Hormone therapy in postmenopausal women does not prevent heart disease but does increase the risk of stroke and blood clots, according to a recently updated Cochrane review .

“Our review findings provide strong evidence that treatment with hormone therapy 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 Dr. Henry Boardman of the University of Oxford John Radcliffe Hospital, and his associates.

The researchers updated a review published in 2013 with data from an additional six randomized controlled trials. The total of 19 trials, involving 40,410 postmenopausal women, all compared orally-administered estrogen, with or without progestogen, to a placebo or no treatment for a minimum of 6 months (Cochrane Database Syst. Rev. 2015 March 10 [doi:10.1002/14651858.CD002229.pub4]).

The average age of the women in the studies, mostly from the United States, was older than 60 years, and the women received hormone therapy anywhere from 7 months to 10 years across the studies. The overall quality of the studies was “good” with a low risk of bias.

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

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

However, the overall risk of stroke for those receiving hormone therapy for both primary and secondary prevention was 24% higher than that of women receiving placebo treatment (relative risk 1.24), with an absolute risk of 6 additional strokes per 1,000 women.

Venous thromboembolic events occurred 92% more and pulmonary emboli occurred 81% more in the hormone treatment groups (RR 1.92 and 1.81, respectively), with increased absolute risks of 8 per 1,000 women and 4 per 1,000 women, respectively.

The researchers calculated the number needed to treat for an additional harm (NNTH) at 165 women for stroke, 118 for venous thromboembolism, and 242 for pulmonary embolism.

Further analysis revealed 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 hormone therapy 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 increased risk of stroke.

Meanwhile, women who started hormone therapy more than 10 years after menopause had a 21% increased risk of stroke and a 96% increased risk of venous thromboembolism, but no reduced risk on overall death or coronary heart disease.

“It is worth noting that 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,” the authors wrote.

These results may reflect the possibility of 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, the researchers wrote .

Eighteen of the 19 trials included in the analysis reported the funding source. One study was exclusively funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-LaRoche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.


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