Recent study results have not supported the cardiovascular protective effects of conjugated equine estrogen, used alone or in combination with progesterone, that were noted in earlier observational studies. Authors of the Women’s Health Initiative (WHI) study of conjugated equine estrogen found that women who took conjugated equine estrogen were at increased risk of stroke and deep venous thrombosis and at decreased risk of osteoporotic fractures. Because of these findings, the study was stopped earlier than planned. A portion of the WHI study that evaluated the effect of conjugated equine estrogen plus a progesterone component on vasomotor symptoms and other health-related quality-of-life issues found only modest gains that were not considered clinically significant; however, the effect on women who have had a hysterectomy was unclear. Therefore, Brunner and associates conducted a randomized, double-blind, placebo-controlled trial to evaluate the effect of conjugated equine estrogen on the health-related quality of life of women who had undergone hysterectomy.
Women who had a hysterectomy (with or without oophorectomy) more than three months before the study and were 50 to 79 years of age were included in the study. They were assigned randomly to receive conjugated equine estrogen in a dosage of 0.625 mg daily or placebo. Patients who were taking hormone therapy before the study had a three-month washout period. Those who had moderate to severe menopausal symptoms during this washout period were encouraged to withdraw from the study but were not excluded.
Six quality-of-life assessments were done at baseline and one year for all patients and at three years for a more ethnically diverse subset of patients. The authors assessed health-related quality of life and functional status, global quality of life, sleep quality, sexual satisfaction, cognitive functioning, and depressive symptoms. The changes in the scores were analyzed to compare treatment effect between the conjugated equine estrogen and placebo groups.
There were 5,310 women randomly assigned to the treatment group and 5,429 assigned to the placebo group. The mean age of the participants was 63.6 years, 75.3 percent were white, 23.9 percent were college educated, 48.4 percent had a history of hormone use, and 17.3 percent had moderate to severe vasomotor symptoms. At one year, participants who received conjugated equine estrogen had a small reduction in sleep disturbances (mean benefit: 0.4 points out of 20) and an even smaller negative effect on social functioning (mean effect: −1.3 on a 100-point scale). No significant improvements were noted in the other quality-of-life scales between the two groups at one year. In the subset of participants who were assessed at year 3, no significant differences in the quality-of-life measurements were noted between the groups. A subgroup of women 50 to 54 years of age who reported moderate to severe vasomotor symptoms also had no significant differences in their quality-of-life measurements when compared with the placebo group.
The authors conclude that oral conjugated equine estrogen does not have a clinically significant effect on health-related quality of life in women who have had a hysterectomy. They add that in the WHI study, the risks and benefits of conjugated equine estrogen use were relatively balanced at six years. They note that vasomotor symptoms will improve in some women, but this is offset by the adverse effects of hormone therapy.