Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study

Exp Gerontol. 2001 Feb;36(2):297-310. doi: 10.1016/s0531-5565(00)00217-5.


In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a significant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a significant diminution of LH in the younger women (43 to 49year-old), while no effect was seen in the older women (50-62years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a significant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of fertility in women. These findings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology
  • Depression / drug therapy
  • Double-Blind Method
  • Female
  • Follicle Stimulating Hormone / blood
  • Gonadal Steroid Hormones / blood
  • Humans
  • Luteinizing Hormone / blood
  • Melatonin / administration & dosage
  • Melatonin / pharmacology*
  • Melatonin / physiology
  • Menopause / drug effects*
  • Menopause / physiology
  • Menopause / psychology
  • Menstrual Cycle / drug effects
  • Middle Aged
  • Premenopause / drug effects*
  • Premenopause / physiology
  • Premenopause / psychology
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood


  • Gonadal Steroid Hormones
  • Triiodothyronine
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Thyrotropin
  • Melatonin
  • Thyroxine