Menopausal Hormone Therapy: Let the Women Decide

Andrew M. Kaunitz, MD


October 07, 2019

This transcript has been edited for clarity.

Once again, we have evidence of potential harms—specifically, invasive breast cancer—associated with menopausal hormone therapy (HT). What does this mean, if anything, for clinical practice?

Systemic HT is still the most effective treatment for bothersome menopausal vasomotor symptoms, including hot flashes. In 2002, initial findings from the Women's Health Initiative (WHI) clinical trial of HT noted an elevated risk for cardiovascular events and breast cancer with estrogen-progestin therapy (EPT). This resulted in major declines in use of HT among US women.

HT's risk-benefit profile is complex. In contrast with the findings of the WHI's EPT trial, subsequent results from the WHI estrogen-only trial of women post-hysterectomy found no elevation in risk for breast cancer. Both EPT and HT were noted to elevate risk for thromboembolism and stroke while reducing the risk for fractures and diabetes.

A recent meta-analysis published in The Lancet aggregated findings from 58 observational studies to assess the association between use of HT and risk for invasive breast cancer.

All systemic HT formulations, including those with oral conjugated estrogen as well as estradiol and transdermal estradiol, were associated with an elevated risk for breast cancer. EPT was associated with a greater elevation in breast cancer risk than estrogen-only regimens. The type of progestin did not appear to be associated with degree of elevation in risk for breast cancer. The use of vaginal estrogen was not associated with breast cancer risk.

In contrast with the meta-analysis of observational studies, the WHI estrogen-alone clinical trial found that conjugated estrogen did not elevate, and in fact reduced, the risk for breast cancer with long-term follow-up.

How can we explain differences in findings between the WHI randomized trials and this new meta-analysis? In observational studies, women using HT have mammograms more frequently than non-users. Accordingly, the detection bias intrinsic to observational studies may account for the differences between the meta-analysis findings and those of the WHI.

Although women are understandably concerned regarding how HT may impact their future risk for breast cancer, decisions regarding use of HT should be informed by the big picture.

In absolute terms, most of the risks associated with systemic HT are modest. And with 18 years of cumulative follow-up, the WHI's findings regarding overall as well as cancer-related mortality are reassuring, especially for women who initiate HT prior to the age of 60.

The largest hazard ratio associated with HT use corresponds to an elevated risk for venous thromboembolism, and using transdermal rather than oral estrogen attenuates or eliminates this excess risk.

Some women, including those at elevated baseline risk for breast cancer, will choose to avoid systemic HT. However, for many well-informed, recently menopausal women with bothersome vasomotor symptoms, initiation of systemic HT represents a prudent choice.

Thank you for the honor of your time. I am Andrew Kaunitz.

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