Hormone replacement therapy (HRT) safety profile

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 increased 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 favoured 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

Reference

1. NICE. Menopause: identification and management. NICE guideline NG23. Published November 2015, last updated November 2024
2. British Menopause Society. HRT - Guide (February 20th 2020