Multispecialty Consensus Statement on Hypertension in Women in India

WCH

WCH refers to elevated BP measured in the clinic, despite normal BP values documented on Home Blood Pressure Monitoring (HBPM) Ambulatory Blood Pressure Monitoring (ABPM). This phenomenon, affecting approximately 25% of individuals in Europe and Asia, is particularly prevalent among older women and pregnant women due to heightened anxiety and hormonal changes. Recent studies indicate that women with WCH have nearly a threefold higher risk of progressing to sustained HTN compared to normotensive individuals. WCH is also associated with increased risks of target organ damage, including left ventricular hypertrophy and carotid atherosclerosis. Diagnosing WCH requires a clinically significant discrepancy between office BP (≥20 mmHg higher systolic or ≥10 mmHg higher diastolic) and out-of-office readings.^[12]

Masked HTN

Masked HTN is defined by normal BP readings in a clinical setting but elevated BP during home or ambulatory monitoring, making it challenging to detect during routine check-ups. The condition affects approximately 7% of untreated women and 18% of untreated men, though its prevalence in women increases with factors such as obesity, diabetes, and alcohol consumption. Women with masked HTN face an increased risk of CV target-organ damage such as left ventricular hypertrophy and chronic kidney disease (CKD) even though their office BP values appear normotensive. Screening for masked HTN is recommended in individuals with high-normal office BP (120–129/75– 79 mmHg) or multiple CV risk factors.^[13]

Nocturnal HTN and non-dipping patterns

Nocturnal HTN and non-dipping patterns, identified through ABPM, are significant predictors of CV events, including stroke and heart failure. Normally, BP drops by 10–20% during sleep (“dipping”), but non-dipping (<10% reduction) is common in women over 70 and is associated with increased CV risk. Reverse dipping, where BP rises during sleep, is even more concerning and linked to a higher incidence of coronary artery disease. Ethnic disparities show that non-Hispanic Black and Asian women have less pronounced nocturnal BP reductions compared to White women, contributing to their elevated CV risks.^[14]

Elevated morning bp surges

Morning BP surges, characterized by an abrupt rise in BP upon waking, are linked to increased risks of stroke and myocardial infarction. Women with comorbid conditions such as diabetes or metabolic syndrome are particularly vulnerable to these surges due to enhanced sympathetic activity during early morning hours. Recent studies indicate that postmenopausal women exhibit higher morning BP surges compared to premenopausal women, likely due to declining estrogen levels, which influence vascular tone and compliance. These surges are a key consideration in CV risk assessment for women.^[15]

Isolated systolic hypertension (ISH)

ISH, defined as SBP ≥140 mmHg with normal DBP (<90 mmHg), is the most common HTN phenotype in women aged 60 and older, affecting more than 50% of this population. The condition arises from age-related arterial stiffness and reduced vascular compliance, with women exhibiting higher rates of ISH than men in older age groups. ISH is strongly associated with an increased risk of heart failure, stroke, and cognitive decline, making it a critical focus for late-life BP management in women [Box 3].^[16]

Birth and early infancy

At birth, SBP and DBP levels are comparable between sexes, with SBP typically ranging from 70 to 90 mmHg and DBP around 40–60 mmHg in healthy full-term neonates. During the 1^st year of life, BP rises steadily as a result of increasing vascular resistance and the maturation of the CV system. By the age of one, average SBP levels reach 90–100 mmHg, while DBP averages 60–70 mmHg, with no significant sex differences.^[18]

Childhood and pre-adolescence

Between the ages of two and seven, BP increases gradually in both sexes. Around age seven, subtle sex-specific differences begin to emerge. Females often exhibit a slightly faster rise in SBP compared to males, with SBP averaging 105–110 mmHg and DBP approximately 65–70 mmHg by this age. From 7 to 12 years, BP trajectories diverge further. While both sexes experience increases in BP, males show a steeper rise, particularly after the onset of preadolescence. By 12 years of age, the average SBP for boys is 115 mmHg, compared to 110 mmHg in girls, while DBP levels remain similar at 70– 75 mmHg.^[19]

