Increases in retail sales of over-the-counter levonorgestrel emergency contraception in the United States, 2016-2022.

OBJECTIVES: To understand patterns in demand for emergency contraception (EC), we characterize the sales of over-the-counter (OTC) levonorgestrel (LNG) EC in the United States from traditional retail outlets. STUDY DESIGN: We describe sales of OTC LNG EC using retail sales data aggregated from traditional retail channels, including grocery stores, drug stores, mass merchandisers, club stores, dollar stores, and military outlets. RESULTS: Sales of OTC LNG EC doubled between 2016 and 2022 (approximately 7.2-14.8 million). CONCLUSIONS: Increasing sales of EC are consistent with increased use and use frequency of EC by those at risk of pregnancy in the United States. IMPLICATIONS: OTC LNG EC sales since 2016 exceed what national survey usage estimates would suggest, indicating that national surveys underreport EC use, those using EC purchase it somewhat frequently, and/or individuals stockpile EC for later use. The role of EC in individual contraceptive strategies, particularly as access to reproductive healthcare is restricted, warrants further study.

Uptake, discontinuation, and continuation rate of long-acting contraceptive methods when offered at no cost in Campinas, Brazil.

OBJECTIVES: This study aimed to compare the uptake, reasons for discontinuation, continuation, and satisfaction of long-acting contraceptive methods (LARC) when offered at no cost in Campinas, Brazil. STUDY DESIGN: This was a prospective cohort study conducted at University of Campinas, Campinas, São Paulo, Brazil, including women aged 18 to 48 years, who adopted one of three methods. Participants underwent telephone follow-up every 3 months for up to 24 months after insertion. Satisfaction was assessed at the end of 2 years of use through the Likert scale. RESULTS: We invited 1222 women, and among the 971 women who volunteered to participate in follow-up, 414 (42.6%) chose the levonorgestrel 52-mg intrauterine device (IUD), 358 (36.9%) chose the etonogestrel (ENG) implant, and 199 (20.5%) chose the TCu380A IUD. Discontinuation due to bothersome bleeding was higher among users of the ENG implant (10/358; 2.4%) and the TCu380A IUD (32/199; 8.9%), and expulsion was higher for the TCu380A IUD (30/199; 15.1%). Women continued at 24 months were 340/414 (82.1%), 270/358 (75.4%), and 119/199 (59.8%) among users of the levonorgestrel 52-mg IUD, ENG implant, and TCu380A IUD, respectively. The users of the levonorgestrel 52-mg IUD (301/339, 88.8%), the ENG-implant (222/270, 82.2%), and the TCu380A IUD (105/119, 88.2%) were satisfied or very satisfied by 24 months of follow-up. CONCLUSIONS: The three LARC methods had great uptake, high continuation, and discontinuation due to bothersome bleeding was higher among users of the ENG implant and the TCu380A IUD, and expulsion was higher for the TCu380A IUD compared to the 52-mg levonorgestrel IUD. Most of the participants reported being very satisfied. IMPLICATIONS: When the LARC methods were offered at no cost in a Brazilian public clinic the uptake, satisfaction and continuation were high by 24 months after device placement, and high level of satisfaction was reported by most of the participants.

Clinical Assessment of 3 Intrauterine Devices in Adolescent Girls: A Randomized Clinical Trial.

STUDY OBJECTIVE: To assess clinical performance, bleeding pattern, dysmenorrhea, and satisfaction up to 1 year after placement of 3 types of intrauterine devices (IUDs) (TCu380A, levonorgestrel 52 mg, and levonorgestrel 19.5 mg) in adolescents METHODS: The study was a randomized trial with 318 adolescents allocated to the 3 IUDs. We assessed reasons for removal, continuation, menstrual patterns, dysmenorrhea, and satisfaction. RESULTS: Participants aged (mean ± SD) 17.9 ± 1.4 years, with 80.8% being nulligravidae. After 1 year, 265 (83.3%) continued using the IUD; however, the continuation rate of TCu380A (75.4 ± 4.2) was lower than that of both the levonorgestrel 52-mg (88.6 ± 3.1) and 19.5-mg IUDs (86.8 ± 3.3), and bleeding/pain and expulsion were the main reasons for removal of the TCu380A IUD. The duration of menstruation was longer among the TCu380A IUD users (6.0 ± 2.0 days) than those using the levonorgestrel 52 mg (2.5 ± 3.9) and 19.5 mg (3.2 ± 3.2) devices, P < .001. Amenorrhea was reported by 49.5% and 37.8% users of the levonorgestrel 52-mg and 19.5-mg devices, respectively, P < .001. Dysmenorrhea was reported in 68.5% of all participants at the baseline; this was 67.9% of the TCu380A group and 33.3% and 36.0% of the levonorgestrel 52-mg and 19.5-mg IUD groups, respectively, P < .001. Satisfaction ranged from 80.7% in the TCu380A group to 97.8% in the levonorgestrel 52-mg group (P = .03). CONCLUSION: The 3 IUDs are suitable for adolescents, with high contraceptive efficacies and rates of continuation within 1 year of use and high degrees of satisfaction. Users of the hormonal IUDs reported lower expulsion rates, more favorable menstrual patterns, and less dysmenorrhea compared with the TCu380A IUD.

