Lipids and clotting factors during low dose transdermal estradiol/norethisterone use.
OBJECTIVE
To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis.


METHODS
A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks.


RESULTS
In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholesterol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year.


CONCLUSIONS
A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.
Brynhildsen
Jan
J
Division of Obstetrics and Gynaecology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linkoping University, S-58185 Linkoping, Sweden. jan.brynhildsen@lio.se
Hammar
Mats
M
D000279:Administration, Cutaneous; D001777:Blood Coagulation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D009426:Netherlands; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077563:Norethindrone Acetate; D017698:Postmenopause; D013548:Sweden; D016896:Treatment Outcome
D015243:Cholesterol, VLDL; D008055:Lipids; D004958:Estradiol; D002784:Cholesterol; D000077563:Norethindrone Acetate; D009640:Norethindrone