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Objective: To evaluate whether a short course of tamoxifen decreases bothersome bleeding in etonogestrel contraceptive implant users., Methods: In a 90-day, double-blind randomized control trial, we enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting. A sample size of 40 per group (N=80) was planned to compare 10 mg tamoxifen or placebo twice daily for 7 days after 3 consecutive days of bleeding or spotting no more than once per 30 days (maximum three treatments). Participants then entered a 90-day open-label study where all received tamoxifen if needed every 30 days (maximum three treatments). Participants used text messages to record daily bleeding patterns. Our primary outcome was the total number of consecutive amenorrhea days after the first treatment. Secondary outcomes included time to bleeding or spotting cessation and restart after first treatment, overall bleeding patterns, and satisfaction., Results: From January 2017 to November 2018, 112 women enrolled in the study; 88 (79%) completed 90 days, and 79 (71%) completed 180 days. Participant characteristics did not differ between groups; mean age 24, majority identified as white not Hispanic with at least some college education. After the first treatment, the tamoxifen group reported an average of 9.8 (95% CI 4.6-15.0) more consecutive days of amenorrhea and more total days of no bleeding (amenorrhea or spotting) in the first 90 days (median 73.5 [range 24-89] vs 68 [range 11-81], P=.001). The placebo group showed a similar treatment benefit after first active use of tamoxifen in the open-label phase. At the end of the randomized study (first 90 days), women who received tamoxifen reported higher satisfaction (median 62 mm [range 16-100]) than those treated with placebo (46 mm [range 0-100]; P=.023)., Conclusion: A short course of tamoxifen reduces problematic bleeding and improves satisfaction in users of etonogestrel implants., Clinical Trial Registration: ClinicalTrials.gov, NCT02903121.

Objective: To determine if a course of oral tamoxifen initiated following placement of a levonorgestrel 52-mg intrauterine system (IUS) reduces bleeding/spotting days over 30 days., Study Design: In this single-center, double-blind, placebo-controlled trial, we recruited women ages 15-45 years initiating the levonorgestrel 52-mg IUS. We randomized eligible women to tamoxifen 10 mg or placebo twice daily for 7 days starting 21 days after levonorgestrel 52-mg IUS insertion. Participants tracked bleeding/spotting days via daily electronic diaries for 30 days after starting drug treatment. We assessed participant satisfaction with their bleeding pattern and the IUS using a visual analog scale (0-100 mm). A sample size of 42 provided 80% power to detect a difference of 7 bleeding/spotting days in 30 days by two-sample t test, accounting for an expected 20% dropout rate., Results: From September 2016 to January 2018, 42 women enrolled. A total of 34 women provided complete bleeding/spotting data, and 30 women provided satisfaction data. Mean bleeding/spotting days over 30 days did not differ between tamoxifen (12.0±5.8 days) and placebo users (16.8±9.0 days), p=.08. We found no significant differences in mean satisfaction with bleeding profiles (51 mm tamoxifen vs. 59 mm placebo, p=.48) or with the IUS (83 mm vs. 75 mm, p=.36) between groups. Both groups reported similar rates of adverse events, with no serious adverse events reported., Conclusion: A course of oral tamoxifen did not improve early breakthrough bleeding or satisfaction in new users of the levonorgestrel 52-mg IUS., Implications: Although tamoxifen treatment caused a trend toward modest bleeding/spotting day reduction in new levonorgestrel 52-mg IUS users, bleeding satisfaction did not improve. Future studies of tamoxifen treatment for IUS-related bleeding issues may be best targeted toward users with ongoing bleeding irregularities or lower-dose IUS products which cause more bleeding irregularities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC)., Objectives: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy., Search Strategy: We searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017., Selection Criteria: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors., Data Collection and Analysis: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively., Main Results: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK., Conclusions: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins., Tweetable Abstract: Rifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Context: Women who are living with HIV use IUDs at a lower rate than the general population, and it is unclear whether health care providers' misconceptions about IUD safety contribute to this disparity., Methods: A 2013-2014 nationwide survey of 1,998 U.S. family planning providers assessed perceptions of IUD safety for women with HIV or other medical conditions. Multivariable logistic regression was used to examine associations between provider characteristics and whether individuals believed IUDs were safe for HIV-positive women. Data from public-sector providers and office-based physicians were analyzed separately., Results: Seven in 10 providers considered IUDs safe for women with HIV, and there were no differences by provider type. Among public-sector providers, some of the characteristics associated with believing that IUDs were unsafe for seropositive women were working at a clinic without Title X funding (odds ratio, 1.5), not being trained in IUD insertion (2.1) and not using the U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) for clinical guidance (1.8). Office-based physicians who did not use the guidelines also had an increased likelihood of believing that IUDs were unsafe for women with HIV (2.9), and physicians who had completed training 25 or more years ago were more likely than those who had done so less than five years ago to consider IUDs unsafe (3.3)., Conclusions: Greater use of evidence-based contraceptive guidance such as the U.S. MEC may help inform provider perceptions of IUD safety and hence contribute to increased contraceptive choice for women with HIV., (Copyright © 2018 by the Guttmacher Institute.)