Adolescence

Adolescence marks a period of significant physiological and hormonal changes, contributing to more pronounced differences in BP between sexes. For females, the onset of puberty, typically marked by menarche, introduces fluctuations in estrogen levels that modulate vascular tone and compliance, often attenuating the increase in BP. By age 13, males exhibit higher SBP levels than females, with the gap widening progressively. At age 18, the average SBP for males is approximately 125 mmHg, compared to 115 mmHg for females, with a similar 10 mmHg difference observed in DBP. The lower BP levels in adolescent females are largely attributed to estrogen-mediated vascular protection. In males, testosterone and its effects on vascular resistance contribute to higher BP levels.^[20]

Recent data from the National Health and Nutrition Examination Survey (NHANES) and regional Indian studies confirm these patterns. NHANES reports that the annual transition rate from optimal BP (<120/<80 mmHg) to prehypertension (120–139/80–89 mmHg) during adolescence is twice as high in males compared to females. Indian studies indicate that 10–15% of adolescents exhibit elevated BP, with a higher prevalence in urban settings due to lifestyle changes, such as increased consumption of high-sodium diets, reduced physical activity, and obesity.

Young adulthood

From late adolescence through early adulthood, males consistently exhibit higher SBP and DBP levels compared to females. This disparity is primarily driven by differences in hormonal profiles and vascular physiology. In males, SBP averages around 125–130 mmHg and DBP approximately 80–85 mmHg during early adulthood, with a steeper annual increase in BP compared to females. In contrast, females typically maintain lower BP levels during this stage, with SBP averaging 110–120 mmHg and DBP around 70–75 mmHg, largely due to the protective effects of estrogen.^[21] Estrogen enhances vasodilation, improves endothelial function, and maintains vascular compliance, delaying the rise in BP observed in males. Young adulthood is also marked by significant lifestyle changes that influence BP levels. Urbanization, sedentary behavior, dietary shifts, and stress are major contributors to rising BP, particularly among women in urban settings.^[22]

The young adulthood in women also coincides with childbearing years (pregnancy), introducing unique BP challenges. In early gestation (0–12 weeks), systemic vascular resistance decreases due to the vasodilatory effects of progesterone and nitric oxide (NO), leading to a reduction in SBP by 5–10 mmHg and DBP by 10–15 mmHg from pre-pregnancy levels. Mid-pregnancy (13–28 weeks) marks the lowest BP levels, with SBP dropping up to 10 mmHg and DBP up to 15 mmHg as vascular compliance improves and cardiac output increases by 30–50%.^[23] In late pregnancy (29–40 weeks), BP gradually rises toward pre-pregnancy levels due to increasing vascular resistance and cardiac workload, stabilizing at approximately 110– 120 mmHg SBP and 70–80 mmHg DBP in normotensive pregnancies.

Midlife and menopause

After the childbearing years, women enter midlife, a phase where BP trajectories diverge significantly from their earlier patterns. By early midlife, the protective effect of estrogen begins to wane in women, particularly during the menopausal transition. On average, SBP increases by 5–10 mmHg during the menopausal transition, with approximately 35% of women often experiencing a steeper rise in BP, especially those with early menopause or vasomotor symptoms. The menopause transition, marked by hormonal fluctuations and a decline in estrogen levels, has a profound impact on BP regulation.^[24] By the postmenopausal phase, SBP often stabilizes around 130–140 mmHg, but this varies based on individual health profiles and the presence of CV risk factors.

PCOS

PCOS is a prevalent endocrine disorder affecting women, particularly during their reproductive years. According to the World Health Organization, approximately 116 million women globally are affected by PCOS.^[42] In India, it is estimated that around 10% of women have PCOS. Given the limited data on PCOS prevalence in South Asian countries, its role as a major contributor to HTN in women must not be overlooked. The condition is characterized by key features such as anovulation, androgen excess, and insulin resistance.^[43]

Evidence suggests that women with PCOS have a higher likelihood of developing HTN compared to those without the condition. Research indicates that hyperandrogenism, a hallmark of PCOS, may contribute to elevated BP levels, independent of obesity or insulin resistance.^[44] In addition, insulin resistance and associated hyperinsulinemia are believed to play a role in vascular abnormalities, such as hypertrophy of the vascular muscle wall and reduced vascular compliance. These factors interfere with mechanisms like endothelium-dependent vasodilation, further exacerbating HTN risk. Findings from large-scale studies, including the Nurses’ Health Study, have revealed that women with irregular menstrual cycles, a common feature of PCOS, are nearly twice as likely to develop HTN. This elevated risk persists even after accounting for BMI.^[45] Furthermore, PCOS has been linked to an increased risk of pregnancy-related complications, particularly hypertensive disorders. A meta-analysis found that women with PCOS are 3.5 times more likely to experience pregnancy-induced HTN or preeclampsia compared to women without the condition. Addressing PCOS-related health concerns during adolescence and continuing through reproductive transitions can help mitigate the long-term CV consequences for affected women [Box 5].

