Gene expression associated with unfavorable vaginal bleeding in women using the etonogestrel subdermal contraceptive implant: a prospective study.

To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21-20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63-17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups.

Site necrosis at the insertion place of the single-rod subdermal contraceptive implant: report of five cases.

OBJECTIVE: Implant-site necrosis is a rare complication. We present a case-series of a necrosis as an adverse effect after the etonogestrel (ENG)-subdermal contraceptive implant placement. MATERIAL AND METHODS: Five women with site necrosis after the ENG-implant placement and their clinical manifestations and treatments. RESULTS: Local pain was the main symptom, appearing within 35 days of placement. Outpatient multidisciplinary treatment was undertaken. Local debridement and implant removal was performed in four out of the five women. Time to complete healing varied from 45 days to 12 months. CONCLUSION: Early diagnosis and multidisciplinary treatment are essential to avoid severe aesthetic or functional damages and major life-threatening complications.

We presented five cases with necrosis at the ENG-implant site of placement in which we proposed an early diagnosis and multidisciplinary treatment to avoid severe aesthetic or functional damages.

Female sexual function in women using LARC methods.

OBJECTIVE: This study aims to assess sexual function (SF) and quality of life (QoL) among women using copper intrauterine devices (Cu-IUD), levonorgestrel-releasing intrauterine system (LNG-IUS) or etonogestrel(ENG)-releasing subdermal implant. METHODS: This is a cross-sectional study involving 213 women who are sexually active, using Cu-IUD, LNG-IUS or ENG implant for at least one year. SF assessment was carried out through the Female Sexual Function Index (FSFI) and QoL was made through The Short Form Health Research. RESULTS: Frequency of sexual dysfunction score in Cu-IUD users was 33.8%; 47.2% in LNG-IUS users and 47.8% in ENG-implant users, without difference between groups. Desire domain had higher score in Cu-IUD users (Cu-IUD:4.20 ± 1.15 × LNG-IUS:3.76 ± 1.17 × ENG-implant:3.63 ± 1.15; p = .009). Between Cu-IUD and LNG-IUS users there was no difference in FSFI score. Total FSFI score was higher in Cu-IUD group when compared only to ENG-implant (Cu-IUD:27.48 ± 6.14 × Implant:25.07 ± 6.89; p = .029). Regarding the QoL score, difference was found only in general health domain (Cu-IUD:65.22 ± 14.91 × LNG-IUS:62.61 ± 19.04 × Implant:58.33 ± 16.46; p = .034), with lower score for implant group. CONCLUSION: There was no difference in the SF total score between the users of Cu-IUD, LNG-IUS and ENG implant. However, the score of the FSFI desire domain and general health status were higher among users of the Cu-IUD.

Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report.

INTRODUCTION: Thalidomide is an immunomodulatory drug and first choice in the treatment of erythema nodosum leprosum. Given its teratogenic potential, it is essential that an effective contraceptive method is used, especially a long-acting reversible contraceptive (LARC) method. The subdermal etonogestrel (ENG)-releasing implant is an adequate method due to the high effectiveness and long-term use. However, interaction between thalidomide and ENG has not been well documented. Concern arises because thalidomide interacts with cytochrome P450 (CYP450) enzymes that metabolize sexual steroids. AIM: We aimed to study the effectiveness and safety of the ENG-implant in a thalidomide user. METHODS: Case report of a sexually active 21-year-old patient with both Hansen's disease and leprosy reaction type 2 treated with thalidomide requiring effective contraception. Follow-up was up to 36 months after implant placement. RESULTS: Contraception with ENG-implant was effective and safe, based on clinical parameters (reduction of menstrual flow and cervical mucus thickening) and laboratory parameters (gonadotropins and sexual steroids). CONCLUSION: To the best of our knowledge, this is the first case reported which presents a patient in simultaneous use of thalidomide and ENG-implant. Although this case report preliminary supports effectiveness and safety of ENG-implant as a contraceptive option in women using thalidomide, rigorous drug-drug interaction research is needed to better characterize the interaction between thalidomide and the ENG-implant.

