Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol152.Issue1.Sep2000:

Atherosclerosis 152 2000 149 – 157 The effect of hormone replacement therapy on arterial distensibility and compliance in perimenopausal women: a 2-year randomised trial I.C.D. Westendorp a , M.J.J. de Kleijn b , M.L. Bots a,b , A.A.A. Bak b , J. Planellas c , H.J.T. Coelingh Bennink c , A. Hofman a , D.E. Grobbee a,b , J.C.M. Witteman a, a Department of Epidemiology and Biostatistics, Erasmus Uni6ersity Medical School, Erasmus Uni6ersity, POB 1738 , 3000 DR Rotterdam, The Netherlands b Julius Center for Patient Oriented Research, Uni6ersity Medical Center, Utrecht, The Netherlands c Research and De6elopment Department, N.V. Organon, Oss, The Netherlands Received 5 May 1999; received in revised form 30 September 1999; accepted 15 October 1999 Abstract A single centre randomised placebo-controlled trial was performed to assess the 2-year effects of hormone replacement therapy compared to placebo on mechanical arterial properties in 99 perimenopausal women recruited from the general population. The trial was double-blind with respect to a sequential combined regimen of oral 17b-oestradiol and desogestrel 17bE 2 -D and the placebo group and open with respect to combination of conjugated equine oestrogens and norgestrel CEE-N. At baseline, distensibility and compliance of the common carotid artery were measured non-invasively with B-mode ultrasound and a vessel wall movement detector system, and the distensibility coefficient DC and compliance coefficient CC were calculated. Measurements were repeated after 6 and 24 months. Change in DC and CC in treatment groups was compared to placebo. After 24 months, changes for 17bE 2 -D compared to placebo were − 1.4 × 10 − 3 kPa 95 CI − 4.4; 1.7, P = 0.39 for DC and 0.26 mm 2 kPa 95 CI − 0.01; 0.53, P = 0.07 for CC. Changes for CEE-N compared to placebo were 0.4 × 10 − 3 kPa 95 CI − 1.0; 1.9, P = 0.79 and 0.11 mm 2 kPa 95 CI − 0.14; 0.37, P = 0.40. For systolic blood pressure SBP, diastolic blood pressure DBP and arterial lumen diameter no changes were found. In this study no significant differences in changes in distensibility and compliance were found between perimenopausal women using 17bE 2 -D or CEE-N and women using placebo after 6 and 24 months. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords : Arterial distensibility; Arterial compliance; Arterial stiffness; Hormone replacement therapy; Oestradiol; Women; Cardiovascular disease www.elsevier.comlocateatherosclerosis

1. Introduction

Epidemiological studies have shown a lower risk of coronary heart disease among postmenopausal users of oestrogen supplements compared to non-users [1 – 3]. Postulated mechanisms for a beneficial effect include changes in lipid and haemostatic variables and direct effects on the arterial wall. In experimental studies in animal oestrogens had direct vasodilatory effects [4 – 7] and were shown to affect the structure and mechanical properties of large arteries [8 – 10]. Improved endothe- lial function has been shown after hormone replace- ment therapy HRT in animal studies [11] and in postmenopausal women [12 – 14], and after oestrogen use in transsexual men [15,16]. Also HRT has been suggested to decrease the pulsatility index, a measure reflecting decreased peripheral vascular resistance [17 – 20]. Data on effects of HRT on distensibility and compliance of large arteries in humans are scarce. In a recent study, oestrogen users, had a higher arterial distensibility than non-users while oestrogen – progestin users had a lower arterial distensibility, and systemic arterial compliance was higher in both oestrogen and oestrogen – progestin users compared to non-users [21]. Corresponding author. Tel.: + 31-10-408-7365; fax: + 31-10-463- 5933. E-mail address : wittemanepib.fgg.eur.nl J.C.M. Witteman. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 3 8 - 4 In another study, HRT-users had a more favourable augmentation index, a measure of pulsatile vascular afterload, than non-users, while there was no difference in pulse wave velocity PWV, a measure of arterial stiffness [22]. Both studies, however, were observa- tional. Rajkumar et al. showed that women using HRT not only had better systemic arterial compliance than non-users, but that withdrawal of therapy, in a small group of women, resulted in a significant decrease of compliance [23]. To the authors’ knowledge no ran- domised studies have been performed to date on effects of HRT on distensibility and compliance of large arteries. The present study was conducted to assess the long- term effect of Liseta ® , a 24-day active, 28-day sequen- tial combined regimen of oral 17b-oestradiol and desogestrel 17bE 2 -D, and Prempak ® , a combination of conjugated oestrogens and norgestrel, on several cardiovascular risk factors Bak, 1998, unpublished re- sults and structural and dynamic arterial characteris- tics of the carotid artery. Here the results showing the effects of HRT, after 6 months and 2 years after arterial distensibility and compliance in perimenopausal women in comparison to placebo are presented.

2. Methods