After menopause, both systolic (SBP) and diastolic (DBP) blood pressure (BP) become higher in women than in men of the same age, suggesting that estrogen deficiency may influence the age-related increase in BP. We studied 30 postmenopausal women (mean age, 55 +/- 5.7 years; time from menopause, 2-5 years) affected by mild hypertension with no target-organ complications by means of 24-h BP monitoring. None of the group were undergoing estrogen replacement therapy or taking antihypertensive drugs. According to a randomized, double-blind protocol, subjects received patches of transdermal estradiol-17beta (E2) or a matched placebo, with crossover after a 7-day washout period. In 12 patients the 24-h peak-to-trough variation in SBP and DBP amounted to less than 10% (nondippers). Administration of E2 significantly decreased 24-h SBP and DBP in the whole cohort (P < .05). Furthermore, E2 restored the expected reduction in BP during nighttime in the nondipper subgroup. It is well known that estrogen replacement therapy protects against the development of both cardiovascular diseases and stroke. Our data suggest that this activity could be attributed, at least in part, to the activity of E2 in preserving physiologic circadian fluctuation of BP.
PMID 9715781 9715781 DOI 10.1016/s0895-7061(98)00096-x 10.1016/s0895-7061(98)00096-x Mercuro et al. 1998, Mercuro 1998
Cite this article
Mercuro, G., Zoncu, S., Piano, D., Pilia, I., Lao, A., Melis, G. B., & Cherchi, A. (1998). Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension. American journal of hypertension, 11(8 Pt 1), 909-913. https://doi.org/10.1016/s0895-7061(98)00096-x
Mercuro G, Zoncu S, Piano D, Pilia I, Lao A, Melis GB, et al. Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension. Am J Hypertens. 1998;11(8 Pt 1):909-913. doi:10.1016/s0895-7061(98)00096-x
Mercuro, giuseppe, et al. "Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension." American journal of hypertension, vol. 11, no. 8 Pt 1, 1998, pp. 909-913.
The incidence of coronary heart disease (CHD) is lower in premenopausal women than in men and post-menopausal women of the same age. The higher CHD rate after menopause is currently attributed to estrogen deficiency: many epidemiological (case-control and prospective) studies have reported a reduced risk (0.5-0.63) of CHD in post-menopausal women receiving hormone replacement therapy (HRT). Moreover, estrogens have multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, the observational studies are subject to several biases that could falsely elevate the apparent benefit of estrogens: women taking estrogens tend to be wealthier, more educated and healthier than untreated women. The american HERS (Heart and Estrogen-progestin Replacement Study; 2.763 women) is a large multicenter randomized study of secondary prevention, designed to evaluate the efficacy of HRT. Results are disappointing, since no reduced risk was observed, and the risk of CHD was even higher in women receiving HRT during the first year: 1.52 (CI 95%: 1.01-2.29). In HERS study, the treatments consisted of conjugated equine estrogens and the synthetic progestin medroxyprogesterone acetate (MPA) which are rarely used in Europe. Indeed, the effects of HRT are not equivalent depending on the dose, the route of administration, the type of progestogen. It should be emphasized that MPA, contrarily to progesterone, inhibits the beneficial effect of estrogens on lipids and experimental atherosclerosis. The route of administration of estrogens is also involved: estrogens alter hemostasis factors, and when orally administered, they have a first pass liver effect, which favors hypercoagulability. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non oral estrogens (gel or patch) associated with natural progesterone.
The incidence of cardiovascular disease in women is negligible before natural or surgically-induced menopause, and increases after menopause. Epidemiological data suggest that estrogen replacement therapy reduces the occurrence of coronary artery, and possibly cerebrovascular, disease by 25 to 50% in treated women compared with non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls. Early reports suggested that up to 60% of the protective effect of estrogens on coronary artery disease was attributable to favourable changes in plasma lipids. Reanalysis of the data indicated that the lipid changes probably account for approximately 25% of the cardioprotective effect of estrogens and that other effects are, therefore, likely to be important. The influence of estrogens on carbohydrate metabolism, atheroma formation and cardiovascular haemodynamics may also play an integral role in the overall beneficial effect of the hormones. Animal and human studies have shown that the administration of estrogens leads to a restoration of endothelial function, an increase in cardiac output, an increase in arterial flow velocity, a decrease in vascular resistance, and a decrease in systolic and diastolic blood pressure. Recent studies on hormone replacement regimens have shown that estrogens may favourably affect fibrinolysis and reduce plasma fibrinogen to premenopausal levels. Despite these effects of estrogens the recent Heart and Estrogen/Progestin Replacement Study (HERS) failed to show a cardioprotective effect of hormone replacement therapy (HRT) in elderly women with coronary artery disease. However, the HERS study has several limitations and stands alone against the large body of evidence that suggest that HRT may reduce cardiovascular mortality and morbidity.
