View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 113–117 Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology jou rnal homepage: www.elsevier.com/locate/ejogrb Effects of a contraceptive containing drospirenone and ethinylestradiol on blood pressure, metabolic profile and neurohumoral axis in hypertensive women at reproductive age a b,c c b Tercio Lemos de Morais , Cassiana Giribela , Marcelo Gil Nisenbaum , Grazia Guerra , c c a,b, Nilson Mello , Edmundo Baracat , Fernanda M. Consolim-Colombo * a Universidade Nove de Julho (UNINOVE), Sa˜o Paulo, Brazil b Hypertension Unit, Heart Institute (InCor), University of Sa˜o Paulo, Sa˜o Paulo, Brazil c Gynecology Department, University of Sa˜o Paulo, Sa˜o Paulo, Brazil A R T I C L E I N F O A B S T R A C T Article history: The use of combined oral contraceptives is widespread among hypertensive women despite being Received 24 April 2014 associated with increased cardiovascular risk. Contraceptives containing drospirenone, which has Received in revised form 27 August 2014 antimineralocorticoid properties, may have a positive or neutral effect on neurohumoral activation and Accepted 3 September 2014 metabolic homeostasis of hypertensive women at reproductive age. Objectives: To evaluate the effect of combined oral contraceptive containing drospirenone + ethiny- Keywords: lestradiol on the systemic blood pressure, metabolic variables and neurohumoral axis in hypertensive Oral contraceptives women in reproductive age. Hypertension Design: Prospective controlled trial with 56 hypertensive women allocated in two groups: 30 Cardiovascular risk volunteers under oral combined contraceptive use and 26 volunteers using non-hormonal contraceptive methods. Subjects were tested before the introduction of the contraceptive method and 6 months after its use. For data acquisition, we used continuous non-invasive beat-to-beat blood pressure curve recordings and, for the biochemical and hormonal analyses two blood samples were obtained. Student’s t test was used to determine differences between groups and moments and p < 0.05 was considered statistically significant. Results: Comparing antropometric and blood pressure measurements, cardiac sympatho-vagal modulation, baroreceptor sensitivity, metabolic and neurohumoral axis variables between baseline and after 6 months, no significant difference was detected in each group or between groups. Except serum triglyceride levels which increased in the group of women using EE + DRSP after 6 months of use. Conclusion: A contraceptive containing 20 mcg of ethinyl estradiol and 3 mg of drospirenone causes no significant changes in clinical and autonomic parameters, metabolic variables and neurohumoral axis of hypertensive women. ß 2014 Elsevier Ireland Ltd. All rights reserved. Introduction issues associated with pregnancy and contraception [1]. Hyperten- sion is a major source of maternal and fetal morbidity and some Hypertension in women of reproductive age presents important methods of contraception may further increase the risk of clinical implications and challenges, not only because of its role as cardiovascular events [2]. a risk factor for cardiovascular disease, but also because of the Combined oral contraceptive (OC) is one of the most commonly prescribed birth control methods, used by millions of women in many countries [3]. OCs induce mild increase of arterial blood * Corresponding author at: Fernanda Marciano Consolim-Colombo Heart pressure in the general population, but in about 5% of the female Institute (InCor), Hypertension Unit, University of Sa˜o Paulo, Av. Dr. Ene´as de users it is likely to get higher results. Adverse effects on blood Carvalho Aguiar, 44, Cerqueira Ce´sar, Sa˜o Paulo, SP CEP 05403-000, Brazil. pressure increase with age, duration of the use of OCs and the Tel.: +55 11 3069 5084; fax: +55 11 3069 5923. presence of other risk factors such as smoking, obesity and prior E-mail addresses: [email protected], [email protected] (F.M. Consolim-Colombo). diagnosis of hypertension. Moreover, OCs may impose additional http://dx.doi.org/10.1016/j.ejogrb.2014.09.006 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved. 114 T.L. Morais et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 113–117 adverse outcomes in women by stimulating the renin angiotensin Experimental design aldosterone system (RAAS) and also by causing metabolic disarrangements and pro-thrombotic effects [4–6]. All selected women were eligible for both the contraceptive Even considering that contraception guidelines point to an methods, i.e., OCs or non-hormonal methods. However, after being indication against the