Rural Appalachian Women Will Suffer Disproportionately if Attempts to Further Restrict Emergency Contraception are Successful.

The removal of federal abortion protection has incited fear that restrictions on contraception may be next. Many states now imposing abortion restrictions and bans are in the South and Appalachian Regions of the U.S., where rates of unplanned pregnancy and poor health outcomes are already disproportionately high. Numerous studies have documented variable access to levonorgestrel EC (LNG EC) in community pharmacies, with particularly low rates of access at independent pharmacies that are more likely to be located in rural communities than chain pharmacies. Since the overturn of Roe v. Wade, some large chain pharmacies and online retailers are restricting the purchase of LNG EC, limiting its availability. Some legislators and activists are calling for a ban on EC based on a misunderstanding about its mechanism of action, equating it with abortion. At a time when access to the full range of contraceptive options is more critical than ever, already limited access to LNG EC is worsening. Extensive data on LNG EC availability in 509 pharmacies and 400 health clinics across West Virginia, contextualized with socioeconomic demographics, illustrate existing disparities in LNG EC access.

Análise de impacto orçamentário de dispositivos contraceptivos na saúde suplementar brasileira / Budget impact analysis of contraceptive devices on Brazilian supplementary health

Objetivo: Analisar o impacto orçamentário da adoção de dispositivos contraceptivos reversíveis de longa duração em uma operadora de plano de saúde localizada no Sul do Brasil. Especificamente, analisamos a incorporação do implante subdérmico de etonogestrel (Implanon®) como alternativa ao sistema intrauterino de levonorgestrel (DIU Mirena® ou DIU Kyleena®), ao longo de um período de 15 anos. Métodos: Realizamos uma análise do impacto orçamentário incremental, considerando a inclusão gradual do implante subdérmico de etonogestrel. Foram considerados dados de uma operadora de planos de saúde com mais de 600.000 beneficiários. O horizonte temporal de 15 anos permitiu uma avaliação abrangente dos efeitos financeiros. Resultados: Identificamos 5.345 pacientes elegíveis para a utilização de contraceptivos reversíveis de longa duração. No cenário em que somente o sistema intrauterino de levonorgestrel era adotado, projetou-se um impacto orçamentário total de R$ 746.379.857,80 ao longo de 15 anos. No cenário alternativo, com a incorporação gradual do implante subdérmico, o impacto orçamentário total foi calculado em R$ 689.800.196,83. Isso resultou em um impacto orçamentário incremental negativo de -R$ 56.579.660,97 ao longo do período. Conclusão: A análise de impacto orçamentário realizada indica um potencial benefício financeiro ao adotar o implante subdérmico de etonogestrel como alternativa ao sistema intrauterino de levonorgestrel para contracepção. Esse achado sugere possíveis reduções de custos na área de saúde suplementar no Brasil, reforçando a importância de avaliar opções economicamente viáveis.

Objective: To analyze the budgetary impact of the adoption of long-acting reversible contraceptive devices in a health plan operator located in southern Brazil. Specifically, we analyzed the incorporation of the etonogestrel subdermal implant (Implanon®) as an alternative to the levonorgestrel intrauterine system (Mirena® IUD or Kyleena® IUD), over a period of 15 years. Methods: We performed an analysis of the incremental budgetary impact, considering the gradual inclusion of the etonogestrel subdermal implant. Data from a health plan operator with more than 600,000 beneficiaries were considered. The 15-year time horizon allowed for a comprehensive assessment of the financial effects. Results: We identified 5,345 patients eligible for the use of long-acting reversible contraceptives. In the scenario where only the levonorgestrel intrauterine system was adopted, a total budget impact of BRL 746,379,857.80 was projected over 15 years. In the alternative scenario, with the gradual incorporation of the subdermal implant, the total budgetary impact was calculated at BRL 689,800,196.83. This resulted in a negative incremental budgetary impact of -R$56,579,660.97 over the period. Conclusion: The budget impact analysis carried out indicates a potential financial benefit in adopting the etonogestrel subdermal implant as an alternative to the levonorgestrel intrauterine system for contraception. This finding suggests possible cost reductions in the supplementary healthcare area in Brazil, reinforcing the importance of evaluating economically viable options.

