WHI Study Update
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Response to “Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women”, JAMA, October, 2010

(brought to you by Bellevue Pharmacy, a ProjectAWARE sponsor)

This follow-up study continues the evaluation of breast cancer outcomes in patients that participated in the Women’s Health Initiative (WHI) trial that took place 1993 to 2002. The WHI trial was stopped when risks were found to exceed benefits, including the increased risk of breast cancer in patients treated with PremPro, a manufactured, non-bioidentical estrogen and progestin combination when compared to patients treated with placebo.

Results from the follow-up study:

  • Over the 8 year follow-up period, breast cancers were reported in both groups: the PremPro treatment group (6,545 participants) reported 385 cases of invasive breast cancers compared to 293 cases in the placebo group (6,243 participants)
  • Breast cancers in the PremPro treatment group were more commonly diagnosed in an advanced stage with more lymph node involvement compared to the placebo treatment group
  • Twice as many woman diagnosed with breast cancer in PremPro treatment group died during the follow-up period compared to placebo treatment group (2.6 deaths per 10,000 patients vs 1.3 deaths per 10,000 patients)


  • The follow-up study targeted use of PremPro, a manufactured prescription hormone therapy of conjugated equine/horse estrogens and medroxyprogesterone, not a customized prescription compound of bioidentical estradiol and progesterone
  • The study only evaluated long-term continuous use of hormone therapy
  • Dosing or route of hormones was not evaluated


The findings of this study are significant to us as clinicians who recommend hormone therapy for treatment of menopausal symptoms. Previous studies like the PEPI and HERS II trials have shown that medroxyprogesterone decreased the heart saving benefit of estrogen and also increased the risk of breast cancer. With the results of the estrogen (Premarin) arm of the WHI study showing no increased incidence of breast cancer, at least over the first 7 years of treatment, combined with the results of this WHI follow-up trial, suggests that it may be the progestin, medroxyprogesterone that increases the risk of breast cancer.

Armed with the results of this study and others, it strengthens the position that hormone therapy should be targeted to the individual patient based on medical history and risk profile. Hormone therapy in the form of human identical hormones, commonly referred to as bioidentical hormones and not “me too” hormones that are not identical to endogenous hormones should be the hallmark of hormone treatment. Other important considerations are the timing of hormone dosing (cyclic vs continuous therapy) and the route of hormone therapy. Several clinical studies suggest cyclic progesterone halts the growth of breast cancer cells. Additionally, transdermal (and sublingual) dosing limits first-pass liver metabolism, which can result in high estrone levels, often associated with higher risks of cancer. Additionally, this liver process elevates creatinine reactive protein (CRP) and other pro-inflammatory markers. Of course, cancer is an inflammatory process.

Due to the potential increased risk of breast cancer with hormone therapy, women should conduct regular breast self-exams, maintain regular physician exams and mammograms.


For questions and further information, contact Bellevue Pharmacy.


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Estrogen and Memory Loss
HRT for Breast Cancer Survivors and Women at High Risk for Cancer
Human Identical Hormones
Premarin, Facts and Opinions
Progesterone FAQ
Synthetic Progestins and Natural Progesterone, Differences
Natural Progesterone, What Role in Women's Healthcare
Tamoxifen for Prevention of Breast Cancer
Testosterone and Its Benefits to Women
Testosterone's Impact on Postmenopausal Women...
Thyroid Hormone, Symptoms, and...
Typical HRT Products
Where to get Natural Hormones
Herbal Allies, An Introduction
Alternative Remedies for Menopausal Symptoms



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