Some of the health risks that halted the Women’s Health Initiative (WHI) trial have dissipated as more time has passed, according to a recent analysis.

The estrogen-alone arm of the WHI trial was stopped a year early in 2004, after a mean 7.1 years of follow-up, due to an increased risk of stroke associated with the use of conjugated equine estrogens (CEE) among participants. However, WHI investigators continued to follow 7,645 consenting surviving participants through August 2009, constituting a mean follow-up period of 10.7 years.

The participants had used CEE for a median of 5.9 years or placebo for a median of 5.8 years during the trial. In the postinter­vention period, the risk for coronary heart disease remained similar to that observed during the intervention. However, the increased risk of stroke among the CEE group was no longer present postintervention, nor was the increase in deep vein thrombosis and pulmonary embolism.

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A reduced risk of breast cancer in CEE users persisted from intervention through postinter­vention, and gained statistical significance with extended follow-up. Colorectal cancer incidence did not differ between the two groups during intervention or postintervention.

Risk of hip fracture, which was lower in the CEE group than in the placebo group during the CEE intervention phase, became slightly higher in the CEE group compared with the placebo group in postintervention.

In addition, “Rates of total mortality and the global index of chronic diseases were essentially the same in the CEE and placebo groups,” noted the authors (JAMA. 2011;305:1305-1314). “Statistically significant age interactions for CEE use, suggesting greater safety and possible benefit among women in their 50s and potential harm among older women, were observed for [coronary heart disease, total MI], colorectal cancer, total mortality, and the global index of chronic diseases.”

The findings emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status. Risks of colo­rectal cancer, death, and the global index of chronic diseases were elevated over the cumulative follow-up period for older women. For younger women, the postintervention period gave rise to no new safety concerns, and some risk reductions became apparent during that phase.