Key messages
• Progestagens (synthetic sex hormones) taken by mouth (orally) probably reduce pain symptoms associated with endometriosis better than a placebo (dummy treatment). How much progestagens reduce pain symptoms depends on the type of pain and duration of treatment. Comparisons of oral progestagens with other hormonal treatment strategies show inconclusive results for overall pain, pelvic pain, painful periods, and painful sex.
• Comparisons of depot (long-acting injectable) progestagens with oral contraceptives, gonadotrophin releasing hormone (GnRH) therapy (GnRH agonists and antagonists, which work by reducing oestrogen and progesterone levels), the levonorgestrel-releasing intrauterine device (a small device inserted into the womb that releases the progestagen levonorgestrel), and the etonogestrel contraceptive implant (a small plastic rod placed under the skin of the arm) show inconclusive results for overall pain, pelvic pain, painful periods, and painful sex. Depot progestagens probably have fewer unwanted effects compared with GnRH agonists. There were no clear differences in unwanted effects when depot progestagens were compared with other treatments.
• Despite limitations, the review highlights the need for additional research into endometriosis treatment.
What is endometriosis?
Endometriosis is a condition where tissue similar to the lining of the womb (uterus) grows in other parts of the body. It affects 5% to 10% of women of reproductive age and an unknown number of gender-diverse individuals. Endometriosis often causes pain, especially during periods. Hormonal pills, injections, or implants – called progestagens – are being studied as treatments. They may shrink hidden growths of endometriosis.
What did we want to find out?
We wanted to know how well progestagens work in people with endometriosis. Specifically, we were interested in the effect of progestagens on pain, quality of life, and patient satisfaction. We also wanted to know if progestagens had any unwanted effects.
What did we do?
We searched for studies that evaluated progestagens against placebo (dummy treatment) or other medicines in people with symptomatic endometriosis. The study selection and analysis involved multiple review authors and tools.
What did we find?
We found 33 trials that recruited 5059 people with endometriosis.
The following findings are limited by the small number of studies for each comparison and each outcome.
• Compared with placebo, oral progestagens likely reduce overall pain at six months and period pain at three months.
• Compared with oral contraceptives and GnRH agonists, oral progestagens have no clear effect on reduction of pain, quality of life, and unwanted effects.
• Compared with GnRH agonists, depot progestagens reduce period pain but may have little to no effect on pelvic pain at six months. The risk of experiencing any unwanted effects is probably lower with depot progestagens than with GnRH agonists.
• Compared with GnRH antagonists, depot progestagens may have little to no effect on pain reduction or the risk of experiencing any unwanted effects. However, people receiving depot progestagens are probably more likely to withdraw from these studies because of unwanted effects.
• We are unsure about the effect of depot progestagens compared with the etonogestrel implant on pain, patient satisfaction, and adverse effects.
The findings suggest varying effectiveness of different progestagens on endometriosis symptoms, emphasising the need for further research.
What are the limitations of the evidence?
There were only a few studies in each comparison group. Many of the studies had few participants. Larger studies with more participants are needed to know whether these findings are conclusive.
How up to date is the evidence?
The evidence is current to 29 October 2024.
阅读完整摘要
Endometriosis is a hormone-sensitive inflammatory condition affecting between 5% and 10% of reproductive-aged women and an unknown number of gender-diverse individuals. It is often associated with debilitating pelvic pain symptoms. Various formulations of progestagens (e.g. oral, depot, implantable) have been studied as potential treatments for endometriosis because they induce atrophy of endometrial tissue.
研究目的
To determine the benefits and harms of progestagens in the treatment of endometriosis-associated pain symptoms.
检索策略
We searched CENTRAL, MEDLINE, Embase, and PsycINFO on 29 October 2024 without language restrictions.
纳入排除标准
We included randomised controlled trials (RCTs) comparing progestagens for symptomatic endometriosis against placebo, other medications, or different doses of progestagens. Studies assessing the levonorgestrel-releasing intrauterine device were ineligible, as a separate Cochrane review covers this intervention. Participants were of reproductive age with a laparoscopic diagnosis of endometriosis and associated pain symptoms. Primary outcomes included endometriosis-associated pain symptoms (overall pain, pelvic pain, and dysmenorrhoea). Secondary outcomes included quality of life, patient satisfaction, and adverse effects.
资料收集与分析
At least two review authors independently selected studies, extracted data, and assessed risk of bias. We reported dichotomous outcomes as risk ratios (RRs) and continuous outcomes as mean differences (MDs), each with its corresponding 95% confidence interval (CI). The meta-analysis employed a fixed-effect model, and we assessed statistical heterogeneity using the I2 statistic. We used GRADE to assess evidence certainty.
主要结果
We included 33 RCTs involving 5059 participants with symptomatic, laparoscopically diagnosed endometriosis. We judged 13 studies at overall low risk of bias.
