Effects of menopausal hormone therapy on hemostatic parameters, blood pressure, and body weight: open-label comparison of randomized treatment with estradiol plus drospirenone versus estradiol plus norethisterone acetate.
OBJECTIVE
Clinical studies have reported changes in hemostatic parameters in women taking menopausal hormone therapy (HT) and a small increased risk of venous thromboembolism. We compared the effects of two different HTs on hemostatic parameters in postmenopausal women.


METHODS
An open-label, randomized study conducted at two centers in Germany compared continuous 28-week combined HT with 17beta-estradiol 1mg plus drospirenone 2 mg (E2/DRSP) daily versus E2 1mg plus norethisterone acetate 0.5 mg (E2/NETA) daily in healthy postmenopausal women. Changes in D-dimer levels from baseline to the end of treatment, as well as effects on further parameters of coagulation, fibrinolysis, and global hemostasis, and effects on bleeding pattern, blood pressure, and body weight were evaluated.


RESULTS
D-dimer levels increased by 9.1% (median change) with E2/DRSP (n=29) and by 15.1% with E2/NETA (n=30). Other hemostatic parameters showed <10% median change from baseline in both treatment groups, except for tissue plasminogen activator antigen (E2/DRSP, -1.9%; E2/NETA, -24.2%). Systolic blood pressure decreased from baseline by 6.4 mmHg in the E2/DRSP group compared with 0.1 mmHg in the E2/NETA group at final examination. Body weight remained stable in the E2/DRSP group (+0.18 kg) compared with a slight increase (+1.00 kg) in the E2/NETA group. In nonhysterectomized women, the mean number of bleeding/spotting days was 5.2 (2.0 bleeding/3.2 spotting) in the E2/DRSP and 8.2 (4.4 bleeding/3.8 spotting) in the E2/NETA group. Most nonhysterectomized women, however, remained amenorrheic during the study period (E2/DRSP, 68%; E2/NETA, 62%).


CONCLUSIONS
Both E2/DRSP and E2/NETA were associated with a minor increase in fibrinolytic activity and a slight change in the concentration of some coagulation factors. Both HTs were well tolerated. The decrease in systolic blood pressure and stable body weight in the E2/DRSP group are consistent with DRSP's anti-aldosterone properties.
Junge
Wolfgang
W
Laboratorium für Klinische Forschung GmbH, Raisdorf, Germany. project@lkf-kiel.de
El-Samalouti
Volker
V
Gerlinger
Christoph
C
Schaefers
Matthias
M
D000368:Aged; D000736:Androstenes / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000009:adverse effects; D011486:Protein C / Q000032:analysis
D000736:Androstenes; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; C036309:fibrin fragment D; D004958:Estradiol; C035144:drospirenone; D009640:Norethindrone