Ectopic Pregnancy Risk in Users of Levonorgestrel-Releasing Intrauterine Systems With 52, 19.5, and 13.5 mg of Hormone.

This study assesses the association between use of levonorgestrel intrauterine systems containing 52, 19.5, and 13.5 mg of hormone and ectopic pregnancy in a nationwide cohort study.

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.

Practice Facilitation Improves Adolescent Reproductive Health Preventive Services in Primary Care.

OBJECTIVES: Provision of reproductive health preventive services to adolescents is critical given their high rates of sexually transmitted infections and unintended pregnancies. Pediatricians are well positioned to provide these services but often face barriers. With this project, we aimed to build quality improvement (QI) capacity within pediatric practices to improve adherence to national guidelines for adolescent reproductive health preventive services. METHODS: In 2016, an accountable care organization overseeing health care delivery for low-income children in the Midwestern United States used practice facilitation, a proven approach to improve health care quality, to support pediatric practices in implementing reproductive health QI projects. Interested practices pursued projects aimed at providing (1) sexual risk reduction and contraceptive counseling (reproductive health assessments [RHAs]) or (2) etonogestrel implants. QI specialists helped practices build key driver diagrams and implement interventions. Outcome measures included the proportion of well-care visits with RHAs completed and number of etonogestrel insertions performed monthly. RESULTS: Between November 1, 2016, and December 31, 2019, 6 practices serving >7000 adolescents pursued QI projects. Among practices focused on RHAs, the proportion of well-care visits with completed RHAs per month increased from 0% to 65.8% (P < .001) within 18 months. Among practices focused on etonogestrel implant insertions, overall insertions per month increased from 0 to 8.5 (P < .001). CONCLUSIONS: Practice facilitation is an effective way to increase adherence to national guidelines for adolescent reproductive health preventive services within primary care practices. Success was driven by practice-specific customization of interventions and ongoing, hands-on support.

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)

Spatial distribution and factors associated with modern contraceptive use among women of reproductive age in Nigeria: A multilevel analysis.

BACKGROUND: Evidence suggests that in countries with high fertility and fecundity rates, such as Nigeria, the promotion of modern contraceptive use prevents approximately 32% and 10% of maternal and child mortality, respectively. Therefore, this study aimed to assess the spatial distribution of modern contraceptive use and its predictors among women of reproductive age in Nigeria. METHODS: The study employed a cross-sectional analysis of population-based data involving 24,281 women of reproductive age in Nigeria. The study adopted both multilevel and spatial analyses to identify the predictors of modern contraceptive use and its spatial clustering among women in Nigeria. RESULTS: Modern contraceptive use among the study population in Nigeria ranged from 0% to 75%, with regional variations. The spatial analysis showed that areas with a low proportion of modern contraceptive use were Sokoto, Yobe, Borno, Katsina, Zamfara, Kebbi, Niger, Taraba and Delta. Areas with a high proportion of modern contraceptive use were Lagos, Oyo, Osun, Ekiti, Federal capital territory, Plateau, Adamawa, Imo, and Bayelsa. The multilevel analysis revealed that at the individual level, women with secondary/higher education, women from the Yoruba ethnic group, those who had four children and above, and those exposed to mass media had higher odds of using modern contraceptives. On the other hand, women who were 35 years and above, those who were married, and women who were practicing Islam were less likely to use modern contraceptives. At the household/community level, women from the richest households, those residing in communities with medium knowledge of modern contraceptive methods, and women residing in communities with a high literacy level were more likely to use modern contraceptives. CONCLUSION: There were major variations in the use of modern contraception across various regions in Nigeria. As a result, areas with low contraceptive rates should be given the most deserving attention by promoting contraceptive education and use as well as considering significant factors at the individual and household/community levels.

Comparison of Female Genital Tract Cytokine and Microbiota Signatures Induced by Initiation of Intramuscular DMPA and NET-EN Hormonal Contraceptives - a Prospective Cohort Analysis.

Background: Cervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives. Methods: We collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis. Results: Cytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota. Conclusions: Both DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.

