Estradiol- and progesterone-related increases in the renin-aldosterone system: Studies during ovarian stimulation and early pregnancy

Jean E. Sealey, Joseph Itskovitz-Eldor, Speranza Rubattu, Gary D. James, Phyllis August, Israel Thaler, Jacob Levron, John H. Laragh

Research output: Contribution to journalArticlepeer-review


To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 ± 255 pg/mL (8430 pmol/L); P4, 103 ± 22 pg/mL (328 pmol/L); PRA, 33 ± 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 ± 28 µgrams/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 ± 283 ng angiotensin-I/mL (n = 8) to 3682 ± 607 (n = 8) on day 7 and to 5353 ± 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis. The changes were not associated with any apparent perturbation of electrolyte homeostasis. The results indicate that estrogen and P, may play important roles in the maintenance of electrolyte homeostasis in coordination with the renin-angiotensin-aldosterone system.

Original languageEnglish
Pages (from-to)258-264
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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