Sex Hormones, Aldosterone, and Hypertension Risk in Women, With Erin Michos, MD

Hypertension confers greater relative cardiovascular risk in women than in men, and this risk begins accelerating at lower blood pressure thresholds in women, according to Erin Michos, MD, MHS, of Johns Hopkins, who discussed the topic with HCPLive following a symposium on hypertension in women at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany.

Sex-Specific Blood Pressure Risk and Reproductive Risk Factors

Some experts have proposed sex-specific blood pressure cut points for diagnosing hypertension as a result, an unresolved question in current guidelines.

A pooled analysis of 4 community-based cohort studies previously found increasing cardiovascular risk beginning at lower systolic blood pressure thresholds in women than in men, with the difference evident for myocardial infarction, heart failure, and stroke. Whether sex-specific thresholds would improve risk detection remains under debate in the hypertension field.¹

Michos also pointed to reproductive risk factors unique to women, linked to both cardiovascular disease and incident hypertension: "Women have unique reproductive risk factors that relate to their increased risks of cardiovascular disease and hypertension that men do not, and this relates to things like early menarche, polycystic ovarian syndrome, or PCOS, having adverse pregnancy outcomes like preeclampsia, gestational diabetes, as well as early menopause, and having frequent or persistent vasomotor symptoms," she said.

Aldosterone, Menopause, and the Case for Treating Women

Michos said dysregulated aldosterone contributes to hypertension even in ranges not meeting clinical criteria for primary aldosteronism, with hormonal factors influencing aldosterone levels across the reproductive lifespan. Oral estrogen-based contraception raises hepatic angiotensinogen production, which can elevate aldosterone, a mechanism supported by prior research on sex hormones and aldosterone biosynthesis.²

"You have to sort of screen for oral contraceptive use as a potential secondary cause of hypertension," Michos said, noting an alternative such as an IUD or progestin-based contraception may be preferable if oral estrogen is contributing to a patient's hypertension.

At the menopause transition, endogenous estradiol normally inhibits aldosterone synthase, and declining estradiol at menopause is associated with rising aldosterone levels, a mechanism described in reviews of sex hormone effects on aldosterone biosynthesis.²

"We know at the menopause transition that aldosterone levels go up in women, so this may contribute to the rise in blood pressure after menopause," Michos said. She added menopause also brings increased visceral adiposity, insulin resistance, salt sensitivity, and sympathetic activity, all of which can further raise blood pressure.

This shifting hormonal profile helps explain why women, who on average have lower blood pressure than men during their reproductive years, experience a steeper rise in blood pressure over the life course and face greater risk for arterial stiffness and heart failure with preserved ejection fraction after menopause. Despite this risk, Michos emphasized randomized trial evidence supports treating women as aggressively as men.

"Randomized clinical trials have shown that antihypertensive therapies benefit women just as much as their male counterparts. We just need to treat women," Michos said, citing a large meta-analysis showing a 5 mm Hg reduction in systolic blood pressure can reduce major cardiovascular events by about 10%.³

She said several questions remain open, including whether sex-specific thresholds are warranted for diagnosing hypertension or dysregulated aldosterone, and how to reconcile the apparent paradox of both declining estrogen at menopause and oral estrogen-based contraception raising aldosterone levels.

Editors’ note: Michos reports relevant disclosures with Arrowhead, Bayer, Boehringer Ingelheim, Eli Lilly, Ionis, Merck, Novo Nordisk, and others.

References

1. Gerdts E, de Simone G. Hypertension in women: should there be a sex-specific threshold? Eur Cardiol Rev. 2021;16:e38. doi:10.15420/ecr.2021.17

2. Vecchiola A, Uslar T, Friedrich I, et al. The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor. Cardiovasc Endocrinol Metab. 2024;13(3):e0305. doi:10.1097/XCE.0000000000000305

3. Blood Pressure Lowering Treatment Trialists' Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397(10285):1625-1636. doi:10.1016/S0140-6736(21)00590-0