Failure of the combination of sequential oral and transdermal estradiol plus norethisterone acetate to affect plasma homocysteine levels

Objective: A high level of plasma homocysteine may be deleterious to vascul ar health. We therefore compared the effect of combinations of sequential o ral and transdermal estradiol plus norethisterone acetate on plasma homocys teine. Design: Prospective, randomized study. Setting: Outpatient department of obstetrics and gynecology in a university hospital. Patient(s): Forty-two healthy, nonsmoking postmenopausal women starting hor mone replacement therapy (HRT) to control climacteric symptoms. Intervention(s): In a randomized order, the women started using either oral HRT (2 mg of estradiol on days 1-12, 2 mg of estradiol plus 1 mg of noreth isterone acetate (NETA) on days 13-22, and 1 mg of estradiol on days 23-28; n = 21) or transdermal HRT (50 mug/d of estradiol on days 1-28 and 250 mug /d of norethisterone acetate on days 15-28, n = 21) for 1 year. Main Outcome Measure(s): Fasting plasma levels of homocysteine were measure d before the treatment and during the combined estradiol-plus-NETA phases o f the sixth and 12th treatment cycles. Result(s): Basal homocysteine levels in the oral group (8.2 +/- 3.1 mu mol/ L, mean plusmn;SD) and transdermal group (8.7 plusmn; 1.8 mu mol/L, mean pl usmn;SD) were not affected by the estradiol-plus-NETA combination. Conclusion(s): Neither an oral nor a transdermal combination of sequential estradiol and NETA causes significant changes in plasma homocysteine in Fin nish postmenopausal women with normal baseline homocysteine levels. (Fertil Steril(R) 2000;74:1081-3. (C) 2000 by American Society for Reproductive Me dicine).