Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase-2 in Women with Polycystic Ovary Syndrome

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 mu g ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

A combined oral contraceptive containing drospirenone changes neither endothelial function nor hemodynamic parameters in healthy young women: a prospective clinical trial

Background: Combined oral contraceptives (COCs) may lead to a rise in cardiovascular disease risk, possibly associated with changes in blood pressure and endothelial function. Study Design: The objective was to evaluate the impact of COC containing 20 mcg of ethinylestradiol (EE) and 3 mg of drospirenone (DRSP) on the arterial endothelial function, systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) of healthy young women. Of the 71 women in the study, 43 were evaluated before the introduction of COC and after 6 months of its use (case group) and 28, COC nonusers, were assessed for the same parameters at the same time interval (control group). Results: No significant changes in endothelium-dependent and endothelium-independent functions or in measures of SBP, DBP, HR, CO and TPR caused by COC use were observed in the case group (p>.05 for all variables) or in the control group. Conclusion: These data suggest COC with 20 mcg EE and 3 mg DRSP does not alter arterial endothelial function or hemodynamic parameters in healthy young women. (C) 2012 Elsevier Inc. All rights reserved.

Women's knowledge of health effects of oral contraceptives in five Brazilian cities

Background: Although acceptability of combined oral contraceptives (COCs) is widespread, patients are often unaware of the noncontraceptive benefits. Study Design: An opinion survey through telephone interview was conducted to evaluate the knowledge of 500 Brazilian women 15-45 years of age who were current users or had recently used COCs. Data were obtained on their knowledge of adverse events, the effects of COCs on health- and menstrual-related symptoms, noncontraceptive benefits and aspects related to sexual response. Results: Most of the women interviewed learned about the pill from doctors or the Internet. Other than the pill, the best-known contraceptive methods were the condom and intrauterine device. The majority of women believe that COCs do not change the risk of gynecological cancers. Most believed that they had no significant effect on sexual response. Conclusions: COCs users in Brazil lack precise information on aspects related to general health, particularly menstrual-related symptoms and noncontraceptive health benefits. (C) 2012 Elsevier Inc. All rights reserved.

Drospirenone and levonorgestrel in combination with either 30 or 20 mcg ethinylestradiol reduce soluble adhesion molecules in Brazilian women; cross-sectional study

Background: The objective of this study was to evaluate the effect of three contraceptive pills containing ethinylestradiol (EE) (20 or 30 mcg) in combination with drospirenone (DRSP) and levonorgestrel (LNG) on plasma concentration of adhesion molecules vascular cell adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Study Design: A cross-sectional study was conducted with 72 participants (18-30 years old) distributed into three groups that used oral contraceptives containing EE 20 or 30 mcg combined with DRSP 3 mg or EE 30 mcg/LNG 150 mcg for at least 6 months. The control group was comprised of nonusers of contraceptives. Soluble VCAM-1, soluble ICAM-1 and soluble E-selectin were evaluated by enzyme-linked immunosorbent assay. Results: Compared to the control group, a significant decrease was found in VCAM-1 and ICAM-1 concentrations with use of DRSP/20 EE and LNG/30 EE. Conclusions: DRSP/20 EE and LNG/30 EE induce favorable changes in endothelial function. (C) 2012 Elsevier Inc. All rights reserved.

Effects of the etonogestrel-releasing contraceptive implant inserted immediately postpartum on maternal hemostasis: A randomized controlled trial

Introduction: The puerperium is the period of highest risk for thrombosis during a woman's reproductive life and it is an important time for initiating an effective contraceptive method in order to increase intergestational interval. Thus, the objective of the present study was to evaluated the effects of the etonogestrel (ENG)-releasing contraceptive implant inserted immediately postpartum on maternal hemostasis markers during the first six weeks of delivery. Materials and Methods: Forty healthy women aged 18 to 35 years-old were randomized to receive either the ENG-releasing implant 24-48 h after delivery (implant group; n=20) or nothing (control group) until the sixth postpartum week. Blood samples were collected at 24-48 h and at 6 weeks after delivery, and hemostatic variables, including fibrinogen, coagulation factors, protein C, free protein S, antithrombin, alpha 2-antiplasmin, plasminogen activator inhibitor 1, thrombin-antithrombin complex (TAT), prothrombin fragment (PF)1+2, and D-dimers, as well as normalized activated protein C sensitivity ratio (nAPCsr), thrombin time, activated partial thromboplastin time, and prothrombin time were evaluated. Results: Insertion of the ENG-releasing contraceptive implant did not change the physiological reduction in overall coagulation (TAT and PF1+2) and fibrinolysis (D-dimer) markers, or nAPCsr. Reductions in factors II, VII, X and fibrinogen and increases in factor V were greater in the control than in the implant group. Clotting factors remained within normal limits throughout the study. Conclusion: The ENG-releasing contraceptive implant inserted immediately postpartum did not have negative effects on physiological variations of the hemostatic system during the first 6 weeks postpartum. (C) 2012 Elsevier Ltd. All rights reserved.

Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sjogren's syndrome

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjogren's syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American-European criteria) and 89 age-gender-ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (a beta 2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney's criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls (p = 0.035). LA was the most common aPL in patients (9 %), followed by a beta 2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney's criteria) and were positive exclusively for LA. Comparison of patients with (n = 16) and without (n = 84) aPL revealed similar mean age, female predominance, and ethnicity (p > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p = 0.021), stroke (12.5 vs. 0 %, p = 0.024), and DVT (18.8 vs. 1.2 %, p = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p a parts per thousand yenaEuro parts per thousand 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.

Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism

Background: Combined oral contraceptives used in an extended regimen have been studied because of their potential benefits; however, there have been few publications on extended regimens of contraceptive vaginal rings. The aim of this study was to assess the effects of these two extended regimens on the lipid metabolism of women using these contraceptive methods during 1 year. Study Design: This prospective study enrolled 150 women: 75 used a vaginal contraceptive ring (11.7 mg etonogestrel and 2.7 mg ethinyl estradiol), and 75 used oral contraceptives (30 mcg ethinyl estradiol and 150 mg desogestrel). Both groups used their respective method for 84 days followed by a 7-day pause during I year. At baseline and every 3 months during the study period, blood was collected to assess total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and apolipoprotein (apo) A-I and B. The analysis of variance test was used to analyze differences in the results of these exams over time. Results: A total of 62 vaginal ring and 61 oral contraceptive users completed the study. There were no significant differences in the discontinuation rate, mean total cholesterol and fraction levels, apo B concentration or apo A-I/apo B ratio. Vaginal ring users had significantly higher apo A-I levels than oral contraceptive users. Conclusion: Despite the vaginal route of administration, the steroids released by the ring had the same effects on the lipid metabolism and lipoprotein levels typically seen with ethinyl estradiol given either by oral or parenteral routes. (C) 2012 Elsevier Inc. All rights reserved.

Combined oral contraceptives and increasing cardiovascular risk: thromboembolism and hypertension

Background: Hormonal contraceptive pills are the most used reversible method for familiar planning in Brazil. The combined pill, with synthetic analogs of estrogen and progestin, is employed by 25% of Brazilian female population. Its use provokes an increase of blood pressure levels, takes patient to a hipercoagulability state and predisposes her to thromboembolic events. Purposes: We aimed to describe mechanisms of hypercoagulability promoted by oral combined contraceptives, to analyze the relative risk of cardiovascular events within users and to list the most common circulatory pathologies in these patients. Methods: Three virtual medical databases were surveyed (Pubmed/Medline, BVS/LILACS and Scielo). Twelve studies were selected: clinical trials, case reports and articles of indexed medical periodic originally published in Portuguese and English about synthetic hormones, oral contraception, coagulation disorders and cardiovascular morbimortality. Results: Synthetic estrogen promotes an increase of some clotting factors' levels (VII, VIII, IX, X, XII, XIII and fibrinogen), such as a reduction of their inhibitors (S protein and antithrombin). Because of this, etinilestradiol is the component most related to venous thrombosis and ischemic diseases of brain and heart. It also improves the releasing of hepatic angiotensinogen, taking to a increase of blood pressure levels. Conclusions: The prescription of oral combined contraceptives needs criteria, notably due to adverse effects of etinilestradiol. It is recommended to avoid the administration of these drugs for patients elder than 35 year-old or with risk factors. For these patients, the use of progestagen-only pills seems to be safer.

Combinazioni androgeno-progestiniche per la contraccezione maschile

La contraccezione è un diritto fondamentale dell’uomo per il suo ruolo sulla salute, sulla qualità della vita e sul benessere della persona. La pianificazione familiare è uno dei principali strumenti che dà la possibilita’ a uomini e donne di condividere le proprie responsabilità sulla scelta contraccettiva e di decidere nella stessa misura della propria vita riproduttiva. Sin dall’introduzione della contraccezione femminile, la responsabilita’ della pianificazione familiare è ricaduta unicamente sulla donna. Attualmente infatti vi sono pochissimi metodi contraccettivi a disposizione degli uomini anche se vi e’ un rinnovato interesse da parte di questi ultimi nel sostenere le proprie partner nella scelta contraccettiva. Questo lavoro riassume i principali studi effettuati negli ultimi 10 allo scopo di sviluppare un contraccettivo che sia sicuro, efficace, reversibile e accettabile per l’uomo.

