Cochrane update: long-term hormone therapy reduced fractures but raised stroke and, when combined, breast cancer

Design

Cochrane systematic review of 24 double-blind randomised trials

Population

45,660 peri- and postmenopausal women, mostly over 60

Primary outcome

Long-term mortality, cardiovascular, cancer and fracture outcomes

Effect

Combined: breast cancer RR 1.27 (1.03–1.56); oestrogen-only: stroke RR 1.33 (1.06–1.67); fractures RR 0.73–0.78

This updated Cochrane review included 24 double-blind randomised trials with 45,660 women taking hormone therapy or placebo for at least a year. About 70% of the data came from the Women's Health Initiative and HERS; most women were over 60 with comorbidities.

In the Women's Health Initiative combined oestrogen–progestogen trial (16,608 women, 5.6 years), therapy probably made little difference to coronary events (RR 1.17), may have increased stroke (RR 1.39) and venous thromboembolism (RR 2.03), probably increased breast cancer (RR 1.27) and probably reduced all clinical fractures (RR 0.78). In the oestrogen-only trial (10,739 women after hysterectomy, 7 years), therapy probably increased stroke (RR 1.33) and gallbladder surgery (RR 1.78), probably made little difference to coronary events and breast cancer, and reduced fractures (RR 0.73).

For geriatricians and GPs, this is most relevant to older women still taking hormone therapy started years ago. The findings apply to oral conjugated equine oestrogen started mostly after 60, and may not reflect transdermal preparations or treatment started at menopause.

• Review the indication for hormone therapy in older women at each medication review
• Weigh stroke and thromboembolism risk against symptom benefit in women over 60
• Consider transdermal oestrogen where continuation is chosen and thrombotic risk is a concern
• Do not start hormone therapy in older women for fracture or cardiovascular prevention

Why it matters

Many older women continue hormone therapy started long ago without a review of its changing risk balance.

Don't overread it

Mostly oral conjugated oestrogen started after 60 — the results may not apply to younger women or transdermal therapy.

The statistics, in plain English

Moderate certainty means the true effect is probably close to the estimate. The venous thromboembolism interval for combined therapy is wide (1.55 to 6.64). These are relative risks; absolute risks depend on each woman's baseline, which rises with age.

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