GnRH drugs for fibroids
In placebo-controlled trials of women with fibroids, about 70% on relugolix or elagolix with add-back hormones reached normal blood loss, against 9% to 19% on placebo, and more anemic women gained 2 g/dL of hemoglobin. Leuprolide shrank the uterus before surgery. Bleeding returned within weeks of stopping. Without add-back, bone density fell about 5 to 6% a year.
Add to Bio HackChecked 2026-11-13
- Status
- Prescription drugs in the US. Myfembree (relugolix with estradiol and norethindrone acetate) is FDA-approved for heavy menstrual bleeding from fibroids and for moderate to severe endometriosis pain in premenopausal women, and Oriahnn (elagolix with estradiol and norethindrone acetate) for heavy menstrual bleeding from fibroids. Both labels limit use to 24 months because of bone loss and carry a boxed warning on clots and vascular events. Lupron Depot 3.75 mg, with iron, is FDA-approved to improve anemia from fibroids before surgery when 3 months of hormonal suppression is judged necessary.
- Also called
- GnRH antagonist, GnRH agonist, gonadotropin-releasing hormone antagonist, gonadotropin-releasing hormone agonist, relugolix, relugolix combination therapy, relugolix estradiol norethindrone acetate, Myfembree, Ryeqo, elagolix, elagolix estradiol norethindrone acetate, Oriahnn, Orilissa, leuprolide, leuprorelin, leuprolide acetate, Lupron Depot, add-back therapy
- Taken for
- heavy periods from fibroids, fibroid bleeding, anemia from fibroids, shrinking fibroids before surgery, fibroid pain, avoiding or delaying surgery, endometriosis pain
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help8
- StrongShown to bring blood loss under 80 mL, with at least a 50% drop, in 69% to 77% of women with fibroids, against 9% to 11% on placebo.Very common
- StrongShown to cut spine bone loss from about 5 to 6% to about 1 to 1.5% over a year when estrogen and progestin add-back accompanied elagolix or leuprolide.
- ModerateShown to bring blood loss under 80 mL with at least a 50% drop in about 72% of women with fibroids, against 15% to 19% on placebo, over 24 weeks.Very common
- ModerateShown to raise hemoglobin by more than 2 g/dL in 44% and 55% of anemic women with fibroids, against 17% and 6% on placebo, in two trials.Very common
- ModerateShown to raise hemoglobin by more than 2 g/dL in 50% and 62% of anemic women with fibroids, against 16% and 21% on placebo, in two trials.Very common
- ModerateShown to raise hemoglobin before fibroid surgery, by about 0.9 g/dL against placebo or no treatment, and with iron 75% reached target levels against 49% on iron alone.Very common
- ModerateShown to shrink the uterus by about 175 mL before surgery against placebo or no treatment, with fewer transfusions and complications at hysterectomy. Fibroids regrew after stopping.
- LimitedOne trial found 70% still had blood loss under 80 mL after 2 years on relugolix combination therapy. After switching to placebo, 88% relapsed, at a median of 5.9 weeks.
