Relugolix
A daily pill that blocks the GnRH receptor: alone for prostate cancer, with add-back hormones for fibroids and endometriosis
Relugolix is a small molecule, not a peptide. It blocks the receptor for the peptide hormone GnRH, so testosterone falls within days, without the surge agonists cause. The US approved it as Orgovyx for prostate cancer in 2020 and, with add-back hormones, as Myfembree in 2021.
What is it?
GnRH, a ten-amino-acid peptide, tells the pituitary to release LH and FSH. Agonists such as leuprolide overstimulate its receptor before shutting it down, so testosterone surges first; relugolix, a small molecule, blocks the receptor, and levels fall from the first dose. The label gives an effective half-life of about 25 hours, which suits a daily pill.
Men with advanced prostate cancer take it alone. In HERO, 930 men were randomised against leuprolide: 96.7% on relugolix stayed castrate through 48 weeks against 88.8%, and 56% were castrate by day 4 against none. Major cardiovascular events were 2.9% against 6.2%, and testosterone recovered faster after stopping. A dose of 360 mg on day one is followed by 120 mg daily.
It can be combined with the newer prostate cancer drugs. In 48 men, relugolix with abiraterone or with apalutamide kept testosterone at castrate levels for a year, though apalutamide called for a doubled relugolix dose of 240 mg; adherence to the daily pill exceeded 97%.
In the US, women take it only as Myfembree, one tablet with estradiol 1 mg and norethindrone acetate 0.5 mg, whose added hormones protect bone. In LIBERTY 1 and 2, 73% and 71% of women with fibroid bleeding met the bleeding target against 19% and 15% on placebo, and bone density held with the combination but fell on relugolix alone. In Japan relugolix alone before fibroid surgery matched leuprorelin injections for blood loss.
For endometriosis, SPIRIT 1 and 2 enrolled 1,261 women: 75% on the combination were period-pain responders at 24 weeks against 27% and 30% on placebo. In the two-year extension the median time to minimal or no period pain was 8 weeks, and spine bone density dipped under 1% before holding.
The combination also stops ovulation: in 70 healthy women it stopped ovulation in everyone who completed 84 days, and ovulation returned about three weeks after stopping. The Myfembree label is still limited to 24 months and carries a boxed warning for blood clots, stroke and heart attack; a 2026 review found no significant rise in venous clots so far.
Orgovyx's own warnings include QT prolongation and angioedema; common effects are hot flushes, raised glucose and triglycerides, musculoskeletal pain and fatigue. A generic tablet holds only a tentative FDA approval, which does not allow sale.
Mechanism of Action
Relugolix blocks the GnRH receptor, so the pituitary stops driving the testes or ovaries.
GnRH receptor block
An oral small-molecule antagonist; testosterone falls from the first dose, with no agonist surge (HERO: 56% castrate by day 4).
Daily dosing
Effective half-life about 25 hours, terminal about 61 hours (Orgovyx label 12.3).
Add-back in women
Estradiol 1 mg with norethindrone acetate 0.5 mg in Myfembree preserves bone density lost on relugolix alone (LIBERTY).
Published Research
The trials behind relugolix, read from their PubMed abstracts: HERO and the combination study with abiraterone or apalutamide in prostate cancer, LIBERTY and SPIRIT with their extensions in fibroids and endometriosis, a Japanese pre-surgery trial, an ovulation study and a review of clot risk. Doses from the Orgovyx and Myfembree labels read October 1, 2026.
HERO: against leuprolide
In 930 men with advanced prostate cancer, 96.7% on relugolix stayed castrate through 48 weeks against 88.8% on leuprolide, and 56% were castrate by day 4 against none. Cardiovascular events: 2.9% against 6.2%. Ninety days after stopping, mean testosterone was 288 ng/dL against 59.
With abiraterone or apalutamide
In 48 men with advanced prostate cancer, relugolix 120 mg daily with abiraterone, or 240 mg daily with apalutamide, kept mean testosterone below castrate level for 52 weeks; adverse events were mostly grade 1-2 and adherence exceeded 97%.
LIBERTY 1 and 2: fibroid bleeding
In two 24-week trials in 770 women with fibroid-related heavy bleeding, 73% and 71% on the combination met the bleeding target against 19% and 15% on placebo. Bone density held with the combination but fell on relugolix alone.
Before fibroid surgery, against leuprorelin
In a Japanese trial, 12 weeks of oral relugolix before laparoscopic myomectomy (32 women) was non-inferior to leuprorelin injections (35) for blood loss during surgery (72.7 against 84.4 mL), with no significant difference in other outcomes; estradiol recovered sooner after relugolix.
SPIRIT 1 and 2: endometriosis pain
In 1,261 women with endometriosis, 75% on the combination were period-pain responders at 24 weeks against 27% and 30% on placebo; for pain between periods, 58% and 66% against 40% and 43%. Spine bone density fell under 1%.
