The effect of menopause on blood lipid and lipoprotein levels

doi:10.1016/S0021-9150(99)00315-9

Atherosclerosis

Volume 147, Issue 1, November 1999, Pages 147-153

https://doi.org/10.1016/S0021-9150(99)00315-9 Get rights and content

Abstract

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality in men and women in the industrialized world. The interactions between the various physiological risk factors for CVD are complex; the incidence of CVD increases with age in both sexes, but in women the risk increases markedly after the menopause and eventually becomes equivalent to that of men. This observation has suggested, but has not proven, that estrogens have a protective effect against CVD [1], [2], [3].

Evidence from epidemiological studies supports the hypothesis that hormone replacement therapy (HRT) has a cardioprotective effect in postmenopausal women [4], [5], although data from a substantial number of randomized clinical trials are lacking. A large number of prospective studies have shown that exogenous estrogen affects the concentrations of lipids and lipoproteins. A dose of 0.625 mg of conjugated equine estrogen, or equivalent, given orally over at least 3 months to postmenopausal women, produces significant decreases in total cholesterol and LDL, and increases in total triglycerides, HDL, HDL₂, and HDL₃. Estrogen increases the hepatic synthesis of LDL receptor (apo B-100), resulting in an increased LDL uptake and therefore decreased circulating LDL levels [6], and also increases the activity of the enzyme lipoprotein lipase, thus raising HDL and lowering triglyceride levels [7]. There is therefore a biological rationale behind the hypothesized benefit of HRT, although randomized clinical trials are essential to establish estrogen’s supposed cardioprotective effect.

The key question for clinicians is whether changes in lipid profile associated with menopause contribute to CVD risk, and whether HRT would then be beneficial in counteracting them [8], [9]. Although the effects of exogenous steroid hormones on lipids and lipoproteins have been demonstrated, the influence of endogenous estrogen and the changes in estrogen concentration that occur around menopause are less clearly documented. These data are necessary to distinguish the contribution of lipid profile changes to the observed increased risk of CVD in women post-menopause, and the corresponding contribution of HRT to prevention. The ICARUS (Italian Climacteric Research Group Study) study was the first trial designed to collect prospective observational data on menopause, its clinical management, and its effect on women’s health specifically in the Italian population. The major aim of the study reported here was to examine the effects of menopause on lipid and lipoprotein profile in a large cohort of women. A cross-sectional analysis of women enrolled up to March 1997 in the ongoing ICARUS study was carried out. The results of this analysis are presented here.

Section snippets

Methods

ICARUS is a prospective, observational study on the effect of menopause and its clinical management, conducted since 1995 in 49 menopause clinics across Italy. All the women attending the participating centers were to be included in the study.

At the first visit, sociodemographic data, reproductive and medical history, menopausal symptoms, the use of female hormones, and risk factors for cardiovascular disease, osteoporosis, and breast, ovarian and endometrial cancer, were collected by trained

Results

The present report focuses on the effect of menopause on blood lipid and lipoprotein levels in women not receiving hormonal treatment. Of the 12 524 women participating in the study by March 1997, 3215 (25.7%) were using HRT and were therefore excluded from this analysis. A total of 9309 women are therefore considered in the present paper.

Table 1 shows the demographic and clinical features of the 9309 women, according to menopausal status. The mean age of pre-, peri- and postmenopausal women

Discussion

A number of observational studies have looked at the effect of menopause on the lipid profile, in particular those lipids known to have an impact on the cardiovascular risk. One study investigated a cohort of 542 healthy, non-obese British women aged 18–70 years, and showed that, compared with premenopausal women, postmenopausal subjects had significantly higher concentrations of total cholesterol (increase of 14%, P<0.001), triglycerides (12% increase, P<0.005), LDL (27% increase, P<0.001),

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¹: The Icarus Study Group: T. Nencioni, M. Ciammella (Milan); G. Bonaccorsi, D. Morano (Ferrara); S. Viglino, C. Artoni (Genoa); E. Grassini, G. Radici (Milan); F. De Cicco, E. Ronsisvalle (Rome); B. Marcacci, Perrone (Porretta Terme); D. De Paoli (Cattolica); N. Colacurci, P. De Franciscis (Naples); G. Lodico, G. Lodico (Palermo); R. Ferreri, V. Loizzi (Bari); P. Giacomelli, E. Benetello (Montebelluna); P. Salmaggi, M. Coniglio (Rome); E. Giussani, R. Comi (Monza); E. Grimaldi, F.P. Mangino (Trieste); S. Bucciantini, V. Checcucci (Florence); C. Nappi, P. Affinito (Naples); C. Campagnoli, M. Lanza (Turin); G. Galbiati, D. Albini (Chiari); G. Lentini, S. Civallelci (Florence); E. Galbignani (Bergamo); M. Franchi, M.G. Terreni (Varese); C. Cicoli, S. Pulisca (Pesaro); R. Chionna, R. Marabini (Milan); A. Cordopatri, I. Spadaro (Messina); A. Cagnacci, A. Volpe (Modena); V. De Leo, A. La Marca (Siena); F. Camanni, C. Manieri (Turin); P. Scognamiglio, L. Romani (Pescia); S. Cargiaghe, L. Mannu (Sassari); P. Masi, G. Fattorini (Bologna); B. Bersellini, L. Biancotti; (Sondrio); D. Marchesoni, M. Dal Pozzo (Padua); F. Ramazzotto, C. Stegher (Brescia); B. Molteni, E. Molteni (Giussano); R. Lombardo, G. Galati (Soriano Calabro); A. Sironi, G. Ranchet (Gallarate); C. Belloni, C. Proietti (Como); R. Lorefice (Lanciano); G. Menozzi, P. Carunchio (Suzzara); E. Rovetta (Voghera); M. Gallo, G. De Luigi (Turin); G. Righetti, P. Favaro (Bussolengo); E. Gentile (Belluno); O. Flangini, L De Stefani (Soave); S.G. Sciacchitano, R. Catrini (Catania); F. Bartiromo, M. Bruno (Naples); G.F. Puggioni, L. Sionis (Nuoro); D. Agostinelli, E. Tajani (Terlizzi); G. Mercuri, P. Petronio (Ascoli Piceno).

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The effect of menopause on blood lipid and lipoprotein levels

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Prev. Med.

J. Biol. Chem.

Am. J. Obstet. Gynecol.

Maturitas

J. Lipid Res.

Atherosclerosis

Maturitas

Maturitas

Maturitas

Lancet

Am. J. Clin. Nutr.

Metabolism