Effects of Estrogen Replacement Therapy on the Renin-Angiotensin System in Postmenopausal Women
Abstract
Background Oral estrogen replacement therapy (ERT) is known to stimulate the synthesis of angiotensinogen. The effects of such therapy on renin, ACE, and aldosterone are less clear. This seems noteworthy, however, since further activation of the system could be disadvantageous to postmenopausal women who replace estrogen in the context of heart failure, coronary artery disease, or hypertension. Methods and Results Estrogen status and components of the renin-angiotensin system were examined in a population-based sample of postmenopausal women and age-matched men. Renin was quantified immunoradiometrically, ie, independent of substrate abundance; aldosterone, angiotensinogen, and ACE activity were determined by standard methods. Renin levels were lower in women with ERT (n=107; 12.0±0.7 mU/L) compared with women without ERT (n=223; 16.6±0.9 mU/L; P =.001) or men (n=342, 20.5±1.5 mU/L, P <.0001). In contrast, angiotensinogen was higher in women with ERT (1.36±0.08 mg/L) compared with women without ERT (1.03±0.02 mg/L; P <.0001) or compared with men (0.97±0.01 mg/L; P <.0001). Renin suppression was seen with either oral or transdermal estrogen replacement (−30% and −31%, respectively; both P <.001). In contrast, the increase of angiotensinogen was limited to women taking oral estrogens (+58%, P <.001). Multivariate analysis revealed that these estrogen effects were independent of age, body mass index, blood pressure, and/or antihypertensive medication. Finally, only marginal differences between groups were observed for serum ACE activity and aldosterone. Conclusions Aside from a well-documented induction of angiotensinogen, ERT is related to a substantial suppression of renin, a phenomenon that might have received little attention because of widely used indirect measurements of the hormone.
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Estrogen inhibits renin secretion.
“Estrogen inhibits renin levels [8,23,24].”
Cites
Hassager, C., Riis, B. J., Strøm, V, Guyene, T. T., & Christiansen, C. (1987) · Circulation · doi:10.1161/01.cir.76.4.753 · Cited by 124 · see citing works
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Physiology of Local Renin-Angiotensin Systems
Paul, M., Poyan Mehr, A., & Kreutz, R. (2006) · Physiological Reviews · doi:10.1152/physrev.00036.2005 · Cited by 1,739 · see citing works
Gender differences in the regulation of blood pressure
Reckelhoff, J. F. (2001) · Hypertension · doi:10.1161/01.hyp.37.5.1199 · Cited by 1,268 · see citing works
Hypertension: Renin–Angiotensin–Aldosterone System Alterations
te Riet, L., van Esch, J. H. M., Roks, A. J. M., van den Meiracker, A. H., & Danser, A. H. J. (2015) · Circulation Research · doi:10.1161/circresaha.116.303587 · Cited by 706 · see citing works
Self-citationEstrogen Modulates AT <sub>1</sub> Receptor Gene Expression In Vitro and In Vivo
Nickenig, G., Bäumer, A. T., Grohè, C., Kahlert, S., Strehlow, K., Rosenkranz, S., Stäblein, A., Beckers, F., Smits, J. F. M., Daemen, M. J. A. P., et al. (1998) · Circulation · doi:10.1161/01.cir.97.22.2197 · Cited by 409 · see citing works
Renin angiotensin system and gender differences in the cardiovascular system
Fischer, M. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00479-5 · Cited by 384 · see citing works
Estrogen regulation of angiotensin-converting enzyme mRNA
Gallagher, P. E., Li, P., Lenhart, J. R., Chappell, M. C., & Brosnihan, K. B. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.323 · Cited by 290 · see citing works
Estrogen-induced cardiorenal protection: potential cellular, biochemical and molecular mechanisms.
