Effects of female sex hormones and contraceptive pill on the diagnostic work-up for primary aldosteronism

Abstract

Due to the widespread use of the aldosterone to renin ratio (ARR), primary aldosteronism is currently recognized as a frequent cause of secondary hypertension. After a positive screening, primary aldosteronism diagnosis needs confirmation by an inhibitory test such as intravenous saline load (ivSLT). The aim of the present study was to investigate the role of female hormones in primary aldosteronism diagnosis, by evaluating possible differences by sex on ARR screening, on the rate of ivSLT response and analyzing the influence of free and oral contraceptive-induced menstrual cycle on ARR. We examined ARR in 103 healthy normotensive volunteers, 81 hypertensive patients who underwent ivSLT, 33 healthy women during free menstrual cycle and after oral contraceptive therapy. A significantly higher proportion of normotensive women than men had an elevated ARR (13.6 versus 2.3%, P < 0.05). In 44 out of 81 hypertensive patients, diagnosis of primary aldosteronism was confirmed by ivSLT. Patients with positive and negative ivSLT differed only for sex distribution: 85.2% of men had the primary aldosteronism diagnosis confirmed, compared with 38.9% of women. In healthy women, renin and aldosterone concentrations increased from the follicular to luteal phase of menstrual period, with unchanged ARR. By contrast, renin nearly halved, aldosterone slightly decreased and ARR doubled after oral contraceptive therapy. ARR screening fails to predict positive ivSLT in most (60.2%) hypertensive women as compared with 14.8% of hypertensive men. ARR is more often increased in normotensive women than men. Oral contraceptive may affect ARR contributing to the diagnostic inaccuracy in women.