Reported risks11
- StrongShown to lower bone density, more over time. With add-back, spine density fell 0.8% to 1.5% at 12 months, and stayed below baseline 12 months after stopping elagolix.Very common
- ModerateShown to raise hot flashes: 22% on Oriahnn against 9% on placebo, 11% on Myfembree against 7%, and 73% on leuprolide without add-back against 18%.Very common
- ModerateShown to raise total and LDL cholesterol in women. On Myfembree, 13.7% with normal cholesterol rose to 200 to 239 mg/dL, against 7.7% on placebo.Very common
- ModerateShown to raise low mood: depression in 2.4% on Myfembree against 0.8% on placebo, and 3% on Oriahnn against 1%. The labels warn of suicidal ideation.Common
- ModerateShown to raise blood pressure in some women: new or worse hypertension in 7.0% on Myfembree against 0.8% on placebo in one trial.Common
- ModerateShown to raise hair loss or thinning: 3.5% on both Myfembree and Oriahnn, against 0.8% and 1.0% on placebo. Whether it reverses is unknown.Common
- ModerateShown to raise ALT or AST to 3 times normal or more in about 1% of women on Oriahnn and under 1% on Myfembree, against 0% to 0.4% on placebo.Common
- LimitedFDA boxed warning: estrogen and progestin combinations, including Myfembree and Oriahnn, raise the risk of clots, stroke and heart attack. Two clots occurred in 453 women on Oriahnn.Uncommon
- LimitedCase reports: on Myfembree, one woman had a fibroid expelled and one had a fibroid prolapse, each 0.4% of those treated, in the fibroid trials.Uncommon
- LimitedCase reports: two breast cancers were diagnosed in 453 women on Oriahnn, 0.4%, and none on placebo. The label contraindicates use with a history of breast cancer.Uncommon
- LimitedThe Myfembree label says to avoid hormonal contraceptives during treatment, as estrogen-containing methods may raise estrogen side effects and lower the drug's effect.How often is not known
What people take it for, and what was found
Shown to help8
Heavy bleeding with fibroids: relugolix combination (Myfembree)
Shown to bring blood loss under 80 mL with at least a 50% drop in about 72% of women with fibroids, against 15% to 19% on placebo, over 24 weeks.
Compared with placebo [1][2]; controls the source abstract does not describe [3]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In LIBERTY 1 and 2, 73% and 71% on relugolix combination therapy responded (blood loss under 80 mL and at least 50% lower), against 19% and 15% on placebo [1]. The label gives 72.1% against 16.8% and 71.2% against 14.7%. Amenorrhea occurred in 50.0% and 50.4% against 6.2% and 3.1%, and mean blood loss fell 82.0% and 84.3% from baseline against 19.1% and 15.1% [2]. A meta-analysis of 6 studies found 31 times the odds of amenorrhea against controls, with 63% of patients reaching amenorrhea [3].
- Population
- 770 premenopausal women with fibroids and blood loss of 80 mL or more a cycle, median age 43, about half Black, for 24 weeks [1][2]; 511 participants in 6 studies [3].
- Sources
- [1], [2], [3]
- Caveats
- The pivotal trials were funded by the manufacturer [1]. The meta-analysis pooled relugolix with and without add-back hormones [3].
Anemia with fibroids: relugolix combination
Shown to raise hemoglobin by more than 2 g/dL in 44% and 55% of anemic women with fibroids, against 17% and 6% on placebo, in two trials.
Compared with placebo [2]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Among women with hemoglobin of 10.5 g/dL or less at the start, 44.2% (L1) and 55.0% (L2) on relugolix combination therapy gained more than 2 g/dL by week 24, against 17.2% and 5.7% on placebo [2]. A meta-analysis reported hemoglobin improved in 46.3% of patients [3].
- Population
- 43 and 40 anemic women on treatment against 29 and 53 on placebo, within 770 women [2]; 511 participants in 6 studies [3].
- Sources
- [2], [3]
- Caveats
- Iron was required for women with hemoglobin of 8 to 10 g/dL, and women under 8 g/dL were excluded [2].
Staying on relugolix for 2 years, or stopping
One trial found 70% still had blood loss under 80 mL after 2 years on relugolix combination therapy. After switching to placebo, 88% relapsed, at a median of 5.9 weeks.
Compared with stopping treatment by switching to placebo [4]
The numbers and sources
- Effect
- Among women who had responded over 52 weeks, 78.4% who continued relugolix combination therapy kept blood loss under 80 mL through week 76 against 15.1% switched to placebo, and 69.8% against 11.8% at week 104. Through week 104, 88.3% on placebo relapsed into heavy bleeding, at a median of 5.9 weeks, and 87 of 89 who restarted responded again. Amenorrhea at week 104 was 58.3% against 10.6% [4].