Provision of the progestogen-only pill by community pharmacies as bridging contraception for women receiving emergency contraception: the Bridge-it RCT.

INTRODUCTION: Unless women start effective contraception after using emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies that are unable to provide ongoing contraception (apart from barrier methods which have high failure rates). This means that women need an appointment with a general practitioner or at a sexual and reproductive health clinic. We conducted a pragmatic cluster randomised cohort crossover trial to determine whether or not pharmacist provision of a bridging supply of a progestogen-only pill plus the invitation to attend a sexual and reproductive health clinic resulted in increased subsequent use of effective contraception (hormonal or intrauterine). METHODS: Twenty-nine pharmacies in three UK cities recruited women receiving emergency contraception (levonorgestrel). In the intervention, women received a 3-month supply of the progestogen-only pill (75 µg of desogestrel) plus a card that provided rapid access to a local sexual and reproductive health clinic. In the control arm, pharmacists advised women to attend their usual contraceptive provider. The primary outcome was reported use of an effective contraception (hormonal and intrauterine methods) at 4 months. Process evaluation was also conducted to inform any future implementation. RESULTS: The study took place December 2017 and June 2019 and recruited 636 women to the intervention (n = 316) and control groups (n = 320). There were no statistically significant differences in demographic characteristics between the groups. Four-month follow-up data were available for 406 participants: 63% (198/315) of the control group and 65% (208/318) of the intervention group. The proportion of participants reporting use of effective contraception was 20.1% greater (95% confidence interval 5.2% to 35.0%) in the intervention group (58.4%, 95% confidence interval 48.6% to 68.2%) than in the control group (40.5%, 95% confidence interval 29.7% to 51.3%) (adjusted for recruitment period, treatment arm and centre; p = 0.011). The proportion of women using effective contraception remained statistically significantly larger, when adjusted for age, current sexual relationship and history of past use of effective contraception, and was robust to the missing data. There were no serious adverse events. CONCLUSION: Provision of a bridging supply of the progestogen-only pill with emergency contraception from a pharmacist and the invitation to a sexual and reproductive health clinic resulted in a significant increase in self-reported subsequent use of effective contraception. This simple intervention has the potential to prevent more unintended pregnancies for women after emergency contraception. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70616901. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 27. See the NIHR Journals Library website for further project information.

The emergency contraceptive pill can prevent pregnancy following unprotected sex or a burst condom; however, unless women start a regular method of contraception they remain at risk of pregnancy. Most women obtain emergency contraception from a community pharmacy (chemist), but then require an appointment with a general practitioner or at a sexual and reproductive health clinic for ongoing contraception. Getting an appointment can take time and unintended pregnancies can occur during this time. If a pharmacist could give women a small supply of a progestogen-only pill or 'mini-pill' with their emergency contraception, together with help to get an appointment at a clinic, then this might help more women to start effective contraception. We undertook a study in 29 pharmacies in Lothian, Tayside and London among women receiving emergency contraception. Pharmacists provided either their standard advice about contraception (control group) or the intervention. The intervention was a 3-month supply of the progestogen-only pill plus a rapid-access card, which, if presented at a sexual and reproductive health clinic, would help women get an appointment for contraception. The order in which the pharmacy provided either control or intervention was randomised. We conducted telephone interviews with the women 4 months later to find out what contraception they were using. A total of 636 women took part in the study, 316 in the intervention group and 320 in the control group. The proportion who said that they were using an effective method of contraception was around 20% larger in the intervention group. In addition, fewer women in this group said that they had used emergency contraception again. This study shows that community pharmacy provision of a small supply of progestogen-only pills and the invitation to attend a sexual and reproductive health clinic results in a large increase in the use of effective contraception after emergency contraception. If this became routine practice then it could help prevent unintended pregnancies.

"It prevents a fertilized egg from attaching and causes a miscarriage of the baby": A qualitative assessment of how people understand the mechanism of action of emergency contraceptive pills.

OBJECTIVE: The mechanism of action (MOA) of emergency contraceptive pills (ECPs) is frequently mischaracterized. Our objective was to identify how members of the general public understand the mechanisms of ECPs. STUDY DESIGN: We recruited a convenience sample from social media for a survey about reproductive health attitudes and analyzed spontaneous descriptions of how ECPs work. We inductively coded responses to create themes and subthemes, and collapsed subthemes into three MOA categories based on previous research. RESULTS: Among 1443 respondents, 533 mentioned an MOA in their description of ECPs. While nearly half of these responses (49.5%) stated that ECPs prevent pregnancy before fertilization occurs (in accordance with most biomedical ECP research), over 60% described a mechanism related to preventing implantation of a fertilized egg. Nine percent of responses described a postimplantation mechanism that would be considered abortion by mainstream medical standards. Some respondents conveyed significant confusion about the biological processes involved with pregnancy and pregnancy prevention. CONCLUSION: Confusion about how ECPs work was common among our sample. The largest group of responses described a mechanism-preventing implantation of a fertilized egg-listed on the Food and Drug Administration (FDA)-approved ECP labels that does not reflect most relevant biomedical research. Mischaracterizations of ECPs' mechanisms have been used to limit access to EC. These misunderstandings were common in our sample and may reflect poor quality sex education and public information, and confusion introduced by the FDA-approved labels. Additional research should identify whether public perception of ECPs' mechanisms influences policy, health care provision, and use of ECPs.

