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Variable effect of the post-partum menstrual cycle on aldosterone and renin in women with recent preeclampsia

Abstract

The purpose of the present study is to identify the impact of the postpartum menstrual cycle on aldosterone, renin, and their ratio of women with and without a preeclamptic pregnancy in the past. To this end, we analysed the data from 59 women with a history of preeclampsia and 39 healthy parous controls. Five to seven months post-partum, we measured aldosterone, renin, and the aldosterone-to-renin ratio during both the follicular and the luteal phase of the menstrual cycle. All measurements were taken in the supine position in the morning. Patients had maintained a standardized sodium diet in the week prior to the measurements. Our results show that in both post-partum women with recent preeclampsia and controls, average levels of renin and aldosterone are significantly elevated in the luteal phase as compared to the follicular phase. The aldosterone-to-renin ratio does not differ between the two phases in either group. Compared to controls, women with recent preeclampsia have significantly lower levels of renin, aldosterone, and aldosterone-to-renin ratio in the follicular phase. This remained consistent in the luteal phase, except for renin. A close correlation existed between the luteal and follicular aldosterone-to-renin ratio in the control group but not in the preeclampsia group. We conclude that both renin and aldosterone are significantly affected by the menstrual cycle whereas the resulting aldosterone-to-renin ratio is not. Post-partum women with recent preeclampsia tend to have lower values for aldosterone and the aldosterone-to-renin ratio than controls.

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Fig. 1: Distributions of renin, aldosterone and the ARR during the two phases of the menstrual cycle.
Fig. 2: Scatterplot of changes in aldosterone concentration in relation to changes in renin.
Fig. 3: Scatterplot of the relationship between the aldosterone-to-renin ratio (ARR) in the follicular and that in the luteal phase.

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Data availability

The data used in this study are available from the authors upon reasonable request.

References

  1. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101:1889–916.

    Article  CAS  PubMed  Google Scholar 

  2. Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, et al. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens. 2020;38:1919–28.

    Article  CAS  PubMed  Google Scholar 

  3. Veldhuizen GP, Alnazer RM, Kroon AA, de Leeuw PW. Confounders of the aldosterone-to-renin ratio when used as a screening test in hypertensive patients: A critical analysis of the literature. J Clin Hypertens (Greenwich). 2021;23:201–7.

    Article  CAS  PubMed  Google Scholar 

  4. Chidambaram M, Duncan JA, Lai VS, Cattran DC, Floras JS, Scholey JW, et al. Variation in the renin angiotensin system throughout the normal menstrual cycle. J Am Soc Nephrol. 2002;13:446–52.

    Article  CAS  PubMed  Google Scholar 

  5. Pizzolo F, Raffaelli R, Memmo A, Chiecchi L, Pavan C, Guarini P, et al. Effects of female sex hormones and contraceptive pill on the diagnostic work-up for primary aldosteronism. J Hypertens. 2010;28:135–42.

    Article  CAS  PubMed  Google Scholar 

  6. Fommei E, Ghione S, Ripoli A, Maffei S, Di Cecco P, Iervasi A, et al. The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women. J Hum Hypertens. 2009;23:130–5.

    Article  CAS  PubMed  Google Scholar 

  7. Ahmed AH, Gordon RD, Taylor PJ, Ward G, Pimenta E, Stowasser M. Are women more at risk of false-positive primary aldosteronism screening and unnecessary suppression testing than men? J Clin Endocrinol Metab. 2011;96:E340–6.

    Article  CAS  PubMed  Google Scholar 

  8. Zelinka T, Petrak O, Rosa J, Holaj R, Strauch B, Widimsky J Jr. Primary Aldosteronism and Pregnancy. Kidney Blood Press Res. 2020;45:275–85.

    Article  CAS  PubMed  Google Scholar 

  9. Piccoli GB, Mannucci C. Preeclampsia: A Diagnosis-Nondiagnosis That Is Too Easily Made: The Case of Primary Hyperaldosteronism. Kidney Blood Press Res. 2020;45:363–7.

    Article  PubMed  Google Scholar 

  10. Kilmartin C, Opu T, Podymow T, Dayan N. Primary hyperaldosteronism presenting as persistent postpartum hypertension: Illustrative case and systematic review. Obstet Med. 2019;12:190–5.

    Article  PubMed  Google Scholar 

  11. Malha L, Sison CP, Helseth G, Sealey JE, August P. Renin-Angiotensin-Aldosterone Profiles in Pregnant Women With Chronic Hypertension. Hypertension. 2018;72:417–24.

