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)

Reference:

• (1) Hickey M, Elliott J, Davison SL.Hormone replacement therapy. BMJ. 2012;344:e763. 
• (2) Currie H, Cochrane R. Current options in the treatment of menopausal symptoms. Prescriber 2010;21(13)