Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women

Menopause. Jul-Aug 2002;9(4):253-63. doi: 10.1097/00042192-200207000-00006.


Objective: To compare the mood and somatic effects during the initial 2 months of medroxyprogesterone acetate (MPA) or progesterone combined with conjugated equine estrogen (CEE) in early postmenopausal women.

Design: Twenty-three nondepressed, early postmenopausal women (average age, 52.5 years) completed a 91-day, single-blind pilot study with the following sequence of treatments: 1 week of no substance; 2 weeks of placebo; 2 weeks of progestogen only; 1 week of placebo; and 2 months of "standard hormone replacement therapy cycles," which consisted of (in order) 2 weeks of 0.625 mg CEE, 2 weeks of CEE plus progestogen, 2 weeks of CEE, and 2 weeks of CEE plus progestogen. Ten women who completed the study received MPA (5 mg/day) as their progestogen, and 13 who completed the study received micronized, oil-suspended progesterone (200 mg/day) as their progestogen. All participants made daily assessments of mood using the Profile of Mood States and daily recordings of somatic symptoms. All subjects had plasma follicle-stimulating hormone of greater than 35 IU/L and had not had spontaneous vaginal bleeding for more than 1 year.

Results: None of the hormone treatments had a detectable effect on mood. MPA users reported more vaginal bleeding and breast tenderness than progesterone users.

Conclusions: In contrast with the widely held belief among psychiatrists that progesterone depresses mood, neither of the progestogens we used in normal, nondepressed and nonanxious women showed this effect. Absence of an effect on mood was also found when the results of the two progestogens were combined. The lesser side effects of the micronized progesterone-containing regimen suggest that some women may prefer it to an MPA-containing regimen.

Publication types

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

MeSH terms

  • Breast / physiopathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Estrogens, Conjugated (USP) / administration & dosage
  • Estrogens, Conjugated (USP) / adverse effects*
  • Female
  • Hot Flashes / physiopathology
  • Humans
  • Medroxyprogesterone / administration & dosage
  • Medroxyprogesterone / adverse effects*
  • Middle Aged
  • Mood Disorders / physiopathology
  • Physical Fitness
  • Pilot Projects
  • Postmenopause / drug effects*
  • Postmenopause / psychology
  • Probability
  • Progesterone / administration & dosage
  • Progesterone / adverse effects*
  • Reference Values
  • Sensitivity and Specificity
  • Treatment Outcome


  • Estrogens, Conjugated (USP)
  • Progesterone
  • Medroxyprogesterone