The Role of Subcutaneous Depot Medroxyprogesterone Acetate in Equitable Contraceptive Care: A Lesson From the Coronavirus Disease 2019 (COVID-19) Pandemic.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, health care professionals have made swift accommodations to provide consistent and safe care, including emphasizing remote access to allow physical distancing. Depot medroxyprogesterone acetate intramuscular injection (DMPA-IM) prescription is typically administered by a health care professional, whereas DMPA-subcutaneous has the potential to be safely self-injected by patients, avoiding contact with a health care professional. However, DMPA-subcutaneous is rarely prescribed despite its U.S. Food and Drug Administration approval in 2004 and widespread coverage by both state Medicaid providers and many private insurers. Depot medroxyprogesterone acetate users are disproportionately non-White, and thus the restriction in DMPA-subcutaneous prescribing may both stem from and contribute to systemic racial health disparities. We review evidence on acceptability, safety, and continuation rates of DMPA-subcutaneous, consider sources of implicit bias that may impede prescription of this contraceptive method, and provide recommendations for implementing DMPA-subcutaneous prescribing.

Impact of one-rod levonorgestrel implant on the blood chemistry profile.

The aim of this study was to investigate the effect of a one-rod levonorgestrel implant on the blood chemistry profile, including random blood glucose (RBG), haemoglobin (Hb), alanine transferase (ALT), aspartate transferase (AST), and the lipid profile, including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. This prospective cohort study was conducted at Raden Saleh Clinic, Jakarta, from 2010 to 2012. The implants were inserted subdermally in 30 patients. The subjects were evaluated every 6 month up to 2 years. Bivariate analysis using t-test or Wilcoxon signed rank test was performed for all variables. p < 0.05 was considered a significant value. The Hb, RBG, AST, and lipid profile levels were significantly different before and 6 months after one-rod implant insertion (p < 0.05). However, for 24 months, all of the parameters were still within normal limits and did not differ clinically. One-rod levonorgestrel implant insertion has a minimal effect on all blood chemistry profiles.

Factors affecting uptake of the levonorgestrel-releasing intrauterine device: A mixed-method study of social franchise clients in Nigeria.

BACKGROUND: Despite the positive characteristics of the levonorgestrel-releasing intrauterine device (IUD)-a long-acting, highly effective contraceptive with important non-contraceptive attributes-the method has not been widely available in low- and middle-income countries. This study of hormonal IUD, copper IUD, implant and injectable users in Nigeria compares their characteristics, reasons for method choice, and experiences obtaining their method. METHODS: We conducted a phone survey with 888 women who received a hormonal IUD, copper IUD, contraceptive implant or injectable from 40 social franchise clinics across 18 states in Nigeria. We analyzed survey data descriptively by method and assessed factors associated with hormonal IUD use through multivariate logistic regression models. Follow-up in-depth interviews conducted with 32 women were analyzed thematically. RESULTS: There were few differences by method used in the socio-demographic profiles and contraceptive history of participants. Among users choosing a long-acting, reversible method, the top reasons for method choice included perceptions that the method was "right for my body," long duration, recommended by provider, recommended by friends/family, few or manageable side effects, and high effectiveness. Among hormonal IUD users, 17% mentioned reduced bleeding (inclusive of lighter, shorter, or no period), and 16% mentioned treatment of heavy or painful periods. Qualitative data supported these findings. Among survey respondents, between 25% and 33% said they would have chosen no method if the method they received had not been available. Both quantitative and qualitative data indicated that partner support can affect contraceptive use, with in-depth interviews revealing that women typically needed partner permission to use contraception, but men were less influential in method choice. CONCLUSIONS: Expanding access to the hormonal IUD as part of a full method mix provides an opportunity to expand contraceptive choice for women in Nigeria. Findings are timely as the government is poised to introduce the method on a wider scale.

Level and Timing of Implanon Discontinuation and Associated Factors among Women Who Used Implanon in Andabet District, Public Health Facilities, North-West Ethiopia.