Manejo farmacológico del sangrado irregular no menstrual asociado al uso de implantes anticonceptivos subdérmicos / Pharmacological management of irregular non-menstrual bleeding associated with the use of subdermal contraceptive implants

El spottingo sangrado irregular no menstrual es uno de los principales efectos secundarios de los implantes anticonceptivos, situación que se recomienda discutir con la usuaria previo a la colocación, para evitar falsas expectativas o temores que lleven a la extracción temprana del dispositivo. A propósito de una paciente sin antecedentes relevantes que consultó al centro de salud por spotting desde la colocación del implante cuatro meses antes, decidimos revisar la evidencia sobre la efectividad de los distintos esquemas farmacológicos disponibles para el manejo de este evento adverso. Luego de realizar una búsqueda bibliográfica concluimos que, si bien existe sustento para indicar algunos de los esquemas farmacológicos, este es aún débil y son necesarios estudios clínicos adicionales que brinden evidencia sólida sobre qué esquema en particular utilizar, evaluando sus riesgos y beneficios. (AU)

Spotting or irregular non-menstrual bleeding is one of the main side effects of contraceptive implants, a situation that health professionals must discuss with the user prior to its placement in order to avoid false expectations or fears that lead to early removal of the implant. Regarding a patient with no relevant history who consulted the health center due to spotting four months after implant placement, we decided to review the evidence onthe effectiveness on different pharmacological schemes available for the management of this adverse event. After performing a literature search, we concluded that, although there is support for indicating some of the pharmacological schemes, this is still weak, and further clinical studies are needed to provide solid evidence on which particular scheme touse, assessing its risks and benefits. (AU)

Twelve-month Continuation of the Etonogestrel Implant in Adolescents With Polycystic Ovary Syndrome.

STUDY OBJECTIVE: To identify why adolescents with polycystic ovary syndrome (PCOS) chose the etonogestrel (ENG) contraceptive implant, to determine the 12-month continuation rate, and to characterize factors related to discontinuation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of adolescents seen at a tertiary care children's hospital between July 1, 2008, and August 30, 2019, with PCOS diagnosis confirmed per National Institutes of Health criteria and ≥12-month ENG follow-up. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic characteristics, reasons for ENG insertion and removal, and information on other hormonal/contraceptive therapies were collected. Patients were categorized as ENG continuers (use ≥12 months) or discontinuers (removal at <12 months), and groups were compared. RESULTS: A total of 96 patients met inclusion criteria (age 17.7 ± 2.2 years, body mass index 34.8 ± 8 kg/m2). Reasons for ENG were documented in 74% (51% contraception, 32% ease of use, 15% other, 13% estrogen avoidance). In all, 27% had never been sexually active, and 67% had had prior sexual activity. Treatments prior to ENG placement included 74% combined hormonal contraception, 20% medroxyprogesterone acetate withdrawal, and 17% depot medroxyprogesterone. A total of 77% continued ENG at 12 months. The main reasons for discontinuation were bleeding (41%), concern about weight gain (23%), and mood changes (18%). No preimplantation characteristics were independently predictive of continuation, although 100% of patients with type 2 diabetes (n = 11) continued. Patients who sought additional care, including telephone calls (41% vs 12%, P = .006) and clinic visits (64% vs 20%, P < .001) were more likely to discontinue. CONCLUSIONS: The ENG implant was well tolerated in adolescents with PCOS and similar to published 12-month continuation rates.

ENG-releasing subdermal implants in postpartum teenagers - an open-label trial study protocol.

