Effect of Contraceptives on Aldosterone/Renin Ratio May Vary According to the Components of Contraceptive, Renin Assay Method, and Possibly Route of Administration

Abstract

The most popular screening test for primary aldosteronism is plasma aldosterone/renin ratio (ARR). Because both estrogen and progesterone affect aldosterone and renin levels, we studied effects of two contraceptives commonly used in our population, one oral and one subdermal, on ARR, measuring renin as both direct renin concentration (DRC) and plasma renin activity (PRA). Normotensive, healthy women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline (menses) and after either 1) 3 wk treatment with oral ethinylestradiol plus drospirenone (n = 17) or 2) 1 wk and 6 wk treatment with subdermal etonogestrel (n = 15), a third-generation progestin. Treatment with oral ethinylestradiol plus drospirenone was associated with significant increases in aldosterone [median (range) at baseline = 131 (85-590) pmol/liter; at 1 wk, 200 (130-784) pmol/liter; and at 3 wk, 412 (199-1010) pmol/liter (P < 0.001, Friedman test)] and PRA [2.1 (1.2-4.7), 3.6 (1.5-7.1), and 4.9 (1.5-10.8) ng/ml · h, P < 0.001] but decreases in DRC [22 (11-36), 21 (8.7-41), and 14 (8.5-39) mU/liter, P < 0.01] leading to increases in ARR calculated by DRC [6.6 (3.3-31.3), 10.9 (5.2-58.9), and 29.8 (5.1-88.5), P < 0.001]. There were no significant changes in ARR calculated by PRA, plasma electrolytes and creatinine, and all urinary measurements. In contrast, treatment with subdermal etonogestrel was associated with no significant changes in PRA, DRC, aldosterone, or ARR at either 1 or 6 wk. The combined oral contraceptive ethinylestradiol plus drospirenone is capable of significantly increasing ARR with risk of false-positive results during screening for primary aldosteronism, but only if DRC is used to calculate the ratio. Subdermal etonogestrel had no effect on ARR after 6 wk.