Gongning granules plus low dose hormone in pubertal functional uterine hemorrhage: Analysis of hemodynamics and clinical efficacy.

To evaluate the clinical effect of Gongning granules combined with low-dose hormone therapy in pubertal dysfunctional uterine bleeding (PDUB) and its effect on uterine hemodynamics. A total of 164 PDUB patients who were treated in the gynecological outpatient department of our hospital from December 2018 to June 2020 were randomized into study group and control group, with 82 cases each. The control group received estrogen progesterone, and the study group received Gongning granules plus. The clinical efficacy and uterine arterial hemodynamics were compared. The clinical efficacy of the study group was superior to the control group (91.46% vs. 76.83%, P<0.05). The study group yielded shorter bleeding control time and complete hemostasis time than the control group (P<0.05). The amount of menstrual bleeding and duration of menstruation in both groups decreased significantly with time and the study group was significantly lower than the control group (all P<0.05). The endometrial thickness in the study group was significantly thinner than the control group, and the maximum follicle diameter was significantly longer than that in the control group (all P<0.05). After treatment, the platelet count, hemoglobin level of peripheral blood, uterine arterial blood flow and mean flow velocity in the study group were significantly higher than those in the control group (all P<0.05). In addition, there was no significant difference in adverse drug reaction (ADR) between the two groups (P>0.05). In PDUB patients, Gongning granules plus low-dose hormone can significantly relieve bleeding symptoms, improve hemodynamic status and has good safety.

The effectiveness of desogestrel for endometrial protection in women with abnormal uterine bleeding-ovulatory dysfunction: a non-inferiority randomized controlled trial.

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference - 9.1-24.4%, non-inferiority limit of - 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Implants for HIV prevention in young women: Provider perceptions and lessons learned from contraceptive implant provision.

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

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.

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.

Overall and bleeding-related discontinuation rates of a new oral contraceptive containing 4 mg drospirenone only in a 24/4 regimen and comparison to 0.075 mg desogestrel.

OBJECTIVES: Progestin-only pills do not increase the risk of venous thromboembolism, stroke, and myocardial infarction but are associated with poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) to improve bleeding patterns and tolerability and reduce discontinuation rates has been introduced into the market. The present study aims to describe the improvement in the acceptability of this DRSP-only pill, e.g. regarding the bleeding profile and the reduction in discontinuation rates due to unacceptable bleeding compared to desogestrel (DSG). STUDY DESIGN: Double-blind, double-dummy prospective phase III study in healthy women aged 18-45 years evaluating a total of 858 women with 6691 DRSP and 332 women with 2487 DSG treatment cycles. RESULTS: Overall, 82 (9.6%) women in the DRSP group and 44 (13.3%) women in the DSG group experienced treatment-emergent adverse events (TEAEs) leading to premature termination of the trial meaning that 32% more women in the DRSP group finished the trial in comparison to the DSG group (based on the AUC of Kaplan-Meier's curves). Discontinuation rates due to abnormal bleeding were 3.7% for DRSP and 7.3% for DSG users. This is a 55.7% lower discontinuation rate in the DRSP group compared to the DSG group. CONCLUSIONS: This report describes the improvement in acceptability and bleeding profile of women using the new DRSP-only oral contraceptive compared to DSG, providing a better quality of life and adherence to the contraceptive method as demonstrated by lower discontinuation rates of women using the estrogen-free DRSP-only pill.

A clinical observational study on the efficacy of subcutaneous etonogestrel implants for adenomyosis in 20 patients.

Objective: To evaluate the efficacy of subcutaneous etonogestrel implants for adenomyosis.Methods: We conducted a clinical observational study of 20 patients suffering from adenomyosis treated with subcutaneous etonogestrel implants from August 2015 to July 2017 and followed up for 36 months. We evaluated the efficacy of subcutaneous etonogestrel implants primarily based on the following indicators: the pictorial blood loss assessment chart (PBAC) for menstrual blood volume, changes in bleeding patterns, the visual analog scale (VAS) pain score for dysmenorrhea, uterine volume, serum cancer antigen 125 (CA125) levels, hemoglobin levels and side effects.Results: During the 3 years of follow-up, subcutaneous etonogestrel implants were removed from six patients, among whom one was diagnosed with endometrial cancer, four had an increased menstrual blood volume, and one entered menopause. In total, 14 patients were treated with subcutaneous etonogestrel implants for 3 years. Among these patients, the number of patients with heavy menstrual bleeding and high PBAC and VAS scores and serum CA125 levels was significantly decreased after implantation compared with that before implantation. In the eight patients with anemia, hemoglobin levels increased gradually. However, the uterine volumes did not significantly change. Bleeding patterns were changed but were tolerable.Conclusion: Subcutaneous etonogestrel implants represent a new option for the clinical treatment of adenomyosis for patients who refuse surgery.