    Article  CAS  PubMed  Google Scholar 

  12. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension. 2018;72:24–43.

    Article  CAS  PubMed  Google Scholar 

  13. O’Shea PM, Griffin TP, Denieffe S, Fitzgibbon MC. The aldosterone to renin ratio in the diagnosis of primary aldosteronism: Promises and challenges. Int J Clin Pr. 2019;73:e13353.

    Google Scholar 

  14. Brown MA, Wang J, Whitworth JA. The renin-angiotensin-aldosterone system in pre-eclampsia. Clin Exp Hypertens. 1997;19:713–26.

    Article  CAS  PubMed  Google Scholar 

  15. Verdonk K, Saleh L, Lankhorst S, Smilde JE, van Ingen MM, Garrelds IM, et al. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression. Hypertension. 2015;65:1316–23.

    Article  CAS  PubMed  Google Scholar 

  16. O’Donnell E, Floras JS, Harvey PJ. Estrogen status and the renin angiotensin aldosterone system. Am J Physiol Regul Integr Comp Physiol. 2014;307:R498–500.

    Article  PubMed  Google Scholar 

  17. Armanini D, Bordin L, Dona G, Sabbadin C, Bakdounes L, Ragazzi E, et al. Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone. Steroids. 2012;77:655–8.

    Article  CAS  PubMed  Google Scholar 

  18. Yang J, Gwini SM, Beilin LJ, Schlaich M, Stowasser M, Young MJ, et al. Effect of oral contraception on screening tests for primary aldosteronism: a 10-year longitudinal study. J Clin Endocrinol Metab. 2023;108:1686-95.

  19. Bentley-Lewis R, Adler GK, Perlstein T, Seely EW, Hopkins PN, Williams GH, et al. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab. 2007;92:4472–5.

    Article  CAS  PubMed  Google Scholar 

  20. Rossi GP, Belfiore A, Bernini G, Fabris B, Caridi G, Ferri C, et al. Body mass index predicts plasma aldosterone concentrations in overweight-obese primary hypertensive patients. J Clin Endocrinol Metab. 2008;93:2566–71.

    Article  CAS  PubMed  Google Scholar 

  21. August P, Helseth G, Cook EF, Sison C. A prediction model for superimposed preeclampsia in women with chronic hypertension during pregnancy. Am J Obstet Gynecol. 2004;191:1666–72.

    Article  PubMed  Google Scholar 

  22. Sabbadin C, Saccardi C, Andrisani A, Vitagliano A, Marin L, Ragazzi E, et al. Role of Renin-Angiotensin-Aldosterone System and Cortisol in Endometriosis: A Preliminary Report. Int J Mol Sci. 2022; 24.

  23. Lewandowski KC, Tadros-Zins M, Horzelski W, Grzesiak M, Lewinski A. Establishing Reference Ranges for Aldosterone, Renin and Aldosterone-to-Renin Ratio for Women in the Third-Trimester of Pregnancy. Exp Clin Endocrinol Diab. 2022;130:210–6.

    Article  CAS  Google Scholar 

  24. Aardenburg R, Spaanderman ME, Ekhart TH, van Eijndhoven HW, van der Heijden OW, Peeters LL. Low plasma volume following pregnancy complicated by pre-eclampsia predisposes for hypertensive disease in a next pregnancy. Bjog. 2003;110:1001–6.

    PubMed  Google Scholar 

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Funding

This study was performed under the auspices of the university without external financial sources.

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Contributions

GPV and RMA acquired the data, drafted, and revised the manuscript and approved the final version. AAK, MEAS and PWdL conceived and designed the work, revised, and approved the manuscript. All authors had full access to the data and take responsibility for all aspects of the work.

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Correspondence to Peter W. de Leeuw.

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The authors declare no competing interests.

Ethical approval

The present study was performed in accordance with all relevant guidelines and regulations and the Declaration of Helsinki. The study received ethical approval from the Medical Research Ethics Committee of the Maastricht University Medical Center (Decision NL47252.068.14).

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Veldhuizen, G.P., Alnazer, R.M., Kroon, A.A. et al. Variable effect of the post-partum menstrual cycle on aldosterone and renin in women with recent preeclampsia. J Hum Hypertens (2024). https://doi.org/10.1038/s41371-024-00926-1

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