Menopausal estrogen-only therapy appears to lower risk of mortality significantly without harmful side effects among women treated in their 50s who had had a hysterectomy and their ovaries removed, the findings of a long-term study conducted at 40 US centers have indicated.

Results from the randomized, double-blind Women’s Health Initiative (WHI) Estrogen-Alone Trial, published online yesterday in the Annals of Internal Medicine, followed 9939 women ages 50 to 79 years for an average 18 years.

However, the mortality benefits of conjugated equine estrogens (CEE) did not extend to women who started estrogen therapy in their 60s or 70s, whether or not their ovaries were removed, JoAnn E. Manson, MD, DrPH, from Harvard Medical School and Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues, report.

The authors note that between one third and one half of women who undergo a hysterectomy also have both ovaries removed (bilateral salpingo oophorectomy [BSO]), to reduce their risk of developing ovarian cancer. Yet, the resultant menopause and loss of estrogen has been linked with other health risks.

Younger women (50 to 59) with BSO who were randomly assigned to the CEE group saw a statistically significant 32% reduction in all-cause mortality in the follow-up years (hazard ratio, 0.68; 95% confidence interval, 0.48 – 0.96). They also saw non-significant trends with 15% to 33% risk reductions in coronary heart disease (CHD), breast cancer and a global index for CHD, breast cancer, and mortality combined.

Younger women whose ovaries were intact did not experience a reduction.

The mortality reduction associated with CEE among younger women with BSO was most notable when women had the surgical procedure before age 45 years, the authors write.

An unfavourable balance of risk and benefits was particularly pronounced for those women, ages 70 to 79 at baseline, who were randomly assigned to CEE. The reason for those findings is unclear, the authors say.

JoAnn Pinkerton, MD, professor of obstetrics and gynaecology and director of midlife health at the University of Virginia Health System in Charlottesville – and also executive director emeritus for the North American Menopause Society – told Medscape Medical News that the thinking has been that women who have early surgical menopause before age 45 or so, should definitely take estrogen until age 51, the average age of menopause, and then re-evaluate.

This study looked at slightly older women — ages 50 to 59 — who had their ovaries removed and the researchers found a reduction in all-cause mortality in this group.

The results should change practice and may alleviate fears, she said: “Women and providers are still very frightened about estrogen therapy and hormone therapy,” Pinkerton said. “Even though we’ve shown that estrogen by itself or estrogen with progesterone, if you have a uterus, is safe and has benefits, women are still frightened to take it.”

This study, she said, further emphasizes that women who have hysterectomies and ovaries removed ought to strongly consider estrogen therapy around the time of menopause for the benefits — not only to combat hot flashes and night sweats, but potentially to lower their risk of heart disease and all-cause death.

“On the other side,” Pinkerton added, “women who are over 70 and have had hysterectomies and ovaries removed saw an increased risk from taking estrogen. And that fits with earlier analysis. Age and time are very important when you’re counselling women about hormone therapy.”

The bottom line, she said, is that young women who have had their ovaries removed should strongly consider estrogen. If under 60, within 10 years of menopause, and have had their uterus and ovaries removed, they are strong candidates for estrogen.

They may also be candidates if they haven’t had their ovaries or uterus out, Pinkerton noted, but that would be primarily for menopausal symptoms.


REFERENCE: Manson et al: Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy: A Randomized Trial;