BACKGROUND: Higher than expected adolescent pregnancy high rates continue globally, with repeated unplanned pregnancy (UP) in this age group is a public health problem. In Brazil, 16% of pregnancies occur in adolescents under 18 years old, with high maternal morbidity and mortality rates in this age group. Effective and safe contraception is required to reduce UP rates. The objective of our study is to evaluate acceptance of etonogestrel (ENG)-releasing subdermal contraceptive implant after childbirth, before discharge, as well as clinical performance up to one year after placement. Comparison between teenagers who opt for ENG-implant versus other contraceptive methods after childbirth will be also evaluated, specifically regarding UP, continuation and discontinuation rates and reasons, body composition, pelvic ultrasound characteristics and user satisfaction. METHODS: A non-randomized open-label trial will be conducted with teenagers after childbirth and followed up to one year at the Women's Hospital, University of Campinas (UNICAMP), Campinas, Brazil. The study group will consist of patients who accepted to use ENG-implant and placed before discharge. The comparison group will include adolescents who choose to use other contraceptive methods at the first postpartum visit (42 ± 3 days after childbirth). All women will follow-up at 40-60 days postpartum, as well as, at 6 and 12 months post-enrollment. Patient satisfaction, contraceptive effectiveness, reasons of discontinuation, continuation rate and body composition will be evaluated. Transvaginal ultrasound and electric bio impedance tests will be performed at all follow-up appointments. A 5% significance level was assumed, as well as, a sampling error (absolute) for 10% prevalence. The sample size was calculated at n = 100, obtaining an estimate of 50 to 70 adolescents who would accept the method offered, according to the prevalence and sample error assumed. DISCUSSION: Long-acting reversible contraceptive (LARC) methods include subdermal implants and intrauterine contraceptives, are considered first line contraception for teenagers. Immediate postpartum use is a safe option, which significantly reduces rates of repeated UP and all the undesirable consequences inherent to this process. TRIAL REGISTRATION: This study was approved by the Ethics and Research Commission of UNICAMP (CAAE: 92869018.5.0000.5404) and the Brazilian Registry of Clinical Trials (REBEC): http://www.ensaiosclinicos.gov.br/rg/RBR-4z7bc6, (number 2.901.752).

Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use?

OBJECTIVES: To evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use. STUDY DESIGN: We reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively. RESULTS: We evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001). CONCLUSION: Implant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

Timing of postpartum etonogestrel-releasing implant insertion and bleeding patterns, weight change, 12-month continuation and satisfaction rates: a randomized controlled trial.

OBJECTIVES: To evaluate whether timing of etonogestrel (ENG) implant insertion during the postpartum period affects maternal bleeding patterns, body mass index (BMI) and 12-month satisfaction and continuation rates. STUDY DESIGN: This is a secondary analysis of an open, randomized, controlled trial. Postpartum women were block-randomized to early (up to 48 h postpartum) or delayed (6 weeks postpartum) insertion of an ENG implant. Bleeding patterns and BMI were evaluated every 90 days for 12 months. At 12 months, we measured implant continuation rates and used Likert and face scales to measure users' satisfaction. The level of significance was 0.4% (adjusted by Bonferroni test for multiplicity). RESULTS: We enrolled 100 postpartum women; we randomized 50 to early and 50 to delayed postpartum ENG implant insertion. Bleeding patterns were similar between groups. Amenorrhea rates were high in both groups during the follow-up (52%-56% and 46%-62% in the early and delayed insertion group, respectively). Prolonged bleeding episodes were unusual in both groups during the follow-up (0-2%). Maternal BMI was similar between groups and decreased over time. Twelve-month continuation rates were similar between groups (early insertion: 98% vs. delayed insertion: 100%, p=.99). Most participants were either very satisfied or satisfied with the ENG implant in both groups (p=.9). CONCLUSION: Women who underwent immediate postpartum insertion of the ENG implant have similar bleeding patterns, BMI changes, and 12-month satisfaction and continuation rates compared to those who underwent delayed insertion. IMPLICATIONS: Our results from a secondary analysis of a clinical trial support that satisfaction, continuation and bleeding patterns do not differ when women received contraceptive implants immediately postpartum or at 6 weeks. However, the emphasis on infant growth in the trial and easy access to delayed placement may have influenced results.

