Postmenopausal Hormone Replacement Reduces Mortality Risk? | by Raymond Ishman, M.D. | CEO, Chief Medical Officer | Cenegenics Philadelphia
The Women’s Health Initiative (WHI) study was prematurely stopped in 2002 due to a reported increase in the incidence of breast cancer in women in the hormone replacement arm of the study. As a result, thousands of women have stopped, or been taken off their hormones unnecessarily. This has lead to needless confusion, suffering and fear, to the point of hysteria in some, regarding the use of hormone replacement therapy (HRT). Since then, many of the main findings of this study have been debunked, albeit with much less media attention.
Multiple studies have challenged the conclusions of WHI. One such study was published in the British Medical Journal and released October 9, 2012. The data came from the Danish Osteoporosis Prevention Study where recently postmenopausal women, ages 45-58, were treated with or without HRT for 10 years. The original study was actually started in the early 1990s. Hormones were stopped at 10 years when the results of the Women’s Health Initiative (WHI) study were released in 2002, with follow up carried out until 2008. In the current report, the same data was analyzed for cardiovascular outcomes, cancer and overall mortality.
In the Danish study, women who previously had a hysterectomy were given oral estradiol. (Topical is now the preferred route.) Women who still had a uterus were given a combination of oral estradiol and a synthetic progestin. ( progesterone is now the preferred “progestin.”)
Conclusions of the analysis were that “After 10 years of randomized treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction (heart attack), without any apparent increase in risk of cancer, venous thromboembolism (blood clots), or stroke.” The mortality risk reduction was about 40%! They went on to state that “early initiation and prolonged hormone replacement therapy did not result in an increased risk of breast cancer or stroke.”
There was no significant difference in the incidence of breast cancer between those who took hormones and those who did not. In fact, women who started hormone therapy prior to age 50 had a significant decrease in the incidence of breast cancer.
What does this study tell us?
- Hormone therapy started in recently menopausal women and continued for a prolonged duration does not increase mortality, stroke, heart failure, or heart attacks.
- The rate of breast cancer or other cancers was not increased in this study.
How can this be reconciled with the findings of the Women’s Health Initiative?
- The Women’s Health Initiative used Premarin (derived from pregnant mare’s urine) and medroxyprogesterone (a synthetic progestin that has been found to increase the risk of breast cancer), not hormones.
- In WHI, the average age of the participants was 64, with many well into their 70s, many of whom were smokers and had other cardiovascular risk factors. These women had never been on hormones prior to the study.
- One post hoc analysis of WHI that only looked at women younger than 60, also found a reduction in heart disease and death, although not statistically significant.
Take home message:
- “HRT” can be safe and effective when done properly.
- Patient selection is important—generally, healthy women within 10 years of menopause at the start of hormone replacement are the best candidates. However, this does not preclude the use of hormones in older healthy women.
- When hormones are started early after menopause, there appears to be a reduction in mortality due to cardiovascular disease.
- There was no increase in breast cancer even with prolonged use in this group of patients.
- Most prior studies that showed no benefit or an increased risk of cancer, heart disease or blood clots, refer to “HRT” which is a general term, not indicating which hormones were used. Most used a Premarin (horse urine estrogen) equivalent and a synthetic progestin, most commonly medroxyprogesterone. The synthetic progestin component appears to be what is mainly responsible for the increase in breast cancer risk seen in some prior studies.
- Studies using progesterone have not shown the increased cancer risk with some studies showing a decreased risk.
- Most prior studies did not specifically look at recently postmenopausal women.
- The results of this study may even have been more favorable if topical (instead of oral) estradiol and progesterone (instead of a synthetic progestin) had been used.
While some clinicians would consider it premature to recommend HRT for mortality reduction, it is increasingly clear that with appropriate patient selection, the use of hormones given via the proper route of delivery, does not pose an increased risk of mortality or cancer, and may even decrease these risks.