top of page

Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation

May 2024

Article: Voordouw BC, Euser R, Verdonk RE, Alberda BT, de Jong FH, Drogendijk AC, Fauser BC, Cohen M. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab. 1992 Jan;74(1):108-17. doi: 10.1210/jcem.74.1.1727807. PMID: 1727807.



This placebo-controlled study of 32 women explored how melatonin alone or melatonin-progestin (norethisterone) in combination may affect pituitary-ovarian function and ovulation. The results showed that higher doses of melatonin alone and in combination with progestins can inhibit ovarian function in women.


SNHI’s Advisory Council comments/takeaway from the article: 

The Advisory Council is commonly asked about the effects of high doses of melatonin for various health conditions and the impact high doses may have on hormones. This study used supraphysiologic doses (300 mg, 75 mg, and 7.5 mg) of melatonin with and without a synthetic progestin and found that each of these high doses can negatively affect ovarian hormones (estradiol, progesterone, luteinizing, and follicle-stimulating hormones). This study's findings reinforce why this advisory council supports the use of lower physiologic dosing of melatonin.



Article summary

Women (N = 32, plus 8 controls), ages 18-37, were divided into melatonin (MLT) alone or melatonin-progestin (MLT-NET) groups and followed for four (4) months.


Population groups

MLT group

  • Group 1: Half was given 300 mg daily

  • Group 2: Half was given 300 mg on days 5-17 of the menstrual cycle.


MEL/NET group 

  • Group 1: 300 mg MEL/0.75 mg NET

  • Group 2: 75 mg MEL/0.75 mg NET

  • Group 3: 7.5 mg MEL/0.75 mg NET

  • Group 4: 75 mg MEL/0.30 mg NET

Melatonin was taken on days 1-21 of the menstrual cycle in all groups.


In addition, a separate arm of four women was studied for two (2) months.

  • Two (2) women were given 300 mg MEL alone on days 1-21 of the menstrual cycle.

  • Two (2) were given 300 mg MEL/0.15 mg NET on days 1-21 of the menstrual cycle.



This study found that LH and estradiol were suppressed in the melatonin-only groups in the fourth month as compared to the first month of treatment. In the combination treatment groups, there was a significant reduction in LH, estradiol, and progesterone surges, supporting luteal insufficiency. No complaints regarding emotions, altered bleeding patterns, or sleep/wake disturbances were reported by the women. In suppressing ovulatory cycles, the authors propose there may be merit in a combination of NET/MEL contraceptive pills to avoid the negative side effects of estrogen-containing contraceptives.


Limitations noted by Author(s):

None were noted


Other limitations noted in this review:

1.  The small sample sizes of each individual group with multiple dosing strategies.

2.  Conventional dosing levels for the progestins were given, but supraphysiologic melatonin levels were administered in most cases, so while this may support the role supraphysiologic doses may play in contraception, it does not correlate with natural biological systems and further supports using physiologic dosing for health.  

3.  The dosing of melatonin was inconsistent on the days it was given to all women in the study.


Article review completed by Mona Fahoum, ND

Content reviewed by Kim Ross, DCN

Date May 24, 2024

bottom of page