Estrogen Therapy After Oophorectomy: Age Matters!

This transcript has been edited for clarity.

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts. I'd like to talk with you about our study with the Women's Health Initiative (WHI) on estrogen-alone therapy and health outcomes among women with and without bilateral oophorectomy. The study was recently published Annals of Internal Medicine^[1] and included 10,000 women with prior hysterectomy who were aged 50-79 at the time of randomization.

In all of the reports from the WHI hormone therapy trial, there has never been a previous study where the estrogen results differed between women who had their ovaries surgically removed versus the women with conserved ovaries. When we looked at the overall cohort across all age groups, we found minimal differences between the women with oophorectomy and those with conserved ovaries. The findings tended to be neutral, null, with no significant increases or decreases in major health outcomes.

However, when we looked at the results stratified by age, there were major differences across age groups among the women with bilateral oophorectomy and minimal differences among the women with conserved ovaries. During the intervention phase of 7 years, there was a generally adverse global index effect of estrogen therapy among women aged 70 and older, a neutral effect among women in their 60s, and a favorable effect among women in their 50s.

These patterns became even clearer with longer-term cumulative follow-up to 18 years. During follow-up, the younger women had a statistically significant 32% reduction in all-cause mortality with estrogen therapy compared with placebo, whereas the other age groups had neutral results. The test for trend for all-cause mortality was significant, at around 0.03.

We were interested in the age at which women underwent bilateral oophorectomy. We saw that the women who had an oophorectomy prior to age 45 seemed to particularly benefit from estrogen therapy, with a 40% significant reduction in all-cause mortality.

So, overall the findings lend support to current guidelines that women who have early surgical menopause may benefit from estrogen therapy, at least until the average age of natural menopause (age 50-51). Women who have moderate to severe symptoms and a favorable benefit-risk profile can continue estrogen therapy through their 50s to age 60, in the absence of contraindications.

But the findings do suggest that women who are more remote from menopause with a history of oophorectomy may have adverse effects from late initiation of estrogen therapy, which may be due to the prolonged period of low estrogen levels. These findings inform clinical decision-making.

Thank you so much for your attention. This is Dr JoAnn Manson.

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