Objectives: To evaluate the effects of concurrent administration of three vaginal miconazole nitrate formulations on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol from a novel contraceptive vaginal ring (NES/EE CVR)., Study Design: This was an open-label, randomized, crossover, drug-drug interaction study conducted over three menstrual cycles in healthy women with regular menses. We compared systemic exposure to NES and EE by determining area under the curve (AUC 8-21d ) with CVR only and CVR with each miconazole treatment. Three different miconazole formulations (single-dose suppository, multiple-dose suppository or multiple-dose cream) were administered in a single dose on day 8 or multiple doses on days 8-10 after CVR insertion. We evaluated safety and tolerability of the CVR in the presence of antimycotic comedication., Results: Forty-five participants were randomized, and 29 completed participation. Systemic exposure to NES and EE released from the CVR increased with single or multiple doses of miconazole suppositories but not with multiple-dose cream. The maximum EE geometric mean ratio (GMR) for AUC 8-21d was 1.67 (1.51-1.86) for single-dose and 1.42 (1.21-1.66) for multiple-dose suppositories. By contrast, systemic exposure to NES and EE was comparable with and without miconazole cream (all GMRs and confidence intervals within 0.80 to 1.25). Adverse events (AEs) were similar with CVR only and with all miconazole treatment groups. There were no serious treatment-related AEs., Conclusions: Miconazole vaginal suppositories were associated with increased systemic levels of NES and EE, while systemic exposure with miconazole vaginal cream was comparable to no miconazole exposure., Implications: Coadministration of miconazole suppositories with the investigational NES/EE CVR led to higher systemic exposure of both hormones, while coadministration with miconazole cream did not affect hormone levels. Women utilizing the NES/EE CVR may be advised to use an oral formulation or miconazole cream rather than suppository to treat vaginal candidiasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine whether interactions between non-rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy., Study Design: We searched MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database inception through June 2016. We included trials, cohort, case-control, and pharmacokinetic studies in any language that addressed pregnancy rates, pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and non-rifamycin antibiotic were administered together vs apart. Of 7291 original records that were identified, 29 met criteria for inclusion., Study Appraisal and Synthesis Methods: Two authors independently assessed study quality and risk of bias using the United States Preventive Services Task Force evidence grading system. Findings were tabulated by drug class., Results: Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring. Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics. No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic. No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic. Ethinyl estradiol area under the curve decreased when administered with dirithromycin, but no other drug., Conclusion: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics. Data are limited by low quantity and quality for some drug classes. Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non-rifamycin antibiotics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The US Medical Eligibility Criteria for Contraceptive Use (MEC) and US Selected Practice Recommendations for Contraceptive Use (SPR) provide evidence-based guidance to safely provide contraception counseling and services. Both documents were updated in 2016 and are endorsed by the North American Society for Pediatric and Adolescent Gynecology. The purpose of this mini-review is to highlight updates to the US MEC and US SPR that are most relevant to health care providers of adolescents to support dissemination and implementation of these evidence-based best practices. This document is intended to highlight these changes and to complement, not replace, the detailed practice guidance within the US MEC and US SPR., (Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI)., Study Design: We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force., Results: From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable., Conclusion: Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness., (Copyright © 2017. Published by Elsevier Inc.)