Normare la vita. Biocontrollo e nuove tecnologie

Questa ricerca, suddivisa in due parti, si concentra sulle problematiche connesse alla normazione della vita e dei corpi delle donne al tempo delle biotecnologie. La Parte I è una genealogia filosofico-politica che ripercorre le tappe analitico-concettuali del dibattito intorno a biopolitica e tecnoscienza, a partire dai contributi teorici di poststrutturalismo e femminismo neomaterialista, e risponde alle domande: Cosa sono diventati i corpi nell’attuale società bio-info-modificata? Qual'è il ruolo delle scienze nelle metamorfosi che interessano soggettività e rapporti di potere? La Parte II è una cartografia dei modi in cui le biotecnologie, riguardanti i corpi delle donne, si sono sviluppate e diffuse. Essa indaga in modo transdisciplinare come in Italia, e più in generale in Europa, sono state normate le tecniche di interruzione volontaria di gravidanza e fecondazione in vitro. Ampio spazio è dedicato ai modi in cui gli attori della bioetica, istituzionale e non, i medici, laici e cattolici, e le case farmaceutiche hanno affrontato questi temi e quello della contraccezione ormonale maschile. Medicina riproduttiva e rigenerativa sono tematizzate sempre in relazione al quadro normativo, per mostrare in che modo esso influenzi l’accesso ai diritti alla salute e all’autodeterminazione delle donne. Il quadro normativo è analizzato, a sua volta, alla luce dei fatti storici più rilevanti e delle culture più diffuse. L’obiettivo della ricerca è duplice: da un lato essa ha il fine di mostrare il modo in cui i corpi delle donne, e la relativa potenza generatrice, siano diventati uno snodo fondamentale nell’articolazione del biocontrollo e nell'apertura dei nuovi mercati legati a medicina riproduttiva e rigenerativa; dall’altro si propone di argomentare come un biodiritto flessibile, a contenuto storico variabile, condiviso e partecipato, sia un’ipotesi praticabile e virtuosa, utile all'eliminazione del gender gap ancora esistente in materia di diritti riproduttivi e sessuali.

Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: executive summary

With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure, and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death.Medical aspects that need to be considered relate to the long-term and multisystemic effects of single-ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the understanding of the late outcomes, genetics, medical therapy and interventional approaches in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. The present executive summary is a brief overview of the new guidelines and includes the recommendations for interventions. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology, including sections on genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy and contraception risks, and follow-up requirements. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

Identifying indicators of sustainable development using the global sustainability quadrant approach

Advances in information technology and global data availability have opened the door for assessments of sustainable development at a truly macro scale. It is now fairly easy to conduct a study of sustainability using the entire planet as the unit of analysis; this is precisely what this work set out to accomplish. The study began by examining some of the best known composite indicator frameworks developed to measure sustainability at the country level today. Most of these were found to value human development factors and a clean local environment, but to gravely overlook consumption of (remote) resources in relation to nature’s capacity to renew them, a basic requirement for a sustainable state. Thus, a new measuring standard is proposed, based on the Global Sustainability Quadrant approach. In a two‐dimensional plot of nations’ Human Development Index (HDI) vs. their Ecological Footprint (EF) per capita, the Sustainability Quadrant is defined by the area where both dimensions satisfy the minimum conditions of sustainable development: an HDI score above 0.8 (considered ‘high’ human development), and an EF below the fair Earth‐share of 2.063 global hectares per person. After developing methods to identify those countries that are closest to the Quadrant in the present‐day and, most importantly, those that are moving towards it over time, the study tackled the question: what indicators of performance set these countries apart? To answer this, an analysis of raw data, covering a wide array of environmental, social, economic, and governance performance metrics, was undertaken. The analysis used country rank lists for each individual metric and compared them, using the Pearson Product Moment Correlation function, to the rank lists generated by the proximity/movement relative to the Quadrant measuring methods. The analysis yielded a list of metrics which are, with a high degree of statistical significance, associated with proximity to – and movement towards – the Quadrant; most notably: Favorable for sustainable development: use of contraception, high life expectancy, high literacy rate, and urbanization. Unfavorable for sustainable development: high GDP per capita, high language diversity, high energy consumption, and high meat consumption. A momentary gain, but a burden in the long‐run: high carbon footprint and debt. These results could serve as a solid stepping stone for the development of more reliable composite index frameworks for assessing countries’ sustainability.