Combined oral HRT significantly increased the aldosterone/renin ratio calculated by direct renin concentration from a median of 7.8 to 30.4 (P<0.001), risking false-positive screening results.
Cohort (n=15)
Does combined hormonal replacement therapy affect the aldosterone/renin ratio in normotensive, healthy postmenopausal women?
Combined oral HRT significantly increases the aldosterone/renin ratio when calculated using direct renin concentration, potentially causing false-positive results in primary aldosteronism screening, but not when using plasma renin activity.
Absolute Event Rate: 30.4% vs 7.8%
p-value: p=<0.001
Background: Plasma aldosterone/renin ratio (ARR) is the most popular screening test for primary aldosteronism (PA). Because both estrogen and progesterone (including in oral contraceptive agents) affect aldosterone and renin levels, we studied the effects of combined hormonal replacement therapy (HRT) on ARR; renin was measured as both direct renin concentration (DRC) and plasma renin activity (PRA). Methods: Fifteen normotensive, healthy postmenopausal women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline and after 2 weeks and 6 weeks of treatment with combined HRT (conjugated estrogens 0.625 mg and medroxyprogesterone 2.5 mg daily). Results: Combined HRT was associated with statistically significant increases in aldosterone median (range): baseline, 150 (85 to 600); 2 weeks, 230 (129 to 790); 6 weeks, 434 (200 to 1200) pmol/L; P < 0.001 (Friedman test) and PRA 2.3 (1.2 to 4.3), 3.8 (1.4 to 7.0), 5.1 (1.4 to 10.8) ng/mL/h, respectively; P < 0.001 but decreases in DRC 21 (10 to 31), 21 (10 to 39), and 14 (8.0 to 30) mU/L, respectively; P < 0.01, leading to increases in ARR calculated by DRC 7.8 (3.6 to 34.8), 11.4 (5.4 to 48.5), and 30.4 (10.5 to 90.2), respectively; P < 0.001. The ARR calculated by DRC exceeded the cutoff value (70) in three patients after 6 weeks. There were no significant changes in ARR calculated by PRA 79 (26 to 184), 91 (23 to 166), and 88 (50 to 230), respectively; P = 0.282, plasma electrolytes and creatinine, or any urinary measurements. Conclusion: The combined oral HRT used in this study is capable of significantly increasing ARR with a risk of false-positive results during screening for PA but only if DRC (and not PRA) is used to calculate the ratio.
Ahmed et al. (Thu,) conducted a cohort in Healthy postmenopausal women (n=15). Combined hormonal replacement therapy (HRT) vs. Baseline was evaluated on Aldosterone/renin ratio (ARR) calculated by direct renin concentration (DRC) (p=<0.001). Combined oral HRT significantly increased the aldosterone/renin ratio calculated by direct renin concentration from a median of 7.8 to 30.4 (P<0.001), risking false-positive screening results.