Melatonin for endometriosis-associated pain

Melatonin for endometriosis-associated pain

Study evaluates the analgesic effects of melatonin in women with endometriosis

Key Points


  • Melatonin with its anti-inflammatory, analgesic, and anti-estrogenic properties, has shown promise as a potential adjunct treatment in previous studies for endometriosis-associated pain.


  • Finding effective treatments for endometriosis-associated pain is crucial to improving the quality of life for women with the condition. 

What’s done here

  • A randomized, double-blinded, placebo-controlled trial was conducted to investigate the analgesic effect of 20 mg melatonin taken orally at bedtime for two menstrual cycles.
  • The trial involved 40 participants, with half receiving melatonin and the other half receiving a placebo. 

Key results:

  • No significant differences were observed in primary or secondary outcomes between the treatment groups.
  • A superior analgesic effect of melatonin compared to placebo was not demonstrated.
  • Sensitivity analysis stratified by hormonal treatment did not show any differences between the groups.
  • No significant differences in the number of days with endometriosis-associated pain or analgesic use between the groups were seen. 

Strengths and limitations:

  • The study had strengths such as adherence to CONSORT guidelines, low dropout rates, and daily assessments to minimize bias.
  • Limitations included a relatively homogenous study population, potential misclassification bias in diagnosis, and underestimation of the standard deviation.

Lay Summary

Treatment options for endometriosis-associated pain include analgesics, hormonal therapy, and surgery. However, these treatments may be ineffective for some women, leading to a search for alternative approaches. Melatonin, a hormone involved in regulating sleep-wake cycles, possesses anti-inflammatory, analgesic, and anti-estrogenic properties, making it a promising candidate for managing EAPP. Previous studies have demonstrated that melatonin can impair the cellular invasion, migration, and proliferation of endometriotic tissue. 

Söderman et al. from Stockholm, Sweden conducted a randomized, double-blinded, parallel placebo-controlled trial on women with endometriosis aiming to investigate the potential use of melatonin as a treatment option for endometriosis-associated pain. The study was published in the June 2023 issue of the journal PLOS ONE.

A total of 40 women with diagnosed endometriosis and severe dysmenorrhea were enrolled with 16 participants in the placebo group and 18 participants in the melatonin group completing the study. Participants were randomly assigned to receive either 20 mg of melatonin or placebo daily for two consecutive menstrual cycles. The primary measured outcome was endometriosis-associated pain, and secondary outcomes included analgesic use, dysuria, dyschezia, dyspareunia, days of pain, absenteeism, quality of life, pain catastrophization, and sleep. Daily assessments were recorded using questionnaires, and data were collected and managed using electronic tools.

The main characteristics of the study population were similar between the groups. No significant differences were observed in primary or secondary outcomes between the treatment groups. The authors state that the analgesic effects of melatonin may be dose-dependent and involve the opioid system which may explain why previous research with a lower dosage of melatonin (10 mg) showed promising results in reducing pain in women with endometriosis. Also, they added that the discrepancy in findings could be attributed to the different pain levels in the study populations, with the current study having lower overall pain scores. It is possible that the analgesic effect of melatonin is more noticeable in higher pain ranges. There were no significant differences in the number of days with endometriosis-associated pain or analgesic use between the groups.

Further research with larger and more diverse study populations is warranted to explore the potential benefits of melatonin in managing endometriosis-associated pain. Additionally, investigating alternative dosages or modes of administration, as well as measuring melatonin levels in plasma, could provide valuable insights into optimizing melatonin as a treatment option for endometriosis.

Research Source:

endometriosis melatonin pain


EndoNews highlights the latest peer-reviewed scientific research and medical literature that focuses on endometriosis. We are unbiased in our summaries of recently-published endometriosis research. EndoNews does not provide medical advice or opinions on the best form of treatment. We highly stress the importance of not using EndoNews as a substitute for seeking an experienced physician.