ReviewMedical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials
Introduction
Endometriosis is a common gynecological disorder that usually affects adolescents and women in their reproductive age. The condition is characterized by the presence of functioning endometrial-like tissue or gland outside the uterine cavity, mainly in the ovary or peritoneal cavity [1]. According to previous epidemiological figures, the prevalence of endometriosis ranges between 10–15% among women aged 18–45 years; moreover, endometriosis accounted for about one-third of the causes of chronic pelvic pain [2]. Although endometriosis can be asymptomatic and discovered accidentally, the majority of the affected women present mainly with irregular menstrual bleeding, as well as menstrual and non-menstrual pelvic pain [3].
Endometriosis-related pain is a distressing chronic condition that can lead to disability and impaired quality of life (QoL); recent reports showed that chronic pain is a leading cause of hospitalization, impairment of different aspects of health-related QoL, and high economic burden in women with endometriosis [4,5]. Endometriosis pain usually arises from tissue damage at the site of lesions, and its severity may be correlated with the depth of infiltration of endometriosis; less likely, the pain can arise from nerve injury leading to neuropathic pain [6]. Different approaches have been proposed for relieving endometriosis-associated pain, including medical therapy, surgical interventions, and acupuncture [7,8].
The medical treatment represents the cornerstone for the management of endometriosis-related pain [9]; non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as first-line options in mild-to-moderate cases [10]. On the other hand, low-dose combined hormonal contraceptives (CHCs) and progestins are effective options for relieving chronic pelvic pain through inhibition of gonadal estrogen production and induction of pseudo-pregnancy state [9]. Both gonadotropin-releasing hormone (GnRH) agonists and antagonists exhibited an acceptable efficacy in reducing moderate to severe pain of endometriosis [11]. Nevertheless, there is scarcity in the published evidence that directly compares the efficacy of those different pharmacological interventions.
Therefore, the present network meta-analysis aimed to synthesize evidence regarding the most effective pharmacological interventions for relieving endometriosis-related pain.
Section snippets
Materials and methods
We run the present systematic review and network meta-analysis according to the recommended standards of the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 [12]. The manuscript was prepared in adherence to the recommendations of Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions (PRISMA-NMA) [13]. Because this study was a systematic review and network meta-analysis, formal ethical approval was not required.
Literature search results
We retrieved 9143 unique citations from the online bibliographic search. From which, 205 full texts were retained for full-text screening. Finally, 36 RCTs (patients no. = 7942) were included in the present systematic review and network meta-analysis.
Fig. 1 shows the PRISMA chart. The network plots illustrating direct evidence between interventions are shown in Supplementary Figs. 1 and 2.
Summary characteristics of included studies
All included studies recruited adult women with chronic pelvic pain due to endometriosis. The sample size
Discussion
There is a plethora of published literature regarding the safety and effectiveness of a wide range of pharmacological interventions for treating endometriosis-related pain. However, evidence that directly compares those different interventions is lacking. In the present network meta-analysis, dienogest, combined hormonal contraceptives (CHCs), and elagolix were the highest-ranked interventions for reducing the severity of pelvic pain at three months, while at six months, GnRH analogues,
Conclusions
The present network meta-analysis showed that CHCs, GnRH analogues, progesterone, and elagolix were the highest-ranked medical options for the management of endometriosis-related pain. Moreover, the pooled analysis did not support the use of NSAIDs, despite their current widespread use. The current published literature is limited by the small number of RCTs in some of the treatment arms, which may limit the confidence in our findings.
Authors contributions
Study Design and Concepts: Ahmed Samy, Ayman Taher, and Sileem A.Sileem.
Data Collection: Ahmed Mohamed Abdelhakim, Mohamed Fathi, Hisham Haggag, Moutaz Elsherbini, Khaled Ashour, and Shady Abdelsattar Ahmed,
Drafting of manuscript: Ahmed Samy, Mohammad Abrar Shareef, Abdulhadi A. AlAmodi, Nawal Hamdy Ahmed Keshta, Hanan Barakat Abu Elyazid Shatat, Doaa M Salah, Ahmed Said Ali, and Eman Abdel Monem El Kattan.
Revision and critical appraisal: Ahmed Samy, Ayman Taher, Sileem A.Sileem, Ahmed Mohamed
Conflict of interest
All authors confirm no financial or personal relationship with a third party whose interests could be positively or negatively influenced by the article’s content.
Funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgments
We thank Mrs. Yasmin Samir Negm (Teacher at Om El Momineen Primary School, Helwan, Egypt) for her invaluable efforts in recording and organizing study data and proofreading of this article. Her remarks enriched this study.
References (72)
- et al.
Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility
Obstet Gynecol Clin North Am
(2012) Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain
J Am Assoc Gynecol Laparosc
(1994)- et al.
Differences in characteristics among 1000 women with endometriosis based on extent of disease
Fertil Steril
(2008) - et al.
Quality of life of the woman carrier of endometriosis: systematized review
Reprodução Clim
(2016) - et al.
Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain
Fertil Steril
(1995) - et al.
A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan
J Chin Med Assoc
(2005) - et al.
Nafarelin versus danazol in the treatment of endometriosis
Am J Obstet Gynecol
(1990) - et al.
An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis
Fertil Steril
(1992) - et al.
Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis: I. Efficacy results
Am J Obstet Gynecol
(1992) - et al.
Lupron * depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study
Fertil Steril
(1990)
Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis
Obstet Gynecol
A randomized, comparative trial of triptorelin depot (D-Trp 6 -LHRH) and danazol in the treatment of endometriosis
Eur J Obstet Gynecol Reprod Biol
Effects of triptorelin versus placebo on the symptoms of endometriosis
Fertil Steril
Leuprolide acetate depot and hormonal add-back in endometriosis: a 12- month study
Obstet Gynecol
Add-back therapy in the treatment of endometriosis-associated pain
Fertil Steril
Goserelin acetate (Zoladex) with or without hormone replacement therapy for the treatment of endometriosis
Fertil Steril
Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study
Fertil Steril
Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis-a randomized, double-blind, multicenter, controlled trial
Fertil Steril
Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial
Fertil Steril
Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain
Fertil Steril
Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis
Int J Gynecol Obstet
Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III–IV. A randomized comparative trial
Fertil Steril
Mifepristone 2.5, 5, 10 mg versus placebo in the treatment of endometriosis
J Reprod Health Med
Interventions for endometriosis-related infertility: a systematic review and network meta-analysis
Fertil Steril
Management of endometriosis
J Gynecol Obstet Hum Reprod
Long-term effect of elagolix on the endometrium: results from two phase 3 extension studies in women with endometriosis-associated pain
Fertil Steril
The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis
Eur J Obstet Gynecol Reprod Biol
The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres
Hum Reprod
The clinical anatomy of endometriosis: a review
Cureus
Effects of acupuncture for the treatment of endometriosis-related pain: a systematic review and meta-analysis
PLoS One
Comparing the efficacy of surgery and medical therapy for pain management in endometriosis: a systematic review and meta-analysis
Pain Physician
World endometriosis society Montpellier consortium. Consensus on current management of endometriosis
Hum Reprod
Medical treatments for endometriosis-associated pelvic pain
Biomed Res Int
Endometriosis: epidemiology, diagnosis and clinical management
Curr Obstet Gynecol Rep
Cochrane handbook for systematic reviews of. Vol. Version 5
The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations
Ann Intern Med
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