Long term hormone therapy for perimenopausal and postmenopausal women

Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004143. doi: 10.1002/14651858.CD004143.pub3.


Background: Hormone therapy (HT) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of the original Cochrane review first published in 2005.

Objectives: To assess the effect of long-term HT on mortality, cardiovascular outcomes, cancer, gallbladder disease, cognition, fractures and quality of life.

Search strategy: We searched the following databases to November 2007: Trials Register of the Cochrane Menstrual Disorders and Subfertility Group, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Biological Abstracts. Also relevant non-indexed journals and conference abstracts.

Selection criteria: Randomised double-blind trials of HT versus placebo, taken for at least one year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via oral, transdermal, subcutaneous or transnasal routes.

Data collection and analysis: Two authors independently assessed trial quality and extracted data.

Main results: Nineteen trials involving 41,904 women were included. In relatively healthy women, combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event (after one year's use), stroke (after three years), breast cancer and gallbladder disease. Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease (after one to two years, three years and seven years' use respectively), but did not significantly increase the risk of breast cancer. The only statistically significant benefits of HT were a decreased incidence of fractures and (for combined HT) colon cancer, with long-term use. Among women aged over 65 who were relatively healthy (i.e. generally fit, without overt disease) and taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism.One trial analysed subgroups of 2839 relatively healthy 50 to 59 year old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thrombo-embolism in women taking combined continuous HT: their absolute risk remained low, at less than 1/500. However, this study was not powered to detect differences between groups of younger women.

Authors' conclusions: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality
  • Estrogen Replacement Therapy / adverse effects
  • Estrogen Replacement Therapy / methods*
  • Estrogens / adverse effects
  • Estrogens / therapeutic use
  • Female
  • Hot Flashes / drug therapy*
  • Humans
  • Middle Aged
  • Neoplasms / chemically induced
  • Neoplasms / mortality
  • Perimenopause*
  • Postmenopause*
  • Progesterone / adverse effects
  • Progesterone / therapeutic use
  • Randomized Controlled Trials as Topic


  • Estrogens
  • Progesterone