Depo-Provera Combined With Premarin May Increase Risk Of Breast Cancer: Study

Taking combination hormone replacement therapy involving Depo-Provera and Premarin may increase a woman’s risk of developing breast cancer, according to the findings of a new study.

In findings published last week in the Journal of the American Medical Association (JAMA), researchers with the Fred Hutchinson Cancer Researcher Center, and several other medical centers nationwide found that taking Premarin alone decreased the risk of cancer among women who had a hysterectomy. However, when added to Depo-Provera, the treatments appeared to increase cancer risks.

Researchers conducted a long-term follow-up of two placebo-controlled randomized clinical trials involving more than 27,000 postmenopausal women ages 50 to 79 with no prior breast cancer diagnosis.

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They used data from the Women’s Health Initiative randomized clinical trial, which enrolled women at 40 U.S. centers from 1993 to 1998.

Roughly 8,500 women were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE), more commonly known by the brand name Premarin. They also received 2.5 mg/d of medroxyprogesterone acetate, a synthetic progestin sold as Depo-Provera. The placebo group, totaling 8,100 women, received no hormones.

The second trial consisted of 10,700 women. Of those, 5100 women received 0.625 mg/d of only Premarin while 5,400 women received a placebo.

Among women who had not undergone hysterectomy and were taking the Premarin plus the Depo-Provera, there was an increased risk of cancer. However, there was no difference seen regarding increased risk of death. However, compared with placebo, women who had a prior hysterectomy and were taking Premarin had a significantly lower risk of breast cancer. They also had a much lower risk of death from breast cancer, up to a 40% reduction in deaths.

The link between menopausal hormone therapy and breast cancer risk is still unclear. A study published in 2015 indicated women taking hormone replacement therapy, like Prempro, an HRT much like Premarin and Depo-Provera combined, increased the risk of ovarian cancer by 43%.

Other studies also have shown use of HRT combining estrogen and progestin increased the risk of breast cancer by 88%.

The findings of the new study indicate a link between combination therapy of estrogen and progestin, or Premarin and Depo-Provera, and an increased risk of cancer. These results reinforce the findings of the prior studies.


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