Symptom experience after discontinuing use of estrogen plus progestin

JAMA. 2005 Jul 13;294(2):183-93. doi: 10.1001/jama.294.2.183.


Context: Little is known about women's experiences after stopping menopausal hormone therapy.

Objective: To describe women's symptoms and management strategies after stopping the intervention in a large estrogen plus progestin trial.

Design, setting, and participants: Cross-sectional survey of 8405 women (89.9%; N = 9351) at 40 clinical centers who were still taking study pills (conjugated equine estrogens plus medroxyprogesterone [CEE + MPA] or placebo) when the estrogen plus progestin intervention (Women's Health Initiative) was stopped. Surveys were mailed 8 to 12 months after the stop date. Logistic regression was used to model vasomotor symptoms and pain or stiffness symptoms as functions of former treatment and baseline symptoms, adjusted for appropriate covariates.

Main outcome measures: Symptoms (vasomotor or pain and stiffness) and management strategies.

Results: Respondents' mean (SD) age at trial stop date was 69.1 (6.7) years. They averaged 5.7 years of taking study pills. Moderate or severe vasomotor symptoms after discontinuing study pill use were reported by 21.2% of former CEE + MPA and 4.8% of placebo group respondents overall and by 55.5% and 21.3%, respectively, with these symptoms at baseline (randomization). Compared with respondents in the former placebo group, moderate or severe vasomotor symptoms (adjusted odds ratio [AOR] 5.82; 95% confidence interval [CI], 4.92-6.89) and pain or stiffness symptoms (AOR, 2.16; 95% CI, 1.95-2.40) were more likely in respondents in the former CEE + MPA group. Both vasomotor symptoms (AOR, 5.36; 95% CI, 4.51-6.38) and pain or stiffness symptoms (AOR, 3.21; 95% CI, 2.90-3.56) also were more likely in women with these symptoms at baseline. Women reported a wide range of strategies to manage symptoms.

Conclusions: More than half of the women with vasomotor symptoms at randomization to active CEE + MPA also reported these symptoms after discontinuing use of the study pills. However, these participants did not include women who were unwilling to be randomized or who had stopped taking the study pills earlier. These findings should be considered when advising women to treat menopausal symptoms with hormone therapy for as short duration as possible. Investigation of alternative strategies to manage menopausal symptoms is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anxiety
  • Cross-Sectional Studies
  • Estrogen Replacement Therapy*
  • Estrogens / pharmacology*
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Humans
  • Logistic Models
  • Medroxyprogesterone Acetate / pharmacology*
  • Menopause* / drug effects
  • Menopause* / physiology
  • Middle Aged
  • Pain
  • Progestins / pharmacology*
  • Randomized Controlled Trials as Topic
  • Substance Withdrawal Syndrome*
  • Vasomotor System


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progestins
  • Medroxyprogesterone Acetate