- Population
- 229 women with fibroids and heavy bleeding who had responded in LIBERTY 1, 2 and the extension [4].
- Sources
- [4]
- Caveats
- Only women who had already responded were randomized. Manufacturer-sponsored trial.
Heavy bleeding with fibroids: elagolix with add-back (Oriahnn)
Shown to bring blood loss under 80 mL, with at least a 50% drop, in 69% to 77% of women with fibroids, against 9% to 11% on placebo.
Compared with placebo [5][6][7][8]; elagolix without add-back hormones [5][7]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In Elaris UF-1 and UF-2, 68.5% and 76.5% on elagolix with add-back responded against 8.7% and 10% on placebo, and 84.1% and 77% on elagolix alone [5]. Mean blood loss fell 177 mL and 169 mL against a 1 mL rise and a 4 mL fall on placebo, and 57% and 61% had no bleeding in the final month against 4% and 5% [6]. Pooled, elagolix raised the chance of blood loss under 80 mL (RR 4.81, 95% CI 2.45 to 9.45) and of a 50% drop (RR 4.87) against placebo. Elagolix alone and with add-back did not differ for blood loss under 80 mL (RR 1.08, 95% CI 1.00 to 1.16) [7]. A second meta-analysis found the same direction against placebo [8]. In an extension, 87.9% met the end point after 12 months [9].
- Population
- 790 premenopausal women with fibroids and blood loss over 80 mL, median age 43, 68% Black [5][6]; 4 trials with 1,949 women [7]; 4 trials in 1,217 patients [8]; 218 women treated 12 months [9].
- Sources
- [5], [6], [7], [8], [9]
- Caveats
- The trials were funded by the manufacturer [5][9]. The two meta-analyses draw on the same pivotal trials [7][8]. The 12-month extension had no placebo arm [9].
Anemia with fibroids: elagolix with add-back
Shown to raise hemoglobin by more than 2 g/dL in 50% and 62% of anemic women with fibroids, against 16% and 21% on placebo, in two trials.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Among women with hemoglobin of 10.5 g/dL or less, 62% (UF-1) and 50% (UF-2) on elagolix with add-back gained more than 2 g/dL by month 6, against 16% and 21% on placebo. Over 90% of these women took iron [6]. A meta-analysis found more women met the hemoglobin end point on elagolix than on placebo [8].
- Population
- 52 and 48 anemic women on treatment against 31 and 24 on placebo [6]; 1,217 patients in 4 trials [8].
- Sources
- [6], [8]
- Caveats
- Nearly all anemic women also took iron, so the rise reflects the drug on top of iron [6].
Anemia before fibroid surgery: leuprolide and other GnRH agonists
Shown to raise hemoglobin before fibroid surgery, by about 0.9 g/dL against placebo or no treatment, and with iron 75% reached target levels against 49% on iron alone.
Compared with iron alone [10]; placebo or no pretreatment [11]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In women with hematocrit of 30% or less or hemoglobin of 10.2 g/dL or less, Lupron Depot 3.75 mg monthly with iron raised hemoglobin by a mean 4.2 g/dL and hematocrit by 10.1% at 3 months. At week 12, 75% on leuprolide with iron reached hematocrit of 36% and hemoglobin of 12 g/dL, against 49% on iron alone [10]. Across 10 trials of GnRH agonists before surgery, preoperative hemoglobin rose 0.88 g/dL more than with placebo or no pretreatment (95% CI 0.68 to 1.08, I² 0%, moderate certainty) [11].
- Population
- 104 women on leuprolide with iron and 98 on iron alone [10]; 834 premenopausal women in 10 trials [11].
- Sources
- [10], [11]
- Caveats
- The Cochrane review pools GnRH agonists as a class, not leuprolide alone [11]. The label notes some women may benefit from iron alone or from 1 to 2 months of treatment [10].
