Effects of transdermal and oral hormone replacement therapies on monocyte chemoattractant protein-1 levels: a randomized clinical trial Tolga Tas ¸c ¸ı, Yavuz Emre S ¸u ¨ ku ¨ r, Batuhan O ¨ zmen, Cem Somer Atabekog ˘lu, Sevim Dinc ¸er Cengiz, Evren Koc ¸bulut, Bu ¨ lent Berker, Murat So ¨ nmezer * Ankara University School of Medicine, Department of Obstetrics and Gynecology, Ankara, Turkey 1. Introduction The definitive effect of hormone replacement therapy (HRT) for the prevention of postmenopausal vasomotor symptoms and osteoporosis has been heavily debated for several decades. According to previous observational studies, the advantages of HRT, which include protection from cardiovascular diseases (CVD), osteoporosis and colon cancer, outweigh the disadvantages such as increased risk of breast cancer and thromboembolism [1]. According to the primary results of randomized clinical trials such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) study, HRT was found not to protect from CVD [2,3]. Conversely, a recent meta- analysis concluded that HRT reduces the risk of CVD events in younger postmenopausal women [4]. It is now well established that there are several early CVD markers such as cholesterol profile, triglyceride, C-reactive protein (CRP), homocysteine, lipoprotein(a) (Lp(a)), and monocyte che- moattractant protein-1 (MCP-1) [5–9]. MCP-1 is expressed by fibroblasts, monocytes, endothelial cells, cardiomyocytes, smooth muscle cells, glomerular mesangial cells, osteoblastic cells, and human pulmonary type-2 like epithelial cells [10–12]. MCP-1 is an important mediator of atherogenic signals which has chemotactic activity for monocytes [9]. Substantial evidence supports a role for MCP-1 in the recruitment of monocytes to the subendothelial space in the pathogenesis of atherosclerosis, which is a chronic inflammatory process [13–15]. It is demonstrated that MCP-1 mRNA levels are increased in atherosclerotic arteries [13,16]. European Journal of Obstetrics & Gynecology and Reproductive Biology 176 (2014) 50–54 ARTICLE INFO Article history: Received 29 November 2013 Received in revised form 2 February 2014 Accepted 14 February 2014 Keywords: Homocysteine Hormone replacement therapy Lipid profile Monocyte chemoattractant protein-1 Transdermal ABSTRACT Objectives: To assess the effects of oral and transdermal hormone replacement therapies (HRT) on levels of important cardiovascular disease (CVD) markers, MCP-1 and homocyteine, in the early postmenopausal period. Study design: Seventy-six healthy, early postmenopausal women were enrolled in the study. Patients were randomly assigned to receive oral or transdermal HRT for 6 months. The first group received continuous combined oral HRT containing 1 mg 17b-estradiol and 0.5 mg norethisterone acetate (n = 39), and the second group received sequential transdermal HRT releasing 50 mg/day estradiol alone given twice a week on days 1–14 and 50 mg/day estradiol plus 0.25 mg/day norethisterone acetate given twice a week on days 15–28 (n = 37). Circulating levels of MCP-1 and homocysteine, along with other CVD markers, were assessed before and after treatment in all patients. Results: There were no significant differences between the baseline characteristics of the two groups. Baseline serum MCP-1 levels were similar between the oral and transdermal HRT groups (150.1 Æ 12.8 vs. 145.2 Æ 11.6 pg/ml; P = .219). The mean MCP-1 levels did not change after 6 months of HRT in both oral (150.1 Æ 12.8 vs. 153.6 Æ 12.5 pg/ml; P = .192) and transdermal HRT groups (145.2 Æ 11.6 vs. 146.1 Æ 15.1 pg/ml; P = .419). Moreover, there was no significant difference between the groups in MCP- 1 serum levels after 6 months of HRT. Similarly, no difference was found in serum homocyteine levels following 6 months of HRT. Conclusions: Both oral continuous and sequential transdermal HRTs do not have significant effects on serum MCP-1 and homocyteine levels in women during the early postmenopausal period. ß 2014 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Ankara U ¨ niversitesi Tıp Faku ¨ ltesi Kadın Hastalıkları ve Dog ˘um A.D., Cebeci, 06100 Ankara, Turkey. Tel.: +90 3125956405; fax: +90 312 320 35 53. E-mail address: msonmezer@gmail.com (M. So ¨ nmezer). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb http://dx.doi.org/10.1016/j.ejogrb.2014.02.034 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.