Timing of Etonogestrel-Releasing Implants and Growth of Breastfed Infants: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the growth of breastfed infants whose mothers had inserted an etonogestrel-releasing implant in the immediate postpartum period. METHODS: An open, randomized controlled, and parallel trial of postpartum women who were block-randomized to early (up to 48 hours postpartum before discharge) or conventional (at 6 weeks postpartum) insertion of an etonogestrel implant. The primary outcome was average infant weight at 12 months (360 days) and a difference of equal to or greater than 10% between groups was considered clinically significant. The secondary outcomes were infant's height and head and arm circumferences. These variables were measured at baseline and at 14, 40, 90, 180, 270, and 360 days postpartum. The mixed-effects linear regression model was used to evaluate the outcomes with a power of 80% and a significance level of 1% for the primary outcome and 0.3% for secondary outcomes as a result of correction for multiple hypothesis testing. RESULTS: From June to August 2015, a total of 100 women were randomized: 50 to early and 50 to conventional postpartum etonogestrel insertion. Sociodemographic characteristics were similar between the groups, except for educational attainment. The conventional insertion group included a higher proportion of women with 8 or more years of formal education than the early insertion group (88% [44/50] compared with 70% [35/50], P=.02). There was no difference in infant weight at 360 days between the groups (early [mean±standard deviation] 10.1±1.2 kg compared with conventional 9.8±1.3 kg, mean difference estimate 0.3 kg, 95% confidence interval 0-0.7 kg). Growth curves, height, and head and arm circumferences did not differ between the groups. CONCLUSION: There is no difference in growth at 12 months among breastfed infants whose mothers underwent early compared with conventional postpartum insertion of the etonogestrel implant. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02469454.

Metabolic safety of the etonogestrel contraceptive implant in healthy women over a 3-year period.

OBJECTIVE: To ascertain whether placement of the etonogestrel contraceptive implant induces significant changes in carbohydrate and lipid metabolism, as reflected by metabolic parameters, in healthy women. STUDY DESIGN: Prospective cohort study of 213 healthy patients who received etonogestrel implants. Weight, BMI, blood pressure and a comprehensive metabolic profile were assessed at baseline, 1, 2 and 3 years. In 21 of the 213 participants, AUC for glucose levels, fasting insulin levels at baseline and year 3 (immediately before implant removal), HOMA-IR score, and the QUICK index were assessed. Parameters were expressed as median and interquartile range. The Wilcoxon test and ANOVA were used for comparison of measurements after implant placement (significance level p<0.05). RESULTS: Median age was 26 years (range, 22-31.5). Results showed a trend toward increase of the variables weight (63.3-66.1) and BMI (24.7-25.7) and a decrease in TC (172-161.5), TG (75-69.5), and LDL (100.5-98.5) (p>0.05). Of the metabolic variables, FBG (85-88) and HDL (53-46) had significant differences (p<0.002). In the subgroup of 21 patients, there were reductions in insulin levels (9.65 vs. 8.4mU/dL, p=0.03), HOMA scores (2.06 vs. 1.75, p=0.02), QUICK index (0.34 vs. 0.35, p=0.03), TC (178 vs. 160mg/dL, p=0.001), HDL (51 vs. 46mg/dL, p=0.009), and LDL (110 vs. 100mg/dL, p=0.035). CONCLUSION: These results provide evidence of the metabolic safety of the ENG implant in healthy women over a 3-year period. Indeed, implant placement induces changes consistent with a lower risk of insulin resistance and dyslipidemia.

A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls.