Combined oral contraceptives (COCs)

COCs are commonly prescribed for birth control and the management of various medical conditions in women, including menstrual irregularities, ovarian cysts, and androgenization. The use of COCs is associated with an increased risk of HTN, as demonstrated by large-scale studies like the Nurses’ Health Study, which examined nearly 70,000 women aged 25–42 years.^[46] This study found a significant correlation between oral contraceptive use and elevated BP. In addition, prolonged COC use, particularly beyond 6 years, has been shown to further increase the risk of developing HTN.

Several factors contribute to heightened susceptibility to COC-induced HTN, including a personal history of pregnancy-related HTN, a family history of HTN, obesity, undiagnosed renal conditions, age over 35 years, and extended durations of contraceptive use.^[47] The mechanisms underlying COC-induced HTN remain unclear, though activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system is thought to play a role. It is uncertain whether these effects are due to estrogen, progesterone, or their interaction. Early formulations of oral contraceptives, which contained higher doses of estrogen (≥50 mg) and progestin (1–4 mg), led to overt HTN in approximately 5% of users. While current low-dose formulations contain <20% of these hormone levels, they are still associated with increased BP.^[48] The elevation in BP caused by COCs is generally reversible. A prospective study involving 32 women found that BP returned to pretreatment levels within 3 months of discontinuing COCs. However, if HTN persists for more than 4 weeks after cessation, an evaluation for chronic HTN is recommended. Importantly, the World Health Organization (WHO) advises against the use of COCs in women with BP levels exceeding 160/100 mmHg. As COCs are increasingly used during the reproductive years, healthcare providers in India must remain vigilant about their association with HTN. Proper screening, monitoring, and counseling regarding the risks and benefits of COCs are essential for ensuring women’s health during this critical stage of life.

Preeclampsia/eclampsia

Preeclampsia is a pregnancy-specific hypertensive disorder that typically develops after 20 weeks of gestation. It is characterized by HTN accompanied by proteinuria or signs of end-organ damage. It impacts 3–8% of all pregnancies worldwide, with the WHO estimating a global prevalence of preeclampsia at 4.6%.^[51] Eclampsia, a severe complication of preeclampsia, occurs in 0.3% of pregnancies and is defined by the onset of new-onset seizures unrelated to pre-existing neurological conditions. Women with a history of preeclampsia are 3–4 times more likely to develop chronic HTN and twice as likely to experience CVD or stroke later in life. The risks are even higher for those with early-onset preeclampsia, particularly before 32 weeks of gestation.^[52]

Historically, preeclampsia and eclampsia were grouped under the term “toxemia of pregnancy,” reflecting the belief that these conditions were caused by toxins in the maternal circulation. Early theories debated whether these toxins were exogenous (e.g., bacterial) or endogenous (e.g., metabolic byproducts of the fetus, mother, or placenta). One hypothesis attributed eclampsia to bacterial toxins produced by a Bacillus named Bacillus eclampsiae. Endogenous theories suggested that autotoxicity from maternal or placental metabolic products played a role. Over time, the term “toxemias of pregnancy” was expanded to include other pregnancy-related conditions, such as hyperemesis gravidarum and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome.^[53]

The pathophysiology of preeclampsia is rooted in inadequate vascular remodeling of the spiral arteries within the placenta. This abnormal remodeling increases placental resistance, reduces uteroplacental blood flow, and causes ischemia. These changes trigger systemic endothelial dysfunction, oxidative stress, and the release of antiangiogenic and pro-inflammatory factors. The effects include capillary leakage, proteinuria, HTN, and organ damage, such as renal insufficiency and hepatic dysfunction. The progression to eclampsia is marked by severe central nervous system disturbances, primarily due to diffuse cerebral vasospasm. This vasospasm decreases cerebral perfusion, leading to cerebral edema and the development of seizures.^[54] Contributing factors to this progression include uteroplacental ischemia, which results in the release of toxic substances into the maternal circulation; heightened sensitivity to angiotensin-II; and underlying metabolic and inflammatory conditions such as maternal obesity or gestational diabetes.^[55]