Hormone replacement therapy (HRT, estrogen plus progestagen) in postmenopausal women has beneficial effects on the cardiovascular system. However, effects on blood pressure, determined with office measurements, remain controversial. We studied the effects of HRT in 29 healthy normotensive postmenopausal women (mean age 52.3 [3.8] years, median duration of amenorrhea 34.5 months), using ambulatory blood pressure monitoring at baseline and at 3 and 12 months of follow-up. Women were randomized to two groups: an HRT group (N = 14), treated with 1 mg 17beta-estradiol once daily and 5 or 10 mg dydrogesterone once daily during the third and fourth week of every 4 weeks; and a control group (C-group, N = 15), which did not receive therapy. Blood pressures did not differ between the groups at baseline (HRT group 117.1 (9.2)/74.4 (6.6) mm Hg, C-group 113.8 (11.2)/71.3 (7.4) mm Hg). During the follow-up period, changes from baseline of office blood pressures did not differ significantly between the groups. However, changes (95% CI) of mean 24-h blood pressures differed significantly between the two groups after 1 year of follow-up: a decrease of blood pressures was observed in the HRT group (delta systolic/delta diastolic = -5.54 [-8.86 to -2.21]/-4.23 [-6.66 to -1.80] mm Hg), whereas an increase was found in the C-group (+3.33 [-0.69 to +7.35]/+1.67 [-1.75 to +5.09] mm Hg; P [HRT v control group] = .001/.005). We conclude that HRT may have blood pressure lowering properties in healthy, normotensive postmenopausal women.
Migraine is a neurologic disorder that disproportionately affects women and undergoes important changes across the menopausal transition. Estrogen fluctuations contribute to migraine expression and underlie the 3:1 female-to-male prevalence. Perimenopause, marked by hormonal variability and rising cardiometabolic risk, presents unique diagnostic and therapeutic challenges. Despite its high prevalence, evidence specific to perimenopausal and postmenopausal women remains limited. This review synthesizes current evidence on the epidemiology, pathophysiology, and management of migraine across the menopausal transition, with attention to hormone therapy, comorbidities, and emerging treatments. We conducted a narrative review of clinical and translational studies published within the past 5 years, supplemented by seminal mechanistic, epidemiologic, and guideline-defining studies published earlier. Relevant guideline statements from neurology, gynecology, and cardiovascular societies were also incorporated. Unstable estradiol and progesterone levels during perimenopause can worsen migraine frequency and predictability. Migraine without aura often improves after menopause, whereas migraine with aura tends to persist and independently increases the risk of ischemic stroke and other vascular events. Midlife comorbidities-including vasomotor symptoms, sleep disturbance, mood disorders, and metabolic disease-further complicate management. Menopausal hormone therapy has variable effects. Oral estrogen, particularly at higher doses, may worsen migraine and elevate vascular risk, especially in women with aura. In contrast, low-dose transdermal estrogen-recommended by the North American Menopause Society-appears safer and better tolerated. Continuous progestogen regimens may reduce withdrawal-related attacks compared with cyclic regimens. Nonhormonal options, particularly selective norepinephrine reuptake inhibitors, may be considered when vasomotor symptoms coexist, whereas migraine-specific prevention should follow established evidence-based therapies. Traditional migraine therapies (triptans, NSAIDs, beta-blockers, topiramate, antidepressants) remain central but require tailoring to vascular, bone, and metabolic health. Newer agents-including calcitonin gene-related peptide monoclonal antibodies, gepants, and ditans-offer effective, non-vasoconstrictive alternatives, especially for women with cardiovascular contraindications. Migraine during the menopausal transition reflects the interplay between hormonal dynamics and systemic health. Management requires balancing efficacy with vascular and metabolic safety while incorporating patient preferences. Evidence gaps include the lack of trials stratified by menopausal stage or migraine subtype. Multidisciplinary, menopause-informed care and prospective studies are needed to optimize outcomes in this population.