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Relationship between Aldosterone and Progesterone in the Human Menstrual Cycle

Division of Endocrinology, Diabetes and Hypertension (E.D.S., G.K.A., J.S.W., D.E.G., T.M.Y., E.W.S.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Department of Medicine (P.N.H.), University of Utah School of Medicine, Salt Lake City, Utah 84132

Address all correspondence and requests for reprints to: Ellen W. Seely, M.D., Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: eseely{at}partners.org.

Context: Aldosterone levels increase during the luteal phase of the menstrual cycle. Prior studies examining relationships between aldosterone and female sex hormones did not control for sodium balance, a major determinant of aldosterone production.

Objectives: The objectives of this study were 1) to compare aldosterone levels between menstrual phases among cycling women in high- and low-sodium balance; and 2) to examine the relationships between aldosterone and female sex hormones in women and the effects of sex hormones on rat zona glomerulosa (ZG) cell aldosterone production in vitro.

Subjects/Interventions: Normotensive, premenopausal women were studied in low- and/or high-sodium balance. Urinary aldosterone, basal serum aldosterone, plasma renin activity (PRA), plasma angiotensin II (AngII), and serum aldosterone after AngII infusion were measured. Isolated rat ZG cells were treated with progesterone, estradiol, or both, and aldosterone was measured.

Results: In high-sodium balance, urinary aldosterone, basal serum aldosterone, and serum aldosterone response to infused AngII were significantly greater (P < 0.05) in the luteal vs. follicular phase. PRA, AngII, and potassium did not differ. Progesterone directly correlated with urinary aldosterone, basal serum aldosterone, and serum aldosterone response to infused AngII. Estradiol did not significantly correlate with aldosterone. In low-sodium balance, no significant differences in aldosterone levels between phases were found. In vitro, progesterone increased ZG cell aldosterone production (P < 0.01), whereas estradiol had no effect.

Conclusions: In women, urinary and serum aldosterone levels are significantly higher during the luteal phase in high- but not low-sodium balance, whereas PRA and AngII do not differ between phases. Progesterone may directly contribute to increased luteal phase aldosterone production, independent of the renin-angiotensin system.

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