Effect of combined hormonal replacement therapy on the aldosterone/renin ratio in postmenopausal women

Ahmed, Ashraf H., Gordon, Richard D., Ward, Gregory, Wolley, Martin, McWhinney, Brett C., Ungerer, Jacobus P. and Stowasser, Michael (2017) Effect of combined hormonal replacement therapy on the aldosterone/renin ratio in postmenopausal women. Journal of Clinical Endocrinology and Metabolism, 102 7: 2329-2334. doi:10.1210/jc.2016-3851


Author Ahmed, Ashraf H.
Gordon, Richard D.
Ward, Gregory
Wolley, Martin
McWhinney, Brett C.
Ungerer, Jacobus P.
Stowasser, Michael
Title Effect of combined hormonal replacement therapy on the aldosterone/renin ratio in postmenopausal women
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 1945-7197
0021-972X
Publication date 2017-03-30
Year available 2017
Sub-type Article (original research)
DOI 10.1210/jc.2016-3851
Open Access Status Not yet assessed
Volume 102
Issue 7
Start page 2329
End page 2334
Total pages 9
Place of publication Cary, United States
Publisher Oxford University Press
Language eng
Abstract 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).

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).

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.

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.
Formatted abstract
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 effects of combined hormonal replacement therapy (HRT) on ARR, measuring renin 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 treatment with combined HRT (conjugated oestrogens 0.625 mg and medroxyprogesterone 2.5 mg daily).

Results:
Treatment with combined HRT was associated with significant increases in aldosterone [baseline median (range) 150 (85-600), 2 weeks 230 (129-790), 6 weeks 434 (200-1200) pmol/L; P<0.001 (Friedman Test)] and PRA [2.3 (1.2-4.3), 3.8 (1.4-7.0), 5.1 (1.4-10.8) ng/mL/h; P<0.001]; but decreases in DRC [21 (10-31), 21 (10-39), 14 (8.0-30) mU/L; P<0.01] leading to increases in ARR calculated by DRC [7.8 (3.6-34.8), 11.4 (5.4-48.5), 30.4 (10.5-90.2); P<0.001]. The ARR calculated by DRC exceeded the cut off value (70) in three patients after 6 weeks. There were no significant changes in ARR calculated by PRA [79 (26-184), 91 (23-166), 88 (50-230); P=0.282], plasma electrolytes and creatinine, and all 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.
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