Medication for endometriosis and uterine fibroids: Elagolix and other treatments

Endometriosis and uterine fibroids are common conditions that affect many women during their reproductive years. Both can cause painful periods, pelvic and lower back pain, and heavy bleeding. Treatment options include pain relievers, hormonal treatments, medications that lower estrogen such as elagolix (Orilissa), and surgery. This article explains how these treatments work, what to know about elagolix, and how your genes can affect elagolix, birth control and pain relievers.

What are endometriosis and uterine fibroids?

• Endometriosis happens when tissue similar to the lining of the uterus grows outside the uterus, for example on the ovaries, fallopian tubes or the lining of the pelvis. It can cause severe period pain, pain during sex, ongoing pelvic pain and trouble getting pregnant.
• Uterine fibroids are non-cancerous growths in the muscle of the uterus. They can cause heavy or long periods, which may lead to anemia (low iron), as well as pelvic pressure and pain.

What role do hormones play?

Both conditions depend on the hormone estrogen. Each month, a hormone from the brain called GnRH signals the pituitary gland to release two other hormones, LH and FSH. These tell the ovaries to make estrogen and progesterone. Estrogen helps endometriosis tissue and fibroids grow. Many treatments work by lowering estrogen or by using a progestin to counter its effects.

How are endometriosis and fibroids treated?

• Pain relievers. Anti-inflammatory painkillers (NSAIDs) such as ibuprofen and naproxen ease period pain and also reduce heavy menstrual bleeding.
• Hormonal treatments. Combined birth control pills, the progestin pill dienogest (Visanne) or a hormonal (levonorgestrel) IUD can reduce pain and bleeding. The hormonal IUD is one of the most effective treatments for heavy bleeding, although it does not shrink fibroids.
• Medications that lower estrogen. These are usually used when first-line treatments are not enough:
  • GnRH agonists, such as leuprolide and goserelin, are given by injection or implant. After a short "flare", they shut down LH, FSH and estrogen.
  • Oral GnRH antagonists, such as elagolix and relugolix, block GnRH right away, without a flare.
• Surgery. Options include removing endometriosis tissue or fibroids, procedures that block the blood supply to fibroids, or removing the uterus.

What is elagolix and how does it work?

Elagolix (Orilissa) is a pill that blocks GnRH in the brain. This lowers LH and FSH, so the ovaries make less estrogen. At 150 mg once a day, it partly lowers estrogen; at 200 mg twice a day, it lowers estrogen almost completely. It is approved for moderate to severe endometriosis pain. For fibroids with heavy bleeding, elagolix and the similar drug relugolix are used in combination pills that also contain low-dose hormones (estrogen and progestin) to reduce side effects. In large trials, relugolix combination therapy reduced endometriosis pain and heavy bleeding from fibroids while protecting bone density.

Are there other medications like elagolix?

Elagolix belongs to a newer class of oral GnRH antagonists. Two other medications in this class are:

• Relugolix, taken once a day as a combination pill with estradiol and norethindrone acetate for heavy bleeding from fibroids and endometriosis pain. On its own, relugolix is also used to treat prostate cancer. Like elagolix, it is affected by medications that change CYP3A4 and the P-gp drug transporter.
• Linzagolix, taken once a day at 100 mg or 200 mg, with or without low-dose hormones. In two large trials, it reduced heavy bleeding from fibroids, and the lower dose taken without hormones may suit women who cannot or prefer not to take hormones.

A 2026 analysis of five trials found that elagolix, relugolix combination therapy and linzagolix with low-dose hormones reduce period pain and pelvic pain from endometriosis to a similar degree. The combination pills with low-dose hormones protect the bones better, so they can usually be used for longer. Availability and approved uses differ from country to country, so ask your prescriber which options are available to you.

What are the side effects and limits of elagolix?

• Menopause-like symptoms, such as hot flashes, night sweats, trouble sleeping, headaches, and mood changes including anxiety and depression.
• Bone loss. Because low estrogen weakens bones, elagolix use is limited to 24 months at 150 mg once a day, or 6 months at 200 mg twice a day. It should not be used by people with osteoporosis.
• Not a contraceptive. Elagolix does not reliably prevent pregnancy and must not be used during pregnancy. Estrogen-containing birth control pills may make elagolix less effective, so a non-hormonal method such as a condom or copper IUD is recommended.
• Liver disease. It must not be used by people with severe liver disease.

Which medications interact with elagolix?

Elagolix is carried into the liver by a transporter protein called OATP1B1 (made by the SLCO1B1 gene) and is broken down mainly by the CYP3A4 enzyme. According to the elagolix clinical pharmacology review:

• Strong OATP1B1 blockers, such as the transplant drug cyclosporine and the cholesterol drug gemfibrozil, can raise elagolix levels several-fold and must not be taken with it.
• Strong CYP3A4 blockers, such as ketoconazole, about double elagolix levels, so treatment time is shortened.
• Elagolix speeds up CYP3A4, which can lower the levels of other medications such as midazolam. It also lowered rosuvastatin (a statin) levels by about 40% and raised digoxin levels, so these may need monitoring.

