Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women.
OBJECTIVE
The effects of hormone replacement therapy (HRT) can affect many aspects relevant to cardiovascular disease, including vasomotor function, inflammation, and hemostasis. Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects. In the current study, we compared the effects of lower doses of HRT (L-HRT) and conventional doses of HRT (C-HRT) on a variety of relevant cardiovascular parameters.


RESULTS
This randomized, double-blind, crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels, but not on low-density lipoprotein cholesterol levels. C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values (both P<0.001) by a similar degree (P=0.719). C-HRT significantly increased high-sensitivity C-reactive protein (hsCRP) levels from baseline values (P<0.001); however, L-HRT did not significantly change hsCRP (P=0.874). C-HRT and L-HRT significantly decreased antithrombin III from baseline values (P<0.001 and P=0.042, respectively). C-HRT significantly increased prothrombin fragment 1+2 (F1+2) from baseline values (P<0.001); however, L-HRT did not significantly change F1+2 (P=0.558). Of interest, the effects of C-HRT and L-HRT on hsCRP, antithrombin III, and F1+2 were significantly different (all P<0.001). C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from baseline values (P=0.002 and P=0.038, respectively) to a similar degree (P=0.184).


CONCLUSIONS
Compared with C-HRT, L-HRT has comparable effects on lipoproteins, flow-mediated dilation, and PAI-1 antigen levels. However, L-HRT did not increase hsCRP or F1+2 levels, and it decreased antithrombin III less than C-HRT.
Koh
Kwang Kon
KK
Department of Cardiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. kwangk@ghil.com
Shin
Mi-Seung
MS
Sakuma
Ichiro
I
Ahn
Jeong Yeal
JY
Jin
Dong Kyu
DK
Kim
Hyung Sik
HS
Kim
Dae Sung
DS
Han
Seung Hwan
SH
Chung
Wook-Jin
WJ
Shin
Eak Kyun
EK
D000990:Antithrombin III / Q000032:analysis; D001916:Brachial Artery / Q000000981:diagnostic imaging; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007249:Inflammation / Q000453:epidemiology; D007723:Korea; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D011374:Progesterone / Q000008:administration & dosage* / Q000494:pharmacology; D011516:Prothrombin / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP); D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; C045879:prothrombin fragment 1.2; D011374:Progesterone; D000990:Antithrombin III; D011516:Prothrombin; D002097:C-Reactive Protein; D005996:Nitroglycerin