The cardiovascular effects of hormone replacement therapy (HRT) vary depending on the age at which women begin taking it after menopause, according to a new systematic review published in The Cochrane Library. The researchers analyzed 19 randomized clinical trials involving 40,410 women, with treatment times ranging from seven months to more than ten years.
Overall, the review found that HRT doesn’t protect against death from cardiovascular disease (CVD), non-fatal heart attacks or angina in either healthy postmenopausal women or those with pre-existing CVD. Instead, the analysis showed a 24 percent rise in risk for stroke in HRT users.
However, among the 9,629 women who were treated within ten years of menopause or before age 60, heart risk fell by 48 percent in those who received HRT, compared to the rate in women who got a placebo. However, even in this subgroup, the therapy had potential harms, including higher risk for deep vein thrombosis (DVT)
Support for the “Timing Hypothesis”
“The evidence we have provides some support for the so-called ‘Timing Hypothesis’, but we should bear in mind the size of this effect,” said study author Dr. Henry Boardman, from the Department of Cardiovascular Medicine at the University of Oxford in England.
“When we looked at the results according to the age of women, or by how long since their menopause that they started treatment, we found that if 1000 women under 60 years old started hormone therapy we would expect six fewer deaths, eight fewer cases of heart disease, and five extra blood clots over about seven years, compared to 1000 similar women who did not start hormone therapy.”
Initially proposed a decade ago, the “timing hypothesis” suggests that there may be a specific window of opportunity during which hormone therapy might help ward off CVD in younger, recently postmenopausal women, while not offering the same benefits in older women.
How Hormones Affect Women’s Hearts
Each year, CVD kills more women than men. What’s more, women’s risk for heart attacks and strokes rises after menopause, prompting scientists to examine the effects of hormones on women’s heart health. Recent findings include the following:
- Estrogen has anti-inflammatory effects on blood vessels, which may help fight CVD in its early stages, according to a recent Medscape paper. However, this benefit appears to be lost later in the disease process, leaving arteries more vulnerable to both blood clots and chronic inflammation–a key culprit in heart attack and stroke risk.
- After menopause, women have a higher ratio of androgens (male hormones) to estrogen, which may speed up the development of CVD. Androgens contribute to narrowing of the arteries and worsen diet-related plaque buildup, the Cochrane review reports.
- Menopause is also linked to other heart risks, including rises in blood pressure, LDL (bad) cholesterol, and triglycerides, according to the American Heart Association, which recommends against using HRT to reduce heart disease or stroke risk.
Key Takeaways for Women and Their Doctors
About 70 percent of women experience menopause symptoms, such as hot flashes and night sweats, for an average of five years, according a recent review published in The Obstetrician & Gynaecologist. Its authors report that HRT is the most effective treatment, particularly for younger women whose periods have recently stopped, but that the risk/benefit ratio remains hotly debated.
In the Cochrane review, “the main analysis that the authors did found no (cardiovascular) benefit, so we need to apply caution to the results from the subgroup analysis,” commented Dr. David Tovey, editor in chief of the Cochrane Library. “However, if true, this apparent benefit in preventing heart disease in younger women should be considered alongside other possible benefits and emerging evidence of harms, including the risk of breast cancer, ovarian cancer, and DVT.”
“Hormone therapy remains a valid treatment option for women who are significantly troubled by menopausal symptoms,” added Dr. Boardman. “However, the risks and benefits of such treatment vary according to age and medical history.” Ultimately, it’s an individual decision for women to make in consultation with their medical providers.