HT post menopause increases stroke risk

Hormone therapy (HT) in postmenopausal women does not prevent heart disease but does increase the risk of stroke and blood clots, according to an updated review.

“Treatment with HT in postmenopausal women for either primary or secondary prevention of cardiovascular disease events has little if any benefit overall, and causes an increase in the risk of stroke, or venous thromboembolic events,” reported by the University of Oxford (England) John Radcliffe Hospital.

They updated a review published in 2013 with data from six randomized controlled trials. The total of 19 trials, involving 40,410 postmenopausal women, compared orally administered estrogen, with or without progestogen, to a placebo or no treatment for a minimum of six months. The average age of the women, mostly from the United States, was older than 60 years. They received HT from seven months to 10 years across the studies.

The sharp rise in cardiovascular disease rates in women after menopause had been hypothesized to be related to a decline in hormone levels that cause a higher androgen-to-estradiol ratio, and observational studies starting in the 1980s showed lower mortality rates and cardiovascular events in women receiving HT compared to those not receiving it.

Two subsequent randomized controlled trials contradicted these observational findings, leading to further study. In this review, HT showed no risk reduction for all-cause mortality, cardiovascular death, nonfatal MI, angina, or revascularization.

However, the overall risk of stroke for those receiving HT for both primary and secondary prevention was 24% higher than that of women receiving placebo treatment (relative risk, 1.~4), with an absolute risk of six additional strokes per 1,000 women.

Venous thromboembolic events occurred 92% more and pulmonary emboli occurred 81% more in the HT groups (RR, 1.92 and 1.81, respectively), with an increased absolute risks of 8 per 1,000 women and four per 1,000 women, respectively.

The researchers calculated the number needed to treat for an additional harm at 165 women for stroke, 118 for venous thromboembolism, and 242 for pulmonary embolism. Further analysis showed that the relative risks or protection hormone therapy conferred depended on how long after menopause women started treatment.

Mortality was reduced 30% and coronary heart disease was reduced 48% in women who began HT less than 10 years after menopause (RR, 0.70, and RR, 0.52, respectively); these women still faced a 74% increased risk of venous thromboembolism, but no reduced risk on overall death or coronary heart disease.

“The benefit seen in survival and coronary heart disease for the group starting treatment less than 10 years after the menopause is from combining five trials all performed in primary prevention populations and all with quite long follow-up, ranging from 3.4 to 10.1 years.”

These results may reflect a time interaction, with coronary heart disease events occurring earlier in predisposed women, making it impossible to say whether short duration therapy is beneficial in this population or not.