Effects of low-dose, continuous combined hormone replacement therapy on sleep in symptomatic postmenopausal women

Maturitas. 2005 Feb 14;50(2):91-7. doi: 10.1016/j.maturitas.2004.04.006.


Sleep disturbances in peri- and postmenopausal women may result from hormonal changes, vasomotor symptoms, and possibly psychological factors. Hormone replacement therapy (HRT) seems to diminish the disruption of sleep in climacteric women. The aim of this study was to determine the effects of a low dose of conjugated equine estrogens (CE) in combination with different progestins (LD-HRT) and evaluate differences between regimens on sleep in symptomatic postmenopausal women. Postmenopausal women were recruited and assigned to calcium-vitamin (control group) or to LD-HRT with 0.3mg of CE associated with a daily administration at bedtime of a progestin (2.5 mg MPA, CE + MPA, n = 20), or 100 mg natural micronized progesterone (CE + P, n = 20). Subjective symptoms were evaluated by the Greene climacteric scale, and by a visuanalogic graduated scale (0-10) at baseline and after 4, 8, and 12 weeks of study. Greene's scores for the control group were similar to those in LD-HRT group at baseline, and showed no significant modification at all subsequent measurements. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident versus corresponding baseline and control group values. Conversely, in LD-HRT group, a significant (P < 0.05) reduction in the scores of all Greene's domains was evident with no difference in the scores of the two treated group. Both CE + MPA and CE + P significantly (P = 0.05) reduced the HF and sleep visuanalogic score in comparison to the control group. The score of sleep was significantly (P = 0.05) lower in the CE + P group in comparison to that measured in the CE + MPA group. No significant correlation between sleep and vasomotor score was found. In conclusion, low estrogen dose may have a value in the treatment of menopausal women in which sleep disturbances may be a symptom of estrogen deprivation. Low-dose estrogen associated with low-dose micronized progesterone may especially benefit women who complain of disturbed sleep.

Publication types

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

MeSH terms

  • Contraceptive Agents, Female / therapeutic use
  • Dose-Response Relationship, Drug
  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use
  • Estrogens, Conjugated (USP) / therapeutic use
  • Female
  • Humans
  • Medroxyprogesterone Acetate / therapeutic use
  • Middle Aged
  • Postmenopause / physiology*
  • Progesterone / therapeutic use
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / physiopathology
  • Treatment Outcome


  • Contraceptive Agents, Female
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progesterone
  • Medroxyprogesterone Acetate