Two years on the combination
Over two years in the open-label extension, 84.8% of women who began on the combination were period-pain responders and 75.8% for pain between periods; bone density dipped under 1%, then held.
SPIRIT extension: minimal to no pain
Of 1,261 women in SPIRIT 1 and 2, 802 entered the extension and 501 completed 104 weeks. Median time to minimal or no period pain was 8 weeks on the combination; the chance of reaching it was 82.5% by week 24 against 22.4% on placebo, and about 95% in every group by week 104.
It stops ovulation
In 70 healthy women aged 18 to 35 taking the relugolix combination for 84 days, ovulation was inhibited in all 67 who completed treatment; estradiol stayed around 37-39 pg/mL, and all ovulated or resumed periods after stopping, on average 23.5 days later.
The clot question
An expert review of the trials, regulators' reports and real-world data found no significant rise in venous clots so far and judged the risk below that of ethinylestradiol pills, while urging careful patient selection.
Dosing Data
Dosed by label: Orgovyx starts with a loading dose; Myfembree is one tablet daily, begun within seven days of a period.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Orgovyx and Myfembree labels.
Contraindications & Cautions
From the labels.
Legal Status
Approved in the US as two products.
Frequently Asked Questions
?Is relugolix a peptide?
No. It is a small molecule that blocks the receptor for GnRH, a peptide hormone, so it is covered beside peptide drugs such as leuprolide.
?How does it differ from Lupron?
Leuprolide is an injected agonist that causes a testosterone surge first; relugolix is a daily pill that lowers testosterone from the start, and testosterone returned faster after stopping in HERO.
?Is there a generic?
Not on sale: FDA's September 2, 2026 approval of a Sandoz tablet is tentative, which does not allow marketing.
?How fast does it lower testosterone?
In HERO, 56% of men were castrate by day 4 on relugolix against none on leuprolide.
?Can it be taken with abiraterone or apalutamide?
A 52-week study in 48 men found both combinations kept testosterone at castrate levels; with apalutamide the relugolix dose was doubled to 240 mg.
?Does Myfembree work as contraception?
It stopped ovulation in all 67 healthy women who completed 84 days in one study, but the label's own contraception advice is what applies.
?How long can women take it?
The Myfembree label limits use to 24 months because of bone loss.
?Does it raise the risk of blood clots?
Myfembree carries a boxed warning for clots, stroke and heart attack; a 2026 review of trials and real-world data found no significant rise in venous clots so far.
References
- [fda-pi] Orgovyx (relugolix) tablets US prescribing information (DailyMed version 12, effective October 10, 2025); read October 1, 2026.
- [fda-pi] Myfembree (relugolix, estradiol and norethindrone acetate) tablets US prescribing information (DailyMed version 18, effective September 4, 2025); read October 1, 2026.
- [clinical-trial] Shore ND, et al. "Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer." N Engl J Med, 2020;382(23):2187-2196. PMID: 32469183.
- [clinical-trial] Al-Hendy A, et al. "Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy." N Engl J Med, 2021;384(7):630-642. PMID: 33596357.
- [clinical-trial] Giudice LC, 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. PMID: 35717987.
- [clinical-trial] Becker CM, et al. "Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study." Hum Reprod, 2024;39(3):526-537. PMID: 38243752.
- [review] Douxfils J, et al. "Venous Thromboembolism Risk Associated With Relugolix-estradiol-norethisterone Acetate Combination Therapy." J Endocr Soc, 2026;10(2):bvaf190. PMID: 41623901.
- [clinical-trial] Lukes AS, et al. "Achieving Minimal-to-No Pain in Women with Endometriosis Treated with Relugolix Combination Therapy: SPIRIT Extension Trial." Int J Womens Health, 2026;18:603470. PMID: 42719373.
- [clinical-trial] Duijkers IJM, et al. "Inhibition of ovulation and pharmacologic mechanism of action of relugolix combination therapy." Fertil Steril, 2025;124(2):344-354. PMID: 40118330.
- [clinical-trial] Kobori H, et al. "The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy: a randomized controlled noninferiority study (MyLacR study)." Fertil Steril, 2026;125(5):904-913. PMID: 41581744.
- [clinical-trial] De La Cerda J, et al. "Safety and Tolerability of Relugolix in Combination with Abiraterone or Apalutamide for Treatment of Patients with Advanced Prostate Cancer: Data from a 52-Week Clinical Trial." Target Oncol, 2025;20(3):503-517. PMID: 40180682.
Sources & Citations
Dosing, warnings and pharmacokinetics from the Orgovyx (version 12) and Myfembree (version 18) labels on DailyMed, read October 1, 2026; approvals from Drugs@FDA; studies from PubMed abstracts.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.