use of OC by uncontrolled hypertensive counseled regarding the advantages, disadvantages and side women or with other cardiovascular risk factors, epidemiological effects of each contraceptive method, the volunteers were free studies have shown that a high rate of hypertensive women are in to choose the type of contraception they wanted to use. Therefore, regular use of OC [1,7]. Furthermore, hypertensive women may women who agreed to participate in the study were allocated into develop adverse effects related to the interaction of antihyperten- two groups, users and nonusers: (1) EE + DRSP group: women sive drugs and OCs. who chose to use an OC containing 20 mcg EE + 3 mg DRSP, with 24 The types and doses of estrogens have been associated with the days of active pills and a 4 day pill-free interval (n = 30), (2) non- adverse effects related to OCs [5,8]. OC group: women who chose to use a non-hormonal method of Recent meta-analysis has shown that even OCs with low contraception (condoms or copper IUD) (n = 30). hormone levels (ethinylestradiol, estradiol (EE)), associated or not All volunteers were evaluated during the same menstrual cycle with new progestogens may still lead to thromboembolic events phase: follicular phase at baseline for both groups; follicular phase causing increased cardiovascular risk in women in general [9–12]. in the follow-up period for the control group; high hormonal phase Drospirenone (DRSP) is the most similar synthetic progestin to in the contraceptive group. All examinations were performed the natural progesterone, and is structurally similar to spirono- during the same time of the day, and were conducted in a lactone, acting as an antagonist of aldosterone receptors with temperature-controlled room. All patients were instructed to clinically recognized antimineralocorticoid activity [13–15]. DRSP abstain from exercise, caffeine and alcohol for 12 h before testing. molecule in combination with EE, initially studied as hormone replacement therapy in hypertensive postmenopausal women Evaluation methods for body mass index and office blood pressure. [16,17], demonstrated a high capability to neutralize the estrogen- induced RAAS activation [18,19]. Moreover, OCs containing Body mass index (BMI) was obtained by using measures of 2 EE + DRSP did not increase blood pressure and had little impact weight and height of each subject (weight/height ) acquired on metabolic profile in both normotensive young women [20] and during the basal evaluation and at the end of the study (6 months). postmenopausal hypertensive women [21–23]. There are few Blood pressure measurement (BP) in the office was obtained informations in the literature regarding to the effects of OCs using the auscultatory method with a calibrated mercury containing EE + DRSP used as a contraceptive method in the sphygmomanometer following the recent guideline technique population of hypertensive women. Therefore, the aim of this recommendations. Hemodynamic parameters obtained during 1 study was to prospectively evaluate the impact of OC containing rest in supine position, with the Finometer device (FMS, Finapres EE + DRSP coadministered with antihypertensive drugs on arterial Medical System, Anhem, The Netherlands) [24,25]. blood pressure, metabolic homeostasis and neurohumoral axis in hypertensive women. Heart rate variability and autonomic nervous system parameters 1 The blood pressure curves obtained with the Finometer device Materials and methods were simultaneously recorded in another computer equipped with biological signal acquisition and signal conversion software (AT/ This study enrolled 60 hypertensive female volunteers MCA-CODAS; DATAC Instruments Inc., Akron, Ohio, USA). The recruited from the outpatient clinics of the Gynecology Depart- sampling frequency of the signals was 1000 Hz. The stored signals ment and Hypertension Unit of the General Hospital, School of were subsequently subjected to an analysis routine that provided Medicine, University of Sa˜o Paulo, Brazil. The Research Ethics values for HR variability, blood pressure and spontaneous Committee of the University of Sa˜o Paulo reviewed and approved baroreflex sensitivity. After these signals were pre-amplified the study. All patients were submitted to a clinical examination by (General Purpose Amplifier; Stemtech, Inc., 4-GPA), they were both a cardiologist and a gynecologist. converted from analog into digital and then stored for later The inclusion criteria were women aged between 20 and analysis. Each heart beat was identified by the use of a specialized 40 years old, with previous diagnosis of essential arterial algorithm implemented