Fibroid and uterine size, and surgery: GnRH agonists
Shown to shrink the uterus by about 175 mL before surgery against placebo or no treatment, with fewer transfusions and complications at hysterectomy. Fibroids regrew after stopping.
Compared with placebo or no pretreatment [11]; other medicines before surgery, including ulipristal [11]
The numbers and sources
- Effect
- GnRH agonists before surgery cut uterine volume by 175.34 mL (95% CI 131.65 to 219.04, 13 studies, 858 women) and fibroid volume by 5.7 to 155.4 mL. At hysterectomy, surgery was 10.11 minutes shorter, blood transfusions were fewer (OR 0.54, 95% CI 0.29 to 1.01) and postoperative complications fewer (OR 0.54, 95% CI 0.32 to 0.91). Before myomectomy, transfusions and complications did not clearly differ. Uterine volume fell 47% on GnRH agonists against 20% and 22% on 5 mg and 10 mg ulipristal [11]. In the label trials, leuprolide cut uterine volume 41% and myoma volume 37%, and mean time back to the pretreatment uterine size was 8.3 months after stopping [10].
- Population
- 41 RCTs with 3,982 premenopausal women having myomectomy, hysterectomy or hysteroscopic resection [11]; women in 4 leuprolide trials, 46 followed after stopping [10].
- Sources
- [11], [10]
- Caveats
- Most results are low certainty, from trials with poor reporting and no blinding [11].
Add-back hormones and bone during GnRH treatment
Shown to cut spine bone loss from about 5 to 6% to about 1 to 1.5% over a year when estrogen and progestin add-back accompanied elagolix or leuprolide.
Compared with the same GnRH drug without add-back [7][9][10][12]
The numbers and sources
- Effect
- After 12 months, lumbar spine bone density fell 4.8% on elagolix alone and 1.5% on elagolix with add-back (difference -3.3, 95% CI -4.1 to -2.5) [9]. More women lost bone density on elagolix alone than with estradiol and norethindrone acetate [7]. On leuprolide alone, spine density fell 3.2% at 24 weeks and 6.3% at 52 weeks, against 0.3% and 1.0% with norethindrone acetate 5 mg a day [10]. With GnRH agonists for fibroids, tibolone (SMD 0.36, 3 studies), raloxifene (SMD 1.01, 1 study) and estriol and ipriflavone (single studies) limited bone loss, while tibolone was linked to larger uterine volume and more bleeding [12].
- Population
- Women with fibroids in elagolix trials [7][9]; women with endometriosis in the leuprolide add-back trials, 29 to 115 per arm [10]; 622 women with fibroids in 12 add-back trials [12].
- Sources
- [9], [7], [10], [12]
- Caveats
- The leuprolide add-back data come from endometriosis trials, and the Lupron Depot label states it is not indicated with norethindrone acetate add-back for fibroid anemia [10]. Add-back trials followed women for up to 6 months, too short to measure fractures [12].
Mixed results1
Fibroid pain and fibroid size: relugolix
Shown to ease fibroid pain and shrink the uterus against placebo. Relugolix combination therapy did not shrink the fibroids themselves, while relugolix alone did.
The numbers and sources
- Effect
- Relugolix combination therapy improved pain, distress from bleeding and pelvic discomfort, and uterine volume against placebo, but not fibroid volume [1]. Pooled across 6 studies, myoma volume fell 28.50% more than on placebo and uterine volume also fell more (reported as -30.31, p = 0.0028), with higher odds of pain relief (OR 9.02). Relugolix alone shrank myomas and the uterus more than combination therapy [3].
- Population
- 770 premenopausal women with fibroids [1]; 511 participants in 6 studies [3].
- Sources
- [1], [3]
- Caveats
- The pooled size results mix relugolix alone, which is not the US-approved form, with combination therapy [3].
