Key messages
-
In the management of endometriosis (a condition where tissue grows outside the womb), studies that compared a progesterone receptor modulator (PRM; a medicine that changes how the hormone progesterone acts in the body) against placebo (a 'dummy' treatment, or sham treatment, that does not contain any medicine but looks or tastes identical to the medicine being tested) found that a PRM called mifepristone may improve painful periods. However, it may cause hot flushes.
-
A PRM called gestrinone may be less effective than medicines known as gonadotropin-releasing hormone (GnRH) analogues (which reduce the amount of oestrogen made by the ovaries) for treating painful periods, but may improve pain during sex. Gestrinone may also cause fewer hot flushes. We do not know how gestrinone compares to a treatment called danazol in terms of pain not related to periods, painful periods or pain during sex. We do not know whether gestrinone or danazol causes more unwanted effects.
-
Future studies should compare progesterone receptor modulators with medicines currently used to treat endometriosis symptoms and focus on assessing pain using recognised and reliable methods. Larger, well-designed studies are also needed to assess the benefits and unwanted effects of progesterone receptor modulators other than mifepristone and gestrinone.
What is endometriosis?
Endometriosis is a condition where tissue similar to the lining of the womb (uterus) grows outside the womb. Endometriosis is oestrogen-dependent and thus is seen mainly during the reproductive years. It can cause pain in the tummy area (abdomen), generally during periods (menstruation) or associated with sexual intercourse.
Endometriosis is treated through different types of medical or surgical treatment. Progesterone receptor modulators (PRMs) are medicines that change how the hormone progesterone acts in the body. PRMs include mifepristone, gestrinone, ulipristal acetate, vilaprisan and asoprisnil. Because they can slow down or stop the growth of tissue in the lining of the uterus, they have been suggested as a treatment for endometriosis.
What did we want to find out?
We wanted to know whether, in patients with endometriosis, PRMs are better than placebo ('dummy' treatment), no treatment or other medical treatment for improving overall pain, pain during periods and pain during sexual intercourse.
We also wanted to know if these medications were safe by assessing unwanted effects experienced by patients, such as hot flushes and feeling sick (nausea).
What did we do?
We searched for studies that investigated the effectiveness of PRMs for symptoms associated with endometriosis and whether they caused unwanted effects. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We included nine studies involving 922 women aged 18 to 45 years. Most studies tested the PRMs mifepristone or gestrinone. One study tested asoprisnil, but the study was published only as a short summary without results that we could use. Two of the studies did not measure any of the effects we were interested in.
Main results
Progesterone receptor modulators versus placebo
When compared to a placebo, mifepristone:
-
may reduce painful periods after three months of treatment (based on 1 study of 342 women);
-
may cause more unwanted effects, such as hot flushes (1 study, 360 women);
-
may make little or no difference to nausea (1 study, 360 women); and
-
we are uncertain whether mifepristone reduces pain during sex (1 study, 223 women).
Progesterone receptor modulators versus other medical treatment
When compared to danazol, one study of 38 women showed that:
-
we do not know whether gestrinone improves pain symptoms after six months of treatment (1 study, 38 women);
-
we do not know whether gestrinone causes more or fewer hot flushes or makes no difference (2 studies, 302 women); and
-
gestrinone and danazol may cause similar rates of nausea, but the results are very uncertain (2 studies, 302 women).
When compared to a GnRH analogue (leuprorelin), one study of 55 women found that:
-
gestrinone may be less efficient in treating painful periods after six months of treatment (1 study, 55 women); but
-
gestrinone may reduce pain during sex (1 study, 52 women);
-
gestrinone may be similar to leuprorelin in terms of general pain experienced (1 study, 55 women);
-
gestrinone may cause fewer hot flushes and similar levels of nausea (1 study, 55 women).
What are the limitations of the evidence?
Our confidence in the evidence is low to very low, mainly because some studies had one or more of these problems:
-
they did not have many people taking part;
-
they focused on specific settings or populations;
-
they used methods likely to introduce errors in their results;
-
they did not clearly report how they were conducted;
-
they did not clearly report whether the people taking part knew which treatment they had received, which could have affected the study results.
How up to date is this evidence?
This review updates a previous review. The evidence is up to date to April 2026.
Read the full abstract
Background
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
Objectives
To assess the effectiveness and safety of progesterone receptor modulators (PRMs) in the management of endometriosis.
Search strategy
To identify studies, we searched online sources, including the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, ClinicalTrials.gov and the WHO (World Health Organization) trial registry up to 16 April 2026. We also checked reference lists and contacted study authors and experts.
Selection criteria
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
Data collection and analysis
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
Main results
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants).
Mifepristone versus placebo
One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.
At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present.
Mifepristone dose comparisons
Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia.
Gestrinone comparisons
Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.
Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).
When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).
Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present.
Asoprisnil versus placebo
One study (n = 130) made this comparison but did not report data suitable for analysis.
Ulipristal versus leuprolide acetate
One study (n = 38) made this comparison but did not report data suitable for analysis.
Authors' conclusions
Mifepristone may improve dysmenorrhoea in women with endometriosis, but it might increase the prevalence of adverse events, such as hot flushes. The evidence is very uncertain regarding its effect on dyspareunia.
Gestrinone may be less effective than leuprorelin in treating dysmenorrhoea, but it may improve dyspareunia. It may be associated with lower rates of hot flushes and similar rates of nausea. We are uncertain about the effect of gestrinone compared to danazol.
We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Funding
This Cochrane review had no dedicated funding.
Registration
Protocol (2012) DOI: 10.1002/14651858.CD009881
Review (2017) DOI: 10.1002/14651858.CD009881.pub2