Custo-efetividade e limiar de custo para o uso do sistema intrauterino liberador de levonorgestrel para o tratamento do sangramento uterino anormal sob a perspectiva do Sistema de Saúde Suplementar no Brasil / Cost-effectiveness and cost threshold for the use of levonorgestrel-releasing intrauterine system for treatment of heavy menstrual bleeding from the Supplementary Health System perspective in Brazil

Objetivo: Definir um limiar de custo para o sistema intrauterino liberador de levonorgestrel 52 mg (SIU-LNG 52 mg) para o tratamento do sangramento uterino anormal (SUA) sob a perspectiva do Sistema de Saúde Suplementar brasileiro. Métodos: Foi elaborado um modelo de custo-efetividade para definir o limiar de custo de inserção de SIU-LNG 52 mg em mulheres com SUA em comparação à histerectomia. Um modelo de Markov foi estruturado com ciclos anuais para reproduzir o tratamento do SUA em um e cinco anos, considerando custos médicos diretos e o percentual de histerectomias evitadas como desfecho. O custo da histerectomia foi variado até o valor de 10.000 reais brasileiros (BRL) com incrementos de 500 BRL a cada nova simulação para avaliar o limiar de custo do SIU-LNG 52 mg para igualar o custo total de tratamento de ambas as estratégias analisadas. Resultados: O SIU-LNG 52 mg demonstrou ser uma opção de tratamento dominante quando comparada à histerectomia, levando à redução da frequência de realização do procedimento cirúrgico em 59,62% das mulheres e redução de 2.557,91 BRL no custo total de tratamento em cinco anos. Ao considerar a histerectomia a 6.000 BRL, o custo do procedimento com SIU-LNG 52 mg poderia ser de até 6.150,35 BRL e 3.994,60 BRL para igualar o custo total de tratamento, em horizontes temporais de um e cinco anos, respectivamente. Conclusão: SIU-LNG 52 mg demonstrou ser uma opção dominante para o manejo do SUA, sendo capaz de atrelar economia para o sistema de saúde a benefícios para a mulher perante a cirurgia.

Objective: To define a cost threshold for the use of levonorgestrel-releasing intrauterine system 52 mg (LNG-IUS 52 mg) for the treatment of heavy menstrual bleeding (HMB) in the Brazilian Supplementary Health System perspective. Methods: A cost-effectiveness model was built to define the cost threshold for insertion of LNG-IUS 52 mg considering women with diagnosis of HMB as the target population and hysterectomy as the comparator. A Markov model was structured with annual cycles to reproduce HMB treatment in 1 and 5 years, considering direct medical costs and the percentage of avoided hysterectomies as the outcome. Hysterectomy cost was varied up to 10,000 Brazilian real (BRL) with increments of 500 BRL at each new simulation to define LNG-IUS 52 mg cost threshold, to provide equal total treatment costs for both strategies. Results: LNG-IUS 52 mg proved to be a cost-saving option when compared to hysterectomy, leading to a reduction in the frequency of the surgical procedure by 59.62% and a total treatment cost reduction of 2,557.91 BRL in 5 years. When considering hysterectomy at 6,000 BRL, the cost of the procedure with LNG-IUS 52 mg could be up to 6,150.35 BRL and 3,994.60 BRL to provide equal total treatment cost in 1 and 5 years time horizon, respectively. Conclusion: LNG-IUS 52 mg has proven to be a cost-saving option for the health system in the management of HMB, in addition to the known benefits for women against surgery.

Provision of the levonorgestrel intrauterine system in Nigeria: Provider perspectives and service delivery costs.

