What does this score mean?
The Confidence Index is not a treatment success rate, but an editorial methodology score indicating to what extent the scientific finding evaluated on this page can be trusted. Study design, risk of bias, sample size, precision, direct applicability, reproducibility, transparency, and clinical relevance are evaluated together.
What did the study investigate?
It evaluated the potential effects of melatonin on pain, sleep, lesion biology, and assisted reproductive outcomes in endometriosis through various human and experimental studies.
How was it conducted?
Randomized human studies from 2013, 2023, 2025, and 2026, experimental cell/animal data, and a meta-analysis in assisted reproduction were evaluated together.
What was found?
While some studies showed positive results regarding pain or sleep, some controlled studies showed no distinct superiority; findings are not consistent across doses and populations.
Limitations of the study
Clinical studies are small and involve varying doses and patient groups; the dropout rate is high in some studies. Experimental lesion findings cannot be directly translated into clinical effects in humans.
What does it mean clinically?
Melatonin may be an adjunctive area worth investigating, but evidence is insufficient to replace established hormonal, surgical, or pain treatments for endometriosis.
What do we not know yet?
The optimal dose, which patient subgroup might benefit, and long-term effects and safety regarding lesions and fertility are not yet clear.
Source
Full citations and links to the sources are preserved in the detailed evaluation section of this page.
Written and medically reviewed by: Dr. Kerem Çağlayan · Information about pain treatment · All Scientific Research
Detailed evaluation
Literature check: September 1, 2026 · Research evaluation
What is endometriosis, and why is melatonin being investigated?
Endometriosis is an estrogen-sensitive chronic disease characterized by the presence of tissue similar to the lining of the uterus outside the uterus. Severe menstrual pain, chronic pelvic pain, pain during intercourse or defecation, and in some individuals, fertility problems can be seen. Pain and sleep disturbance can adversely affect each other. [7]
Melatonin plays a role in regulating the circadian rhythm. In experimental research, its antioxidant, inflammation-modulating, and cell-proliferation-affecting properties are also investigated. These biological properties make melatonin interesting for endometriosis research; however, demonstrating a mechanism alone does not prove that the treatment works in patients. [3]
2024 study: Intervening in the growth signaling of cells
The study in the Journal of Pineal Research evaluated human endometriosis cell lines and a mouse model. Melatonin suppressed cell proliferation and lesion growth in mice. The researchers obtained findings demonstrating the binding of melatonin to EGFR and a decrease in the phosphorylation of this receptor. EGFR is one of the receptors that transmits growth signals to the cell. [3]
- Melatonin–EGFR interaction
Decrease in EGFR phosphorylation - Decrease in PI3K/AKT signaling
Suppression of cellular growth signaling - Decrease in Cyclin D1 levels
Slowdown of cell cycle progression - Less proliferation in experimental models
Lesion shrinkage in humans has not yet been proven.
These findings provide a rationale for new treatment research. However, the cellular conditions and animal results used in the experiment cannot be directly translated to the patient or an oral dosage.
What was found in human studies?
Four studies approach the same question with different patient groups, doses, and durations. The doses below describe only research protocols; they are not personal usage recommendations.
| Study | Participants / duration | Key finding | How should it be interpreted? |
|---|---|---|---|
| 2013 · 10 mg/night | 40 women; 8 weeks | Positive outcomes regarding pain, menstrual pain, and sleep. | Small Phase II study; verification is needed. [1] |
| 2023 · 20 mg/night | 40 women; two menstrual cycles | No significant superiority over placebo was shown in pelvic pain. | A higher dose does not automatically mean a higher benefit. [2] |
| 2025 · 5 mg | 80 infertile women; 2 months | Statistical improvement in sleep and pelvic pain scores. | The sleep difference did not reach the predetermined threshold for clinical significance. [4] |
| 2026 · Melatonin added to dienogest | 94 randomized participants; 6 months | Additional reduction in menstrual pain; no distinct additional superiority in other pain domains and quality of life. | Only 52 people completed the protocol; dizziness was reported more frequently. [5] |
2013: A positive, but small preliminary study
The double-blind, placebo-controlled Phase II study evaluated 10 mg of melatonin for eight weeks. Positive outcomes were reported in terms of daily pain, dysmenorrhea, sleep quality, and analgesic requirement. Because the number of participants is limited, this study alone does not constitute a routine treatment recommendation. [1]
2023: The same positive outcome was not replicated
In the randomized study using 20 mg of melatonin, the mean pain score was 2.9 in the melatonin group and 3.3 in the placebo group; the difference between the groups was not significant (p=0.45). Placing different studies side by side is not a dose-comparison trial. Therefore, it cannot be concluded that 5 or 10 mg is more effective than 20 mg. [2]
2025: A statistical difference is not the same as the difference a patient will feel
In the triple-blind study in 80 women with endometriosis, infertility, and sleep disorder, two months of 5 mg melatonin improved sleep and pelvic pain scores. The between-group difference on the sleep scale was approximately 1.7 points; it remained below the 3-point threshold determined for clinical significance. Although the findings are positive, the extent to which they will make a difference in daily life must be carefully evaluated. [4]
2026: In which domain is the additional benefit to hormone therapy?