Preeclampsia is diagnosed based on specific clinical criteria. Preeclampsia is diagnosed using defined clinical criteria, which include new-onset hypertension along with evidence of proteinuria either through a raised protein/creatinine ratio or a positive dipstick test when more advanced testing is not available. In the absence of proteinuria, preeclampsia can be identified by signs of end-organ damage, such as thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or neurological symptoms such as headaches and visual disturbances. HELLP syndrome, a severe form of preeclampsia, is characterized by hemolysis, elevated liver enzymes, and low platelet counts. It can occur without significant HTN or proteinuria in approximately 15% of cases. Eclampsia, a severe complication of preeclampsia, is diagnosed when generalized seizures occur in the context of preeclampsia, typically during the antepartum, intrapartum, or immediate postpartum period. Preeclampsia and eclampsia can result in serious complications for both the mother and the fetus. Maternal complications include cerebral hemorrhage, pulmonary edema, renal failure, disseminated intravascular coagulation, and CV issues. Neonatal complications include preterm delivery, low birth weight, neonatal asphyxia, and perinatal death.^[56]

The management of preeclampsia depends on its severity. For mild cases, close monitoring, anti-hypertensive therapy, and regular fetal surveillance are recommended. Severe preeclampsia requires hospitalization, administration of magnesium sulfate for seizure prophylaxis, and expedited delivery if maternal or fetal conditions deteriorate.^[49] Eclampsia management involves immediate stabilization of the patient with magnesium sulfate to control seizures, anti-hypertensive therapy to prevent further complications, and prompt delivery of the fetus, often through cesarean section, irrespective of gestational age. Preventive strategies include low-dose aspirin in high-risk pregnancies, lifestyle modifications for women with obesity or metabolic syndrome, and calcium supplementation in populations with low dietary calcium intake [Box 7].^[57]

Chronic HTN

Chronic HTN, defined as HTN present before pregnancy or diagnosed within the first 20 weeks of gestation, is a significant risk factor for the development of preeclampsia. Chronic HTN in pregnancy is typically characterized by BP ≥140/90 mmHg measured on two separate occasions at least 4 h apart. Chronic HTN is seen in 1–2% of pregnancies globally, with its prevalence increasing due to rising rates of obesity and advanced maternal age.^[58] Approximately 90% of cases are attributed to primary HTN, often associated with genetic predisposition or lifestyle factors, such as obesity and sedentary behavior. Secondary HTN accounts for the remaining 10% and may result from renal, vascular, or endocrine disorders, including CKD, coarctation of the aorta, or hyperaldosteronism.^[59]

The underlying mechanisms of chronic HTN involve sustained elevated systemic vascular resistance and endothelial dysfunction, contributing to increased afterload on the heart and reduced uteroplacental perfusion. This impaired placental blood flow predisposes women to complications such as preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery.^[60] In addition, chronic HTN exacerbates oxidative stress and inflammation, which further compromises vascular function. Diagnosis is based on consistent BP. Additional investigations may include urinalysis, renal function tests, and serum electrolytes to evaluate potential secondary causes. In cases of suspected secondary HTN, imaging studies, endocrine evaluations, or renal Doppler studies may be warranted.^[61,62]

