\Stopping Dysmenorrhea: A Systematic Review of Drugs Inhibiting Uterine Contractions.
NSAIDs are the most effective treatment for reducing menstrual pain and uterine contractions in dysmenorrhea, but other therapies require further evaluation.
Where it sits
this study against the rest of the oxytocin corpusSummary and findings
This systematic review evaluated the efficacy of drugs aimed at reducing uterine contractions in individuals with primary dysmenorrhea. A total of 447 participants across 25 trials were analyzed, focusing on various pharmacologic therapies compared to placebo. Nonsteroidal anti-inflammatory drugs (NSAIDs) were found to consistently reduce menstrual pain and uterine contractions.
Abstract
Dysmenorrhea is highly prevalent and undertreated, substantially impairing quality of life in reproductive-age individuals. Excessive uterine contractility is widely considered a key mechanistic contributor to menstrual pain. We conducted a systematic search of PubMed and Embase from inception to 24 July 2024 using MeSH and Emtree terms related to dysmenorrhea, uterine contractions and pharmacologic therapy. We included English-language human clinical trials in non-pregnant, reproductive-age participants with primary dysmenorrhea evaluating drugs intended to reduce uterine contractions and menstrual pain, compared with placebo or pre-treatment baseline. Two reviewers independently extracted data using a piloted Cochrane-based form; risk of bias was assessed using RoB 2 and ROBINS-I with disagreements resolved by consensus. Across 25 eligible trials (447 participants), nonsteroidal anti-inflammatory drugs (NSAIDs) most consistently reduced both menstrual pain and uterine contractions. Smaller trials suggested potential benefits for additional pharmacologic classes, including prostaglandin synthesis inhibitors, vasopressin antagonists, beta-adrenergic agonists, combined oral contraceptives, calcium channel blockers, and selective estrogen receptor modulators, whereas oxytocin antagonists showed mixed results. Risk of bias was low in nine studies, moderate in 12, and high in four. These findings support that established therapies for dysmenorrhea (NSAIDs and hormonal contraception) reduce pain and uterine activity, and suggest that other contractility-targeting agents warrant further rigorous evaluation, particularly given meaningful non-response to NSAIDs. PROSPERO registration: CRD42023442828 (registered 24 July 2023).
Background
Dysmenorrhea is a common condition that significantly affects the quality of life in reproductive-age individuals. Previous research has identified excessive uterine contractility as a major contributor to menstrual pain. This study systematically reviews existing clinical trials to evaluate the effectiveness of various pharmacologic agents in reducing uterine contractions and associated pain.
Methods
The systematic review included human clinical trials published in English, focusing on non-pregnant, reproductive-age participants with primary dysmenorrhea. Trials evaluated drugs intended to reduce uterine contractions compared to placebo or pre-treatment baseline. Data extraction was performed by two independent reviewers, and risk of bias was assessed using established tools.
Results
The review included 25 trials with a total of 447 participants. NSAIDs were identified as the most effective agents in reducing menstrual pain and uterine contractions. The risk of bias varied, with nine studies rated low, 12 moderate, and four high.
Interpretation
The findings align with prior literature that supports the efficacy of NSAIDs and hormonal contraception in managing dysmenorrhea. While NSAIDs showed consistent results, the clinical significance of other pharmacologic classes remains uncertain due to mixed results and varying study quality. The presence of high-risk bias studies may limit the reliability of the conclusions drawn.
Key findings
- 447 participants across 25 eligible trials.
- NSAIDs most consistently reduced both menstrual pain and uterine contractions.
- Risk of bias was low in nine studies, moderate in 12, and high in four.
Limitations
- mixed results for oxytocin antagonists
- risk of bias varied across studies
- not all pharmacologic classes were equally evaluated