Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women

J Clin Endocrinol Metab. 2011 Apr;96(4):E614-23. doi: 10.1210/jc.2010-2558. Epub 2011 Feb 2.


Context: A number of neuroactive progesterone metabolites produce sedative-like effects. However, the effects of progesterone administration on sleep are not well characterized.

Objective: To investigate the effects of a 3-wk progesterone administration on sleep architecture and multiple hormonal profiles.

Subjects: Eight healthy postmenopausal women, 48-74 yr old, without sleep complaints or vasomotor symptoms. None was on hormone replacement therapy. They did not take any medication for ≥ 2 months.

Design: Randomized, double-blind, placebo-controlled study. For 3 wk, subjects took daily at 2300 h a capsule of either 300 mg of progesterone or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were obtained at 15-min intervals for 24 h.

Results: During the first night (no blood sampling), sleep was similar in both conditions. Under placebo, blood sampling procedure was associated with marked sleep disturbances, which were considerably reduced under progesterone treatment: mean duration of wake after sleep onset was 53% lower, slow-wave sleep duration almost 50% higher, and total slow-wave activity (reflecting duration and intensity of deep sleep) almost 45% higher under progesterone than under placebo (P ≤ 0.05). Nocturnal GH secretion was increased, and evening and nocturnal TSH levels were decreased under progesterone (P ≤ 0.05).

Conclusions: Progesterone had no effect on undisturbed sleep but restored normal sleep when sleep was disturbed (while currently available hypnotics tend to inhibit deep sleep), acting as a "physiologic" regulator rather than as a hypnotic drug. Use of progesterone might provide novel therapeutic strategies for the treatment of sleep disturbances, in particular in aging where sleep is fragmented and of lower quality.

Publication types

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

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Aged
  • Double-Blind Method
  • Estrogen Replacement Therapy / methods
  • Female
  • Gonadal Steroid Hormones / analysis
  • Gonadal Steroid Hormones / blood
  • Human Growth Hormone / blood
  • Human Growth Hormone / metabolism*
  • Humans
  • Hydrocortisone / blood
  • Melatonin / blood
  • Melatonin / metabolism*
  • Middle Aged
  • Placebos
  • Postmenopause / blood
  • Postmenopause / drug effects*
  • Postmenopause / metabolism
  • Progesterone / pharmacology
  • Progesterone / therapeutic use*
  • Sleep Wake Disorders / prevention & control*
  • Thyrotropin / blood
  • Thyrotropin / metabolism*
  • Thyroxine / blood


  • Gonadal Steroid Hormones
  • Placebos
  • Human Growth Hormone
  • Progesterone
  • Adrenocorticotropic Hormone
  • Thyrotropin
  • Melatonin
  • Thyroxine
  • Hydrocortisone