BACKGROUND: Implanon discontinuation is unacceptably high in developing countries, including Ethiopia. Furthermore, there is an observed problem of high unintended pregnancy after method discontinuation that strides to program failure. Therefore, the purpose of this study was to assess the level and determinants of Implanon discontinuation among women who used Implanon in Andabet district, public health facilities, North-West Ethiopia, 2017. METHODS: Facility-based cross-sectional study design was employed among 537 women from Feb. 03 to April 28, 2017. Study participants were selected using a systematic random sampling technique. A face-to-face interview was employed to collect data. Epi-Info version 7 was used for data entry and SPSS version 20 for analysis. Both descriptive and analytical statistical analysis was computed. On multivariable binary logistic regression, a p value of less than 0.05 was used to declare statistical significance. RESULTS: About 37% of Implanon users have discontinued the method before the intended time. About 86% of them discontinued Implanon before two years of insertion. Women who had no live child (AOR = 2.17, 95% CI: 1.25-3.77), women who did not receive preinsertion counseling (AOR = 1.85, 95% CI: 1.15-2.97), women who developed Implanon-related side effect (AOR = 5.17, 95% CI: 3.18-8.40), and women who did not satisfy by the service provided (AOR = 5.40, 95% CI: 3.04-9.57) had higher odds of Implanon discontinuation. On the other hand, women who received appointment follow-up (AOR = 0.23, 95% CI: 0.13-0.41) had lower odds of Implanon discontinuation. CONCLUSIONS: The level of Implanon discontinuation before its intended time was high in the district. Hence, strengthening preinsertion counseling and appointment follow-up as well as improving the clients' level of service satisfaction could increase Implanon's continuation.

Pain scores at the insertion of the 52 MG levonorgestrel-releasing intrauterine system among nulligravidas and parous women.

PURPOSE: This study aimed to assess the pain scores at the insertion of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) among nulligravidas, parous women with previous vaginal delivery and parous women with elective caesarean-delivery without any previous labour or cervix dilation. MATERIALS AND METHODS: The present research is a prospective, single-cohort study that included 413 women aged 15-49 years who opted for LNG-IUS placement for contraception or treatment of heavy menstrual bleeding. Women who participated in the present study were not submitted to any pharmacological pain-relieving intervention to perform the procedure. Pain at insertion was evaluated by using a Visual Analogue Scale (VAS). Pain was classified as absent (0), mild (1-3), moderate (4-6), or severe (7-10). The women were divided as: (1) nulligravidas, (2) parous women with a previous vaginal delivery, or (3) parous women with elective caesarean-delivery without any previous labour or cervix dilation. RESULTS: Nulligravidas women presented a higher mean pain score, when compared to women with elective caesarean-delivery and women with previous vaginal delivery (6.6 ± 2.0 vs 5.5 ± 2.1 and 3.9 ± 2.4, respectively; p < 0.001). Nulligravidas and women with elective caesarean-delivery were more likely to have pain classified as moderate or severe (in relation to absent or mild) than women with previous vaginal delivery (p < 0.001). Multiple Linear Regression Analysis demonstrated that 29.5% of all variability of the pain score was explained by two predictor/independent variables: nulligravidas or women with elective caesarean and difficulty at IUD insertion. CONCLUSIONS: Women with previous vaginal delivery had lower pain scores at LNG-IUS insertion when compared to nulligravidas and women with elective caesarean-delivery without any previous labour.

Update to U.S. Selected Practice Recommendations for Contraceptive Use: Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetate.

U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), adapted by CDC from global guidance developed by the World Health Organization (WHO), provides evidence-based guidance on contraceptive use for U.S. health care providers (1). During January-February, 2021, CDC evaluated the 2019 WHO recommendation on self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (2). CDC adopted the WHO recommendation on the basis of moderate-certainty evidence that self-administered DMPA-SC is safe and effective, and has higher continuation rates compared with provider-administered DMPA. The new U.S. SPR recommendation states that self-administered DMPA-SC should be made available as an additional approach to deliver injectable contraception. Provider-administered DMPA should remain available. Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be offered in a noncoercive manner through a shared decision-making process between patients and their health care providers, with a focus on patient preferences and equitable access to the full range of contraceptive methods.

Increasing uptake of long-acting reversible contraception with structured contraceptive counselling: cluster randomised controlled trial (the LOWE trial).

