Table 3.

Pharmacological sex-differences in antihypertensive treatment.

Drug/Drug class	Sex difference	References
ARBs	No PK sex-differences for candesartan, losartan and valsartan (after adjustment for weight). Higher Cmax in women for telmisartan compared to men.	(Rabi et al., 2008; Thoenes et al., 2010; Cabaleiro et al., 2013)
ACEIs	Enalapril: –No PK sex-differences –Lower minimum ACE activity after administration of enalapril in women compared to men. More frequent cough in women compared to men.	(Zapater et al., 2004; Rabi et al., 2008; Thoenes et al., 2010)
Beta-blockers	Metoprolol: –lower oral Cl in women compared to men. –50% higher Cmax and AUC in women compared to men. More adverse drug reactions for CYP 2D6 dependent beta-blockers (metoprolol, carvedilol, nebivolol and propranolol) in women. Women are less sensitive to sympathetic vasoconstrictor activity compared to men.	(Luzier et al., 1999; Thürmann et al., 2006; Eugene, 2016)
Calcium channel blockers	Amlodipine: –No PK sex-differences (after adjustment for weight). –Greater changes in BP for women compared to men. Verapamil: –Higher IV Cl in women compared to men. –Lower oral Cl in women compared to men. Higher incidence of edema in women compared to men.	(Kloner et al., 1996; Krecic-Shepard et al., 2000; Abad-Santos et al., 2005; Dadashzadeh et al., 2006)
Thiazide diuretics	Hydrochlorothiazide: –No PK sex-differences More frequent hyponatremia and hypokalemia in women compared to men.	(Musini et al., 2014; Rydberg et al., 2018)

ARB, Angiotensin receptor blocker; ACEI, Angiotensin converting enzyme inhibitor; Cmax, peak concentration; AUC, area under the curve; PK, pharmacokinetic; Cl, clearance; ADR, adverse drug reactions.