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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women
Kwang Kon Koh1, Mi-Seung Shin, Ichiro Sakuma
1Department of Cardiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. kwangk@ghil.com
Insights
Lower-dose hormone replacement therapy (HRT) offers cardiovascular benefits comparable to conventional doses, with a potentially safer profile. L-HRT did not increase inflammatory markers or clotting factors like conventional HRT, suggesting improved cardiovascular safety.
Area of Science:
- Cardiovascular Endocrinology
- Pharmacology
- Women's Health
Background:
- Hormone replacement therapy (HRT) impacts cardiovascular disease risk factors, including vasomotor function, inflammation, and hemostasis.
- Current HRT doses present a mix of cardiovascular protective and adverse effects.
- The differential effects of varying HRT doses on cardiovascular parameters require further investigation.
Purpose of the Study:
- To compare the cardiovascular effects of lower-dose hormone replacement therapy (L-HRT) versus conventional-dose hormone replacement therapy (C-HRT).
- To assess the impact of L-HRT and C-HRT on lipid profiles, endothelial function, inflammation, and coagulation parameters.
Main Methods:
- A randomized, double-blind, crossover study involving 57 women.
- Participants received either C-HRT (conjugated equine estrogen 0.625 mg + micronized progesterone 100 mg) or L-HRT (conjugated equine estrogen 0.3 mg + micronized progesterone 100 mg) daily for 2 months.
- Cardiovascular parameters including lipid levels, flow-mediated dilation, hsCRP, antithrombin III, F1+2, and PAI-1 antigen were measured.
Main Results:
- L-HRT demonstrated comparable effects to C-HRT on high-density lipoprotein cholesterol, triglycerides, and flow-mediated dilation.
- Unlike C-HRT, L-HRT did not significantly increase high-sensitivity C-reactive protein (hsCRP) or prothrombin fragment 1+2 (F1+2) levels.
- Both C-HRT and L-HRT decreased antithrombin III and PAI-1 antigen levels, with L-HRT showing a less pronounced reduction in antithrombin III.
Conclusions:
- L-HRT exhibits comparable efficacy to C-HRT regarding lipid profiles, endothelial function, and PAI-1 levels.
- L-HRT presents a potentially improved safety profile by not elevating inflammatory markers (hsCRP) or key coagulation activation markers (F1+2).
- L-HRT's modulation of hemostasis differs from C-HRT, warranting consideration in clinical practice.
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.
Methods And 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.
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