Real-world cost-effectiveness of etonogestrel implants compared to long-term and short term reversible contraceptive methods in France.

BACKGROUND: To estimate the cost-effectiveness (CE) of etonogestrel implants compared to other long-term and short-term reversible contraceptive methods available in France. RESEARCH DESIGN AND METHODS: A 6-year Markov model compared effectiveness between the implant and six other contraceptive methods in sexually active, not-pregnancy-seeking French females of reproductive age. Contraception efficacy, switch rates and outcomes were based on French current medical practice. Incremental CE ratios (ICERs) were calculated as incremental cost per unintended pregnancy (UP) avoided. Efficiency frontier was plotted to identify cost-effective methods. Uncertainty was explored through sensitivity analyses. RESULTS: The implant was on the efficiency frontier along with combined oral contraceptive pill (COC) and copper IUD. Implant avoids between 0.75% and 3.53% additional UP per person-year compared to copper IUD and second generation COC, respectively, with an ICER of €2,221 per UP avoided compared to copper IUD. For the 240,000 French women currently using the implant, up to 8,475 UPs and up to 1,992 abortions may be prevented annually. CONCLUSION: With more unintended pregnancies avoided and comparable costs to copper IUD, the implant is a cost-effective option among long-term and short-term reversible contraceptive methods.

In vivo effects of AZD4547, a novel fibroblast growth factor receptor inhibitor, in a mouse model of endometriosis.

Endometriosis is a chronic disease, characterized by the growth of endometrial-like cells outside the uterine cavity. Due to its complex pathophysiology, a totally resolving cure is yet to be found. The aim of this study was to compare the therapeutic efficacy of AZD4547, a novel fibroblast growth factor receptor inhibitor (FGFRI), with a well-characterized progestin, etonogestrel (ENG) using a validated in vivo mouse model of endometriosis. Endometriosis was induced by transplanting uterine fragments from donor mice in proestrus into the peritoneal cavity of recipient mice, which then developed into cyst-like lesions. AZD4547 and ENG were administered systemically either from the day of endometriosis induction or 2-weeks post-surgery. After 20 days of treatment, the lesions were harvested; their size and weight were measured and analyzed histologically or by qRT-PCR. Stage of estrous cycle was monitored throughout. Compared to vehicle, AZD4547 (25 mg/kg) was most effective in counteracting lesion growth when treating from day of surgery and 2 weeks after; ENG (0.8 mg/kg) was similarly effective in reducing lesion growth but only when administered from day of surgery. Each downregulated FGFR gene expression (p < 0.05). AZD4547 at all doses and ENG (0.008 mg/kg) caused no disturbance to the estrous cycle. ENG at 0.08 and 0.8 mg/kg was associated with partial or complete estrous cycle disruption and hyperemia of the uteri. AZD4547 and ENG both attenuated endometriotic lesion size, but only AZD4547 did not disrupt the estrous cycle, suggesting that targeting of FGFR is worthy of further investigation as a novel treatment for endometriosis.

Implante subdérmico de etonogestrel na prevenção da gravidez não planejada por mulheres adultas em idade reprodutiva entre 18 e 49 anos / Subdermal etonogestrel implant for prevention of unplanned pregnancy by adult women in reproductive age between 18 and 49 years old

