Middle-Aged Women Often Develop Hypertension

Hypertension (HTN) is implicated in about 20% of deaths among American women,^1,2 and women are more likely to develop HTN than men.³

Women are also more likely to develop related pathophysiologic damage, such as chronic kidney disease, diabetes, diastolic dysfunction, heart failure, increased arterial stiffness, and left ventricular hypertrophy.^1-3 For this reason, controlling HTN in women is critical. Lowering blood pressure (BP) reduces adverse cardiovascular outcomes.⁴

HTN is a leading risk factor for cardiovascular disease and in turn, cardiovascular disease is the leading cause of death among women.⁵ About 50 million women have HTN, and more than 41 million do or would benefit from antihypertensive medications.³ Table 1^6-8 lists HTN’s risk factors.

The basic approach to HTN management in women is well documented. Targets include consuming adequate folic acid intake, diets favoring fruits and vegetables, limiting alcohol and nonnarcotic analgesics, reaching and maintaining a healthy body mass index, regular physical exercise, and restricting fat and salt. For many women, these goals are challenging, and for middle-aged women who are dealing with menopausal transition, hormonal changes often cause or contribute to HTN.⁹

HTN and menopause have been linked in several studies, and systolic BP seems to be affected more than diastolic, increasing about 5 mm Hg over 5 years.¹⁰ Increasing age and a slowing metabolism are also associated with weight gain.¹¹

MECHANISMS AT MENOPAUSE THAT AFFECT BP

Some research suggests that menopause may trigger expression of certain genetic susceptibilities that modulate BP in women.¹² Geneticists have identified 35 loci with physiological roles in BP regulation. Polymorphism in men and women differ, with the β-adrenergic receptor and angiotensinogen receptor elevating BP in men and the β-adrenergic receptor and the α2A-adrenergic responsible in women.¹³ In addition, with age, endothelial function declines pursuant to reduced endogenous estrogen stimulation of nitric oxide synthesis.¹⁴ Menopause reduces the estradiol and estrogen/testosterone ratio, which also contributes to endothelial dysfunction.¹⁵

TREATMENT STRATEGIES

The American College of Cardiology/American Heart Association 2017 Hypertension Guideline indicates that men and women should start treatment for HTN at the same thresholds.4 Clinical trials have examined many drugs and strategies, with none clearly preferred in women, except possibly thiazide diuretics, which reduce calcium excretion and may prevent osteoporosis.¹⁶

Limited research suggests that women respond to certain BP medications, such as angiotensin-converting enzyme inhibitors, β-blockers and diuretics, better than men.^17-20 Gender-related differences in pharmacodynamics and pharmacokinetics may explain the differences. Metabolizing enzymes and sex hormones interact, altering adverse effects (AEs), drug exposure, effectiveness, and elimination. For example, CYP2D6 metabolizes metoprolol. Healthy women’s metoprolol drug exposure is higher than men’s, although their elimination half-lives and heart rates are similar.²¹ Some research proposes that prescribing 50 mg of metoprolol creates an exposure equivalent to a 100-mg dose in men.²² Women taking CYP2D6-metabolized β-blockers (table 2²³) tend to have more AEs than men but similar profiles with non-CYP2D6 metabolized β-blockers.²³ Study results have also shown that women clear amlodipine and verapamil faster than men and respond better to amlodipine, but they experience more edema.²⁴

Women generally experience more and more severe adverse effects from antihypertensives than men. For example, diureticsassociated arrhythmia, hypokalemia, or hyponatremia are more common in women than men. However, men are more likely to develop gout.²⁵ Women are also more likely to develop peripheral edema when they take calcium channel blockers and are more likely to develop minoxidil-induced hirsutism than men. Given the same dose of verapamil, women’s plasma levels are higher than men’s, probably because they have higher CYP3A4 or lower P-glycoprotein activity.^26,27

Sexual dysfunction has been reported in women who take β-blockers, centrally acting antihypertensives, and thiazide diuretics.²⁸ Women are also more likely to develop an ACE inhibitor— induced cough. This issue is more pronounced in African American women, who are 3 times more likely to develop a cough than men.²⁹

ADHERENCE IS KEY

Among women, dissatisfaction with a health care provider and symptoms of depression are more likely to affect adherence.²⁹ Pharmacists can make note of these factors and discuss these topics if they have female patients with adherence issues, as forging bonds with patients helps.³⁰ Additional strategies include providing patient education, reducing costs, simplifying regimens, and teaching patients to self-monitor BP. A critical component is repeating the message often and well.³¹

CONCLUSION

Hypertension often develops in the perimenopausal period for many reasons. With clear links to morbidity and mortality, hypertension needs to be addressed aggressively. Encouraging women to check their BP, seek treatment if necessary, and adhere to medication can prevent many poor outcomes.

Jeannette Y. Wick, MBA, RPh, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.

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