Abstract glass spheres in teal and gold light; conceptual editorial artwork, not ovarian anatomy.

Do ovaries make melatonin? The science behind the PCOS connection

Ovarian biology · PCOS · Sleep

From ovarian biology to sleep, hormones, and IVF: what human studies are revealing about melatonin and PCOS.

Evidence reviewed October 6, 2026 · About 8 minutes

When you hear “melatonin,” you probably think about bedtime. The brain’s pineal gland releases this hormone in response to darkness, helping coordinate our daily sleep–wake rhythm.12 But melatonin also appears in an unexpected place: the ovary.

Research supports the possibility that human ovarian tissue makes melatonin locally. For people with polycystic ovary syndrome (PCOS), that opens an interesting scientific question: could this local melatonin system be part of the ovarian changes seen in the condition?1,3

There is clinical research worth paying attention to. Small human trials have reported benefits in sleep quality, selected hormone and metabolic measures, and IVF laboratory outcomes. These findings make melatonin a promising area of PCOS research, with important questions about who benefits and which outcomes improve.13,15,16

What scientists found in human ovaries

A foundational 1999 study detected melatonin, its chemical precursors, and activity of two enzymes involved in melatonin synthesis in human ovarian tissue. Those findings support the ovary’s capacity for local production. They do not tell us exactly how much it produces in everyday life, or how much ovarian melatonin comes from the bloodstream.1

Melatonin is also present in follicular fluid, the fluid surrounding an egg as it develops inside a follicle. Studying this local environment gives researchers a different view from measuring hormones in a blood sample.2

Educational ovarian follicle schematic showing follicular fluid, an egg, and granulosa cells. Not to scale.
Original educational schematic of a developing follicle. Not to scale; colors do not represent measured melatonin levels.

Why this interests PCOS researchers

Granulosa cells help support the developing egg. Scientists are investigating how melatonin interacts with these cells’ mitochondria, which help produce cellular energy, and with pathways involved in oxidative stress and inflammation.

In a 2025 study, researchers compared granulosa cells from 20 women with PCOS and 20 without it. They found lower expression of melatonin-synthesis enzymes in the PCOS group. Separate mouse and laboratory-cell experiments suggested that melatonin could modify mitochondrial and inflammatory pathways.3

These experiments help explain why melatonin is being studied. A treatment that changes a pathway in a laboratory still needs reliable human trials to show whether it improves symptoms, pregnancy, or live birth.

Does PCOS mean low melatonin?

The answer depends on where and when researchers measure it. One study of 71 women undergoing IVF found lower follicular-fluid melatonin in the PCOS group. It was observational, so it could not establish whether lower melatonin caused an ovarian problem or resulted from one.2

Other research has found higher morning blood melatonin and an altered night-to-morning pattern in women with PCOS.4 A blood level and a follicular-fluid level describe different biological settings. PCOS cannot be reduced to a simple whole-body melatonin deficiency.

What do supplement studies show?

The 2022 review Nutritional Supplements and Complementary Therapies in Polycystic Ovary Syndrome, by Alesi and colleagues, includes melatonin among supplements with potential benefit. Its melatonin section summarizes encouraging hormonal and reproductive findings, while its conclusion calls for stronger, more consistent clinical evidence.14

Several human studies help explain that interest:

Study What improved How to interpret it
Sleep and metabolism
58 women; randomized trial; 12 weeks.16 		Self-reported sleep quality, insulin-resistance estimates, and some cholesterol measures improved versus placebo. A small, short trial; a better sleep questionnaire score does not establish remission of diagnosed insomnia.
Hormones and oxidative stress
56 women; randomized trial; 12 weeks.15 		Lower testosterone, a small improvement in excess-hair scores, and favorable changes in inflammatory and antioxidant markers. Both groups also received metformin and cyclic medroxyprogesterone. This tested added melatonin within a treatment plan.
Menstrual cycles
40 women; pilot study; 6 months.17 		More frequent menstrual cycles and lower androgen levels were reported. There was no placebo or untreated comparison group, so the study cannot establish that melatonin caused these changes.

A closer look at the 2023 IVF paper

The Boosting Effects of Melatonin on the In Vitro Fertilization (IVF) of Women with Polycystic Ovary Syndrome studied 320 women. The authors reported better egg-maturation and embryo-quality measures, plus more early pregnancies, with melatonin added to metformin compared with metformin alone.13

The paper has inconsistencies in its dosing and pregnancy statistics, and it did not report live births. It supports further investigation, but cannot provide a dependable estimate of how much melatonin might improve someone’s chance of having a baby.

What still needs a clearer answer?

Results vary with the population, dose, timing, and accompanying treatment. For example, a 2021 randomized study also found better sleep-quality scores with melatonin, whereas a 2025 trial in women preparing for ICSI did not show a statistically significant advantage over placebo for insomnia or overall sleep-quality scores.18,19

A 2024 meta-analysis found an improvement in total antioxidant capacity, but did not establish consistent effects on several hormonal and metabolic outcomes.5 The Alesi review also noted that an earlier fertility benefit was not statistically significant when analysis was restricted to oral-treatment trials.14 Better antioxidant markers or embryo grades do not automatically translate into more live births.

