obstetricians and Gynecologists (ACOG) recommends myomectomy, or surgical removal of individual fibroids, for women who desire uterine preservation or future pregnancy. And the literature here is solid, according to Singh, who found that 95% of myomectomy patients achieved control of their bleeding symptoms, whether it was via laparoscopy, hysteroscopy, or laparotomy. Up to 40% of women may develop new fibroids, or leiomyomas, within 3 years, although only 12.2% required a second surgery up to after 5 years.
But myomectomy is invasive, requiring general anesthesia, incisions in the uterus, and stitches to close the organ.
Newer techniques have emerged that can effectively treat symptoms of fibroids without requiring surgery. Uterine artery embolization (UAE), which involves passing a catheter into the femoral artery, or laparoscopic uterine artery occlusion can be used to cut off the blood supply of the fibroid. Other techniques, including focused ultrasound surgery and radiofrequency ablation (RFA), use various forms of energy to heat and ablate fibroids. The latter two can be performed in outpatient settings and often without general anesthesia.
Approved for use in 1994, UAE has the most data available, with reduction in the volume of fibroids and uterine tissue lasting up to 5 years, and rates of re-intervention of 19%-38% between 2 and 5 years after the procedure. Singh’s review found that 79%-98.5% of recipients of the procedure reported declines in bleeding that persisted for several years, which is comparable to myomectomy. Quality of life and pain scores also showed good improvement, with follow-up in the different studies ranging from 12 months to over 5 years, the analysis showed.
UAE does have its drawbacks. In rare cases, embolization can deprive the entire uterus and ovaries of blood, which can cause ovarian dysfunction and potentially result in premature menopause, although this outcome is most common in women who are older than 45 years. The procedure can often also be painful enough that overnight hospitalization is required.
Focused ultrasound surgeries, which include magnetic resonance–guided focused ultrasound surgery (MRgFUS) and high-intensity focused ultrasound (HIFU), were approved by the FDA in 2004. Focused ultrasound waves pass through the abdominal wall and produce significant heating, causing a burn that destroys the targeted tissue without damaging surrounding tissue. As with UAE, improvements in fibroid-associated bleeding and measures of quality of life were similar to those after myomectomy up to 3 years later.
But Singh noted that both focused ultrasound and RFA can damage the skin or internal organs. “[As] always with the thermal interventions, there is the probability of skin as well as internal organs that might get the thermal energy if it’s not focused correctly on to the fibroid itself,” he said. In addition, MRgFUS is not an option for women who are not good candidates to undergo an MRI, such as those with claustrophobia or pacemakers. Also, with focus ultrasound and RFA, “we do worry about that fibroid getting blood flow back,” which can lead to recurrence of heavy menstrual bleeding, Laughlin-Tommaso noted.
Although data on RFA are limited to 12 months of follow-up, most women reported meaningful reductions in bleeding symptoms. Longer follow-up has been reported for bleeding symptoms after MRgFUS, with similar results up to 3 years later.
For Leslie Hansen-Lindner, MD, chief of obstetrics and gynecology at Atrium Health in Charlotte, North Carolina, choosing the right procedure starts with a patient-centered conversation weighing the pros and cons of the options and the woman’s goals.
“Is their goal to reduce the size and impact of their fibroid, bleed less, and have a better quality of life on their period?” Hansen-Lindner said. “Or is their goal to have the entire fibroid removed?”
If the former, an RFA is appealing to many women. If the latter, laparoscopic or mini-laparotomy myomectomy might be a better choice. Although fewer than 10% of patients require surgical reintervention at 3 years of follow-up for RFA, myomectomy has more consistent long-term evidence showing that fewer women require re-intervention and preserve their fertility, she added.
Age also plays a role in the decision: The closer a woman is to menopause, the less likely she is to experience a recurrence, so a less-invasive procedure is preferable. But for younger women hoping to become pregnant, the lower risk for recurrence and good prognosis for future fertility might sway the choice toward myomectomy.
The first laparoscopic RFA procedures were approved for uterine fibroids in 2012. Hansen-Lindner is a proponent of transcervical fibroid ablation (TFA), a newer RFA procedure that the FDA approved in 2018. Performed through the cervix, TFA requires no incisions and can generally be done without general anesthesia. Eligible candidates would be any woman with symptomatic fibroids, such as heavy menstrual bleeding, pain, or bulk symptoms. The contraindications are few.
“It’s going to come down to size and location of fibroids, and whether or not they would be accessible by the TFA,” Hansen-Lindner said. “I have to make sure that there isn’t a fibroid blocking their cervix and that the fibroids are accessible with this device.”