Objective: The etonogestrel (ENG) subdermal implant can cause frequent breakthrough bleeding in some users. The objective of this study was to evaluate whether a short course of tamoxifen reduces bleeding/spotting days compared to placebo in ENG implant users., Study Design: In this double-blind trial, we randomized ENG implant users with frequent or prolonged bleeding or spotting to tamoxifen 10 mg or placebo twice daily for 7 days, to be started after 3 consecutive days of bleeding/spotting. Treatment was repeated as needed up to three times in 180 days. Subjects completed a daily text message bleeding diary. A sample size of 56 provided 80% power to detect a difference of 6 days of bleeding/spotting per 30 days by two-sample t test. Ovulation was monitored by urinary metabolites of progesterone., Results: From March 2014 to February 2015, 56 women enrolled. Fifty-one completed at least 30 days of follow up, and 34 completed 180 days. Compared to women randomized to placebo, women randomized to tamoxifen reported 5 fewer days of bleeding/spotting over 30 days (95% confidence interval [CI] -9.9 to -0.05, p=.05), and 15.2 more continuous bleeding-free days (95% CI 2.8-27.5 days, p=.02) after first use of study drug. Conclusions could not be drawn after 30 days due to higher-than-expected dropout. No ovulation was detected., Conclusion: First use of tamoxifen by ENG implant users reduces bleeding/spotting days and provides a longer cessation of bleeding/spotting than placebo, without compromising ovulation suppression. Further study is needed to determine whether this effect is maintained with repeat use., Implications: Women with frequent ENG implant-related breakthrough bleeding may experience a reduction in bleeding/spotting days and an increase in continuous bleeding-free days in the month following first use of tamoxifen. This short course of tamoxifen was well tolerated with bleeding cessation noted within a median of 5 days., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We modeled the potential cost-effectiveness of increasing access to contraception in Puerto Rico during a Zika virus outbreak. The intervention is projected to cost an additional $33.5 million in family planning services and is likely to be cost-saving for the healthcare system overall. It could reduce Zika virus-related costs by $65.2 million ($2.8 million from less Zika virus testing and monitoring and $62.3 million from avoided costs of Zika virus-associated microcephaly [ZAM]). The estimates are influenced by the contraception methods used, the frequency of ZAM, and the lifetime incremental cost of ZAM. Accounting for unwanted pregnancies that are prevented, irrespective of Zika virus infection, an additional $40.4 million in medical costs would be avoided through the intervention. Increasing contraceptive access for women who want to delay or avoid pregnancy in Puerto Rico during a Zika virus outbreak can substantially reduce the number of cases of ZAM and healthcare costs.

Context: Combined hormonal contraceptive (CHC) use may modify the risk of cardiovascular events in obese [body mass index (BMI) ≥30kg/m 2 ] women., Objective: The objective was to evaluate from the literature whether CHC use modifies the risk of acute myocardial infarction (AMI), stroke, cerebral venous thrombosis (CVT) and venous thromboembolism (VTE) in obese women and to evaluate evidence for a dose-response relationship between BMI and VTE., Methods: We searched PubMed for all articles published between database inception and February 2016 providing direct evidence on BMI, CHCs, and cardiovascular outcomes. We also searched for indirect evidence related to a dose-response relationship between BMI and risk of VTE in the general population, as these data were lacking for CHC users. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force., Results: The direct evidence search yielded 3 pooled analyses, 11 case-control studies and 1 cohort study. There was conflicting evidence about the risk of AMI or stroke among obese combined oral contraceptive (COC) users compared to obese nonusers, with one study finding no increased risk for AMI or stroke for COC users overall or stratified by BMI. A second study found significantly increased risk of AMI and stroke for COC users, with the highest risk estimates for high-BMI COC users. A single study suggested that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. For VTE, obese COC users consistently had a risk that was 5 to 8 times that of obese nonusers and approximately 10 times that of nonobese nonusers. Five prospective cohort studies were identified as indirect evidence, and all found increased risk for VTE as BMI increased, suggesting a dose-response relationship between BMI and risk for VTE. No studies on the contraceptive patch or vaginal ring were identified that met the inclusion criteria., Conclusion: Limited evidence of Level II-2, fair quality, concerning whether CHC use modifies the risk of AMI and stroke in obese women is inconclusive, while a single study of Level II-2, poor quality, found that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. Both COC use and higher BMI increase risk for VTE, and the greatest relative risks are for those with both risk factors based on a body of evidence graded as Level II-2, fair to poor quality. It is not possible to estimate absolute risk of VTE among women with both of these risk factors; however, the absolute risk of VTE in healthy women of reproductive age is small., (Published by Elsevier Inc.)