CONTEXTO: A gravidez não intencional se caracteriza como um problema de saúde pública e abrange de forma ampla a gravidez não planejada e a gravidez não desejada. A taxa global de gravidez não intencional tem apresentado declínio nos últimos anos em todo o mundo. No Brasil, estima-se que mais da metade das gravidezes podem ser consideradas como não planejadas. A contracepção é a prevenção intencional da gravidez e é capaz de reduzir a mortalidade materna e neonatal. Contudo, muitas mulheres que desejam evitar a gravidez não utilizam contraceptivos, usam de forma inconsistente ou incorreto. O aconselhamento sobre os métodos contraceptivos e a educação sexual são estratégias que auxiliam a evitar a gravidez não intencional. O SUS disponibiliza uma variedade de métodos contraceptivos, reversíveis ou permanentes, além de ações e políticas voltadas para a saúde sexual e o planejamento familiar. TECNOLOGIA: Implante contraceptivo subdérmico de etonogestrel (IMPLANON NXT®). PERGUNTA: O uso do implante subdérmico de etonogestrel por mulheres adultas em idade reprodutiva é eficaz na prevenção de gravidez não planejada, custo-efetivo, e apresenta maior adesão ou satisfação comparadas aos contraceptivos oferecidos pelo SUS? EVIDÊNCIAS CLÍNICAS: O conjunto da evidência clínica de eficácia, adesão e segurança do implante subdérmico de etonogestrel para mulheres adultas em idade reprodutiva, maiores de 18 anos, é proveniente de três ensaios clínicos e cinco estudos de coorte, que foram avaliados como de baixa a moderada qualidade metodológica. O implante subdérmico de etonogestrel demonstrou maior eficácia contraceptiva e maior taxa de continuação de uso no decorrer de três anos frente ao DIU de cobre, embora as suas taxas de eficácia e continuação de uso também sejam elevadas. Ao final de um ano, o implante de etonogestrel demonstrou maior taxa de satisfação do que o DIU de cobre, embora a sua taxa de satisfação também seja elevada. De um modo geral, alterações no peso corporal e no índice de massa corporal foram maiores entre as usuárias do implante de etonogestrel e do injetável trimestral de acetato de medroxiprogesterona quando comparado ao DIU de cobre, embora para alguns autores estes achados não possuem significância clínica. O distúrbio do sangramento está entre as principais causas para a descontinuação de uso do implante subdérmico de etonogestrel, seguido por ganho de peso, e a expulsão do dispositivo e o distúrbio do sangramento estão entre as principais causas para a descontinuação de uso do DIU de cobre. Não foram encontrados estudos que preenchessem os critérios de inclusão da pergunta de pesquisa e que comparassem o implante subdérmico de etonogestrel frente aos demais contraceptivos reversíveis disponíveis no SUS. AVALIAÇÃO ECONÔMICA: Análise de custo-efetividade, com horizonte temporal de três anos, na perspectiva do SUS, comparou o implante subdérmico de etonogestrel frente ao DIU de cobre, aos injetáveis mensal e trimestral, à pílula e à minipílula disponível no SUS. Frente ao DIU de cobre, o implante resultou em uma razão de custo-efetividade incremental (RCEI) de R$ 6.356,07 por gravidez não planejada. O implante de etonogestrel foi dominante frente aos demais contraceptivos disponíveis no SUS. Em suas análises de sensibilidade, os resultados se mantiveram e o custo do implante de etonogestrel se destacou entre as variáveis que mais impactam no modelo. Foram identificadas algumas incertezas nos parâmetros, que podem estar impactando consideravelmente nos resultados, desfavorecendo os comparadores. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Na perspectiva da população por demanda aferida, o demandante estimou um incremento de R$5.924.413 no primeiro ano, para uma população de 3.869.561, e uma economia de R$4.426.700 no quinto ano, para uma população de 3.911.195. Ao final de cinco anos, uma economia de R$ 6.780.627,00. Na perspectiva epidemiológica da população, foi estimado um incremento de R$40.890.518 no primeiro ano, para uma população de 26.707.854, e uma economia de R$30.553.251, para uma população de 26.995.213. Ao final de cinco anos, uma economia de R$ 46.800.143,00. Para se chegar a estes valores, o demandante contabilizou os gastos com os métodos contraceptivos e com a gravidez não planejada, e subtraiu os valores entre cenários sem e com o implante subdérmico, considerando uma possível incorporação. As incertezas descritas podem estar subestimando o impacto orçamentário incremental, favorecendo a intervenção. Em cenários alternativos, desconsiderando os gastos com gravidez não planejada, estes valores podem variar de R$ 183.017.788,83 a R$ 1.263.195.588,17 ao final de cinco anos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foi detectado um anel vaginal de etinilestradiol associado com segestrone, indicado para mulheres adultas e em idade reprodutiva. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 93ª Reunião Ordinária, realizada no dia 09 de dezembro de 2020, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar desfavorável à incorporação do implante subdérmico de etonogestrel para prevenção da gravidez não planejada por mulheres adultas em idade reprodutiva entre 18 e 49 anos no SUS. Considerou-se que as evidências são favoráveis ao implante de etonogestrel, mas que a ampla população proposta pelo demandante juntamente com o impacto orçamentário estimado dificultaria a incorporação desta tecnologia no SUS. ANÁLISE DE IMPACTO ORÇAMENTÁRIO DE ACORDO COM O SEGMENTO POPULACIONAL DELINEADO PELA SVS E PELA SAPS: A Secretaria de Vigilância em Saúde (SVS) e a Secretaria de Atenção Primária à Saúde (SAPS) propuseram, na 92ª Reunião da Conitec, delinear um segmento da população que mais se beneficiaria com a possível incorporação do implante subdérmico de etonogestrel. De acordo com o levantamento, esta população seria compreendida por: mulheres usuárias de drogas; mulheres em situação de rua; mulheres vivendo com HIV; mulheres em idade fértil e em uso de talidomida; mulheres privadas de liberdade; mulheres cis trabalhadoras do sexo e mulheres em idade fértil em tratamento com tuberculose e em uso de aminoglicosídeos. Desta forma, o quantitativo apresentado desta população foi de 356.381 indivíduos. Desconsiderando os custos da gravidez não planejada, o percentual de uso do implante subdérmico de etonogestrel no cenário base e atualizando os custos de alguns métodos contraceptivos, o novo cenário apresentou um incremento de R$ 1.747.690,30 no primeiro ano e de R$ 5.580.520,95 no quinto ano. Ao final de cinco anos, o impacto orçamentário incremental de uma possível incorporação do implante subdérmico de etonogestrel no SUS para o segmento populacional proposto foi de R$ 17.710.388,26. CONSULTA PÚBLICA: A consulta pública (CP) nº 01/2021 foi realizada entre os dias 12/01/2021 a 01/02/2021. Foram recebidas 191 contribuições, sendo 72 pelo formulário para contribuições técnico-científico e 119 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. De um modo geral, os participantes da CP discordaram da recomendação preliminar da Conitec. As contribuições versaram sobre a eficácia, a efetividade e a segurança do implante de etonogestrel, além dassuas altastaxas de continuação e satisfação das usuárias. O desejo de se ampliar os contraceptivos disponíveis no SUS e de favorecer o planejamento familiar também foi mencionado. Outro ponto muito destacado foi acerca do benefício do implante hormonal para um grupo mais vulnerável da população. A redução no número de gravidez não planejada também foi amplamente considerada nas participações, e os seus custos foram atribuídos de forma intercalada entre indivíduo, SUS e sociedade. Por fim, conclui-se que as contribuições recebidas na CP sobre o implante subdérmico de etonogestrel para prevenção da gravidez não planejada por mulheres adultas em idade reprodutiva, entre 18 e 49 anos, foram importantes e evidenciaram o desejo de que este método pudesse ser disponibilizado a um subgrupo mais vulnerável da população. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário presentes na 95ª Reunião Ordinária da Conitec, no dia 03 de março de 2021, deliberaram, por maioria simples, sem nenhuma declaração de conflito de interesses, recomendar a incorporação, condicionada à criação de programa específico, do implante subdérmico de etonogestrel na prevenção da gravidez não planejada por mulheres em idade fértil: em situação de rua; com HIV/AIDS e em uso de dolutegravir; em uso de talidomida; privadas de liberdade; cis trabalhadoras do sexo; e em tratamento de tuberculose, usando aminoglicosídeos. Considerou-se que as evidências são favoráveis ao implante de etonogestrel e que o segmento da população delineada pela SVS e pela SAPS seria a que mais se beneficiaria do implante subdérmico de etonogestrel. Foi assinado o Registro de Deliberação nº 594/2021. DECISÃO: Incorporar o implante subdérmico de etonogestrel, condicionada à criação de programa específico, na prevenção da gravidez não planejada para mulheres em idade fértil: em situação de rua; com HIV/AIDS em uso de dolutegravir; em uso de talidomida; privadas de liberdade; trabalhadoras do sexo; e em tratamento de tuberculose em uso de aminoglicosídeos, no âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria nº 13, publicada no Diário Oficial da União nº 74, seção 1, página 235, em 22 de abril de 2021.

Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception.

To compare etonogestrel pharmacokinetic and pharmacodynamic outcomes by both self-reported race/ethnicity and genetically determined ancestry among contraceptive implant users. We conducted a secondary analysis of our parent pharmacogenomic study of 350 implant users. We genotyped these reproductive-aged (18-45 years) women for 88 ancestry-informative single nucleotide polymorphisms. We then assigned each participant a proportion value for African (AFR), European (EUR), and Indigenous American (AMR) ancestry based on reference population data. We correlated genetic ancestry with self-reported race/ethnicity and utilized genetic ancestry proportion values as variables for previously performed association analyses with serum etonogestrel concentrations and progestin-related side effects (e.g., bothersome bleeding and subjective weight gain). We successfully estimated genetically determined ancestry for 332 participants. EUR, AFR, and AMR ancestry were each highly correlated with self-reported White/non-Hispanic race (r = 0.64, p = 4.14 × 10-40 ), Black/African American race (r = 0.88, p = 1.36 × 10-107 ), and Hispanic/Latina ethnicity (r = 0.68, p = 4.03 × 10-47 ), respectively. Neither genetically determined ancestry nor self-reported race/ethnicity were significantly associated with serum etonogestrel concentrations. AFR ancestry and self-reported Black race had similar associations with reporting monthly periods (odds ratio [OR] 2.18, p = 0.09 vs. OR 2.22, p = 0.02) and having received treatment for bothersome bleeding (OR 5.19, p = 0.005 vs. OR 4.73, p = 2.0 × 10-4 ). In multivariable logistic regression for subjective weight gain, AMR ancestry dropped out of the model in preference for self-reported Hispanic/Latina ethnicity. We found no new associations between genetically determined ancestry and contraceptive implant pharmacodynamics/pharmacokinetics. Self-reported race/ethnicity were strong surrogates for genetically determined ancestry among this population of contraceptive implant users. Our data suggest that self-reported race/ethnicity, capturing societal and cultural aspects, remain important to the investigation of progestin-related side effects.

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.

Impact of the menstrual cycle and ethinyl estradiol/etonogestrel contraceptive vaginal ring on granulysin and other mucosal immune mediators.

PROBLEM: Changes in sex hormones during the menstrual cycle and contraceptive vaginal ring (CVR) use influence immunity within the female genital tract, but the magnitude of these effects and their anatomical location are unclear. METHOD OF STUDY: In a prospective study, 29 women were assessed at three-time points: follicular phase, luteal phase, and one month after initiation of the ethinyl estradiol/etonogestrel CVR (NuvaRing®, Merck). We performed microarrays on endocervical cytobrushes and measured immune mediators in cervicovaginal fluid, adjusting for bacterial vaginosis and the presence of blood. We compared these results to public gene expression data from the fallopian tubes, endometrium, endo- and ectocervix, and vagina. RESULTS: Immune-related gene expression in the endocervix and immune mediators in cervicovaginal fluid increased during CVR use versus both menstrual phases, and in the follicular versus luteal phase. The antimicrobial protein granulysin was high during CVR use, intermediate in the follicular phase, and nearly absent from the luteal phase. Re-analysis of public gene expression data confirmed increased immune-related gene expression in the endocervix during the follicular phase. However, in the fallopian tube, endometrium, and vagina, the follicular phase showed immunosuppression. CONCLUSIONS: Immune-related genes in the cervicovaginal tract were highest during CVR use, intermediate in the follicular phase, and lowest in the luteal phase. Granulysin is a potential biomarker of menstrual phase: Frequently detected in follicular samples, but rare in luteal. Lastly, immunological differences between the follicular and luteal phases vary throughout the female genital tract.

Effects of Etonogestrel implants on pelvic pain and menstrual flow in women suffering from adenomyosis or endometriosis: Results from a prospective, observational study.

ABSTRACT: Adenomyosis and endometriosis are common causes of pelvic pain in women of reproductive age. Furthermore, adenomyosis is a major cause of menorrhagia. This study aimed to evaluate the effects of Etonogestrel implants on pelvic pain and menstrual flow in women requiring long-acting reversible contraception and suffering from adenomyosis or endometriosis.One hundred women with adenomyosis or endometriosis and asking for contraception with Etonogestrel implants were enrolled in this study and were followed-up for 24 months. Patients were interviewed on pelvic pain by visual analog scale (VAS) pain score, menstrual flow by the number of sanitary napkins, menstrual bleeding pattern, weight gain, breast pain, and any other treatment side effects.Seventy four patients who were treated with Etonogestrel implants completed the 24-month follow-up in which we found a significant decrease in pelvic pain VAS scores comparing baseline scores to 6, 12, and 24 months (baseline: 6.39 ±â€Š2.35 to 24-month: 0.17 ±â€Š0.69, P < 0.05). The menstrual volume decreased significantly compared with that at baseline ((40.69 ±â€Š30.92) %, P < 0.05). However, vaginal bleeding, amenorrhea, weight gain, and acne occurred after treatment in some patients.Etonogestrel implants were effective in reducing pelvic pain and menstrual flow of adenomyosis or endometriosis.