Background: Several organizations in Nigeria are leading pilot introduction programs of the levonorgestrel intrauterine system (LNG-IUS). We conducted a qualitative assessment of providers' experiences across the five programs and an analysis of service delivery costs in one program. Methods: We conducted 20 in-depth interviews (IDIs) with providers. We used project expenditure records to estimate incremental direct service delivery costs of introducing the LNG-IUS in 40 social franchise clinics supported by the Society for Family Health (SFH). We then compared the direct service delivery costs per couple years of protection (CYP) for the LNG-IUS to other family planning methods. Results: Providers appreciated the therapeutic benefits of the LNG-IUS, especially reduction of heavy bleeding. They said that women generally accepted bleeding changes with counseling but noted complaints about spotting and mixed acceptability of amenorrhea. Providers indicated being comfortable with both the insertion and removal process and believed their equipment and infection prevention protocols were adequate. Lack of awareness among women, limited availability, current pricing, and resistance to uterine placement among some women were perceived as barriers. The estimated direct service delivery cost of introducing the LNG-IUS in pilot settings, inclusive of up-front provider training costs, was USD 34 per insertion. Direct service delivery costs at a 'steady state' (i.e., without training costs included for any method) of the LNG-IUS per CYP was similar to that of other contraceptive methods distributed in Nigeria. Conclusion: Providers' positive experiences with the LNG-IUS and direct service delivery costs per CYP that align with those for other methods suggest that the LNG-IUS could be an important addition to the method mix in Nigeria. Product introduction strategies will need to address both the supply and the demand sides, as well as consider appropriate pricing of the LNG-IUS relative to other methods and particularly the copper IUD.

Free-of-charge long-acting reversible contraception: two-year discontinuation, its risk factors, and reasons.

BACKGROUND: Since 2013, the residents of the city of Vantaa, Finland, have been offered their first long-acting reversible contraceptive method (levonorgestrel-releasing intrauterine system, implant, and copper intrauterine device) free of charge. OBJECTIVE: The primary aim of this study was to assess the 2-year cumulative discontinuation rates of long-acting reversible contraceptive methods when provided free of charge for first-time users in a real-world setting. Additional aims were to describe factors associated with discontinuation and to evaluate the reasons for discontinuation. STUDY DESIGN: This is a retrospective register-based cohort study of 2026 nonsterilized women aged 15 to 44 years, who initiated a free-of-charge long-acting contraceptive method in 2013-2014 in the city of Vantaa. Removals within 2 years after method initiation and reasons for discontinuation were obtained from electronic health records and from national registers. We calculated the 2-year cumulative incidence rates of discontinuation with 95% confidence intervals for each method. Furthermore, we assessed crude and adjusted incidence rate ratios of discontinuation with 95% confidence interval by Poisson regression models comparing implants and copper intrauterine device with levonorgestrel-releasing intrauterine systems. RESULTS: During the 2 -year follow-up, 514 women discontinued, yielding a cumulative discontinuation rate of 28.3 per 100 women-years (95% confidence interval, 26.2-30.4). Among the 1199 women who initiated the levonorgestrel-releasing intrauterine system, the cumulative discontinuation rate was 24.2 per 100 women-years (95% confidence interval, 21.7-26.9); among the 642 implant users, 33.3 per 100 women-years (95% confidence interval, 29.5-37.4); and among the 185 copper intrauterine device users, 37.8 per 100 women-years (95% confidence interval, 31.0-45.7). Compared with women aged 30 to 44 years, women aged 15 to 19 years (adjusted incidence rate ratio, 1.58; 95% confidence interval, 1.17-2.14) and 20 to 29 years (adjusted incidence rate ratio, 1.35; 95% confidence interval, 1.11-1.63) were more likely to discontinue. We observed a higher discontinuation rate in women who had given birth within the previous year (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.13-1.65), spoke a native language other than Finnish or Swedish (adjusted incidence rate ratio, 1.31; 95% confidence interval, 1.06-1.63), and had a history of a sexually transmitted infection (adjusted incidence rate ratio, 1.62; 95% confidence interval, 1.07-2.46). No association was found in marital status, overall parity, history of induced abortion, socioeconomic status, education level, or smoking status. The most common reason for discontinuation was bleeding disturbances, reported by 21% of women who discontinued the levonorgestrel-releasing intrauterine system, by 71% who discontinued the implant, and by 41% who discontinued the copper intrauterine device. One in 4 women who discontinued the copper intrauterine device reported heavy menstrual bleeding, whereas only 1% who discontinued the levonorgestrel-releasing intrauterine system and none who discontinued implants reported this reason. Abdominal pain was the reported reason for discontinuation in 20% of both intrauterine device users and in only 2% who discontinued implants. CONCLUSION: At 2 years, the use of implants and copper intrauterine devices was more likely to be discontinued than that of the levonorgestrel-releasing intrauterine system. Women younger than 30 years and those who gave birth in the preceding year, spoke a native language other than Finnish or Swedish, or had a history of sexually transmitted infections were more likely to discontinue. The levonorgestrel-releasing intrauterine system was least likely to be removed owing to bleeding disturbances.

