Fine-Tuning Our Knowledge About Hormone Replacement Therapy

Some menopausal women experience uncomfortable symptoms, such as hot flashes and mood swings, and some are at risk of bone fractures because producing less estrogen impairs the body’s ability to rebuild bone. For a long time, hormone replacement therapy (HRT) to address these concerns has been the subject of scientific study and commentary.

We blogged last year about the U.S. Preventive Services Task Force (USPSTF) confirming a 10-year-old recommendation not to use HRT long term because of increased risk of stroke, blood clots, some kinds of cancer and other serious problems.

But the science is evolving, and a new study published in JAMA Internal Medicine has parsed different risks associated with different forms of HRT.

As reported on, for postmenopausal women, conjugated equine estrogens (CEEs) were associated with about twice the risk of venous thrombosis (blot clots) and possibly myocardial infarction (heart attack) as estradiol. Both are used in compounding hormone replacements.

The CEE form of estrogen is extracted from the urine of pregnant horses and contains several active estrogen compounds. Estradiol contains only a single synthetic hormone made by human ovaries.

The association between CEEs and blot clots was clear, but the association with heart risk didn’t meet the threshold for “significant.” The researchers also reported no association with stroke risk. The results were from the Heart and Vascular Health Study, which examines cardiovascular events among members of a large health maintenance organization in Washington state.

The study looked for cases of blood clots, heart attacks and stroke among menopausal women taking oral hormones after Jan. 1, 2003. As noted on MedPageToday, that’s about six months after the landmark publication of the findings of the Women’s Health Initiative Study (WHI), a huge trial involving hundreds of thousands of people that started the whole HRT debate, and prompted many doctors and their patients to alter their meds.

The WHI study compared hormone therapy with a placebo, or inert, fake treatment. It found that hormone therapy increased the risks for several adverse events.

The new study compared estrogen drugs among users, not users versus nonusers. It showed that using oral CEEs, compared with oral estradiol, was associated with:

  • an increased venous thrombosis risk;
  • an apparent increase in the risk of heart attack, although the value wasn’t significant;
  • no increase in ischemic stroke risk.

The researchers said that the findings needed additional trials for confirmation, and that they concern only active use of hormones that indicate nothing about the relative risks of even starting HRT. But this refinement of the research is valuable nonetheless to spur conversation between doctors and patients about the risks and benefits generally of HRT, and if it’s initiated, to choose the form of hormone best suited to each patient’s medical profile.

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