hormone replacement therapy (HRT) safety profile

Last reviewed 08/2021

safety profile of HRT

Use of HRT for ≤5 years is safe and effective in a majority of symptomatic women.

The Women’s Health Initiative Study and the Nurses’ Health Study  has estimated benefits and risks of oral HRT in postmenopausal women aged 50-59 years, or <10 years after menopause and according to these studies

  • majority of HRT related adverse effects increases with age
  • risks will differ with age and current health status  (1)

The main risks which should be considered when on HRT are:

  • thromboembolic disease (venous thromboembolism and pulmonary embolism)
    • the risk is increased with oral HRT (in both combined and oestrogen only pills)
    • the type, dose and delivery system may also affect  the risk
      • a recent systematic review found out that the risk of venous thromboembolism is incrased in oral HRT(but not transdermal)
      • in another large prospective observational study, the incidence of venous thromboembolism in low risk populations was not increased with low dose (≤1.5 mg oral, or ≤50 μg transdermal) oestradiol
    • hence a transdermal preparation and a reduced oestrogen dose is favored in women with increased risk of thromboembolic disease (1)
  • stroke
    • HRT increases the risk of stroke
    • HRT or tibolone should be avoided in women at high risk of stroke
  • cardiovascular disease
    • although the relationship between HRT and cardiovascular disease is questionable, the timing and duration of HRT, as well as pre-existing cardiovascular disease seems to have an effect on the outcome                                                                                                `
  • breast cancer
    • the risk of breast cancer diagnosis or breast cancer mortality is greater with combined HRT than with oestrogen alone
    • the risk with tibolone is not established (but large observational studies have shown an increased risk)
  • endometrial cancer
    • the risk is not increased with combined continuous HRT (when adequate duration and dose of progestogen are used) but risk may be increased with sequential HRT
    • risk of endometrial hyperplasia or cancer is not present in Tibolone users
  • gallbladder disease
    • HRT increases the risk of cholecystitis but can be reduced by using transdermal rather than oral HRT (1)