Indications and reasons for discontinuing the levonorgestrel-releasing intrauterine system (LNG-IUS) / Indicações e razões para descontinuação do sistema intra-uterino liberador de levanogestrel (SIU-LNG)

Abstract Objectives: to identify the main indications and reasons for discontinuing the use of the Levonorgestrel-Releasing Intrauterine System (LNG-IUS). Methods: a cross-sectional study was carried out from medical records of 327 women who used the LNG-IUS 52mg between January 2011 and December 2016 at a public hospital in the Northeast of Brazil. Results: the main indications for the use of the LNG-IUS were: contraception (32.7%), myoma/metrorrhagia (28.7%) and endometriosis/pelvic pain (22.3%). Of the 327 women, 68 (20.8%) had discontinued using the device. The most frequent reasons for discontinuation were: expulsion (9.2%), LNG-IUS expiration (3.7%), bleeding (2.4%) and pain (1.5%). Most patients had no difficulty in the insertion and did not require anesthesia/sedation. Among the 30 women who expelled the device, 17 (56.7%) had used it for metrorrhagia and myoma, 8 (26.7%) for contraception, and 5 (16.6%) for endometriosis/pelvic pain. Conclusions: the LNG-IUS is a well-accepted contraceptive method, with therapeutic applications for some gynecological conditions and a low expulsion rate.

Resumo Objetivos: identificar as principais indicações e razões para a descontinuação do uso do sistema intra-uterino liberador de levanogestrel (SIU-LNG). Métodos: foi realizado um estudo transversal a partir de prontuários de 327 mulheres que usaram o SIU-LNG 52mg entre janeiro de 2011 e dezembro de 2016 em um hospital público do Nordeste do Brasil. Resultados: as principais indicações para o uso do SIU-LNG foram: contracepção (32,7%), mioma / metrorragia (28,7%) e endometriose / dor pélvica (22,3%). Das 327 mulheres, 68 (20,8%) haviam descontinuado o uso do dispositivo. Os motivos mais frequentes de descontinuação foram: expulsão (9,2%), expiração de SIU-LNG (3,7%), sangramento (2,4%) e dor (1,5%). Conclusão: a maioria dos pacientes não teve dificuldade na inserção e não necessitou de anestesia / sedação. Entre as 30 mulheres que expulsaram o dispositivo, 17 (56,7%) o utilizaram para metrorragia e mioma, 8 (26,7%) para contracepção e 5 (16,6%) para endometriose / dor pélvica. O SIU-LNG é um método contraceptivo bem aceito, com aplicações terapêuticas para algumas condições ginecológicas e baixa taxa de expulsão.

Aldo-keto reductase 1C3-Assessment as a new target for the treatment of endometriosis.

Endometriosis is a common gynecological disorder, which is treated surgically and/ or pharmacologically with an unmet clinical need for new therapeutics. A completed phase I trial and a recent phase II trial that investigated the steroidal aldo-keto reductase 1C3 (AKR1C3) inhibitor BAY1128688 in endometriosis patients prompted this critical assessment on the role of AKR1C3 in endometriosis. This review includes an introduction to endometriosis with emphasis on the roles of prostaglandins and progesterone in its pathophysiology. This is followed by an overview of the major enzymatic activities and physiological functions of AKR1C3 and of the data published to date on the expression of AKR1C3 in endometriosis at the mRNA and protein levels. The review concludes with the rationale for using AKR1C3 inhibitors, a discussion of the effects of AKR1C3 inhibition on the pathophysiology of endometriosis and a brief overview of other drugs under clinical investigation for this indication.

Análisis de la costo-efectividad del sistema intrauterino liberador de levonorgestrel, como alternativa a histerectomías, en dos países latinoamericanos / Analysis of the cost-effectiveness of the levonorgestrel intrauterine system as alternative to histerectomies in two latin american countries

Resumen Objetivo: El sistema intrauterino con levonorgestrel ha demostrado un fuerte efecto supresor endometrial de mucha utilidad en gran variedad de problemas ginecológicos. Existen numerosos estudios y revisiones del sistema intrauterino con levonorgestrel que avalan su uso en sangrado uterino anormal, como también bastantes publicaciones que demuestran su costo-efectividad. No se encontraron publicaciones latinoamericanas. El objetivo del estudio es desarrollar un modelo para valorar el beneficio en costos del uso del dispositivo como manejo alternativo del sangrado uterino anormal. Métodos : Se realizó modelo fármaco-económico que ayudará a comparar costos y efectividad de sistema intrauterino con levonorgestrel, inserción, controles clínicos más ultrasonido transvaginal al mes, y anuales, y se comparó con los costos directos de histerectomía. Los costos de histerectomía se obtienen mediante GRD-WinSIG en Chile y los costos reales directos en Costa Rica. El modelo es básicamente comparar los costos de la inserción de sistema intrauterino con levonorgestrel más las fallas del tratamiento versus histerectomías. Resultados: El modelo permite demostrar que al utilizar el sistema intrauterino con levonorgestrel como alternativa a la histerectomía en pacientes seleccionadas, se produce un ahorro en costos, aun asumiendo el costo de las fallas. Estos modelos no consideran los costos asociados a las complicaciones eventuales de todo acto quirúrgico, de tal forma que el ahorro generado por el uso del sistema intrauterino con levonorgestrel podría ser mayor. Conclusión: La inclusión del sistema intrauterino con levonorgestrel en guías de práctica clínica permite la posibilidad de disminuir las histerectomías en pacientes refractarias a tratamiento médico convencional, y que cumplan con criterios de inclusión y exclusión estrictos. El modelo permitió demostrar que al utilizar el sistema intrauterino con levonorgestrel como alternativa a la histerectomía, se produce un gasto que es solo un tercio del generado al realizar histerectomías.

