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Review
. 2025 Jun 13;10(4):e1299.
doi: 10.1097/PR9.0000000000001299. eCollection 2025 Aug.

Efficacy and safety of drug combinations for chronic pelvic pain: a systematic review

Mohammed Mohiuddin  1 , Rex Park  1 , Ursula Wesselmann  2 , Caroline Pukall  3 , Keith Jarvi  4 , J Curtis Nickel  5 , R Christopher Doiron  5 , Sandra Halliday  6 , Ian Gilron  1   7   8   9
Affiliations
Review

Efficacy and safety of drug combinations for chronic pelvic pain: a systematic review

Mohammed Mohiuddin et al. Pain Rep. .

Abstract

Clinical disorders associated with chronic pelvic pain (CPP) cause demonstrable emotional and physical dysfunction as well as increased health care utilization. Interventions that have been studied for the treatment of CPP often provide inadequate relief and/or intolerable adverse effects. The common practice of combining multiple CPP treatments needs more supportive evidence, and emerging combination trials have been evaluated in this systematic review. We searched MEDLINE and EMBASE and CENTRAL databases for CPP combination trials. This review included double-blind randomized controlled trials comparing combinations of 2 or more agents to at least 1 monotherapy in adults with CPP. The primary outcome was reduction in pain intensity or pain relief, and secondary outcomes included adverse events, quality of life, and other symptoms. Risk of bias was assessed. Nine studies (1,299 participants) were included and involved various different treatments including ciprofloxacin, tamsulosin, pentosan polysulfate, hyaluronic acid, chondroitin, hydroxyzine, troxerutin, carbazochrome, linzagolix, and allopurinol. Studies were heterogenous according to several features including studied treatments, dose and route of administration, and underlying condition such that no studies could be combined for meta-analysis. None of the included studies reported a significant difference in reducing pain intensity for combination therapy vs monotherapy. If future proof-of-concept studies demonstrate that a given combination is superior to all monotherapy components, subsequent large, double-blind randomized, controlled clinical trials of such combinations for CPP are required to better elucidate the role of combination therapy in clinical settings.

Keywords: Chronic pelvic pain; Combination therapy; Systematic review.

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Conflict of interest statement

M.M. has no conflicts to disclose. R.P. has no conflicts to disclose. U.W. serves on the External Consultant Board for the “NIH Preclinical Screening Platform for Pain” at the National Institutes of Health (NIH/NINDS). In her capacity as a special government employee of the US Food and Drug Administration (FDA), she has served as a voting member of the FDA Anesthetic and Analgesic Drug Products Advisory Committee. She serves as an elected member on the Council of International Association for the Study of Pain. In the past 3 years, she has received compensation for serving on advisory boards or for consulting activities for Aphrodite Health Inc., Wilmington, DE; Avenue Therapeutics Inc., New York, NY; Bayer Aktiengesellschaft, Leverkusen, Germany; Biohaven Pharmaceuticals, New Haven, CT; Hillhurst Biopharmaceuticals, Montrose, CA; Seikagaku Corporation, Tokyo, Japan and Syneos Health, Morrisville, NC, all unrelated to the submitted work. C.P. is a Research Consultant for Initiator Pharma and a Clinical and Research Consultant for Pelva Health. K.J. has no conflicts to disclose. J.C.N. has no conflict of interest in any of the subjects or interventions described in this review. R.C.D. has no conflicts to disclose. I.G. has received support from Vertex and Combigene and has received grants from the Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, and Queen's University. S.H. has no conflicts to disclose.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram.
Figure 2.
Figure 2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 3.
Figure 3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

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