June 26, 2021

For patients with uterine fibroids whose heavy menstrual bleeding was unresponsive to elagolix with add-back therapy — a medication alternative to hysterectomy — investigators in a multisite trial found no specific characteristics predicting the lack of response. Findings appeared in the January 2021 issue of the American Journal of Obstetrics and Gynecology. This study served as a secondary analysis by the same investigators who published findings in The New England Journal of Medicine in January 2021 indicating that this treatment was effective and did not demonstrate severe side effects.

"The initial study showed that between 68% and 76% of women had dramatically decreased menstrual bleeding with this therapy. Women who did not respond did not differ in baseline menstrual blood loss, uterine or fibroid volume, or fibroid location," says Elizabeth (Ebbie) A. Stewart, M.D., a reproductive endocrinologist at Mayo Clinic's campus in Rochester, Minnesota, and senior author of the study subgroup publication. "I was surprised. I would've expected some factor would've pointed to a group that didn't respond to this therapy."

Dr. Stewart says the research team also noted a trend toward patients classified as having more-severe disease experiencing better response to elagolix plus add-back therapy, which is a positive because this group is hard to treat for fibroids.

This study is significant in that if elagolix with add-back therapy is used as an alternative to hysterectomy for patients with uterine fibroids, investigators don't have to go through a complicated decision-making process to understand fully for whom it works.

"The more we can understand who does and doesn't respond, the more we can have customized therapy," says Dr. Stewart. "We know so little about fibroids compared with heart disease or cancer. I hope the day is coming where we say women with fibroids don't have to have a hysterectomy — it's on its way out."

Search for medical options to better quality of life

In May 2020, the Food and Drug Administration (FDA) approved elagolix with add-back therapy for treatment of heavy menstrual bleeding due to uterine fibroids. The FDA approved the drug combination for up to two years' use, which Dr. Stewart hopes will give patients time to reach either menopause or readiness for pregnancy. This drug combination was part of a larger effort by gynecologists to find potential medical alternatives to hysterectomy due to the surgery's potential long-term side effects.

"Hysterectomy can take care of the problem — heavy bleeding — but can lead to long-term health risk even if the surgeon leaves the ovaries. These risks include coronary artery disease, mood disorders and hypertension," says Dr. Stewart.

Older drugs for uterine fibroid therapy have proved effective, but associated side effects have prevented their use long-term. For instance, gonadotropin-releasing hormone (GnRH) agonists resulted in side effects such as bone loss and hot flashes, which restricted their use to 3 to 6 months of therapy. Progesterone receptor modulators have been widely used outside the United States, yet rare but serious problems with liver function have kept them from approval here. An advantage of elagolix plus add-back therapy is its potential use for a much longer time period for more patients.

Women with uterine fibroids have significant quality of life issues and health risks, indicates Dr. Stewart. Thus, the safest resolution of their heavy bleeding, as well as other symptoms, is critical. Bleeding is the most common symptom for women who have symptomatic fibroids and the most frequent reason for hysterectomy.

"It's pretty severe," says Dr. Stewart. "They may have anemia from all the bleeding and need transfusion. Some of them can't even go to work — they may have bleeding for 10 to 14 days a month, and if they go to a meeting, they may stain the chair."

With the elagolix plus add-back therapy combination, gynecologists are able to maintain reproductive levels of the hormones estrogen and progesterone, limiting side effects and protecting bone health.

Practice applications and resources

Dr. Stewart notes that uterine fibroids are very common in the community and that many gynecologists may incorporate use of elagolix plus add-back therapy into their practices, phasing out hysterectomy where unnecessary.

For further resources, she explains that Mayo Clinic has a multidisciplinary fibroid team available for questions and consultation, which she suggests is simple to do through a virtual meeting, an eConsult. Also, physicians external to Mayo Clinic may meet virtually along with a patient and a member of the Mayo fibroid team, avoiding a potential long drive for the patient and bolstering the relationship between Mayo Clinic and local physicians. All of these options can be arranged by calling the Mayo Clinic referring physician line at 800-533-1564 or using Mayo Clinic CareLink, an online referral portal.

Ongoing study on uterine fibroids

Dr. Stewart says that currently an extension study is looking at any other factors, such as concomitant disease, that might impact the effectiveness of elagolix plus add-back therapy.

Overall, Dr. Stewart says she's grateful for movement in the field. "It's been a long time since we've had something new for uterine fibroids," she says.

For more information

Al-Hendy A, et al. Predictors of response for elagolix plus add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids. American Journal of Obstetrics and Gynecology. 2020;224:72.e1.

Schaff WD, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. The New England Journal of Medicine. 2020;382:328.

Mayo Clinic CareLink.