Antioxidant effects of hormone replacement therapy in postmenopausal women

Original article S W I S S M E D W K LY 2 0 0 6 ; 1 3 6 : 5 1 0 – 5 1 4 · w w w . s m w . c h 510 Peer reviewed article Antioxidant effects of hor...
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Original article

S W I S S M E D W K LY 2 0 0 6 ; 1 3 6 : 5 1 0 – 5 1 4 · w w w . s m w . c h

510

Peer reviewed article

Antioxidant effects of hormone replacement therapy in postmenopausal women Tuncay Delibasi a, Cem Kockar b, Alper Celikc, Olga Kockar d a b c d

Ankara Numune Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey Ankara Oncology Hospital Department of Internal Medicine, Ankara, Turkey Ankara Oncology Hospital, Department of General Surgery, Ankara, Turkey Ankara Hospital, Department of Radiology, Ankara, Turkey

Summary Questions under study: Postmenopausal women are more likely to develop coronary artery disease than premenopausal women of the same age. Postmenopausal oral oestrogen therapy is associated with increased levels of high-density lipoprotein (HDL) cholesterol and decreased levels of lowdensity lipoprotein (LDL) cholesterol. In this study we investigated the direct contribution of hormone replacement therapy on total antioxidant capacity rather than its effects on the serum lipid profile. Methods: At the time of enrolment and after the drug delivery plasma total cholesterol, triglycerides (TG), HDL, LDL, uric acid, total bilirubin, albumin, oestradiol levels and total antioxidant capacity of plasma were assessed.

Results: Levels of plasma TG and total antioxidant capacity were significantly increased in the study group. Conclusions: Our results suggest that oestrogen has an antioxidant effect following 3 months of hormone replacement therapy. Progesterone in combination with oestrogen does not have this effect. Also plasma TG levels increased in those patients receiving HRT after 3 months. Key words: menopause; hormone replacement therapy; antioxidants; cardiovascular disease; atherosclerosis

Introduction

Financial supports: This work was carried out in the Ankara Numune Hospital, Department of Endocrinology and Metabolism and was not supported by any financial grant.

Menopause concerns a large population of women. It is supposed that by the year 2025, 20% of the world will consist of people above age 60. Therefore women who spend 2/3 of their life in postmenopausal term will increase in number and will be affected by the outcomes of hormonal changes. Hormone replacement therapy (HRT) is of paramount importance in assessing adequate quality of life caused by oestrogen deficiency. Coronary heart disease, another dilemma, is one of the major causes of death in the elderly women. The reduction in Cardio Vascular Disease (CVD) during HRT is contradicted by a recent Women’s Health Initiative (WHI) Study [1]. However, a large num-

ber of epidemiological studies mentioned that HRT is associated with increased levels of HDL cholesterol and decreased LDL cholesterol, which explains the protective effect on CVD [2]. On the other hand, the lipoprotein theory failed to demonstrate the reason for the decreased incidence of coronary heart disease in 50–75% of patients receiving HRT [3, 4]. Exposure of normal coronary vascular endothelium to oxidised LDL results in impaired functions of endothelium. Recent evidence suggests that oestrogens possess antioxidant activity [5]. In this study our goal was to investigate whether the cardio-protective effect of HRT was due to the antioxidant system.

S W I S S M E D W K LY 2 0 0 6 ; 1 3 6 : 5 1 0 – 5 1 4 · w w w . s m w . c h

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Subjects and methods Sixty postmenopausal normocholesterolaemic (total cholesterol 40 I.U./l) volunteered to participate in the study. Data were analysed prospectively. Subjects were randomised into two groups: the study group consisted of 30 patients who received HRT. The control group consisted of 30 patients who rejected or delayed HRT. Each woman in the study group was matched with one control who was closest in age and weight. Initial data in the two groups are shown in table 1. None of the patients had a history of previous HRT, and smokers, diabetics, patients with chronic inflammatory conditions, hepatic or respiratory disease, and those on antioxidants, vitamin or other medication were excluded from the study. Each subject underwent a comprehensive history and physical examination including a standard electrocardiogram. At the time of enrolment and after the medication, venous blood samples from each subject obtained from the antecubital vein between 8–11 a.m. was drawn into ethylenediamine tetraacetic acid (EDTA, 1 mg/ml blood) containing tubes. After centrifugation of the blood for 15 minutes at 3000 g the plasma obtained was stored in several aliquots at –25 ºC until assay. Plasma total cholesterol,

triglycerides (TG), uric acid albumin, and total bilirubin levels were quantified using enzymatic methods. Plasma oestradiol was measured using chemiluminesence method. HDL was measured after phosphotungsticMgCl2 precipitation of apoprotein B containing VLDL and LDL. The LDL-C was calculated according to the equation described by Friedewald et al. [6]. Plasma TAC was measured using the ABTS (Amino-diethyl-benzthiazoline sulfate) method with a total antioxidant status kit (from Randox Laboratories Ltd. UK) and the results are expressed as mmol/l [7]. The study group received 0.625 mg oestrogen and 2.5 mg medroxyprogesterone acetate orally per day, for a period of 3 months. Overall, 57 women completed the study. 1 patient from the control group and 2 women from the study group dropped out. Two-way ANOVA was used to analyse differences between the groups in subject characteristics, all biochemical parameters and treatment induced changes. Age and body weight were used as covariates. Multivariate linear regression analysis for each biochemical parameter with treatment group, age, weight and baseline value as predictors was performed by using SPSS, version 10.0 (SPSS, Chicago, IL, USA). A cut-off of P

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