Summary Objective: The intrauterine system with levonorgestrel has demonstrated a strong endometrial suppressive effect that is useful in a wide variety of gynecological problems. There are numerous studies and reviews of the levonorgestrel intrauterine system that support its use in abnormal uterine bleeding, as well as numerous publications that demonstrate its cost-effectiveness. As far as we know, there are no Latin American publications in this regard. The objective of the present study was to develop a model to assess the costs benefits of the use of the devices as alternative management of abnormal uterine bleeding. Methods: A pharmacoeconomic model was performed comparing costs and effectiveness with costs of levonorgestrel intrauterine system, insertion, clinical controls plus ultrasounds per month and annually, compared with the direct costs of hysterectomy. Hysterectomy costs were obtained through DRG-WinSIG or direct real costs in Chile and Costa Rica respectively. Results: Our model demonstratde that when using the levonorgestrel intrauterine systsem as an alternative to hysterectomy in selected patients there is an expenditure of only one third of the costs of performing the hysterectomies in the same patients, even assuming failures with the dispositive. These model did not consider the costs associated with the eventual complications of any surgical act, thus, savings generated by use of the levonorgestrel intrauterine system in these patients could be even greater. Conclusión: The inclusion of the levonorgestrel intrauterine system in clinical practice guidelines could allow the possibility of reducing hysterectomies in patients refractory to conventional medical treatment and who meet strict inclusion and exclusion criteria. Our models demonstrate that when using the levonorgestrel intrauterine system as an alternative to hysterectomy in selected patients there is a reduction in costs.

Ulipristal acetate compared to levonorgestrel emergency contraception among current oral contraceptive users: a cost-effectiveness analysis.

OBJECTIVE: To estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy. METHODS: We built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8-14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs. RESULTS: We found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy. CONCLUSION: Our models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA. IMPLICATIONS: Ulipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

Assessment of endocrine disruptor effects of levonorgestrel and its photoproducts: Environmental implications of released fractions after their photocatalytic removal.

The presence of levonorgestrel (LNG) in water bodies via direct discharge and human excretion has been reported worldwide, but its effects on the reproduction of aquatic species and humans are still unknown. Owing to its recalcitrant properties, LNG is not completely removed during wastewater treatment plants, and many species may be exposed to low traces of this compound from discharged effluents. Thus, in this study, a photocatalytic process for removing LNG along with screening of endocrine disruptor effects for risk assessment was applied. Although the removal rate of LNG by ultraviolet C (UV-C) radiation was >90%, reproductive toxicity testing using the BeWo cell line exposed to LNG and its degraded fraction showed the reduced production of basal human chorionic gonadotropin hormone (ß-hCG) by more than 73%, from 8.90 mIU mL-1 to <2.39 mIU mL-1, with both LNG and the degraded fraction. ß-hCG hormone has been implicated in the viability of trophoblastic cells during the first trimester of pregnancy; therefore, degraded fractions and waterborne LNG may affect reproduction in some aquatic species and humans with low level of exposure.

Comparing options for women seeking permanent contraception in high-resource countries: a protocol for a systematic review.

BACKGROUND: For women seeking permanent contraception, there are a variety of options available including surgical techniques such as tubal ligation or bilateral salpingectomy, in-clinic procedures such as hysteroscopic techniques using micro-inserts, or the levonorgestrel-releasing intrauterine contraceptive. Despite the various methods available for women who are seeking permanent contraception, there is not a review or decision-making tool that systematically brings together outcomes related to effectiveness, tolerability, adverse effects, non-contraceptive benefits, recovery, or accessibility: all of which are important for shared decision-making between patients and health care providers. METHODS: We registered our protocol [on Prospero: CRD42016038254] following PRISMA guidelines. A search strategy was created in collaboration with a librarian, and three databases (EMBASE, PubMed, Web of Science) will be searched along with secondary screening of relevant articles. A third reviewer will adjudicate any discrepancies. Data will be extracted independently according to population, intervention, comparison, outcomes (PICOS); length of follow-up; and funding. Articles will be assessed for bias using the Newcastle-Ottawa Scale and the Cochrane Collaboration tool. If appropriate, a network meta-analysis will be conducted to rank and analyze each method according to each objective. If heterogeneity between studies is too high or it is not possible to conduct a network meta-analysis, a narrative analysis of the study results will be provided. DISCUSSION: Clinicians and their patients seeking permanent contraception have several options, yet we were unable to find a systematic review or decision support tool helping to facilitate shared decision-making. This systematic review can inform patients, providers, and health policy decision-makers about which options of permanent contraception will meet different reproductive goals according to various outcomes, which can lead to better health, social, economic, and mental well-being for reproductive age women. This can also aid our understanding of resulting costs to the health care system. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016038254.