Dubey, R. K., & Jackson, E. K. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.280.3.f365 · Cited by 263 · see citing works
Impact of gender on the renal response to angiotensin II
Miller, J. A., Anacta, L. A., & Cattran, D. C. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00260.x · Cited by 255 · see citing works
Langrish, J. P., Mills, N. L., Bath, L. E., Warner, P., Webb, D. J., Kelnar, C. J., Critchley, H. O. D., Newby, D. E., & Wallace, W. H. B. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.126516 · Cited by 207 · see citing works
Effect of oral contraceptives on the renin angiotensin system and renal function
Kang, A. K., Duncan, J. A., Cattran, D. C., Floras, J. S., Lai, V., Scholey, J. W., & Miller, J. A. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.280.3.r807 · Cited by 103 · see citing works
Ovarian Cycle and Sympathoexcitation in Premenopausal Women
Carter, J. R., Fu, Q., Minson, C. T., & Joyner, M. J. (2013) · Hypertension · doi:10.1161/hypertensionaha.112.202598 · Cited by 105 · see citing works
“However, other data suggest that only progesterone activates the RAAS, whereas estrogen might inhibit the activation of this system.(30,31) Szmuilowicz et al(27) reported that progesterone may directly contribute to increased luteal phase aldosterone production independent of the RAAS.”
BackgroundMacova, M., Armando, I., Zhou, J., Baiardi, G., Tyurmin, D., Larrayoz-Roldan, I. M., & Saavedra, J. M. (2008) · Neuroendocrinology · doi:10.1159/000150977 · Cited by 75 · see citing works
Fu, Q., VanGundy, T. B., Shibata, S., Auchus, R. J., Williams, G. H., & Levine, B. D. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.151787 · Cited by 62 · see citing works
Sex-specific long-term blood pressure regulation: Modeling and analysis
Leete, J., & Layton, A. T. (2019) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2018.11.002 · Cited by 58 · see citing works
The Renin-Angiotensin-Aldosterone System in Postmenopausal Women: The Promise of Hormone Therapy
Gersh, F. L., O’Keefe, J. H., Lavie, C. J., & Henry, B. M. (2021) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2021.08.009 · Cited by 57 · see citing works
The effect of oral contraceptives on the nitric oxide system and renal function
Cherney, D. Z. I., Scholey, J. W., Cattran, D. C., Kang, A. K., Zimpelmann, J., Kennedy, C., Lai, V., Burns, K. D., & Miller, J. A. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00351.2007 · Cited by 33 · see citing works
The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill
La Corte, A. L. C., Carter, A. M., Turner, A. J., Grant, P. J., & Hooper, N. M. (2008) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320308096405 · Cited by 21 · see citing works
Modulation of blood pressure by estrogen: A modeling analysis
Layton, A. T. (2026) · Mathematical Biosciences · doi:10.1016/j.mbs.2025.109610 · Cited by 1 · see citing works
Stadt, M. M., & Layton, A. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.01.651663
“The enzyme renin is secreted by the juxtaglomerular cells of the kidneys to convert AGT to Ang I. Estrogen inhibits renin levels [8,23,24].”
- Authors
- Schunkert, H., Danser, A. H. J., Hense, H.-W., Derkx, F. H. M., Ku¨rzinger, S., & Riegger, G. A. J.
- Affiliations
- University of Münster (DE)
- the Klinik und Poliklinik fu¨r Innere Medizin II, University of Regensburg (Germany) (H.S., S.K., G.A.J.R.); the Departments of Pharmacology and Internal Medicine, Erasmus University, Rotterdam, the Netherlands (A.H.J.D., F.H.M.D); and Institut fu¨r Epidemiologie und Sozialmedizin, University of Mu¨nster (Germany), and GSF Forschungszentrum, Institut fu¨r Epidemiologie, Munich-Neuherberg, Germany (H.-W.H.).
- Venue
- Circulation
- Published
- 1997-01-07
- Volume
- 95
- Issue
- 1
- Pages
- 39-45
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2012816393
- Cited by
- 438
- References
- 1
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 17 · 2023: 14 · 2022: 9 · 2021: 19 · 2020: 12 · 2019: 15 · 2018: 10 · 2017: 18 · 2016: 9 · 2015: 12 · 2014: 16 · 2013: 14 · 2012: 16
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen replacement therapy, renin-angiotensin system, postmenopausal women, renin suppression, angiotensinogen, angiotensin-converting enzyme, aldosterone, transdermal estrogen, oral estrogen, sex differences
- MeSH terms
- Aged, Aldosterone, Analysis of Variance, Angiotensinogen, Estradiol, Estriol, Estrogens, Conjugated (USP), Female, Humans, Hypertension, Male, Middle Aged, Renin, Renin-Angiotensin System, Estrogen Replacement Therapy, Postmenopause
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