Objectives: The purpose of the study is to assess the endometrial contribution of serum CA-125 using exogenous estrogen administration by ruling out ovarian activity. A. randomized, controlled, prospective study was designed to assess the endometrial contribution of serum CA-125 and its influence from estrogen administration in menopausal women. Methods: Twenty menopausal women with intact uterus and ovaries (study group) and 10 cases with previous total hysterectomy with intact ovaries (control group) were included in the study. The mean age of subjects in the study and control groups were similar at 53 +/- 1.9 (S.D.) and 51 +/- 2.7 years. The length of menopause in the study and control groups were also similar at 61.0 +/- 18 and 52.6 +/- 26.5 months, respectively. Group 1 consisted of 10 randomly selected cases and five controls who received 15 days of 50 mug/day transdermal 17beta-estradiol (TE). Group 2 consisted of the next randomly selected 10 cases and five controls who had 15 days of transdermal 100 mug/day 17beta-estradiol (Estraderm-Ciba) administration. Serum CA-125 and estradiol were measured at day 0, 15 by radioimmunoassay (RIA). Results. Serum mean CA-125 levels increased significantly in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6%, respectively (P = 0.03 and P = 0.05, respectively). Interestingly, the increase in serum estradiol levels accompanied this change only in group 2. Conclusions: These results suggest that endometrial CA-125 secretion to serum is dependent on the dose of administered exogenous estrogen. (C) 2002 International Federation of Gynecology and Obstetrics. All rights reserved.