Estrogen vs. Breast Cancer in Postmenopausal Hysterectomized Women

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Alvin B. Lin, MD, FAAFP

Associate Professor of Family and Community Medicine, University of Nevada School of Medicine

Adjunct Professor of Family Medicine and Geriatrics, Touro University Nevada College of Medicine

Advisory Medical Director, Infinity Hospice Care

Medical Director, Lions HealthFirst Foundation

Dr. Lin maintains a small private practice in Las Vegas, NV. The posts represent the views of Dr. Lin, and in no way are to be construed as representative of the above listed organizations. Dr. Lin blogs about current medical literature and news at


When you look at the design of the Women's Health Initiative (WHI) involving women who have an intact uterus and those who've undergone hysterectomy, it's striking that everyone in both arms was randomized to conjugated equine estrogen (CEE) or a placebo, regardless of uterine status, while only those with an intact uterus were given medroxyprogesterone acetate (MPA) in conjunction with CEE and placebo in conjunction with placebo.

In that case, let's assign the variable A to CEE and variable B to MPA. In other words, the two arms of WHI then become trials of A+B vs placebo (intact uterus) and A vs placebo (post-hysterectomy). At that point, you can then look at the two arms together as A+B vs A. In which case, it's always seemed strange to me that when A+B (CEE +MPA) was associated with negative outcomes but A alone (CEE) was not, we lumped both regimens together and threw the baby out with the bath water.

They say time heals old wounds. More data has been analyzed and reanalyzed since the first announcement of WHI. In this latest analysis published early online almost 3 weeks ago in Lancet, the authors continued to follow for close to 12 years 10,739 postmenopausal hysterectomized women, aged 50 to 79 years, at the start of the trial. They concluded that, compared to placebo, those randomized to 6 years of CEE alone had a lower risk of breast cancer. In fact, fewer women died from breast cancer when randomized to CEE than compared to those randomized to placebo.

Yet when you look at the parallel CEE+MPA arm (A+B), you find an increase risk of breast cancer and mortality. So while the authors conclude that differences in hormone therapy may account for the different results, I can't help but wonder why they can't come out and state that MPA may not be as safe as we've been led to think. After all, the effects of MPA are quite different from that of bio-identical progesterone, sold as FDA approved Prometrium. In the meantime, while I can't recommend CEE alone to prevent breast cancer, certainly one can feel more comfortable and safe about taking it during menopause.