94 women with ovarian endometrioma were divided into groups receiving melatonin or placebo in addition to dienogest. In the six-month study, an additional benefit was reported regarding menstrual pain; no significant additional superiority was demonstrated in non-menstrual pelvic pain, dyspareunia, dyschezia, and general quality of life. The fact that 52 people completed the protocol is a significant limitation. The more frequent reporting of dizziness in the melatonin group also requires that benefit and tolerability be evaluated together. [5]
Does it shrink lesions, does it prevent disease progression?
Does it have any significance for fertility?
A 2025 meta-analysis pooled 11 randomized trials involving a total of 1,481 women receiving assisted reproductive therapy. Positive outcomes were reported for clinical pregnancy rates and the number of high-quality embryos. However, not all participants had endometriosis; nor are clinical pregnancy and live birth the same outcome measure. These data do not prove that melatonin increases the likelihood of pregnancy or live birth in endometriosis-related infertility. [6]
Safety and clinical approach
Although melatonin is a natural hormone, its use as a supplement is not automatically suitable for everyone. Drowsiness, headache, dizziness, and nausea may occur. Physician evaluation is particularly important in individuals taking blood thinners or those with epilepsy. Safety data during pregnancy and breastfeeding, just like the safety of long-term use, are limited. [8]
There is no established “optimal melatonin dose” for endometriosis. The decision should be individualized by considering symptoms, sleep patterns, current medications, and pregnancy plans. The standard approach includes pain management, hormonal options, surgery when needed, and fertility planning. Melatonin should not replace these. [7]
Addressing pain and sleep complaints together is valuable. For a broader approach, you can consult our guides on pain treatment and clinical evaluation. The diagnostic and treatment plan for endometriosis should be managed through an obstetrics and gynecology evaluation.
Frequently asked questions
Does melatonin treat endometriosis?
Some studies have reported positive findings regarding menstrual pain and sleep. Because results are not yet consistent, melatonin is not recognized as a standard or definitive treatment for endometriosis.
Does it shrink endometrioma?
Its effect on lesions is being investigated; clinical data confirming shrinkage in humans are not yet sufficient. To what extent experimental findings translate to patients must also be demonstrated.
How many mg should be used?
A standard dose for endometriosis has not been established. The study doses mentioned here are not a prescription; they must be evaluated especially in light of pregnancy plans and current medications.
Can it replace dienogest or other hormone therapies?
Maintaining current hormone therapy is important; research does not support melatonin replacing these treatments. Additional use should be evaluated together with the treating physician.
Conclusion: A promising research area, not yet an established treatment
What makes melatonin intriguing is that it brings sleep patterns, pain, and cellular growth mechanisms together within the same field of research. As of today, the most accurate approach is to clearly recognize its limitations without overlooking positive signals. Larger and longer-term studies must clarify which patients will benefit, safety, and the actual clinical impact on lesions.
References
- Schwertner A et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154:874–881. DOI: 10.1016/j.pain.2013.02.025.
- Söderman L et al. Adjuvant use of melatonin for pain management in endometriosis-associated pelvic pain. PLoS One. 2023. DOI: 10.1371/journal.pone.0286182.
- Li Y et al. Melatonin Inhibits Endometriosis Growth via Specific Binding and Inhibition of EGFR Phosphorylation. J Pineal Res. 2024;76:e70022. DOI: 10.1111/jpi.70022.
- Esmaeilzadeh S et al. Melatonin and sleep parameters in infertile women with endometriosis. PLoS One. 2025;20:e0321635.
- Rezaeinejad M et al. Synergistic effects of melatonin and dienogest on pain relief in endometriosis: a randomized controlled trial. Obstet Gynecol Sci. 2026. DOI: 10.5468/ogs.25053.
- Wu Y et al. Melatonin improved the outcomes of women with ART: a systematic review and meta-analysis of randomized trials. Front Reprod Health. 2025. DOI: 10.3389/frph.2025.1680984.
- ESHRE. Guideline: Endometriosis. 2022.
- NCCIH. Melatonin: What You Need To Know. Safety, interactions, and limits of evidence.
This article is for scientific informational purposes; it is not personal diagnostic or treatment advice. The cover image is a representative scene created with artificial intelligence; it does not contain a real patient or treatment result.