The management of chronic HTN in pregnancy focuses on optimizing maternal BP while minimizing risks to the fetus. For mild chronic HTN (SBP 140–159 mmHg or DBP 90–109 mmHg), conservative management with close monitoring is often recommended. Severe HTN (SBP ≥160 mmHg or DBP ≥110 mmHg) requires pharmacological intervention to reduce the risk of complications such as stroke and placental abruption.^[63] Preferred antihypertensive agents in pregnancy include labetalol, nifedipine, and methyldopa, as these have been shown to be safe and effective. Angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and direct renin inhibitors are contraindicated due to their teratogenic effects. Regular fetal surveillance, including ultrasound assessments of fetal growth and amniotic fluid volume, is essential to monitor the impact of maternal HTN on the fetus. Recent studies emphasize the importance of preconception counseling and lifestyle modifications in women with chronic HTN. Weight loss, sodium restriction, and regular physical activity before pregnancy can improve CV outcomes. Aspirin prophylaxis (low dose) initiated between 12 and 16 weeks of gestation has been shown to reduce the risk of superimposed preeclampsia. Emerging research highlights the potential role of biomarkers and angiogenic factors in predicting adverse outcomes, which may guide early interventions.^[64]

Chronic HTN and superimposed preeclampsia

Superimposed preeclampsia complicates approximately 20% of pregnancies in women with chronic HTN, significantly increasing maternal and perinatal morbidity compared to preeclampsia alone. This condition is associated with higher rates of adverse outcomes, including preterm delivery, small-forgestational-age neonates, operative deliveries, Neonatal Intensive Care Unit ( NICU) admissions, and maternal complications such as pulmonary edema.^[65] Women with chronic HTN are 5–6 times more likely to develop preterm superimposed preeclampsia compared to normotensive counterparts after adjusting for confounding factors. Diagnosing superimposed preeclampsia is challenging due to overlapping features with chronic HTN.^[66] Traditional diagnostic criteria for preeclampsia, which include new-onset HTN and significant proteinuria, are less reliable in this population. In chronic HTN, elevated BP predates pregnancy, and approximately 10% of women may already have proteinuria, often due to nephrosclerosis or underlying renal diseases.^[67]

To address these limitations, the ACOG and the International Society for the Study of HTN in pregnancy have expanded the diagnostic criteria for preeclampsia. The diagnosis of superimposed preeclampsia now includes the development of thrombocytopenia, liver dysfunction, renal insufficiency, or neurologic symptoms indicative of end-organ damage in women with pre-existing chronic HTN.^[68] This broader definition underscores the systemic, multiorgan nature of preeclampsia and emphasizes the need for careful clinical assessment beyond proteinuria and BP measurements. Superimposed preeclampsia is closely linked to the severity of preexisting endothelial dysfunction, which underpins the heightened risk in this population.^[69] Central to its pathogenesis is an antiangiogenic state driven by placental dysfunction, contributing to the endothelial damage characteristic of the disease. Biomarkers such as soluble fms-like tyrosine kinase-1 and placental growth factor have shown promise in predicting preeclampsia in the general obstetric population but are less discriminatory in chronic HTN due to baseline impairments in these angiogenic factors.

Alternative biomarkers have been explored, including renal markers such as uric acid and pro-B-type natriuretic peptide (proBNP), as well as inflammatory mediators such as tumor necrosis factor-alpha, interleukin-6, and endothelin. While these markers show some differences between women who develop superimposed preeclampsia and those who do not, their predictive value remains modest. ProBNP, a marker of early cardiac dysfunction, has been suggested to reflect the CV reserve and adaptability to the hemodynamic demands of pregnancy. However, current evidence indicates that it is not a reliable predictor of superimposed preeclampsia.^[70]

Managing superimposed preeclampsia requires a multidisciplinary approach to balance maternal and fetal risks. BP control is crucial, with agents such as labetalol, nifedipine, and methyldopa remaining the mainstay of treatment. Severe HTN warrants prompt pharmacologic intervention to prevent complications such as stroke or placental abruption. Aspirin prophylaxis initiated early in pregnancy (12–16 weeks) has been shown to reduce the risk of preeclampsia in high-risk women, including those with chronic HTN [Box 8].^[71]