Objective: The objective was to assess risk of pelvic inflammatory disease (PID) among women with current asymptomatic undiagnosed cervical infection or who are at high risk of sexually transmitted infections (STIs), comparing those who have a copper-bearing (Cu-) or levonorgestrel (LNG-) intrauterine device (IUD) placed with women who do not., Study Design: We searched PubMed and Cochrane Library for articles from January 1984 through January 2016 addressing our objective. We assessed study quality using the United States Preventive Services Task Force evidence grading system., Results: Our search strategy yielded 2220 articles, of which 10 met inclusion criteria. Two studies provided direct evidence of PID rates in women with undiagnosed gonococcal or chlamydial (GC/CT) infection or at high risk for STIs initiating IUDs versus other contraceptive methods (level II-2, fair to poor), and neither study found a difference. Eight studies provided indirect evidence (II-2 to II-3, fair to poor). One study found no difference in PID rates between initiators of Cu- versus LNG-IUDs. Five studies compared algorithms based on patient factors with laboratory GC/CT screening to predict cervical infection. Based on likelihood ratios, none of these algorithms adequately identified women at high risk of asymptomatic cervical infection who should not undergo IUD placement. Two studies compared IUD placement on the same day as STI screening with delayed placement after screening and found no difference in PID rates., Conclusion: Limited evidence suggests that IUD placement does not increase the risk of PID compared with no IUD placement among women with asymptomatic undiagnosed cervical infection or at high risk of STIs. Algorithms based on patient characteristics to identify women with asymptomatic GC/CT may be overly restrictive, leading to missed opportunities for IUD initiation. Historical concerns about higher PID risk among women at risk for STIs who use IUDs may not be relevant with modern devices and STI screening and treatment practices., (Published by Elsevier Inc.)

Objective: To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug., Methods: We searched PubMed and Cochrane libraries for clinical or pharmacokinetic (PK) studies that examined co-administration of any HC with psychotropic drugs [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors (MAOIs), or atypical antipsychotics] in reproductive aged women., Results: Of 555 articles identified, 22 articles (18 studies) met inclusion criteria. We identified 5 studies on SSRIs, four on TCAs, one on bupropion, three on atypical antipsychotics and five on oral benzodiazepines. No articles met inclusion criteria for SNRIs, mirtazapine, trazadone, buspirone, hydroxyzine or MAOIs. Overall, clinical studies did not demonstrate differences in unintended pregnancy rates when HCs were administered with and without psychotropic drugs or in psychotropic drug treatment outcomes when psychotropic drugs were administered with and without HCs. PK studies did not demonstrate changes in drug exposure related to contraceptive safety, contraceptive effectiveness or psychotropic drug effectiveness for most classes of psychotropic drugs. However, limited PK data raise concern for HCs increasing systemic exposure of amitriptyline and imipramine (both TCAs), theoretically posing safety concerns., Conclusion: Limited quality and quantity evidence on use of psychotropic drugs and HCs suggests low concern for clinically significant interactions, though no data exist specifically for non-oral formulations of HC. Given the high frequency of use for both HCs and psychotropic drugs among reproductive-age women in the US, this review highlights a need for further research in this area., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Problem/condition: Since 1969, CDC has conducted abortion surveillance to document the number and characteristics of women obtaining legal induced abortions in the United States., Period Covered: 2013., Description of System: Each year, CDC requests abortion data from the central health agencies of 52 reporting areas (the 50 states, the District of Columbia, and New York City). The reporting areas provide this information voluntarily. For 2013, data were received from 49 reporting areas. For trend analysis, abortion data were evaluated from 47 areas that reported data every year during 2004-2013. Census and natality data, respectively, were used to calculate abortion rates (number of abortions per 1,000 women) and ratios (number