How does the postmenopausal use of estrogen plus progestin affect a women's risk of breast cancer?

Updated: Dec 26, 2019
  • Author: Graham A Colditz, MD, DrPH; Chief Editor: Chandandeep Nagi, MD  more...
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Answer

The addition of a progestin to estrogen regimens has become increasingly common, as it minimizes or eliminates the increased risk of endometrial hyperplasia and cancer associated with using unopposed estrogens. In the United States, by the mid-1980s, almost 30% of postmenopausal hormone prescriptions included a prescription for progestin. The impact of an added progestin to the risk of breast cancer has been evaluated only in the last 20 years.

Two of the first studies to assess this relationship suggested that the addition of a progestin could decrease breast cancer risk. However, these studies were small, and potentially important confounders (eg, age, parity) were not accounted for in the analyses. Since this time, additional studies have assessed this relationship and together indicate that there is no protective effect of typical doses used in postmenopausal hormone therapy. [41] More recent studies also support this increase in risk with combination estrogen plus progestin. [44]

In addition to their effect on breast cancer, postmenopausal hormones also have a major impact on other aspects of women’s health. Results from the WHI (a large randomized clinical trial) definitively show that, after 5 years of use, estrogen plus progestin does more overall harm to women than good. Although the WHI studied only one specific type and dose of estrogen plus progestin (Prempro), because widespread use of estrogen plus progestin is relatively recent, few data are available to evaluate the effect of different formulations, doses, or schedules of use of progestin on risk of breast cancer.

The British Million Women Study, with over 9,000 cases of breast cancer during follow-up, again confirms the excess risk of breast cancer among women currently using combination estrogen plus progestin and notes this is a significantly greater RR than using estrogen alone. Risk increased with duration of use but did not vary significantly according to the progestogen content or whether use was sequential or continuous. [46] The possibility remains that dose of progestogen is important, but variation in studies to date has not allowed rigorous and valid comparisons.


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