Miscellaneous

Premenopausal HTN

Premenopausal women, generally aged between 30 and 40 years, tend to have lower BP levels and a reduced risk of HTN compared to age-matched men, primarily due to the protective effects of sex hormones. Estrogen plays a critical role in BP regulation by enhancing NO-mediated vasodilation and modulating endothelin-1, a potent vasoconstrictor.^[91] Research has shown that endothelin-1 receptor ET1A expression is higher in males than females, a difference attributed to the opposing effects of androgens and estrogen on endothelin receptor activity. During the reproductive years, HTN in premenopausal women is more commonly secondary, often linked to underlying conditions such as obesity, PCOS, OSA, autoimmune diseases, and endocrine disorders, including hyperaldosteronism, hypothyroidism, and pheochromocytoma.^[92] Kidney diseases and the use of medications such as corticosteroids and hormonal contraceptives can also contribute. Oral contraceptives, particularly those containing estrogen, are associated with an increased risk of HTN through activation of the RAAS, promoting sodium retention and plasma volume expansion.^[80] For women at higher risk of HTN, alternatives such as progestin-only pills or combined contraceptives with drospirenone and low doses of estradiol may provide effective contraception with a lower hypertensive risk.^[93]

Perimenopause HTN

Perimenopause is the transitional phase leading up to menopause, characterized by hormonal, biological, and clinical changes that can persist up to 1 year after a woman’s last menstrual period. Typically occurring between the ages of 40 and 60 years, this phase affects a significant global population.^[94] During perimenopause, many women experience symptoms of perimenopausal syndrome, which includes autonomic nervous system dysfunctions and neuropsychological issues resulting from hormonal fluctuations. Common symptoms include hot flashes, menstrual irregularities, emotional instability, fatigue, insomnia, and musculoskeletal pain. These issues can significantly impact physical and mental health, daily activities, and interpersonal relationships.^[95]

HTN becomes increasingly significant during perimenopause due to hormonal changes and the loss of the protective effects of estrogen. Research shows that postmenopausal women are 4 times more likely to develop HTN compared to premenopausal women, with increased risks of target organ damage and CVDs such as arterial stiffness, coronary artery disease, and stroke.^[96] Contributing factors include increased BMI, dyslipidemia, chronic inflammation, oxidative stress, and endothelial dysfunction, which are exacerbated during and after the menopause transition. Although it remains unclear whether the rise in BP is directly due to menopause or age-related factors, the loss of estrogen appears to be a key driver. Estrogen’s cardioprotective effects, including its role in regulating vascular tone and reducing oxidative stress, diminish after menopause, leaving women as vulnerable to CV risks as men of the same age.^[97] Addressing these risks requires a better understanding of the relationship between perimenopause, HTN, and CV health. Targeted research and public health initiatives focusing on this life stage are essential for developing effective prevention and management strategies to mitigate the elevated CV risks associated with perimenopause.^[98]

Postmenopause HTN

Postmenopausal HTN is closely linked to changes in heart structure, function, and arterial compliance. Women in this stage experience a higher prevalence of left ventricular hypertrophy and are more prone to developing diastolic dysfunction compared to their younger counterparts. The deficiency of estrogen following menopause plays a central role in the development of HTN. Studies using animal models, such as hypertensive rats and mice with ovarian failure, have demonstrated that estradiol has a protective effect in lowering BP.^[81] In the absence of estradiol, androgen levels increase, contributing to elevated BP. Estradiol replacement therapy has been shown to mitigate these effects by reducing BP and preventing complications related to HTN.

Estrogen exerts its vasodilatory effects through various mechanisms, including the modulation of the reninangiotensin system, NO pathways, endothelin activity, and the immune system. Estradiol suppresses angiotensin-converting enzyme activity, reduces plasma renin levels, and influences the expression of genes associated with the RAAS, thereby decreasing vasoconstriction.^[80] In addition, it enhances the production of endothelial NO synthase, improving NO availability and promoting vasodilation. Conversely, estrogen deficiency leads to reduce NO activity and increased oxidative stress, exacerbating vascular dysfunction. Elevated levels of endothelin, a potent vasoconstrictor, are often observed in postmenopausal women, further aggravating HTN. Estrogen counteracts these effects by inhibiting endothelin synthesis and reducing the expression of ET1A receptors.^[82]

Progesterone and androgens in postmenopausal HTN

In addition to estrogen deficiency, menopause is marked by a significant decline in progesterone levels, which has also been implicated in arterial HTN. Progesterone exhibits vasodilatory properties by counteracting noradrenaline-induced vasoconstriction in vascular smooth muscle cells. Studies have shown that natural progesterone can lower diastolic and mean BP in postmenopausal women. Furthermore, combining progesterone with estrogen in hormone replacement therapy enhances CV benefits without diminishing estrogen’s positive effects.^[83]