OBJECTIVE: To evaluate the effect of structured contraceptive counselling on the uptake of long-acting reversible contraceptives (LARCs) and pregnancy rates. DESIGN: Cluster randomised trial. SETTING: Abortion, youth and maternal health clinics in Stockholm, Sweden. POPULATION: Sexually active women aged ≥18 years without a wish for pregnancy seeking abortion and/or contraceptive counselling. METHODS: For participants in clinics randomised to intervention, trained healthcare providers implemented a study-specific intervention package designed for structured contraceptive counselling. Participants in the control clinics received routine counselling. MAIN OUTCOME MEASURES: The primary outcome was choice of LARCs at first visit. Secondary outcomes were LARC initiation at 3 months and pregnancy rates at 3 and 12 months. We used logistic mixed-effects models with random intercept for clinic to account for clustering. RESULTS: From September 2017 to May 2019, 28 randomised clinics enrolled 1364 participants. Analyses including 1338 subjects showed that more participants in the intervention group compared with the control group chose LARCs: 267/658 (40.6%) versus 206/680 (30.3%) (OR 2.77, 95% CI 1.99-3.86). LARC initiation was higher in the intervention group compared with the control group: 213/528 (40.3%) versus 153/531 (28.8%) (OR 1.74, 95% CI 1.22-2.49). At the abortion clinics, the pregnancy rate was significantly lower at 12 months in the intervention group compared with the control group: 13/101 (12.9%) versus 28/103 (27.2%) (OR 0.39, 95% CI 0.18-0.88). CONCLUSIONS: Structured contraceptive counselling increased LARC uptake in all clinics and significantly reduced unintended pregnancy rates in abortion clinics at the 12 months follow-up. TWEETABLE ABSTRACT: Structured contraceptive counselling increased LARC uptake and reduced pregnancy rates at 12 months.

Major nerve injury in association with use of contraceptive implants. / Alvorlige nerveskader ved bruk av p-stav.

BACKGROUND: Subcutaneous contraceptive implants are recommended to be placed in the medial upper arm. Here, the implant lies close to important neurovascular structures. CASE PRESENTATION: We have treated two women with ulnar nerve injuries after removal of such implants. Patient 1 sustained a near complete nerve injury. Despite nerve grafting and a distal nerve transfer, she had a poor outcome. Patient 2 had a partial injury and has made a reasonable recovery after neurolysis of the ulnar nerve that was entrapped in scar tissue. INTERPRETATION: Prognosis after peripheral nerve injuries in the upper arm in adults is poor, and as such these injuries are particularly serious. Any patient with an implant that is not readily palpable in the subcutaneous tissue should be referred to a hand surgeon who has training in exploring peripheral nerves. If emergent nerve injury is suspected, referral to a department of hand surgery is vital.

Single-dose pharmacokinetics and pharmacodynamics assessment of oestriol and trimegestone containing vaginal rings in healthy women with childbearing potential.

PURPOSE: To evaluate the pharmacokinetics and pharmacodynamics of oestriol (E3) and trimegestone (TMG) in healthy women after application of three different vaginal rings over 21 days. The vaginal rings had a nominal delivery rate of 0.413/0.050 mg/day (Test 1), 0.311/0.090 mg/day (Test 2) and 0.209/0.137 mg/day (Test 3) E3/TMG. METHODS: Thirty-five healthy women were randomised to receive a single application of Test 1, 2 or 3 (Clinical Trial NCT03343912). The E3 and TMG plasma concentration was determined by LC-MS/MS. Oestradiol (E2) and progesterone (PG) serum concentrations, and bleeding patern were determined as pharmacodynamic parameters. Safety was assessed by evaluation of adverse events and local tolerability. RESULTS: The total and maximum exposure of E3 and TMG increased in a proportional ratio to dose. However, not in a magnitude which was expected from the dose differences for E3. During Test 2 and 3 treatment all E2 and PG values remained on a well suppressed level until end of treatment. E2 and PG serum levels increased distinctly earlier after ring removal with Test 1 compared to Test 2 and 3. Test 3 achieved 95.24% of "no bleeding" days under treatment followed by Test 1 (91.67%), and Test 2 (86.15%). CONCLUSIONS: The Test 3 formulation presented the best dose combination of E3/TMG for contraception. Moreover, all vaginal rings were well tolerated.

