Melatonin: A new therapeutic agent for women affected by PCOS.

Posted By Braverman IVF & Reproductive Immunology || 27-Feb-2018

A recent study published this month in the journal Reproductive Sciences showed the beneficial role of Melatonin for women with polycystic ovary syndrome (PCOS). 

The article presents recent findings from a prospective study including N=40 normal-weight women with PCOS and investigates the effects of melatonin administration for 6 months on clinical, endocrine, and metabolic features of women affected by PCOS. Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting about 6-10% of women of childbearing age depending on ethnicity, with approximately 5 million of women being affected in the United States (1). It is characterized by both gynecological and endocrine symptoms such as:

  • chronic anovulation: missed or absence of period.
  • Hyperandrogenism: higher levels of androgens (male hormones) leading to excess of facial hair growth and acne.
  • Several cysts on the ovaries

    In addition, obesity, insulin resistance, and hyperinsulinemia commonly occur in PCOS patients, increasing their susceptibility for metabolic disorders such as type 2 diabetes or hypertension (2). Being the most common endocrine cause of infertility, a large proportion of women affected by PCOS ignore their condition and are not yet diagnosed, due to subtle or not classical signs, until trying and failing to conceive. When pregnant, PCOS patients are more prone to obstetrical complications leading to pregnancy losses in 50% of cases (3). Although the precise etiology remains unknown, many symptoms in PCOS patients (reproductive and metabolic manifestations) could be attributed to oxidative stress (excess of free radicals) contributing to a proinflammatory state that induces insulin resistance and hyperandrogenism (4) with dramatic consequences on oocyte quality.

    Melatonin is a hormone secreted by the pineal gland that controls the wake/sleep cycles, circadian rhythms and reproduction (5) During the follicle development (leading to a mature and fertilizable egg), very high levels of melatonin have been found in the follicular fluid (6) which may, thanks to its free radical scavenger properties, protect the developing oocyte against oxidative stress (7). It is well described in the scientific literature that the oocyte environment including the follicular fluid, directly impacts the oocyte quality (8). In PCOS patients, there is a premature arrest in the follicle development, that leads to the follicle atresia and the accumulation of small follicles responsible of a hyperproduction of AMH (9).

    In the present study, melatonin was administrated to PCOS patients at a dose of 2mg for 6 months after thorough clinical evaluation and laboratory workup. After 6 months and without any modification of their diet or lifestyle, patients showed a significant:

  • Decrease in androgen levels (-26%)
  • Decrease in AMH levels (-30%)
  • Decrease in LDL cholesterol (-11%)
  • Decrease in BMI (weight loss) although minor (-3%)
  • Increase in FSH levels (+28%)

    Most importantly, 95% of PCOS patients experienced an amelioration of their menstrual cycles with a number of menstrual cycles that almost doubles within 6 months as compared to a 6-month period with no melatonin supplementation. In comparison, Vitex agnus-castus (herbal medicine) may present some benefits in restoring menstrual cyclicity in PCOS patients with a study reporting a non-significant improvement in clinical parameters in only 57% of treated patients (9).

    Reducing oxidative stress in the oocyte is of prime clinical importance when treating sub-fertility in PCOS patients or in any patients whose oocyte quality is affected by high levels of oxidative stress such as endometriosis patients or Correctible Reoccurring Aneuploid Conversion Syndrome (CRACS) patients.

    As world leader in the field of Reproductive Immunology, we have, at Braverman Reproductive Immunology, developed a dietary supplement “The Endo-Optimize” containing many ingredients including melatonin, with beneficial actions on reducing ROS and free-radicals’ production and enhancing oocyte maturation and quality. In addition, this “all in one” pill contains many other ingredients enhancing mitochondrial activity (a key component in oocyte development) and reducing inflammation thus allowing optimal microenvironment for the oocyte to develop and mature into a fertilizable egg (for more information read our blog “ENDO-optimize: an "all in one" dietary supplement with beneficial effects on egg quality, endometriosis and PCOS”).

    Our diet supplements are available for purchase. For more information about our supplements range, please consult our website.

    Questions? Call 516.584.8710  We would be happy to help you take control of your fertility journey and answer any questions you may have.


    1. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R: Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998, 83(9):3078–3082.

    2. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of clinical endocrinologists, American College of Endocrinology, and androgen excess and PCOS Society disease state clinical review: Guide to the best practices in the evaluation and treatment of polycystic ovary endocrinologists, American College of Endocrinology, and androgen excess and PCOS society disease state clinical review: guide to the best practice in the evaluation and treatment of polycystic ovary syndrome-Part 2. Endocr Pract. 2015 Dec;21(12):1415-26.

    3. Ford HB, Schust DJ (2009) Recurrent pregnancy loss: etiology, diagnosis and therapy. Rev Obstet Gynecol 2: 76–83.

    4. Gonzalez F, Rote NS, Minium J, Kirwan JP. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome.J Clin Endocrinol Metab. 2006;91(1):336-340.

    5. Cipolla-Neto J, Amaral FG, Afeche SC, Tan DX, Reiter RJ. Melatonin, energy metabolism, and obesity: a review. J Pineal Res. 2014;56(4):371-381.

    6. Y.Nakamura,H. Tamura,H.Takayama, andH.Kato, “Increased endogenous level of melatonin in preovulatory human follicles does not directly influence progesterone production,” Fertility and Sterility, vol. 80, no. 4, pp. 1012–1016, 2003.

    7. H. Tamura, Y. Nakamura, A. Korkmaz et al., “Melatonin and the ovary: physiological and pathophysiological implications,”Fertility and Sterility, vol. 92, no. 1, pp. 328–343, 2009.

    8. Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertil Steril. 2015 Feb;103(2):303-16.

    9. Broekmans FJ, Visser JA, Laven JS, Broer SL, Themmen AP, Fauser BC. Anti-Mullerian hormone and ovarian dysfunction. Trends Endocrinol Metab. 2008;19(9):340-347.

    10. Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC Complement Altern Med. 2014 Dec 18; 14:511.

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