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

PURPOSE: To explore how diet and exercise habits associate with serum etonogestrel concentrations among contraceptive implant users. MATERIALS AND METHODS: We conducted a secondary analysis of healthy, reproductive-age women using etonogestrel implants. This study was registered on ClinicalTrials.gov, NCT03092037. We assessed diet and exercise habits with two validated surveys: Healthy Eating Vital Signs and the Stanford Brief Activity Survey. Participants previously had their serum etonogestrel concentrations measured using a validated liquid-chromatography mass-spectrometry assay. We then used linear modelling to test for associations between survey responses and serum etonogestrel concentrations. RESULTS: Among 129 participants, diet and exercise habits had no significant associations with serum etonogestrel concentrations (p = 0.22-0.72), with inconsistent effects found for increased caloric intake and sedentary lifestyle. CONCLUSION: This exploratory study found no significant effect of diet or exercise habits on steady-state pharmacokinetics among contraceptive implant users. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03092037.

A Pilot Study to Understand the Adolescent Pain Experience During Contraceptive Implant Insertion.

PURPOSE: In adolescents, concrete thinking may present as avoidance of an immediate, painful or uncomfortable experience despite long-term benefits, which may affect contraceptive choice. In this pilot study, we sought to better understand the pain that adolescents and young adults experience during contraceptive implant insertion. MATERIALS AND METHODS: In this cohort study, we surveyed 30 adolescents and young adults at their implant insertion visit about pre-procedure anxiety and pain experienced during lidocaine injection and Nexplanon™ placement. RESULTS: The average pre-procedure anxiety (Visual Analog Scale-Anxiety) score was 40 ± 29 mm. The average pain reported during lidocaine injection was 19 ± 21 mm and 6 ± 11 mm for implant insertion. Pre-procedure anxiety was not associated with pain during lidocaine injection (P = .61) or implant placement (P = .85). CONCLUSION: Pain scores were low with both lidocaine injection and implant placement. Pre-procedure anxiety did not predict pain during lidocaine or implant placement. Patients considering an implant should be reassured by these data.

Attendance of an Initial Follow-up Visit after Long-Acting Reversible Contraception Insertion and Method Continuation Among Adolescents and Young Adults: A Retrospective Study.

STUDY OBJECTIVE: To assess attendance of an initial follow-up visit after long-acting reversible contraception (LARC) insertion and whether follow-up was associated with a higher likelihood of method continuation in adolescents and young adults (AYAs). DESIGN: Retrospective chart review including patients receiving LARC (etonogestrel 68 mg implant, levonorgestrel 52 mg intrauterine device, or copper intrauterine device) between January 1, 2014, and August 1, 2017. SETTING: An urban adolescent center providing primary care and reproductive health services. PARTICIPANTS: A total of 331 patients 13-28 years of age. INTERVENTIONS: Attendance of a follow-up visit 4-8 weeks after LARC insertion. MAIN OUTCOME MEASURES: Follow-up was defined as visits addressing LARC method or routine physical examinations in the adolescent center or affiliated school-based health clinics. Continuation and discontinuation were defined as documented presence or removal, respectively, of device at various time points. Descriptive analyses, χ2 test, Fisher exact test, t test, and survival analysis were used. RESULTS: Approximately one-third (29.3%) of the patients attended a follow-up visit. Follow-up was associated with a higher likelihood of LARC removal in the first year (hazard ratio [HR] = 2.10, 95% confidence interval [CI] 1.33-3.32). At 500 days post-insertion and beyond, there was no difference in LARC continuation between AYAs who followed-up and those who did not (HR = 1.07, 95% CI 0.67-1.71). CONCLUSION: Few AYAs attended an initial follow-up visit after LARC placement. These visits were associated with an increased likelihood of LARC removal in the first year; however, this association was not observed long term. More information is needed to determine how to approach follow-up this population.