of abortions per 1,000 live births)., Results: A total of 664,435 abortions were reported to CDC for 2013. Of these abortions, 98.2% were from the 47 reporting areas that provided data every year during 2004-2013. Among these 47 reporting areas, the abortion rate for 2013 was 12.5 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 200 abortions per 1,000 live births. From 2012 to 2013, the total number, rate, and ratio of reported abortions decreased 5%. From 2004 to 2013, the total number, rate, and ratio of reported abortions decreased 20%, 21%, and 17%, respectively. In 2013, all three measures reached their lowest level for the entire period of analysis (2004-2013). In 2013 and throughout the period of analysis, women in their 20s accounted for the majority of abortions and had the highest abortion rates; women in their 30s and older accounted for a much smaller percentage of abortions and had lower abortion rates. In 2013, women aged 20-24 and 25-29 years accounted for 32.7% and 25.9% of all abortions, respectively, and had abortion rates of 21.8 and 18.2 abortions per 1,000 women aged 20-24 and 25-29 years, respectively. In contrast, women aged 30-34, 35-39, and ≥40 years accounted for 16.8%, 9.2%, and 3.6% of all abortions, respectively, and had abortion rates of 11.8, 7.0, and 2.5 abortions per 1,000 women aged 30-34 years, 35-39 years, and ≥40 years, respectively. During 2004-2013, the decrease in abortion rates among adult women aged 20-39 years ranged from 8% to 27% across these age groups, whereas the abortion rate was stable for women aged ≥40 years. In 2013, adolescents aged <15 and 15-19 years accounted for 0.3% and 11.4% of all abortions, respectively, and had abortion rates of 0.6 and 8.2 abortions per 1,000 adolescents aged <15 and 15-19 years, respectively. From 2004 to 2013, the percentage of abortions accounted for by adolescents aged 15-19 years decreased 31% and their abortion rate decreased 46%. These decreases were greater than the decreases for women in any older age group. In contrast to the percentage distribution of abortions and abortion rates by age, abortion ratios in 2013 and throughout the entire period of analysis were highest among adolescents and lowest among women aged 30-39 years. Abortion ratios decreased from 2004 to 2013 for women in all age groups, except for adolescents aged <15 years. In 2013, the majority (66.0%) of abortions were performed by ≤8 weeks' gestation, and nearly all (91.6%) were performed by ≤13 weeks' gestation. Few abortions were performed between 14 and 20 weeks' gestation (7.1%) or at ≥21 weeks' gestation (1.3%). From 2004 to 2013, the percentage of all abortions performed at ≤13 weeks' gestation remained consistently high (≥91.5%) and among those performed at ≤13 weeks' gestation, the percentage performed at ≤6 weeks' gestation increased 16%. In 2013, among the 43 reporting areas that included medical (nonsurgical) abortion on their reporting form, a total of 67.9% of abortions were performed by curettage at ≤13 weeks' gestation, 22.2% were performed by early medical abortion (a nonsurgical abortion at ≤8 weeks' gestation), and 8.6% were performed by curettage at >13 weeks' gestation; all other methods were uncommon. Among abortions performed at ≤8 weeks' gestation that were eligible for early medical abortion on the basis of gestational age, 32.8% were completed by this method. From 2012 to 2013, the percentage of abortions reported as early medical abortions increased 5%. Deaths of women associated with complications from abortion for 2013 are being investigated as part of CDC's Pregnancy Mortality Surveillance System. In 2012, the most recent year for which data were available, four women were identified to have died as a result of complications from known legal induced abortion. No reported deaths were associated with known illegal induced abortion., Interpretation: Among the 47 areas that reported data every year during 2004-2013, the decreases in the total number, rate, and ratio of reported abortions that occurred during 2009-2012 continued from 2012 to 2013, resulting in historic lows for all three measures of abortion., Public Health Action: The data in this report can help program planners and policymakers identify groups of women with highest rates of abortion. Unintended pregnancy is the major contributor to abortion. Increasing access to and use of contraception, including the most effective methods, can reduce unintended pregnancies and further reduce the number of abortions performed in the United States.

