New Data Upends Timing Hypothesis

When the Womens Health Initiative came out almost 9 years ago, it really upset the traditional apple cart regarding the use of hormonal therapy to prevent heart disease.  Overnight, prescriptions & sales of estrogen/progestin products to combat menopausal symptoms went down the drain.  During the ensuing years, the pendulum has swung back towards the midline, as we've moved towards prescribing smaller doses for shorter periods of time.  Part of the swing has been due to subgroup analyses, discussions over bio-identical hormones vs non-bio-identical (still not an accepted & recognized portion of traditional medicine's lexicon), and to development of the timing hypothesis.

Specifically, the timing hypothesis addressed what appeared to be a decrease risk of cardiovascular disease in those women who received hormone replacement soon after entering the menopause, as compared to those who didn't receive any hormone replacement until they were at least 10 years out from menopause (and presumably completely asymptomatic at that time).

However, in a paper just released by the Journal of the National Cancer Institute to be published next month, a review of data from the United Kingdom's Million Women Study concluded that women who started hormone replacement therapy (either estrogen alone or estrogen + progestin) within 5 years of entering menopause had a significantly higher risk of developing breast cancer compared to those who started more than 5 years post-menopause.

The above findings relating to time of initiation are similar to those from a French cohort published almost 2 years ago.  Of note, when they specifically looked at those women who received progesterone, there was no increase risk of breast cancer compared to those who received other progestins.  Interestingly, the Million Women data also demonstrated an increase risk of breast cancer in those who received combination estrogen + progestin therapy compared to those who received estrogen alone.  This makes one question the effect of the non-bio-identical progestin on breast cancer risk.  Luckily, the authors also noted that risk of breast cancer returns to baseline within 3-4 years after cessation.

So what is one to do?  I suggest we continue what we've always done as family physicians:  have a heart-to-heart discussion w/our patients concerning the risks, benefits and alternatives, in this case possibly trading an increase risk of breast cancer early on for a lower risk of heart disease.  By the way, do you know what's the number cause of death in women?  It's not breast cancer - it's heart disease!