ESTRADIOL-RELATED AND PROGESTERONE-RELATED INCREASES IN THE RENIN-ALDOSTERONE SYSTEM - STUDIES DURING OVARIAN STIMULATION AND EARLY-PREGNANCY

To investigate the degree to which endogenous increases in estradiol ( E(2)) and progesterone (P-4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for i n vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were fol lowed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E(2) i ncreased 10-fold, PRA increased 2- fold, and absolute levels of E(2) a nd P-4 were positively correlated (r = 0.63; P < 0.05). After ovulatio n, which was induced by hCG, E(2) fell by 50% (day 7), but there was a 50-fold increase in P-4 and a further 5-fold increase in PRA. By day 14, E(2) increased again in the women who conceived, to levels even hi gher than those in the follicular phase, and both P-4 and PRA increase d 2- to 3-fold between days 7 and 14. In contrast, E(2), P-4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E (2), P-4, and PRA remained very high in the pregnant women [E(2), 2297 +/- 255 pg/mL (8430 pmol/L); P-4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pr egnancy, there was a positive relationship between PRA and P-4 (r = 0, 68; P < 0.05). There was also a positive relationship between PRA and E(2) (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E(2) 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 pre gnant women, reaching very high levels [135 +/- 28 mu g/day (375 nmol/ day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). P lasma 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) o n day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldost erone. There was no hypokalemia. These results demonstrate marked incr eases in plasma renin and UA in coordination with increases in plasma E(2) and P-4 during ovarian stimulation and early pregnancy, and coord inated falls during luteolysis. The changes were not associated with a ny apparent perturbation of electrolyte homeostasis. The results indic ate that estrogen and P-4 may play important roles in the maintenance of electrolyte homeostasis in coordination with the renin-angiotensin- aldosterone system.