Elsevier

American Heart Journal

Volume 134, Issue 4, October 1997, Pages 764-771
American Heart Journal

Effects of hormone-replacement therapy on hemostatic factors, lipid factors, and endothelial function in women undergoing surgical menopause: Implications for prevention of atherosclerosis,☆☆,,★★

https://doi.org/10.1016/S0002-8703(97)70062-0Get rights and content

Abstract

Women with premature menopause are at high risk for vascular compications associated with thrombogenesis and atherogenesis. The use of hormone-replacement therapy (HRT), however, may protect against these complications. Hemostatic abnormalities and endothelial function are closely related to the processes of thrombogenesis and atherogenesis. The purpose of the study was to evaluate the effects of premature menopause on markers of hemostasis, platelet function, and endothelial function and the effects of starting HRT. This is a prospective longitudinal study of premenopausal women undergoing surgical menopause in whom estrogen HRT is started. We measured sequential changes in plasma levels of the hemostatic factors (fibrinogen, fibrin d -dimer, and plasminogen activiator inhibitor [PAI]), markers of platelet function (soluble leukocyte adhesion molecule P-selectin) and endothelial function (von Willebrand factor [vWf], soluble thrombomodulin [sTM], and tissue plasminogen activator [TPA]), and serum lipid levels, including lipoprotein A. Twenty-seven premenopausal women (mean age 43.6 ± 6.5 years) undergoing hysterectomy and bilateral salpingo-oophrectomy were studied. In the postsurgical menopausal state (visit 2), there was a significant elevation in sTM levels (paired Wilcoxon test, p = 0.008). There was also a trend toward higher median soluble P-selectin, PAI, and mean TPA levels and lower vWf levels. After 6 weeks of HRT (visit 3), there was a significant reduction in mean vWf (paired Wilcoxon test, p = 0.0026), sTM ( p = 0.039), and TPA levels ( p = 0.02) compared with premenopausal levels. There were no significant changes in plasma fibrinogen, fibrin d -dimer, and PAI levels at visit 2 or visit 3 compared with premenopausal levels. There was a significant increase in serum lipoprotein A (paired Wilcoxon test, p = 0.008), cholesterol, and triglyceride levels after surgical menopause (paired t test, p < 0.01). Lipoprotein A and cholesterol levels after HRT (visit 3) were not significantly different from prehysterectomy levels, although triglyceride levels were increased further. HRT results in a significant reduction in vWf, sTM, and TPA levels, suggesting beneficial effects on endothelial function and atherogenesis. Although there was a significant increase in serum lipoprotein A and cholesterol levels after surgical menopause, lipoprotein A and cholesterol levels after HRT were not significantly different from presurgery levels. These observations are consistent with the beneficial effects of HRT in cardiovascular hemodynamics and cardiovascular disease. (Am Heart J 1997;134:764-71.)

Section snippets

Methods

We conducted a prospective study to investigate the effect of introducing estrogen-only HRT (oral conjugated estrogens as Premarin, 0.625 mg) in consecutive women undergoing (premature) surgical menopause after hysterectomy and bilateral oophrectomy during a 6-month period. Women were generally undergoing the surgery for previous dysfunctional uterine bleeding. Patients were studied before the hysterectomy (visit 1), 6 weeks after the hysterectomy (visit 2, at which time HRT was started), and

Results

We studied 27 premenopausal women (mean age 43.6 ± 6.5 years) undergoing hysterectomy and bilateral salpingo-oophrectomy, who consented to participate in this study. All the patients had menopausal symptoms by 6 weeks after surgical menopause, which was followed by (reported) symptomatic relief from these symptoms after the introduction of HRT.

Plasma levels of follicle-stimulating hormone and luteinizing hormone were normal before hysterectomy, with elevations in plasma follicle-stimulating

Discussion

This study is limited by the small sample size and short follow-up periods (6 weeks) after surgical menopause and the introduction of HRT. Thus changes in the various markers that were measured might have been more impressive if there had been longer follow-up periods while the patients were menopausal (i.e., after hysterectomy but before HRT) and after the introduction of HRT. However, because many women in the study had symptoms, there remains an ethical consideration if HRT were withheld for

Acknowledgements

We thank Dr. John Zarifis and Michèle Beevers, SRN, for assistance with data collection and Dr. P. Davies for valuable statistical advice.

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      Most studies that were about normal menopause or did not evaluate the effects of hormone therapy were excluded at the screening phase. Among the 28 articles excluded through full text reading, 13 were excluded because the study participants were on average older than 40 years at baseline (Baksu et al., 2007; Basbug et al., 1997; Bhattacharya and Jha, 2010; Castelo-Branco et al., 1993; Eeles et al., 1991; Haines et al., 1995; Kilic et al., 2010; Lip et al., 1997; Lyritis et al., 1995; Madalinska et al., 2006; Sherwin and Gelfand, 1985a,b; Somunkiran et al., 2007), and seven because the study interventions (Bakhsh et al., 2015; Christ et al., 2018; Honigberg et al., 2019; Wong et al., 2018) or outcomes (Elkind-Hirsch et al., 1992, 1993; Kapetanakis et al., 1982) were not compatible with the review entry criteria (Figure 1). Five studies were also excluded that evaluated hormone therapy in women with POI but had a cross-sectional design (Bachelot et al., 2016; Benetti-Pinto et al., 2019; Cardona Attard et al., 2019; Giraldo et al., 2017; Kurabayashi et al., 1993), one study protocol (Mittal et al., 2013), one possible overlap with another report (Li et al., 1991) and a review (Atsma et al., 2006).

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    Supported by Dr. J. Amiral (Serbio, Gennevilliers, France).

    ☆☆

    aRecipient of the 1994 Edith Walsh and Ivy Powell Research Awards and the 1995 Nathaniel Bishop Harman Award for Cardiovascular Disease Research from the British Medical Association.

    Reprint requests: G. Y. H. Lip, MD, Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England.

    ★★

    0002-8703/97/$5.00 + 0 4/1/83869

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