Doses studied
The relugolix trials used relugolix 40 mg with estradiol 1 mg and norethindrone acetate 0.5 mg once daily for 24 weeks, or relugolix 40 mg alone for 12 weeks followed by the combination [1][2]. The elagolix trials used elagolix 300 mg twice daily with estradiol 1 mg and norethindrone acetate 0.5 mg once daily, for 6 months and up to 12 months, with an elagolix-alone arm at the same dose [5][9]. The leuprolide fibroid trials used Lupron Depot 3.75 mg by monthly intramuscular injection for 3 to 6 months, with iron in the anemia trial [10]. The leuprolide add-back trials used norethindrone acetate 5 mg daily for up to 12 months [10].
Risks
Reported risks11
Bone density loss
Shown to lower bone density, more over time. With add-back, spine density fell 0.8% to 1.5% at 12 months, and stayed below baseline 12 months after stopping elagolix.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- On Myfembree, lumbar spine density changed -0.23% against +0.18% on placebo at 6 months, and -0.80% at 12 months. A drop of more than 3% at 12 months occurred in 23% on Myfembree and in 17.4% of untreated women with fibroids in an observational cohort. Four women on Myfembree had low-trauma fractures [2]. On Oriahnn, spine density fell 0.7% against 0.1% on placebo at 6 months, and 1.5% at 12 months, with a drop of more than 3% in 27%. Twelve months after stopping, spine density was still 0.72% below baseline, and loss continued in 24%, partly recovered in 46% and fully recovered in 30%. Fractures occurred in 7 of 453 women on Oriahnn (1.5%) and 1 of 196 on placebo (0.5%) [6]. Without add-back, spine density fell 4.8% at 12 months on elagolix [9], 2.7% after 3 months of leuprolide in a fibroid trial, and 6.3% at 52 weeks of leuprolide in endometriosis trials [10]. Pooled trials found more bone loss on elagolix than on placebo [7][8].
- Population
- 254 women on Myfembree and 256 on placebo, 163 followed to 12 months [2]; 305 women on Oriahnn and 150 on placebo, 175 at 12 months [6]; women in the elagolix, leuprolide and pooled trials [7][8][9][10].
- Sources
- [2], [6], [9], [10], [7], [8]
- Caveats
- Both labels state the effect of these losses on long-term bone health and fracture risk in premenopausal women is unknown, and limit use to 24 months [2][6].
Hot flashes
Shown to raise hot flashes: 22% on Oriahnn against 9% on placebo, 11% on Myfembree against 7%, and 73% on leuprolide without add-back against 18%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Hot flushes affected 22% on Oriahnn and 9% on placebo [6], vasomotor symptoms 10.6% on Myfembree and 6.6% on placebo [2], and hot flashes or sweats 73% on leuprolide and 18% on placebo in fibroid trials [10]. GnRH agonists before surgery raised adverse events overall against placebo or no pretreatment (OR 2.78, 95% CI 1.77 to 4.36) and hot flushes against other medicines (OR 2.83) [11].
- Population
- 395 women on Oriahnn and 196 on placebo [6]; 254 on Myfembree and 256 on placebo [2]; 166 on leuprolide and 163 on placebo [10]; 41 trials before surgery [11].
- Sources
- [6], [2], [10], [11]
- Caveats
- Leuprolide rates come from trials without add-back hormones [10].
Cholesterol rises
Shown to raise total and LDL cholesterol in women. On Myfembree, 13.7% with normal cholesterol rose to 200 to 239 mg/dL, against 7.7% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Among women with total cholesterol under 200 mg/dL, 13.7% on Myfembree rose to 200 to 239 mg/dL and 1.7% to 240 or above, against 7.7% and 0.6% on placebo. LDL rose to 130 to 159 mg/dL in 9.3% against 6.5% [2]. On Oriahnn, total cholesterol, LDL, triglycerides and apolipoprotein B rose, and 9 of 54 women with LDL of 130 to 159 mg/dL rose to 190 or above, against none on placebo [6]. On leuprolide, mean cholesterol rose 11 to 29 mg/dL in women with fibroids [10].
