PROTEIN-S LEVELS DURING THE NORMAL MENSTRUAL-CYCLE AND DURING ESTROGEN THERAPY FOR PREMATURE OVARIAN FAILURE

Protein S levels have been reported to be decreased in pregnancy and w ith oral contraceptive use. This study monitored the effects of estrog en shifts on protein S levels. Four patients with premature ovarian fa ilure were treated with either oral or transdermal patch estrogen repl acement. Blood drawn on days 1, 14, and 28 of therapy was analyzed for estradiol, estrone, free and total protein S, and C4b-binding protein (C4b-BP) levels. Similar studies were performed on six normally cycli ng control patients and seven postmenopausal women. In healthy females , total levels of protein S fell from 22.1 +/- 0.73 mug/mL on day 1 to 19.2 +/- 1.29 mug/mL on day 14 (p < 0.023). Free protein S levels dec lined from 6.45 +/- 0.70 mug/mL to 5.59 +/- 0.69 mug/mL (p < 0.016). C 4b-BP levels did not change during the normal menstrual cycle. Baselin e total protein S (44.1 +/- 7.0 mug/mL) and C4b-BP (193 +/- 18%) level s were elevated in patients with premature ovarian failure. On oral th erapy, there was a strong, negative correlation (r = -0.979, p < 0.021 ) between C4b-BP and estradiol levels. C4b-BP levels did not change in patients with the patch. Both estrogen therapies produced similar dec lines (44 to 26 mug/mL) in total protein S levels. In all cases, total protein S levels changed as a reciprocal function of estradiol. C4b-B P (128 +/- 6.5%) and total protein S (32.2 +/- 3.0 mug/mL) levels were higher in postmenopausal women than in nonmenopausal females. Free pr otein S levels in postmenopausal women (9.6 +/- 0.6 mug/mL) were norma l. In conclusion, C4b-BP levels are elevated mildly in postmenopausal women and markedly elevated in patients with premature ovarian failure . Because of concurrent elevations of total protein S, free protein S levels are normal in both groups of patients. Although the cause of in creased C4b-BP levels is uncertain, C4b-BP levels have a significant n egative correlation with estradiol.