The rising rate of overweight and obesity is a public health crisis in the United States and increasingly around the globe. Rates of contraceptive use are similar among women of all weights, but because contraceptive development studies historically excluded women over 130% of ideal body weight, patients and providers have a gap in understanding of contraceptive efficacy for obese and overweight women. Because of a range of drug metabolism alterations in obesity, there is biologic plausibility for changes in hormonal contraception effectiveness in obese women. However, these pharmacokinetic changes are not linearly related to body mass index or weight, and it is unknown what degree of obesity begins to affect pharmacokinetic or pharmacodynamics processes. Overall, most studies of higher quality do not demonstrate a difference in oral contraceptive pill effectiveness in obese compared with non-obese women. However, data are scant for women in the highest categories of obesity, and differences by progestin type are incompletely understood. Effectiveness of most non-oral contraceptives does not seem to be compromised in obesity. Exceptions to this include the combined hormonal patch and oral levonorgestrel emergency contraception, which may have lower rates of effectiveness in obese women. The purpose of this review is to summarize evidence on contraceptive use in women with obesity, including differences in steroid hormone metabolism, contraceptive effectiveness, and safety, compared with women of normal weight or body mass index using the same methods., (Copyright © 2016 American Society for Reproductive Medicine. All rights reserved.)

The 2016 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and consultation with national experts who met in Atlanta, Georgia, during August 26-28, 2015. The information in this report updates the 2010 U.S. MEC (CDC. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010:59 [No. RR-4]). Notable updates include the addition of recommendations for women with cystic fibrosis, women with multiple sclerosis, and women receiving certain psychotropic drugs or St. John's wort; revisions to the recommendations for emergency contraception, including the addition of ulipristal acetate; and revisions to the recommendations for postpartum women; women who are breastfeeding; women with known dyslipidemias, migraine headaches, superficial venous disease, gestational trophoblastic disease, sexually transmitted diseases, and human immunodeficiency virus; and women who are receiving antiretroviral therapy. The recommendations in this report are intended to assist health care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health care providers should always consider the individual clinical circumstances of each person seeking family planning services. This report is not intended to be a substitute for professional medical advice for individual patients. Persons should seek advice from their health care providers when considering family planning options.

As the proportion of women with obesity increases worldwide, understanding the influence of body weight on sexual behavior, fertility, and contraceptive effectiveness is critical for health-care professionals and patients. Although many have theorized that obese women are different from normal-weight women regarding sexual health and behavior, current evidence for the most part disproves this. The exception is in adolescents where body image may play a role in riskier behavior, placing them at a greater risk of an unintended pregnancy. Given that most modern contraceptives were not originally evaluated in obese women, understanding how weight affects contraceptive pharmacokinetics and efficacy should be a focus of ongoing research. Evidence is reassuring that most modern contraceptive methods are safe and effective in obese women. This paper reviews what is known about sexual and contraceptive behavior, as well as the effectiveness and pharmacokinetics of modern contraceptives, for overweight and obese women., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Many women who intend to use long-acting, reversible contraceptives (LARCs) postpartum do not follow through with initiating use. The objectives of this study were to determine whether support from a contraceptive personal assistant could increase the uptake of LARCs by 3 months postpartum, and to identify risk factors for nonuptake of LARCs among women who planned LARC use., Study Design: This is a randomized, controlled trial of 50 low-income postpartum women who desired LARC. The intervention group received telephone contact from a personal assistant who provided contraception education, facilitation of insurance coverage, appointment scheduling and assistance with childcare and transportation. The control group received routine follow up. Women were surveyed immediately and 3 months postpartum regarding contraceptive use and anticipated barriers to LARC use., Results: A similar proportion of women in both groups received LARC [control 16/24 (67%), intervention 18/25 (72%), p=.76]. More primiparous (86.4%) than multiparous (55.5%) women obtained LARC (p=.04). In addition, women with more prenatal visits were more likely to have initiated LARC (odds ratio, 95% confidence interval for each increased visit: 1.50, 1.15-1.96). No other demographic factors were related to LARC uptake., Conclusions: Providing telephone assistance to help navigate barriers did not increase postpartum uptake of LARCs. A personal history of clinic visit no-shows and/or infrequent prenatal visits were related to poor uptake of LARCs postpartum., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4(+) RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.

