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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 with oral contraceptive use. This study monitored the effects of estrogen shifts on protein S levels. Four patients with premature ovarian failure were treated with either oral or transdermal patch estrogen replacement. Blood drawn on days 1, 14, and 28 of therapy was analyzed for estradiol, estrone, free and total protein S, and C4b-bind-ing protein (C4b-BP) levels. Similar studies were performed on six normally cycling control patients and seven postmenopausal women. In healthy females, total levels of protein S fell from 22.1 ± 0.73 μg/mL on day 1 to 19.2 ± 1.29 μg/mL on day 14 (p < 0.023). Free protein S levels declined from 6.45 ± 0.70 μg/mL to 5.59 ± 0.69 μg/mL (p < 0.016). C4b-BP levels did not change during the normal menstrual cycle. Baseline total protein S (44.1 ± 7.0 μg/mL) and C4b-BP (193 ± 18%) levels were elevated in patients with premature ovarian failure. On oral therapy, 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 declines (44 to 26 μg/mL) in total protein S levels. In all cases, total protein S levels changed as a reciprocal function of estradiol. C4b-BP (128 ± 6.5%) and total protein S (32.2 ± 3.0 μg/mL) levels were higher in post-menopausal women than in nonmenopausal females. Free protein S levels in postmenopausal women (9.6 ± 0.6 μg/mL) were normal. 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 increased C4b-BP levels is uncertain, C4b-BP levels have a significant negative correlation with estradiol.