title: Effect of Combined Hormonal Replacement Therapy on the Aldosterone/Renin Ratio in Postmenopausal Women.
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.
authors.affiliation: Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane 4102, Australia.
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Ahmed
authors.affiliation: Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane 4102, Australia.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gordon
authors.affiliation: Sullivan & Nicolaides Pathology, Brisbane 4068, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ward
authors.affiliation: Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane 4102, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Wolley
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
authors.forename: Brett C
authors.initials: BC
authors.lastname: McWhinney
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Ungerer
authors.affiliation: Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane 4102, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Stowasser
mesh_terms: D000450:Aldosterone / Q000097:blood*; D001800:Blood Specimen Collection / Q000379:methods; D004338:Drug Combinations; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000175:diagnosis; D008525:Medroxyprogesterone / Q000494:pharmacology; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D012083:Renin / Q000097:blood* / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); D000450:Aldosterone; D012083:Renin; D008525:Medroxyprogesterone