- Population
- Premenopausal women with fibroids in the placebo-controlled trials [2][6][10].
- Sources
- [2], [6], [10]
- Caveats
- Shifts between bands, measured at the end of 6-month trials.
Mood changes and depression
Shown to raise low mood: depression in 2.4% on Myfembree against 0.8% on placebo, and 3% on Oriahnn against 1%. The labels warn of suicidal ideation.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- On Myfembree, depression was reported by 2.4% against 0.8% on placebo, irritability by 2.4% against 0%, and anxiety by 1.2% against 0.8%. Suicidal ideation was reported in endometriosis trials, all in women with a history of depression or anxiety [2]. On Oriahnn, depression, depressed mood or tearfulness affected 3% against 1%, and one woman taking lower-dose elagolix for another condition died by suicide [6]. On leuprolide, depression or emotional lability affected 11% against 4% on placebo [10].
- Population
- Women in the placebo-controlled fibroid trials [2][6][10].
- Sources
- [2], [6], [10]
- Caveats
- Single suicide cases cannot give a rate.
Raised blood pressure
Shown to raise blood pressure in some women: new or worse hypertension in 7.0% on Myfembree against 0.8% on placebo in one trial.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- In LIBERTY 1, new or worsening hypertension occurred in 7.0% on Myfembree against 0.8% on placebo [2]. On Oriahnn, systolic pressure rose a mean 5.1 mm Hg more than placebo (95% CI 2.68 to 7.59), and systolic pressure of 160 or above occurred in 7.1% against 3.7% [6].
- Population
- Women in the placebo-controlled fibroid trials [2][6].
- Sources
- [2], [6]
- Caveats
- The label reports the hypertension excess in one of the two trials, LIBERTY 1 [2].
Hair loss
Shown to raise hair loss or thinning: 3.5% on both Myfembree and Oriahnn, against 0.8% and 1.0% on placebo. Whether it reverses is unknown.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- Hair loss or thinning affected 3.5% on Myfembree and 0.8% on placebo [2], and 3.5% on Oriahnn and 1.0% on placebo, where 4 of 14 affected women stopped treatment and 2 still had hair loss 12 months after stopping [6].
- Population
- Women in the placebo-controlled fibroid trials [2][6].
- Sources
- [2], [6]
- Caveats
- Small numbers of affected women.
Liver enzyme rises
Shown to raise ALT or AST to 3 times normal or more in about 1% of women on Oriahnn and under 1% on Myfembree, against 0% to 0.4% on placebo.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- ALT rose to 3 times the upper limit or more in 1.1% (4 of 379) on Oriahnn and AST in 1.3% (5 of 379), against none on placebo, peaking at 8 and 6 times the limit, and returning to baseline within 4 months [6]. On Myfembree in fibroid trials, ALT rose in 0.4% (1 of 254) and AST in 0.8% (2 of 254), against 0% and 0.4% on placebo [2]. On leuprolide, 3% of women with fibroids had post-treatment transaminases at least twice baseline and above normal [10].
- Population
- Premenopausal women with fibroids in the placebo-controlled trials [2][6][10].
- Sources
- [6], [2], [10]
- Caveats
- Few events. Both labels contraindicate use in liver disease [2][6].
Boxed warning: clots, stroke and heart attack (Myfembree, Oriahnn)
FDA boxed warning: estrogen and progestin combinations, including Myfembree and Oriahnn, raise the risk of clots, stroke and heart attack. Two clots occurred in 453 women on Oriahnn.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- Both labels state that estrogen and progestin combinations increase the risk of pulmonary embolism, deep vein thrombosis, stroke and heart attack, especially in women over 35 who smoke and women with uncontrolled high blood pressure, and contraindicate use in women with past or current clots [2][6]. In the elagolix fibroid trials, 2 of 453 women (0.4%) on Oriahnn had a clot, one in the calf and one pulmonary embolism [6]. On Myfembree, one woman treated for endometriosis had a deep vein thrombosis and a pulmonary embolism after 38 days [2].