Do genes affect elagolix?

Yes, but modestly. About 2.5% of people have two reduced-function copies of the SLCO1B1 gene, and their elagolix levels were up to about 80% higher. The manufacturer considers this not large enough to change the dose. Still, higher drug levels together with interacting medications may add to side effects such as hot flashes and bone loss, so it is useful for your prescriber to know your SLCO1B1 and CYP3A4 results and all the medications you take.

How do genes affect other treatments for endometriosis and fibroids?

• Birth control and blood clots. Inherited clotting variants in the F5 gene (Factor V Leiden) and F2 gene (prothrombin) greatly increase the risk of blood clots with estrogen-containing birth control pills, such as Yaz and Yasmin. Progestin-only options, such as the hormonal IUD, carry little or no added clot risk and may be a safer choice for carriers. Read more in Birth control and blood clots and Hormonal contraceptives, depression and blood clots.
• Anti-inflammatory painkillers. Ibuprofen, celecoxib and meloxicam are broken down by the CYP2C9 enzyme. According to the CPIC guideline, CYP2C9 poor metabolizers should start ibuprofen or celecoxib at a lower dose and avoid long-acting meloxicam, to lower the risk of stomach bleeding and other side effects. Read more in Are you a Tylenol or Advil person? Alleviating pain with genetics.

How can a pharmacogenetic test help?

A Pillcheck test reports SLCO1B1, CYP3A4, CYP2C9, F5, F2 and other genes that affect elagolix, birth control, painkillers and many other medications. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications, checks for interactions and recommends safer options and doses to discuss with your prescriber.

Summary

• Endometriosis and fibroids depend on estrogen and can cause pain and heavy bleeding.
• Pain relievers and hormonal treatments, including birth control pills, dienogest and the hormonal IUD, are usually tried first.
• Elagolix lowers estrogen and treats endometriosis pain, but bone loss limits how long it can be used.
• Relugolix and linzagolix are other oral medications in the same class; they reduce endometriosis pain about as well as elagolix and are often given with low-dose hormones to protect the bones.
• Strong OATP1B1 blockers such as cyclosporine and gemfibrozil must not be taken with elagolix, and elagolix can change the levels of other medications.
• SLCO1B1 variants modestly raise elagolix levels; F5 and F2 variants affect the safety of estrogen-containing birth control; CYP2C9 affects anti-inflammatory painkillers.
• A pharmacogenetic test and pharmacist review can help choose safer treatments.

Frequently asked questions

Is elagolix a good treatment for endometriosis?

Elagolix can reduce period pain and pelvic pain from endometriosis. It is usually used when pain relievers and hormonal treatments are not enough, and bone loss limits how long it can be taken.

Can elagolix treat fibroids?

For heavy bleeding from fibroids, elagolix or relugolix is used in combination pills that also contain estrogen and progestin to protect the bones and reduce side effects.

Are there alternatives to elagolix in the same class?

Yes. Relugolix and linzagolix are oral GnRH antagonists that work the same way. They are usually given with low-dose estrogen and progestin to protect the bones. Availability differs by country.

Which drugs should not be taken with elagolix?

Strong OATP1B1 blockers such as cyclosporine and gemfibrozil must not be taken with elagolix. Strong CYP3A4 blockers shorten how long it can be used. Tell your pharmacist about all your medications, including statins and digoxin.

Do NSAIDs make heavy periods worse?

No. NSAIDs such as ibuprofen and naproxen reduce heavy menstrual bleeding and period pain. CYP2C9 poor metabolizers may need a lower dose.

Is birth control safe if I carry Factor V Leiden?

Estrogen-containing pills greatly increase the risk of blood clots in carriers of Factor V Leiden or the prothrombin variant. Progestin-only options such as the hormonal IUD are usually safer. Talk to your prescriber about your options.

References

Shebley M, Polepally AR, Nader A, et al. Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis. Clin Pharmacokinet. 2020;59(3):297-309.

Giudice LC, As-Sanie S, Arjona Ferreira JC, et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022;399(10343):2267-2279.

Al-Hendy A, Lukes AS, Poindexter AN, et al. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021;384(7):630-642.

Donnez J, Taylor HS, Stewart EA, et al. Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials. Lancet. 2022;400(10356):896-907.

Hsu R, Han ES, Farrow M, et al. Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Endometriosis-Associated Pain: A Systematic Review and Meta-Analysis. J Minim Invasive Gynecol. 2026;33(10):1526-1532.

Bofill Rodriguez M, Lethaby A, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2019;9:CD000400.

Bofill Rodriguez M, Lethaby A, Jordan V. Progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2020;6:CD002126.

Theken KN, Lee CR, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clin Pharmacol Ther. 2020;108(2):191-200.