Facilitators and Barriers to Implementation of Long-Acting Reversible Contraceptive Services for Adolescent Girls and Young Women in Gaborone, Botswana.

STUDY OBJECTIVE: Botswana has a high pregnancy rate among adolescent girls and young women (AGYW). Long-acting reversible contraceptive (LARC) use among AGYW in Botswana is low, despite its high effectiveness for preventing pregnancy. Using an implementation science framework, we assessed barriers and facilitators to LARC implementation among AGYW in Botswana. DESIGN: Cross-sectional mixed methods. SETTING: Gaborone, Botswana. PARTICIPANTS: Twenty sexually active AGYW ages 18-24 years; 20 health system stakeholders. INTERVENTIONS: Surveys and semistructured interviews grounded in the Consolidated Framework for Implementation Research. MAIN OUTCOME MEASURES: Themes reflecting barriers and facilitators of LARC implementation. RESULTS: The median age for AGYW was 22 (interquartile range, 21-23) years. Twenty percent were using an implant and none had ever used an intrauterine device. Barriers and facilitators of LARC implementation spanned factors at each Consolidated Framework for Implementation Research domain: (1) LARC characteristics like side effects; (2) the clinics' inner settings, including availability of youth-friendly services; (3) characteristics of health system stakeholders, such as LARC skills, and AGYW experiences, attitudes, and beliefs about LARCs; (4) the outer setting external to clinics and Botswana's health system including reproductive health law and policy for minor adolescents; and (5) the implementation process level such as the availability of free or low-cost LARCs. CONCLUSION: We identified multilevel, context-specific factors that affect LARC implementation. Our findings can inform the development of interventions to increase LARC implementation in Botswana by addressing intersecting factors across patient, clinic, health system, and sociopolitical levels, such as providing confidential services to minors and improving LARC training and supply chain pipelines.

A rodent model of human dose-equivalent progestin-only implantable contraception.

BACKGROUND: Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. METHODS: Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30µg/d, medium-0.17µg/d, low-0.09µg/d, placebo-0.00µg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. RESULTS: Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. CONCLUSION: Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

Genital and systemic immune effects of the injectable, contraceptive norethisterone enanthate (NET-EN), in South African women.

PROBLEM: Injectable hormonal contraceptives (IHC) have been associated with altered mucosal and systemic milieu which might increase HIV risk, but most studies have focused on DMPA and not NET-EN, despite the growing popularity and lower HIV risk associated with the latter in observational studies. METHOD OF STUDY: We used high-performance liquid chromatography in combination with tandem triple quadrupole mass spectrometry (HPLC-LC-MS/MS) to measure steroid hormones in plasma samples of CAPRISA004 study participants. Concentrations of 48 cytokines were measured in the cervicovaginal lavage (CVL) and plasma, and their expression was compared between participants with detectable NET-EN (n = 201) versus non-detectable IHC (n = 90). Each log10 cytokine concentration was tested as an outcome in linear-mixed models, with NET-EN detection as the main explanatory variable. Multivariable models were adjusted for potential confounders. RESULTS: In bivariate analysis, detectable NET-EN was associated with reduced cervicovaginal M-CSF (P = 0.008), GM-CSF (P = 0.025) and G-CSF (P = 0.039), and elevated levels MIF (P = 0.008), IL-18 (P = 0.011), RANTES (P = 0.005) and IL-1Rα (P < 0.001). Lower G-CSF (P = 0.011) and elevated IL-1Rα (P = 0.008) remained significant in adjusted models. Multivariable analyses of plasma samples obtained from NET-EN-detectable women showed a significant increase in IP-10 (P = 0.026) and reductions in TNF-ß (P = 0.037), RANTES (P = 0.009), and M-CSF (P < 0.001). While similar growth factor reduction in CVL was noted for both DMPA and NET-EN, similar trends were not observed for endogenous progesterone. CONCLUSIONS: Detectable NET-EN was associated with reduced growth factors in the plasma and genital tract; particularly G-CSF and M-CSF. Our results suggest that while NET-EN is not inflammatory, it may have important immunological effects.