The following comparisons are limited by the small number of studies reporting each outcome. Pain outcomes, quality of life, and patient satisfaction were measured at six months unless otherwise specified.
Oral progestagens versus placebo or no treatment (8 studies)
Oral progestagens compared with placebo probably reduce overall pain measured on a visual analogue scale (VAS; MD −2.58, 95% CI −3.13 to −2.03; moderate certainty), and probably reduce dysmenorrhoea at three months (RR 0.21, 95% CI 0.07 to 0.70, moderate certainty), but may have little to no effect on pelvic pain at three months (RR 0.7, 95% CI 0.29 to 1.69; low certainty). Oral progestagens improve quality of life (SF-36 score; MD 4.11, 95% CI 2.41 to 5.82, high certainty). There is probably little to no difference between the interventions in study withdrawal due to adverse effects (RR 2.36, CI 0.74 to 7.52, moderate certainty) and cumulative side effects (RR 1.18, 95% CI 0.94 to 1.46, moderate certainty).
Oral progestagens versus oral contraceptives (4 studies)
Oral progestagens compared with oral contraceptives probably have little to no effect on pelvic pain measured on a VAS (MD 0.38, 95% CI −0.46 to 1.22, moderate certainty). There was very low-certainty evidence about their effect on dysmenorrhoea at 12 months (MD −0.57, 95% CI −1.29 to 0.15), quality of life (SF-36 general health perception; MD 5.2, 95% CI −1.3 to 11.70), and patient satisfaction (RR 1.18, 95% CI 0.88 to 1.57). Oral progestagens may lead to better quality of life (SF-36 pain score; MD 11.5, 95% CI 2.35 to 20.65, low certainty). There may be little to no difference between oral progestagens and oral contraceptives in study withdrawal due to adverse effects (RR 0.75, 95% CI 0.27 to 2.07, low certainty), and there is probably little to no difference in cumulative side effects (RR 1.13, 95% CI 0.8 to 1.60, moderate certainty).
Oral progestagens versus gonadotropin-releasing hormone (GnRH) agonists (10 studies)
Oral progestagens compared with GnRH agonists may have little to no effect on overall pain measured on a VAS (MD −0.01, 95% CI −0.30 to 0.28), risk of pelvic pain (RR 1.12, 95% CI 0.80 to 1.59), dysmenorrhoea (RR 1.45, 95% CI 0.71 to 3.00), SF-36 physical health score (MD 0.40, 95% CI −1.58 to 2.38), SF-36 mental health score (MD −0.50, 95% CI −3.75 to 2.75), patient satisfaction (RR 1.08, 95% CI 0.92 to 1.26), and study withdrawal due to adverse effects (RR 0.9, 95% CI 0.34 to 2.43). All these outcomes had low-certainty evidence. The risk of cumulative side effects was probably higher with oral progestagens (RR 1.44, 95% CI 1.11 to 1.86, moderate certainty).
Depot progestagens versus GnRH agonists (2 studies)
Depot progestagens compared with GnRH agonists reduce dysmenorrhoea risk slightly (RR 0.93, 95% CI 0.89 to 0.97, high certainty) but may have little to no effect on pelvic pain (RR 0.96, 95% CI 0.87 to 1.07, low certainty). The interventions may be similar in study withdrawal due to adverse effects (RR 1.41, 95% CI 0.24 to 8.32, low certainty), but the risk of cumulative side effects is probably lower with depot progestagens (RR 0.03, 95% CI 0.01 to 0.11, moderate certainty).
Depot progestagens versus GnRH antagonist (1 study)
Depot progestagens compared with GNRH agonists may have little to no effect on pelvic pain (RR 0.85, 95% CI 0.7 to 1.03, low certainty), dysmenorrhoea (RR 0.85, 95% CI 0.7 to 1.03, low certainty), and cumulative adverse effects (RR 1.04, 0.95 to 1.14, low certainty). Study withdrawal due to side effects is likely higher with depot progestagens (RR 2.02, 95% CI 1.04 to 3.94, moderate certainty).
Depot progestagens versus the etonogestrel implant (1 study)
There was very low-certainty evidence about the effect of depot progestagens versus the etonogestrel implant on overall pain measured on a VAS (MD 0.80, 95% CI − 0.42 to 2.02), patient satisfaction (RR 0.96, 95% CI 0.56 to 1.66), and study withdrawal due to adverse effects (RR 1.84, 95% CI 0.63 to 5.33).
作者结论
In individuals with endometriosis, oral progestagens compared with placebo likely reduce overall pain and dysmenorrhoea and may reduce pelvic pain. Compared with other hormonal suppression strategies, the evidence is less certain due to the small number of studies for each comparison and outcome.
Despite such limitations, this update provides a comprehensive overview and valuable insights on progestagen treatment for endometriosis, emphasising the nuanced balance between efficacy, adverse effects, and patient satisfaction.