- Population
- 453 women on Oriahnn in 3 trials [6]; women in the Myfembree trials [2].
- Sources
- [2], [6]
- Caveats
- The trials were too small to measure a rate against placebo. The warning rests on the estrogen and progestin component.
Fibroid prolapse or expulsion
Case reports: on Myfembree, one woman had a fibroid expelled and one had a fibroid prolapse, each 0.4% of those treated, in the fibroid trials.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- Serious reactions on Myfembree included one uterine myoma expulsion with heavy bleeding and one fibroid prolapse, each 0.4% of 254 women. The label advises women with submucosal fibroids of this possibility [2].
- Population
- 254 women on Myfembree in LIBERTY 1 and 2 [2].
- Sources
- [2]
- Caveats
- Single events.
Breast cancer cases on Oriahnn
Case reports: two breast cancers were diagnosed in 453 women on Oriahnn, 0.4%, and none on placebo. The label contraindicates use with a history of breast cancer.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- Two of 453 women on Oriahnn (0.4%) were diagnosed with breast cancer during the trials, one after 34 days of extension treatment, and none on placebo [6].
- Population
- 453 women on Oriahnn in 3 trials [6].
- Sources
- [6]
- Caveats
- Two cases cannot show cause. Short trials.
Use with hormonal birth control
The Myfembree label says to avoid hormonal contraceptives during treatment, as estrogen-containing methods may raise estrogen side effects and lower the drug's effect.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The Myfembree label directs stopping hormonal contraceptives before starting, and using non-hormonal contraception during treatment and for one week after [2]. The Oriahnn label states the effect of hormonal contraceptives on its efficacy is unknown and directs non-hormonal contraception during treatment and for 28 days after [6].
- Population
- Label statements [2][6].
- Sources
- [2], [6]
- Caveats
- No trial measured the combination.
Possible, not studied in people1
Pregnancy
Not studied in people. Relugolix caused pregnancy loss in rabbits, and both combination labels contraindicate use in pregnancy. Reduced bleeding can delay noticing a pregnancy.
No study in people. This rests on animal studies, how it acts in the body.
The numbers and sources
- Effect
- In pregnant rabbits, relugolix caused spontaneous abortion and total litter loss at about half the human exposure, with no fetal malformations in rabbits or rats [2]. The labels state limited human data are insufficient to evaluate risk, that the drugs may cause early pregnancy loss, and that amenorrhea may delay recognizing pregnancy [2][6]. The Lupron Depot label also warns of embryo-fetal toxicity [10].
- Population
- Rabbits and rats [2]; label statements [6][10].
- Sources
- [2], [6], [10]
- Caveats
- Animal findings do not show what happens in human pregnancy.
Claims tested and not found
- That relugolix combination therapy shrinks fibroids. In LIBERTY 1 and 2, fibroid volume did not change significantly against placebo, although uterine volume did [1].
- That bleeding stays controlled after stopping. After switching responders to placebo, 88.3% relapsed into heavy bleeding, at a median of 5.9 weeks [4].
Related
Sources
- Al-Hendy A, Lukes AS, Poindexter AN, et al. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. New England Journal of Medicine. 2021. https://doi.org/10.1056/nejmoa2008283
- US Food and Drug Administration label. MYFEMBREE (relugolix, estradiol, and norethindrone acetate) tablets. DailyMed. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8
- Kalpina F, Kumar D, Taj J, et al. Efficacy and safety of relugolix therapy for symptomatic uterine fibroids: a systematic review and meta-analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2026. https://doi.org/10.1016/j.ejogrb.2025.114889
- Al-Hendy A, Venturella R, Arjona Ferreira JC, et al. LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. American Journal of Obstetrics and Gynecology. 2023. https://doi.org/10.1016/j.ajog.2023.08.030
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