Effects of four different regimens of hormone replacement therapy on hemostatic parameters: a prospective randomized study.
OBJECTIVE
To compare the effects of four different regimens including oral and transdermal formulations with or without progestins on the hemostatic system in a prospective randomized fashion.


METHODS
Eighty-eight women were randomized to four groups receiving continuous transdermal estradiol 50 microg/day (tE2), oral conjugated equine estrogen 0.625 mg/day (CEE 0.625 mg), oral conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day (CEE 0.625 mg/MPA 2.5 mg), or oral 2 mg 17-beta estradiol combined with 1 mg norethistrone acetate (E2/norethistrone). The hysterectomized patients received only estrogen, and the remaining women received the estrogen plus progesterone combination regimens. As a marker of hemostatic system fibrinogen, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured initially, and after 1 and 6 months of therapy.


RESULTS
The treatment groups were well matched for baseline characteristics including age, height, weight, body mass index, and systolic and diastolic blood pressures. During the study period fibrinogen levels were below the baseline values in all groups. However, the decrease was only statistically significant in patients treated with oral 0.625 mg/day CEE. tPA levels were decreased significantly by tE2, CEE 0.625 mg, and CEE 0.625 mg/MPA 2.5 mg. PAI-1 levels were decreased significantly by CEE 0.625 mg, and CEE 0.625 mg/MPA 2.5 mg. When the effects of the four different regimens were compared using percentage changes from the baseline, no significant difference was found among the treatment groups.


CONCLUSIONS
One of the treatment regimens resulted in a more coagulable state. Oral therapy with CEE decreased the levels of all parameters, and MPA did not impair this beneficial effect, except for in fibrinogen. Transdermal therapy had a minimal effect. No significant difference was noted among the four regimens.
Gazi University, Faculty of Medicine, Department of Obstetrics and Gynecology, Ciğdem Mah. 30. Cadde, 310 Sokak, Ulusoy Apt. 2/14, Karakusunlar, Ankara, Turkey. mztaner@yahoo.com
M Zeki
MZ
Taner
Erdinc
E
Ozpolat
Cagatay
C
Taskiran
M Anil
MA
Onan
Turkiz
T
Gursel
Erdem
E
Karabulut
Rifat
R
Gursoy
Ozdemir
O
Himmetoglu
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007044:Hysterectomy; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects*; D016896:Treatment Outcome
D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); D017395:Plasminogen Activator Inhibitor 1; D004958:Estradiol; D005340:Fibrinogen; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D010959:Tissue Plasminogen Activator; D009640:Norethindrone