While synthetic progestins used in contraceptives and hormone replacement therapy may have androgenic effects, natural progesterone does not, making it a safer option for CV health. On the other hand, androgens play a more complex role. High androgen levels are associated with increased CV risks, but androgen deficiency in postmenopausal women has been linked to higher mortality rates. The dual nature of androgens continues to be a focus of research to better understand their impact on CV health during postmenopause.^[84]

Autonomic nervous system and postmenopausal HTN

Postmenopausal HTN is also influenced by age-related changes in autonomic nervous system regulation. Sympathetic nerve activity (SNA) tends to increase with age and is more pronounced in postmenopausal women compared to men of the same age. Experimental studies in hypertensive animal models have shown that reducing renal SNA is particularly effective in lowering BP in older females. In addition, postmenopausal women exhibit heightened adrenergic sensitivity and reduced beta receptor-mediated vasodilation, further contributing to elevated BP.^[85] The brain regions involved in autonomic BP control include the hypothalamic paraventricular nucleus, nucleus tractus solitarius, and rostral ventrolateral medulla. Estrogen receptors (ER) (ERα and ERβ) located in these areas play a vital role in regulating sympathetic activity.^[86] Activation of these receptors suppresses sympathetic outflow, reduces BP, and promotes vasodilation through mechanisms involving NO and reduced oxidative stress. Emerging evidence highlights the importance of ERβ signaling in central autonomic regulation. Activation of these receptors has been shown to prevent neurogenic HTN in experimental models, underscoring estrogen’s crucial role in maintaining autonomic stability and CV health during postmenopause.

Mechanisms of HTN in aging women

The rise in BP with aging in women is influenced by various physiological and pathophysiological factors. Life events such as menarche, menstrual cycles, pregnancy, menopause, and hormone therapies significantly impact the CV system over a woman’s lifespan. One key mechanism is the decline in endothelial function with age, which is more pronounced in women than in men due to the loss of estrogen after menopause.^[92] Estrogen stimulates NO synthesis, promoting vasodilation and maintaining vascular health. Following menopause, reduced NO activity and increased oxidative stress contribute to impaired endothelial function, particularly during physical activity, leading to exaggerated BP responses.^[93]

Sex hormones also play a critical role. Higher levels of endogenous estradiol (E2), testosterone (T), and dehydroepiandrosterone (DHEA), combined with lower sex-hormone binding globulin (SHBG), have been associated with a greater incidence of HTN in aging women. While the associations for E2, T, and DHEA are largely mediated by adiposity, the relationship with SHBG is independent of factors like inflammation and insulin resistance, highlighting its distinct role in BP regulation.^[94]

Benefits and challenges of BP treatment in elderly women

Optimal BP management in elderly women requires individualized approaches, but definitive thresholds, targets, and drug choices remain inconclusive. The 2017 ACC/ AHA HTN guidelines indicate no significant differences in BP treatment recommendations between men and women. Evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) Study suggests that intensive SBP lowering benefits both frail and non-frail individuals, including those with CKD.^[95] In the SPRINT subgroup analysis, which included nearly 38% older women, intensive BP control was generally beneficial, with no significant differences in primary outcomes or adverse events between sexes. However, certain outcomes, such as stroke and renal complications, appeared to differ between men and women, though these did not reach statistical significance.^[39]

Among antihypertensive agents, thiazide diuretics are particularly advantageous for older women, as they reduce calcium excretion, helping to prevent osteoporosis and fractures. Despite clear evidence supporting the benefits of BP lowering in older adults, treatment and control rates remain suboptimal in elderly women. Studies such as the Framingham Heart Study and the Women’s Health Initiative (WHI) have shown that BP control rates decline with advancing age, underscoring the need for improved strategies to enhance adherence and treatment efficacy in this population.^[96]

Managing HTN in elderly women is critical for reducing the burden of CV and cognitive complications. Earlier intervention at midlife and a focus on personalized treatment plans can help mitigate risks. Addressing barriers such as physician inertia, poor adherence, and inappropriate medication use, while prioritizing agents like thiazide diuretics for their dual benefits, may improve outcomes. As the elderly female population continues to grow, targeted research and public health initiatives are essential to optimize BP control and enhance the quality of life for aging women [Box 9].^[97]