Addressing Disparities in Care in Women’s Reproductive Health - Episode 7

GnRH Receptor Antagonists in UF

Dr Al-Hendy highlights the oral GnRH receptor antagonists as first-line therapy for UF.

Ayman Al-Hendy, MD, PhD, FRCSC, FACOG, CCRP: As far as how to adjust treatment based on the patient response and severity of symptoms, you factor that in. With the newly FDA-approved options, we have reliable long-term treatment options against fibroids. They have very high response rates, so the lack of response is becoming less of an issue. The remaining important items that decide which treatment line or algorithm you go through is if the patient is interested in fertility. If the patient is interested in preserving her fertility, then hysterectomy isn’t an option. Even with myomectomy, the effect on enhancing fertility has been controversial in the literature. Medical treatment options become very attractive, and only for those who might not respond or might have contraindication to medical therapy do we then consider surgical options.

We understand the pathophysiology of uterine fibroids: they need estrogen and progesterone for their growth and lifeline. Most of the treatment against fibroids has been directed against those, either inhibiting the effect of estrogen and progesterone or withdrawing estrogen and progesterone from the patient’s system to deprive fibroids from their lifeline. This eventually shrinks them and improve the symptoms. Most of the treatment options for fibroids have been hormonal.

Recently, we had 2 FDA-approved medical treatment options against fibroids based on high-quality phase 3 studies. One is elagolix, and the other is relugolix. There’s a similarity in the name because they belong to the same family of compounds, called oral GNRH antagonists. The members of this family—elagolix, relugolix, and a third candidate that’s the pipeline but not FDA approved—share the same mechanism of action. The way this medication works is, first, they’re oral because they’re nonpeptides. The patient can use them orally without worrying about them being digested in the GI [gastrointestinal] tract. They go into the anterior pituitary gland in the brain and bind to the receptor of the GNRH analog or GNRH-releasing hormone that’s supposed to stimulate the pituitary gland. By doing that, they inhibit ovarian function. They give the ovary a rest, or put the ovary in a sleep, so it doesn’t produce estrogen and progesterone. That’s the main source of estrogen and progesterone in a woman’s body, so you can imagine the effect. Once you deprive fibroids from estrogen and progesterone, they start to struggle and shrink. By shrinking, the symptoms related to fibroids start to improve—the bleeding starts to get better, the pain, etc. That’s the mechanism of action for those members of this family, the oral GNRH antagonist.

We have 2 medications approved, elagolix and relugolix. The FDA approved them to be used daily for up to 2 years in patients. For the first time, we have effective, reliable, long-term treatment options against fibroids. What are the other options? Birth control pills, oral contraceptives, have been used for a long time, especially when we didn’t have other FDA-approved options to decrease the bleeding associated with uterine fibroids. Unfortunately, they’re not specific. They haven’t been evaluated in high-quality clinical trials against fibroids. But they might give temporary short-term improvement in the heavy bleeding, so they found their place. When we didn’t have any other options, they became a common prescription to use initially. Along those same lines, there’s an intrauterine device [IUD] with progesterone. Mirena was the first 1, but there are others available now. It’s also been used for the same reason because it makes the lining of the uterus, the endometrium, quite thin, but they haven’t been evaluated in uterine fibroids. If you have a high number of fibroids, the cavity of the uterus becomes irregular, and there’s a higher chance of expulsion. The IUD would fall out of the uterus in patients with fibroids, but it’s been included in the treatment option.

Collectively, these are the hormonal and medical treatment options against fibroids. There’s only 1 other medication that’s nonhormonal, and it’s called tranexamic acid or Lysteda. It’s an oil therapy that you use 3 times a day during the menses. You use it once you start the bleeding. It tends to decrease bleeding, and you use it for 5 or 6 days during the menses. It’s been approved for use in nonfibroid heavy bleeding. But because we didn’t have other options a few years ago, it’s moved off-label in women with fibroids. It hasn’t been evaluated against fibroids, and that’s why its effectiveness is limited and shorter, but it’s 1 option you can consider for patients with uterine fibroids. These are the medical treatment options available.

This transcript has been edited for clarity.