Source update: a separate melatonin–myo-inositol IVF trial by Pacchiarotti and colleagues was retracted in 2026. It appeared in earlier reviews and is excluded from the affirmative evidence here. This is a different paper from the 2023 Pilehvari study discussed above.5,6,7

PCOS, insomnia symptoms, and sleep apnea

Sleep deserves a place in the PCOS conversation. An Australian community study of 6,578 women found more self-reported sleep difficulties among those with PCOS, even after accounting for factors including BMI and depressive symptoms. These were reported symptoms, rather than confirmed insomnia diagnoses.21

Obstructive sleep apnea (OSA) is another concern. In a large UK study, women with PCOS were more likely to receive an OSA diagnosis during follow-up, after adjustment for age, BMI, and other factors. The international PCOS guideline recognizes the increased prevalence and recommends assessing symptoms such as snoring with unrefreshing sleep or daytime sleepiness.20,11

Insomnia symptoms and sleep apnea need appropriate assessment; they are not evidence by themselves of melatonin deficiency. The PCOS supplement studies do not establish melatonin as a treatment for sleep apnea. For chronic insomnia, cognitive behavioral therapy for insomnia (CBT-I) is a recommended treatment; suspected OSA may require a formal sleep study.22,11

What can you take from this research?

Bring both sleep and reproductive goals into the conversation. Ask your clinician whether the findings are relevant to your symptoms, medications, and current PCOS treatment. A fertility protocol, a study of hormone markers, and treatment for a sleep disorder answer different questions.

For readers comparing bedtime supplements, WrenLife Effervescent Sleep Aid is a cherry-lime effervescent drink mix with melatonin.

Discuss supplements in the context of your own treatment. Studies use different doses, timings, and accompanying fertility medications. There is no established routine melatonin regimen for PCOS in the guideline.11 If you are trying to conceive or receiving fertility treatment, involve your treating clinician before starting it. Safety information during pregnancy and breastfeeding is limited, and melatonin can interact with medicines and cause sleepiness, headache, or dizziness.12

At WrenLife, we believe women deserve access to the encouraging findings and their context. Melatonin’s relationship with PCOS is a developing story, with enough human evidence to take seriously and enough unanswered questions to keep asking.

Educational content, not an individual treatment plan. WrenLife is a supplement brand. Some source titles below are shortened for readability; DOI and PubMed links identify the original records.

Scientific references

  1. Itoh MT et al. (1999). Human ovarian melatonin, precursors and enzyme activity. Molecular Human Reproduction 5:402–408.
  2. Li H, Liu M, Zhang C (2022). Follicular melatonin and sleep in women with PCOS. BMC Women’s Health 22:79.
  3. Chen W et al. (2025). Melatonin, ovarian mitochondria and the CLOCK pathway. Cellular and Molecular Life Sciences 82:104.
  4. Terzieva et al. (2013). Serum melatonin in women with PCOS. Folia Medica; PubMed 24191394.
  5. Ziaei S et al. (2024). Meta-analysis of melatonin trials in PCOS. Journal of Ovarian Research 17:138.
  6. Shoarishoar SS et al. (2025). Systematic review of melatonin supplementation in PCOS. Health Science Reports 8:e71269.
  7. Retraction notice (2026). Retraction of the Pacchiarotti melatonin–myo-inositol IVF trial. Gynecological Endocrinology; PubMed 41626704.
  8. Qiang R et al. (2026). Meta-analysis of oral antioxidants in assisted reproduction. Frontiers in Endocrinology 17:1891276.
  9. Jaiswar S, Bhise M, Shukla P (2026). Systematic review of melatonin in PCOS assisted reproduction. Antioxidants 15:896.
  10. Farajneia Hosseinabad M et al. (2026). Melatonin or sildenafil added to metformin in PCOS. Journal of Gynecology Obstetrics and Human Reproduction 55:103165.
  11. International PCOS Guideline (2023). Assessment and management recommendations. ASRM; sleep apnea recommendations 1.10.1–1.10.3.
  12. NIH National Center for Complementary and Integrative Health. Melatonin: What You Need To Know. Safety, interactions and pregnancy information.
  13. Pilehvari S et al. (2023). Melatonin added to metformin during IVF for PCOS. Chonnam Medical Journal 59:188–193.
  14. Alesi S et al. (2022). Nutritional Supplements and Complementary Therapies in Polycystic Ovary Syndrome. Advances in Nutrition 13:1243–1266.
  15. Jamilian M et al. (2019). Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome. Frontiers in Endocrinology 10:273.
  16. Shabani A et al. (2019). Effects of melatonin administration on mental health parameters, metabolic and genetic profiles in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Journal of Affective Disorders 250:51–56.
  17. Tagliaferri V et al. (2018). Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study. Reproductive Sciences 25:269–275.
  18. Alizadeh M et al. (2021). Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome. Nutrition & Metabolism 18:57.
  19. Yazdchi et al. (2025). In Women with Polycystic Ovarian Syndrome (PCOS), Oral Melatonin Supplementation Had a Modest Effect on Sleep and No Effect on Depression—Results from a Randomized Clinical Trial. Journal of Psychiatry and Brain Science 10:e250018.
  20. Kumarendran B et al. (2019). Increased risk of obstructive sleep apnoea in women with polycystic ovary syndrome: a population-based cohort study. European Journal of Endocrinology 180:265–272.
  21. Mo L et al. (2019). Sleep disturbances in women with and without polycystic ovary syndrome in an Australian National Cohort. Clinical Endocrinology 90:570–578.
  22. Edinger JD et al. (2021). Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. Journal of Clinical Sleep Medicine 17:255–262.
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