TFA also is not suitable for removing most submucosal lesions, which typically must be removed by hysteroscopic myomectomy. Hansen-Lindner said that she often uses TFA in conjunction with hysteroscopic myomectomy for this scenario. Although data on pregnancy after RFA (including TFA), MRgFUS, and HIFU are lacking, Gynesonics, the manufacturer of the Sonata System (the device that delivers radiofrequency energy to shrink the fibroid) has documented 79 pregnancies among the 2200 women who have undergone TFA in the United States since 2018.
Disparities Hampering Care
Uterine fibroids are a particular problem for Black women, whose symptoms are more likely to be ignored by clinicians, according to Jodie Katon, PhD, a core investigator at the Veterans Affairs (VA) Greater Los Angeles Center for the Study of Healthcare Innovation, Implementation and Policy. Katon cited studies in which Black women interviewed about their experiences reported a consistent theme: Clinicians dismissed their symptoms, told them these were nothing to worry about, and advised them to lose weight. Those interactions not only delayed diagnosis among Black women but also led many of them to mistrust clinicians and avoid the healthcare system altogether.
The failure of clinicians to take their complaints seriously is just one of the disparities affecting Black women. In reviewing the literature, Laughlin-Tommaso, who also serves as the associate dean for Education Diversity, Equity, and Inclusion at Mayo, found that African American women experience two to three times the risk for fibroids compared with White women as well as earlier onset and more severe disease, as measured by number and size of the lesions.
According to Katon, the etiology of fibroids is still poorly understood. “What we do know is that Black women are disproportionately exposed to a variety of factors that we have shown through observational studies are associated with increased risk of development of uterine fibroids.”
The list includes factors like stress; interpersonal racism; early age at menarche; various indicators of poor diets, such as vitamin D deficiency; the use of certain beauty products, specifically hair straighteners; as well as exposure to air pollution and other environmental toxins.
Laughlin-Tommaso also pointed to historical disparities in management, citing a two-times greater risk for hysterectomy for Black women in a study published in 2007 despite survey data suggesting that Black women report being more interested in uterine-preserving therapies rather than a hysterectomy.
Breaking Down Barriers of Access to New Treatments
Laughlin-Tommaso looked at more recent trends in the management of fibroids using data from the multicenter COMPARE-UF study, which enrolled women between 2015 and 2020 undergoing fibroid treatment into a longitudinal registry to track their outcomes. She found that Black women underwent hysterectomies at a lower rate than did White women and were instead more likely to undergo myomectomy or UAE.
Some of the change may reflect lack of approved minimally invasive procedures before 2000. “But now that we have expanded options, I think most women are opting not to have a hysterectomy,” Laughlin-Tommaso said.
Katon has research funding from the VA to look more closely at racial disparities in the treatment of fibroids. In a study published earlier this year, she reported some surprising trends.
During the period from 2010 to 2018, she found that Black veterans diagnosed with fibroids were less likely than White veterans were to receive treatment, regardless of their age or the severity of their symptoms. This finding held even among women with anemia, which should have been a clear indication for treatment.
But, as in the COMPARE-UF study, the subset of Black veterans who received an interventional treatment were less likely than their White peers were to undergo hysterectomy in favor of a fertility-sparing treatment as their initial procedure. Katon called it a “welcome but unexpected finding.”
But another significant barrier remains: The two newest types of procedures, RFA and guided focused ultrasound, are not commonly performed outside of tertiary care facilities. However, studies have found that all these procedures are cost effective (studies for myomectomy, UAE, MRgFUS, and TFA). The implementation of a category 1 billing code for laparoscopic RFA in 2017 has led more insurance companies to cover the service, and a category 1 code will be available for TFA effective January 2024.
Although RFA does require investment in specialized equipment, which limits facilities from offering the procedure, any gynecologist who routinely performs hysteroscopy can easily learn to do TFA. And the VA, which is committed to eliminating disparities in women’s health, established a 2-year advanced fellowship in minimally invasive gynecologic surgery in 2022 to help expand their capacity to offer these procedures.
The VA has been rapidly expanding their gynecology services, and Katon said that she is confident that ultrasound-guided procedures and RFA will become more available within the system. “I would say we’re keeping pace,” she said. “And in some ways, you know, as a national system we may be positioned to actually outpace the rest of the US.”
Segars reports prior research funding for clinical trials from BioSpecifics Technologies, Bayer, Allergan, AbbVie Inc, and ObsEva and currently receives funding from Myovant Sciences. Hansen-Lindner reports personal fees from Gynesonics. Singh, Laughlin-Tommaso, and Katon report no financial conflicts of interest.
Ann Thomas, MD, MPH, is a pediatrician and epidemiologist living in Portland, Oregon.
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