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Hormone therapy and urine protein excretion

a multiracial cohort study, systematic review, and meta-analysis

Kattah, Andrea G. MD, MSc1; Suarez, Maria L.G. MD1; Milic, Natasa MD, PhD2; Kantarci, Kejal MD3; Zeydan, Burcu MD3; Mosley, Thomas PhD4; Turner, Stephen T. MD1; Ware, Erin B. PhD, MPH5,6; Kardia, Sharon L.R. PhD5; Garovic, Vesna D. MD, PhD1

doi: 10.1097/GME.0000000000001062
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Objective: Experimental models suggest estrogen has a renoprotective effect, but human studies show variable results. Our objective was to study the association of hormone therapy (HT) and albuminuria in postmenopausal women and to synthesize the results with outcomes from prior studies.

Methods: We analyzed data from postmenopausal women who participated in the second study visit (2000-2004) of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The exposure was self-reported HT use and the outcome was albuminuria (urine albumin-to-creatinine ratio >25 mg/g creatinine). We also conducted a systematic review and meta-analysis on the association of HT and urine protein in postmenopausal women. Continuous and dichotomous measures of protein excretion were converted to a standardized mean difference (SMD) for each study.

Results: In the GENOA cohort (n = 2,217), there were fewer women with albuminuria among HT users than nonusers (9% vs 19%, P < 0.001). HT use was associated with decreased odds of albuminuria (odds ratio 0.65, 95% confidence interval (CI), 0.45-0.95), after adjusting for significant differences in age, race, education, comorbidities, and the age at and cause of menopause. The SMD of the effect of HT on urine proteinuria/albuminuria in the randomized control trials (n = 3) was 0.02 (95% CI, −0.29 to 0.33) and −0.13 (95% CI, −0.31 to 0.05) in the observational studies (n = 9). There was significantly less albuminuria among HT users (SMD −0.15, 95% CI, −0.27 to −0.04) in the 9 studies that only reported albuminuria as an outcome and in the 10 studies with a comparator arm (SMD −0.15, 95% CI, −0.26 to −0.04).

Conclusions: HT is associated with decreased odds of albuminuria, but some of the observed benefits may be related to reported outcomes, the presence of a comparator arm, and the type of study design.

1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN

2Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

3Department of Neuroradiology, Mayo Clinic, Rochester, MN

4Memory Impairment and Neurodegenerative Dementia Center, University of Mississippi, Jackson, MS

5Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI

6Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI.

Address correspondence to: Vesna D. Garovic, MD, PhD, Mayo Clinic, Division of Nephrology and Hypertension, 200 First Street SW, Rochester, MN 55905. E-mail: garovic.vesna@mayo.edu

Received 6 September, 2017

Revised 14 December, 2017

Accepted 14 December, 2017

Funding/support: This publication was supported by Grant No. UL1 TR000 135 from the National Center for Advancing Translational Sciences (NCATS), as well as Grant Numbers HL054464, HL054457, HL054481, HL087660, and HL119443 from the National Heart, Lung, and Blood Institute (NHLBI) Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Financial disclosure/conflicts of interest: None reported. The results of this study have not been published previously in whole or part, except in abstract form.

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© 2018 by The North American Menopause Society.