Endometriosis affects 10-15% of women of reproductive age and is the most significant cause of chronic pelvic pain symptoms in women. Endometriosis pain generally arises from tissue damage at the lesion site, which correlates with the degree of infiltration of the lesion into the tissue. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), low-dose combined oral contraceptives (COCs), progestins, gonadotropin-releasing hormone (GnRH) agonists, and GnRH antagonists.
This meta-analysis compared medical treatments for endometriosis and ranked by highest effectiveness in relieving endometriosis pain symptoms. This meta-analysis included 36 RCT studies (n=7942) that examined the effectiveness of multiple endometriosis treatment regimens in adult women with symptoms of chronic pelvic pain due to endometriosis. The study compared gestrinone and danazol; compared mifepristone at different doses (2.5; 5; 10 mg) with placebo; comparing letrozole with aromatase inhibitors and danzole; comparing GnRH analogs such as nafarelin, goserelin, leuprolide acetate, and triptorelin; evaluate the addition of add-back hormonal therapy to the administration of GnRH agonists; compared elagolix (75, 150, and 200 mg) with a GnRH antagonist and placebo or subcutaneous medroxyprogesterone acetate (DMPA-SC); comparing DMPA-SC with dienogest and levonorgestrel-releasing intrauterine system (LNG-IUS), and evaluate the administration of COCs in endometriosis.
The results of the visual analog scale (VAS) score for pelvic pain at three months showed that the administration of dienogest therapy, COC, elagolix 150 mg, elagolix 250 mg, and COC showed the best pain resolution. If sorted by best based on p-score, then dienogest showed the best solution, followed by COC, elagolix 150 mg, then elagolix 250 mg. VAS scores after six months were shown in several studies in the form of comparisons of a placebo, GnRH analogs, LNG-IUS, and dienogest. The best resolution results based on the highest p-score were GnRH analog, followed by LNG-IUS, dienogest, desogestrel, and placebo.
Changes in dysmenorrhoea score at three months showed that GnRH analogs significantly improved dysmenorrhoea scores compared to danazol, elagolix (250, 150, and 75 mg), DMPA-SC, and placebo. DMPA-SC and elagolix also significantly improved dysmenorrhoea scores when compared to placebo. GnRH analogs led the order of highest effectiveness based on p-scores at three months, followed by danazol, elagolix 150 mg, and elagolix 250 mg. Changes in dysmenorrhoea scores after six months of therapy showed that COC and GnRH analogs decreased scores significantly compared to all doses of elagolix, GnRH with add-back treatment, DMPA-SC, danazol, and placebo. Elagolix with a dose of 250 mg was better than doses of 150 and 75 mg and better than danazol and placebo in reducing dysmenorrhoea scores. COCs led the highest order by p-score, followed by GnRH analogs, elagolix 250 mg, GnRH analogs with add-back therapy, desogestrel, and DMPA-SC.
The results of the non-menstrual pelvic pain score parameter study showed that the best effectiveness based on the p-score was GnRH analogue, followed by elagolix 150 mg, elagolix 75 mg, DMPA-SC, placebo, and lastly, danazol. After six months, the order of highest effectiveness was desogestrel, followed by COC, elagolix 250 mg, elagolix 150 mg, elagolix 75 mg, DMPA-SC, placebo, then followed by dienogest, GnRH analog, GnRH analog with add-back therapy, and Finally, danazol.
Several studies assessed the reuse of analgesic agents within three months of therapy. The use of dienogest and elaolix 250 mg was associated with the most use of analgesics compared to elagolix 150 mg and placebo. Pain symptom recurrence was also compared in several studies with results that did not show significant differences. However, in the best order, GnRH analogs have the lowest pain recurrence compared to gestrinone and danazol. Several studies reported the discontinuation of therapy due to adverse events and compared in 2 network meta-analyses (NMA). The highest order of discontinuation of treatment due to side effects was led by placebo, followed by elagolix 150 mg, elagolix 75 mg, elagolix 250 mg, dienogest, GnRH analogs, DMPA-SC, and the best was COC. The second NMA compared the three treatment regimens, with the best-being gestrinone, followed by danazol, and GnRH analogs being the worst at discontinuing therapy due to side effects.
Improvements in QoL have also been reported, two studies suggesting that medroxyprogesterone acetate and leuprolide acetate have been shown to increase QoL by relieving endometriosis-associated pain. Dienogest was also associated with better QoL improvement than leuprolide acetate and placebo. Other studies have shown that GnRH analogs, diet therapy, and oral monophasic contraceptives provide significant QoL improvements compared to placebo. Research on elagolix also mentions elagolix in doses of 150 mg and 250 mg, which improves QoL.
Based on the results of this meta-analysis, it concludes that the medical therapy for pain due to endometriosis has the highest effectiveness, followed by COC, followed by GnRH analogs, progesterone, and elagolix. In addition, this study did not show any benefit from the use of NSAIDs.
Image: Illustration (Photo by Ivan Samkov from Pexels)
Reference:
Samy A, Taher A, Sileem SA, Abdelhakim AM, Fathi M, Haggag H, et al. Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials. Journal of Gynecology Obstetrics and Human Reproduction. 2020;50(1):101798.