TCR revision is a tolerance mechanism by which self-reactive TCRs expressed by mature CD4(+) peripheral T cells are replaced by receptors encoded by genes generated by post-thymic DNA rearrangement. The downmodulation of surface TCR expression initiates TCR revision, and serves as a likely trigger for the induction of the recombinase machinery. We show here in a Vβ5 transgenic mouse model system that downregulation of the self-reactive transgene-encoded TCR is not maintained by transgene loss or diminished transcription or translation. The downregulation of surface TCR expression likely occurs in two stages, only one of which requires tolerogen expression., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Peripheral CD4(+)Vβ5(+) T cells are tolerized to an endogenous mouse mammary tumor virus superantigen either by deletion or TCR revision. Through TCR revision, RAG reexpression mediates extrathymic TCRβ rearrangement and results in a population of postrevision CD4(+)Vβ5(-) T cells expressing revised TCRβ chains. We have hypothesized that cell death pathways regulate the selection of cells undergoing TCR revision to ensure the safety and utility of the postrevision population. In this study, we investigate the role of Bcl-2-interacting mediator of cell death (Bim)-mediated cell death in autoantigen-driven deletion and TCR revision. Bim deficiency and Bcl-2 overexpression in Vβ5 transgenic (Tg) mice both impair peripheral deletion. Vβ5 Tg Bim-deficient and Bcl-2 Tg mice exhibit an elevated frequency of CD4(+) T cells expressing both the transgene-encoded Vβ5 chain and a revised TCRβ chain. We now show that these dual-TCR-expressing cells are TCR revision intermediates and that the population of RAG-expressing, revising CD4(+) T cells is increased in Bim-deficient Vβ5 Tg mice. These findings support a role for Bim and Bcl-2 in regulating the balance of survival versus apoptosis in peripheral T cells undergoing RAG-dependent TCR rearrangements during TCR revision, thereby ensuring the utility of the postrevision repertoire.

Background: The usefulness of the 2-step tuberculin skin test as a tool for monitoring tuberculosis exposure among health care workers is controversial., Objectives: We aimed to determine the cost-effectiveness and influence of initiation of a preemployment, 2-step tuberculin skin-testing program on the annual tuberculin skin conversion rate among a university hospital's health care workers., Methods: The tuberculin skin test conversion rates among the recipients of 31,729 tuberculin skin tests over 10 years were retrospectively analyzed. Data from the first 6 years of this study were generated when a single preemployment tuberculin skin test was utilized. Data from the last 4 years were gathered after the advent of a preemployment 2-step program. A cost analysis of the 2-step tuberculin skin test process was performed to determine the annual cost of this program., Results: Relative risk of a conversion was 8.43 times less during the 2-step period when compared with the years when a single tuberculin skin test was given at the start of employment (P < .001). A cost analysis showed that the annual added cost of the 2-step program was approximately 9,565 US dollars., Conclusion: A greater than 8-fold reduction in the number of annual tuberculin skin test conversion coincided with, but could not be attributed solely to, the initiation of a 2-step program in our hospital. The Infection Control Committee concluded that the 2-step testing program is essential to achieve the hospital's goal of a 0% annual tuberculin skin test conversion rate and that the annual cost is justified.