STUDY QUESTION: Is there any difference in the clinical performance of the 3-year one-rod etonogestrel (ENG)- and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception, in particular complaints possibly related to hormonal contraceptives? SUMMARY ANSWER: The cumulative contraceptive effectiveness after 3 years and method continuation through 2.5 years were not significantly different between ENG and LNG implants, but both outcomes were significantly worse in the non-randomized age-matched group of IUD users than in the combined implant group. WHAT IS KNOWN ALREADY: ENG- and LNG-releasing implants are safe and highly efficacious contraceptives with pregnancy rates reported to be 0.0-0.5 per 100 women-years (W-Y). No head-to-head comparative study of the two implants has been undertaken, and little information is available on comparisons of complaints of side effects of implant and copper IUD users. STUDY DESIGN, SIZE, DURATION: This was an open parallel group RCT with 1:1 allocation ratio of the ENG and the LNG implants with non-randomized control group of women choosing TCu380A IUD to address lack of reliable data on common side effects typically attributed to the use of progestogen-only contraceptives. After device(s) placement, follow-ups were at 2 weeks, 3 and 6 months, and semi-annually thereafter for 3 years or until pregnancy, removal or expulsion of the implant/IUD occurred. PARTICIPANTS, SETTING, METHODS: The study took place in family planning clinics in Brazil, Chile, Dominican Republic, Hungary, Thailand, Turkey and Zimbabwe. Women seeking long-term contraception were enlisted after an eligibility check and informed consent, and 2982 women were enrolled: 1003, 1005 and 974 in the ENG-implant, LNG-implant and IUD groups, respectively; 995, 997 and 971, respectively, were included in the per protocol analysis reported here. MAIN RESULTS AND THE ROLE OF CHANCE: ENG and LNG implants each had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y [95% confidence interval (CI) 0.1-1.4]. A weight of ≥70 kg at admission was unrelated to pregnancy. Method continuation rates for ENG and LNG implants at 2.5 years were 69.8 (95% CI 66.8-72.6) and 71.8 per 100 W-Y (68.8-74.5), and at 3 years 12.1 (95% CI 5.2-22.0) and 52.0 per 100 W-Y (95% CI 41.8-61.2), respectively. Bleeding disturbances, the most frequent reason for method discontinuation, were significantly more common in the ENG group [16.7 (95% CI 14.4-19.3)] than in the LNG group [12.5 (95% CI 10.5-14.9)] (P 0.019). The 3-year cumulative loss to follow-up was lower in the ENG- than in the LNG-implant group, 8.1 (95% CI 6.4-10.2) and 14.4 per 100 W-Y (95% CI 12.1-17.1), respectively. The median duration of implant removal was 50 s shorter among women with ENG than among women with LNG implant (P < 0.0001). In the observational comparison between IUD and implant users, the 3-year relative risk for pregnancy in IUD group compared with the combined implant group was 5.7 per 100 W-Y (95% CI 4.4-7.3) (P = 0.0003). The 3-year expulsion rate of the IUD was 17.8 per 100 W-Y (95% CI 14.5-21.9), while the discontinuation rate for bleeding disturbances was 8.5 (95% CI 6.7-10.9). Frequency of complaints of headache and dizziness was not significantly different between implant and IUD users (P = 0.16 and 0.77, respectively), acne and bleeding irregularities were more frequent among implant users (P < 0.0001), while heavy bleeding and lower abdominal pain occurred more often among IUD than implant users (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Few women were ≤19 years old or nulligravida, the proportion of implant users ≥70 kg was <20% and <8% were obese. WIDER IMPLICATIONS OF THE FINDINGS: Findings of the study can inform policy makers and clinicians about choice of implant, but also about TCu380A IUD in relation to implants. STUDY FUNDING/COMPETING INTERESTS: UNDP/UNFPA/WHO/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization (WHO). This report contains the views of an international expert group and does not necessarily represent the decisions or the stated policy of the WHO. TRIAL REGISTRATION: ISRCTN33378571 registered on 22 March 2004. The first participant was enrolled on 12 May 2003.

Body composition and bone mineral density in users of the etonogestrel-releasing contraceptive implant.

PURPOSE: There is scarce information about bone mineral density (BMD) and body composition (BC) among users of the etonogestrel (ENG)-releasing implant. AIMS: To evaluate BC and BMD in ENG-releasing implant users as compared to copper intrauterine device (Cu-IUD)-users. METHODS: A prospective study was conducted on 75 users of both contraceptive methods. BMD was evaluated at femoral neck (FN) and lumbar spine (LS) (L1-L4) and BC at baseline and at 12 months after insertion. RESULTS: The mean (±SD) age was 30.4 ± 6.8 and 29.8 ± 8.4 years and body mass index (kg/m(2)) was 24.9 ± 4.1 and 24.6 ± 3.5 in ENG-releasing implant- and Cu-IUD-users, respectively. ENG-releasing implant users did not show significant differences on BMD at the LS and FN at 12 months of use. Furthermore, ENG-implant users had an increase in body weight at 12 months (p < 0.001) and an increase of 2 % in the percentage of body fat, when compared with Cu-IUD users. There was a significant increase in lean mass in ENG-implant users at 12 months (p = 0.020). CONCLUSIONS: No significant changes of BMD were seen after the first year of use among the ENG-releasing implant-users, albeit an increase of weight and fat mass was seen when compared to Cu-IUD users.