Seeking emergency contraception in the United States: A review of access and barriers.

Federal regulations governing access to levonorgestrel (LNG) emergency contraception (EC) have evolved since its introduction in the 1990s. LNG EC was initially available by prescription only, but is now available over-the-counter to consumers of all ages. Nonetheless, consumers seeking EC in their communities may face ongoing barriers to access, including low stock and inaccurate information provided by pharmacy staff. We conducted a review of LNG EC secret shopper studies to describe changes in EC access and barriers over time. EC access was compared across all applicable studies, which were published during 2003-2016. When possible, reasons for EC unavailability, helpfulness of pharmacy staff when EC was not in stock, and accuracy of EC information provided by pharmacy staff were described. Overall, access to EC appeared to be improving. However, EC was unavailable during 31 percent of encounters. Pharmacy staff attributed this to "low demand" (30 percent) or EC being "out of stock" (21 percent). Personal objections (9 percent) and store policy (10 percent) were also cited in studies from earlier years. Inaccurate information provided by pharmacy staff persists regarding federal EC regulations, mechanism of action, and drug administration. Pharmacy staff should remain informed about EC and its regulations in order to reduce remaining access barriers.

Assessment of biomarkers in women with endometriosis-associated pain using the ENG contraceptive implant or the 52 mg LNG-IUS: a non-inferiority randomised clinical trial.

OBJECTIVE: The aim of the study was to assess the serum levels of the following biomarkers in women with endometriosis-associated pelvic pain before and after six months of using the etonogestrel (ENG) contraceptive implant or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS): cancer antigen (CA)-125, cluster of differentiation (CD) 23 and endometrial nerve fibre density. METHODS: The study was conducted at the Department of Obstetrics and Gynaecology, University of Campinas Medical School, Brazil. A total of 103 women with endometriosis-associated pain diagnosed by surgery, transvaginal ultrasound and/or magnetic resonance imaging were included. Endometrial nerve fibre density and serum levels of CA-125 and soluble CD23 were assessed before and after six months of using the allocated method and were correlated to 10 cm visual analogue scale (VAS) scores for non-cyclical pelvic pain and dysmenorrhoea. RESULTS: Both contraceptive methods significantly reduced concentrations of serum soluble CD23 and endometrial nerve fibre density (p < .001); however, CA-125 was significantly reduced only among users of the ENG implant (p < .05). No correlation was observed between reduction of biomarkers and improvement of VAS pain and dysmenorrhoea scores. No differences were observed between the ENG implant and the LNG-IUS. CONCLUSION: Both progestin-only contraceptives significantly reduced two out of the three biomarkers evaluated. These two biomarkers could, therefore, be used as surrogate markers to follow up medical treatment of endometriosis-associated pain.

Experiences with the levonorgestrel-releasing intrauterine system in Kenya: qualitative interviews with users and their partners.

OBJECTIVES: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an underused contraceptive method in sub-Saharan Africa. A recent market assessment in Kenya found that if a more affordable version of the method were available it may increase demand and uptake of the method. We therefore aimed to examine attitudes and perceptions around the LNG-IUS and experiences of method use, including exploring attributes such as bleeding changes, contraceptive-related amenorrhoea and perceived non-contraceptive benefits. METHODS: Qualitative interviews were conducted among 29 women who were current or recent users of the LNG-IUS, and among a subset (n = 9) of their husbands/partners. RESULTS: Our findings indicate that women's main reason for choosing the LNG-IUS for contraception was their perception that the method had fewer side effects compared with other contraceptive methods. Women had favourable attitudes towards using the LNG-IUS. Husbands were also very positive about their partner's use of the method. CONCLUSION: Understanding the motivations and experiences of early adopters of the LNG-IUS can help inform the development of demand creation and communication strategies to influence uptake and continuation of the LNG-IUS both in Kenya and perhaps more broadly. Communication efforts that emphasise the positive attributes of the LNG-IUS could help promote wider use of the method, especially if new, more affordable product(s) become available.