The authors tested suprathreshold intensity perception of gustatory and olfactory stimuli in a 70-year-old right-handed man following a left posterior insular stroke and compared his results with those of age-matched controls. Both modalities revealed significant differences between left (ipsilateral to lesion) and right (contralateral) ratings of intensity. In both gustation and olfaction, these differences were driven primarily by trends toward increased contralateral sensitivity relative to controls. Intensity changes were most pronounced for unpleasant odors and for tastes perceived strongly as either pleasant (sweet) or unpleasant (salty, bitter). These results show that a left posterior insula lesion may affect taste and olfactory perception similarly by increasing sensitivity contralateral to the lesion. One possible mechanism is release from inhibition at the cortical level., (Copyright (c) 2006 APA, all rights reserved.)

Flavor perception arises from the central integration of peripherally distinct sensory inputs (taste, smell, texture, temperature, sight, and even sound of foods). The results from psychophysical and neuroimaging studies in humans are converging with electrophysiological findings in animals and a picture of the neural correlates of flavor processing is beginning to emerge. Here we used event-related fMRI to evaluate brain response during perception of flavors (i.e., taste/odor liquid mixtures not differing in temperature or texture) compared with the sum of the independent presentation of their constituents (taste and/or odor). All stimuli were presented in liquid form so that olfactory stimulation was by the retronasal route. Mode of olfactory delivery is important because neural suppression has been observed in chemosensory regions during congruent taste-odor pairs when the odors are delivered by the orthonasal route and require subjects to sniff. There were 2 flavors. One contained a familiar/congruent taste-odor pair (vanilla/sweet) and the other an unfamiliar/incongruent taste-odor pair (vanilla/salty). Three unimodal stimuli, including 2 tastes (sweet and salty) and one odor (vanilla), as well as a tasteless/odorless liquid (baseline) were presented. Superadditive responses during the perception of the congruent flavor compared with the sum of its constituents were observed in the anterior cingulate cortex (ACC), dorsal insula, anterior ventral insula extending into the caudal orbitofrontal cortex (OFC), frontal operculum, ventral lateral prefrontal cortex, and posterior parietal cortex. These regions were not present in a similar analysis of the incongruent flavor compared with the sum of its constituents. All of these regions except the ventrolateral prefrontal cortex were also isolated in a direct contrast of congruent - incongruent. Additionally, the anterior cingulate, posterior parietal cortex, frontal operculum, and ventral insula/caudal OFC were also more active in vanilla + salty minus incongruent, suggesting that delivery of an unfamiliar taste-odor combination may lead to suppressed neural responses. Taken together with previous findings in the literature, these results suggest that the insula, OFC, and ACC are key components of the network underlying flavor perception and that taste-smell integration within these and other regions is dependent on 1) mode of olfactory delivery and 2) previous experience with taste/smell combinations.

The present investigation was designed to evaluate the effect of selected peptides on pupillary diameter and intraocular pressure (IOP) in rabbits. Intracameral (IC) administration of neurotensin (NT) in doses of 5-100 micrograms produced a significant, long lasting and dose-dependent decrease in pupillary diameter without affecting IOP. NT-induced miosis appears to be relatively specific because a variety of peptides including Gn-RH, somatostatin, met-enkephalin, bombesin, leu-enkephalin or NT1-6, (a biologically inactive N-terminal fragment of NT), produced no effect on pupillary diameter; only substance P produced miosis similar to NT when tested in a dose equimolar to 30 micrograms of NT. In addition, peripheral (intravenous) administration of NT (100 micrograms/kg) was equally ineffective. Inhibition of prostaglandin synthesis with indomethacin, did not prevent subsequent NT-induced miosis. Finally, IC administration of an effective dose of NT (30 micrograms) did not alter the protein concentration in the aqueous humor. These results indicate that NT-induced miosis is not mediated by endogenous prostaglandins and that this effect of NT does not appear to involve disruption of the blood-aqueous barrier, suggesting that NT may play a role in regulation of pupillary diameter.