Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women

Abstract

Objective Research comparing hormone therapy (HT) doses, regimens, and routes of delivery in relation to cardiovascular disease (CVD) outcomes have been limited. This study directly compared different estrogen doses, routes of delivery, and HT formulations in postmenopausal women in relation to the risk of coronary heart disease (CHD), stroke, CVD mortality, total CVD, and all-cause mortality. Methods The Women’s Health Initiative Observational Study (WHI-OS) is a multi-center prospective cohort study conducted at 40 US sites. Analyses included 93,676 postmenopausal women, aged 50-79 years at study entry and recruited September 1994 - December 1998, with annual follow-up through August 14, 2009. Results Average follow-up was 10.4 years. In direct comparisons, oral estradiol was associated with lower hazard ratios (HRs) for stroke than oral conjugated equine estrogens (CEE) (HR 0.64; 95% CI 0.40, 1.02), but statistical power was limited. Similarly, transdermal estradiol was associated with a moderate but non-significant lower risk of CHD compared to oral CEE (HR 0.63; 95% CI 0.37, 1.06). For other outcomes, comparisons revealed no appreciable differences by estrogen doses, formulations, or routes of delivery. Absolute risks of CVD events and all-cause mortality were markedly lower in younger, compared to older, women. Conclusion In direct comparisons, various HT doses and regimens were associated with similar rates of cardiovascular events and all-cause mortality. However, oral estradiol may be associated with a lower risk of stroke and transdermal estradiol with a lower risk of CHD, compared to conventional-dose oral CEE. Additional research is needed to confirm these hypotheses.

Sex Steroids Block the Initiation of Atherosclerosis

“…[3][4][5][6][7][8] Since coronary events usually follow the cessation of ovarian function in women, it has long been supposed that sex steroids, particularly estrogen, are cardioprotective, and that approximately 10 years were needed to develop clinical disease. 9 Observational studies support this conclusion, and we know menopausal women who are treated with hormone replacement therapy within the first several years of menopause onset showed improvement in cardiovascular markers of disease.…”

“…[3][4][5][6][7][8] Since coronary events usually follow the cessation of ovarian function in women, it has long been supposed that sex steroids, particularly estrogen, are cardioprotective, and that approximately 10 years were needed to develop clinical disease. 9 Observational studies support this conclusion, and we know menopausal women who are treated with hormone replacement therapy within the first several years of menopause onset showed improvement in cardiovascular markers of disease.3,10-16 Age-adjusted subanalysis and long-term follow-up of the estrogen-only arm of the Women's Health Initiative (WHI) hormone treatment study and other prospective observational studies on women who received conjugated estrogens alone have confirmed that estrogen-treated postmenopausal women have a slower thickening of their internal carotid artery intimal-medial (CIMT), indicating slower vascular plaque formation 17 ; a recent prospective randomized trial of estrogen administration to menopausal women has confirmed that estrogen slows the progression of CIMT. 13 Today, we know that prescient studies from Thomas Clarkson's laboratory explain almost all aspects of the turbulent decades since the first announcement of the WHI's hormonal cardiovascular prevention trials.…”

Menopausal Hormone Therapy

“…45 In other observational studies, no differences by estrogen dose were noted in CVD outcomes. 46,47 The 14-mg transdermal E 2 patch maintains E 2 levels within the normal postmenopausal range (<20 pg/mL), and in 2 trials of women older than age 60, during 2 years of therapy, spinal bone mineral density was observed to increase with this low-dose regimen. 48,49 In these and two 12-week trials conducted in younger women, ages 53 to 57, VMS improved, 49,50 as did vaginal symptoms 51,52 and signs.…”

Evolution of menopausal hormone therapy: from standard to ultra-low doses

“…Целью исследования, по замыслу авторов, явилось определение распространенности и тяжести менопау-зальных симптомов у женщин в поздней постменопаузе и обоснование необходимости их лечения [4].…”

“…На каждую 1 000 женщин при своевременном назначении менопаузальная гормональная терапия (МГТ) может спа-сти 6 жизней, предупредить развитие болезней сердца у 8 женщин, предотвратить развитие тромбоза у 5 женщин [4].…”