Systolic BP significantly increases with HT for postmenopausal women
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Postmenopausal women with hypertension taking estrogen alone or combined with progesterone had a statistically significant increase in systolic blood pressure compare with placebo, according to an analysis of WHI data.
“Although recent guidelines for the prevention and management of hypertension listed oral contraceptives as agents that may impair blood pressure control and should be avoided among women with uncontrolled hypertension, no guidance was provided for hormone therapy use,” Xuezhi Jiang, MD, PhD, NCMP, physician in the department of OB/GYN at Reading Hospital/Tower Health and Drexel University, Philadelphia, and colleagues wrote.
Researchers conducted a secondary analysis of the double-blind, randomized, placebo-controlled Woman’s Health Initiative studies of postmenopausal women aged 50 to 79 years. The WHI studies assessed the effects of HT with conjugated equine estrogens 0.625 mg per day or conjugated equine estrogen plus medroxyprogesterone acetate 2.5 mg per day on the risks for coronary heart disease and invasive breast cancer.
This secondary analysis evaluated a subsample of 9,332 women with hypertension at baseline with 2,202 women in the estrogen-only group and 2,512 in the estrogen plus progesterone group. Researchers measured BP at baseline and at up to 10 annual follow-up visits during the study period.
Estrogen alone was associated with higher systolic BP during the intervention phase (P = .02) compared with placebo. In addition, for cumulative follow-up, postmenopausal women taking estrogen alone experienced increased systolic BP (P = .02).
Taking estrogen plus progesterone also was associated with increased systolic BP (P < .001) compared with placebo. For cumulative follow-up, estrogen plus progesterone also was associated with increased systolic BP (P < .001).
At each follow-up visit, the mean number of antihypertensive medications taken did not differ between groups during the intervention or during the long-term follow-up period of 16 years.
“Further research is needed to determine whether the effect of HT on systolic BP and hypertension mediated the effect of HT on risk of cardiovascular disease in postmenopausal women,” the researchers wrote.
Perspective
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Holly L. Thacker, MD
Menopausal hormone therapy has complex cardiometabolic effects. Age, time since menopause, type and route of administration of HT and concomitant disease are all factors in the response to HT and the risk-benefit equation.
In general, both estradiol and progesterone are vasodilatory but when given orally can lead to activation of the renin-angiotensin-aldosterone system. Activation of the RAAS system can lead to vasoconstriction with some fluid retention and resultant increase in BP. Estradiol can increase the production of renin while simultaneously reducing the effects of renin. Estradiol has positive effects on calcium channel blocking, nitric oxide, lipids and body composition. Conversely oral HT can increase clotting proteins and triglyceride levels and can affect MMP9 levels, which can destabilize atherosclerotic plaque.
In this study of the WHI using oral conjugated estrogens (women who had had hysterectomy) or oral conjugated estrogens with medroxyprogesterone acetate (women with a uterus), a small, clinically insignificant increase in BP was noted.
The WHI age-stratified data showed that for women under age 60 years and/or within 10 years of menopause who took oral HT, there was a reduction in death rate and CV morbidity and mortality.
My takeaway is that for women with hypertension and/or worsening BP control, transdermal HT should be considered; however, in most recently menopausal women within 10 years of menopause the benefits of HT outweigh the risks. I would not summarily favor transdermal over oral HT even if the BP increases by a few points as other factors — patient preference, cost, convenience, comorbidities — also factor into shared patient-physician decision-making of selecting oral HT, transdermal HT or nonhormonal alternatives.
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