Metabolic effects of the contraceptive skin patch and subdermal contraceptive implant in Mexican women: a prospective study.

BACKGROUND: The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women. METHODS: An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed. RESULTS: Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up. CONCLUSIONS: The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out.

Combined oral contraceptives: venous thrombosis.

BACKGROUND: Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. OBJECTIVES: To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. SEARCH METHODS: Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. SELECTION CRITERIA: We selected studies including healthy women taking COC with VT as outcome. DATA COLLECTION AND ANALYSIS: The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. MAIN RESULTS: 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. AUTHORS' CONCLUSIONS: All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 µg ethinylestradiol with levonorgestrel.

Association of estrogen receptor alpha gene polymorphisms with autonomic modulation of heart rate in users and nonusers of oral contraceptives.

BACKGROUND: This study examined the association between estrogen receptor α gene (ESR1) polymorphisms and blood pressure (BP), heart rate (HR) and autonomic modulation of HR in a sample population. STUDY DESIGN: Two hundred thirty-two young healthy women were selected, and those using oral contraceptives (OC) were compared with nonusers (control group). Short-term HR variability (HRV) was evaluated in both the supine and sitting positions using temporal indices rMSSD [square root of the mean squared differences of successive R-R intervals (RRi) divided by the number of RRi minus one], SDNN (root mean square of differences from mean RRi, divided by the number of RRi) and frequency domain methods. Power spectral components were reported at low frequency (LF) and high frequency (HF) and as LF/HF ratio. ESR1 c.454-397T>C (rs2234693) and c.454-351A>G (rs9340799) polymorphisms were determined by polymerase chain reaction and fragment restriction analysis. RESULTS: The ESR1 T>C and A>G polymorphisms had no effect on HR, rMSSD, SDNN, LF, HF or LF/HF ratio (supine or sitting), independently of OC use. The ESR1 T-A, T-G, C-A and C-G haplotypes were not associated with HR, BP or HRV. CONCLUSIONS: ESR1 variants had no effect on the autonomic modulation of HR in young women users and nonusers of OC and may not be implicated in cardiovascular risk in young women.

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, α2-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.

Impact of etonogestrel-releasing implant and copper intrauterine device on carbohydrate metabolism: a comparative study.

BACKGROUND: We investigated the influence of an etonogestrel-releasing (ETG) implant and copper intrauterine device (IUD) on carbohydrate metabolism. STUDY DESIGN: In this nonrandomized, open-label, prospective controlled trial, 40 healthy women received an implant or IUD (20 per group). Outcome measures were fasting glucose, fasting insulin, oral glucose tolerance test (OGTT) and glycosylated hemoglobin A(1)C (HbA(1)C) levels at baseline and after 6 and 12 months. RESULTS: The groups were similar in age, body mass index and laboratory parameters at baseline. Carbohydrate metabolism was not modified by the ETG implant at baseline and at 6 and 12 months (mean ± SD) (fasting glucose: 85.9 ± 5.13, 87.05 ± 5.36, 88.19 ± 5.05; insulin: 7.77 ± 2.42, 10.64 ± 9.4, 8.82 ± 3.73; OGTT: 94.8 ± 25.28, 96.5 ± 19.67, 99.47 ± 24.6; HbA(1)C: 5.27 ± .34, 5.55 ± .39, 5.7 ± 0.37). The same was true for the IUD (fasting glucose: 88.87 ± 7.2, 89.65 ± 5.86, 88.75 ± 4.79; insulin: 7.94 ± 3.6, 8.3 ± 4.1, 7.34 ± 3.02; OGTT: 96.85 ± 15.16, 97.48 ± 13.42, 91.3 ± 22.16; HbA(1)C: 5.41 ± .49, 5.75 ± .41, 5.9 ± 0.73). CONCLUSIONS: The ETG-releasing implant did not affect carbohydrate metabolism in normal women after 12 months.

[Combined hormonal contraception in cycles artificially extended]. / Anticoncepción con hormonales combinados en ciclos extendidos artificialmente.

OBJECTIVE: To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. MATERIAL AND METHODS: Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. CONCLUSION: Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.