Effect of progestin on thyroid function in female Wistar rats.

Introduction: To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Methods: Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Results: Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Discussion: Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.

Offering extended use of the contraceptive implant via an implementation science framework: a qualitative study of clinicians' perceived barriers and facilitators.

BACKGROUND: The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years. However, studies that suggest efficacy up to 5 years. There is little information on the prevalence of extended use and the factors that influence clinicians in offering extended use. We investigated clinician perspectives on the barriers and facilitators to offering extended use of the contraceptive implant. METHODS: Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured qualitative interviews. Participants were recruited from a nationwide survey study of reproductive health clinicians on their knowledge and perspective of extended use of the contraceptive implant. To optimize the diversity of perspectives, we purposefully sampled participants from this study. We used content analysis and consensual qualitative research methods to inform our coding and data analysis. Themes arose deductively and inductively. RESULTS: We interviewed 20 clinicians including advance practice clinicians, family medicine physicians, obstetrician/gynecologist and complex family planning sub-specialists. Themes regarding barriers and facilitators to extended use of the contraceptive implant emerged. Barriers included the FDA approval for 3 years and clinician concern about liability in the context of off-label use of the contraceptive implant. Educational materials and a champion of extended use were facilitators. CONCLUSIONS: There is opportunity to expand access to extended use of the contraceptive implant by developing educational materials for clinicians and patients, identifying a champion of extended use, and providing information on extended use prior to replacement appointments at 3 years.

Nexplanonectomy-the surgical removal of an embolized implanted contraceptive device: a case report and review of the literature.

BACKGROUND: Nexplanon implants are a common hormonal contraceptive modality. Though rare, these devices can embolize into the injured wall of the basilic vein, through the right heart, and finally wedge itself into a pulmonary artery. With adherence to the arterial wall over time, it becomes less amenable to endovascular retrieval. Patients may present with symptoms mimicking a pulmonary embolism, or without any symptoms at all. In asymptomatic cases, endovascular retrieval and/or surgery is required when patients wish to begin having children prior to biological inactivity. The current literature showed as little as nine case reports detailing lung tissue removal in the aim of reversing a patient's implanted contraceptive device. CASE PRESENTATION: A 22-year-old asymptomatic active-duty Caucasian female presented for elective outpatient Nexplanon removal. The suspicion of possible implant migration arose when it was discovered to be non-palpable in her left arm. After plain film x-rays failed to localize the implant, a chest x-ray and follow-up Computed Tomography (CT) scan revealed that the Nexplanon had migrated to a distal branch of the left pulmonary artery. Due to the patient's strong desires to begin having children, the decision was made for removal. Initial endovascular retrieval failed due to Nexplanon encapsulation within the arterial wall. Ultimately, the patient underwent a left video-assisted thoracoscopic surgery (VATS) for exploration and left lower lobe basilar S7-9 segmentectomy, which successfully removed the Nexplanon. CONCLUSIONS: Implanted contraceptive devices can rarely result in migration to the pulmonary vasculature. These radiopaque devices are detectable on imaging studies if patients and clinicians are unable to palpate them. An endovascular approach should be considered first to spare lung tissue and avoid chest-wall incisions, but can be complicated by encapsulation and adherence to adjacent tissue. A VATS procedure with single-lung ventilation via a double-lumen endotracheal tube allows surgeons to safely operate on an immobilized lung while anesthesiologists facilitate single-lung ventilation. This patient's case details the uncommon phenomenon of Nexplanon migration, and the exceedingly rare treatment resolution of lung resection to remove an embolized device.

Migration of etonogestrel subcutaneous contraceptive implants: systematic review and recommendations for practice.

INTRODUCTION: Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. PURPOSE: To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature. METHODS: A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded. RESULTS: Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels (n = 74), in non-pulmonary blood vessels (n = 16) and extravascular (n = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration. CONCLUSION: Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.

This systematic review documents and characterises 148 cases of vascular and extravascular etonogestrel contraceptive implant migration. Healthcare professionals must be aware of this rare but serious complication and be adequately trained to insert and remove contraceptive implants.

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

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

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

AIMS: The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. METHODS: Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. RESULTS: For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). CONCLUSION: The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

Pilot study of a novel, alternative subdermal scapular insertion site for the etonogestrel contraceptive implant.

OBJECTIVES: To assess the pharmacokinetics and pharmacodynamics of the etonogestrel (ENG) contraceptive implant when inserted at an alternative scapular site. STUDY DESIGN: We conducted a pilot study of healthy, reproductive-age females who underwent subdermal insertion of an ENG implant over the inferior edge of the nondominant scapula (scapular insertion). We measured serum ENG levels over 1 year at nine time points. Participants completed questionnaires on insertion site and bleeding side effects. We collected photographs and video recordings of insertion and removal techniques. RESULTS: We enrolled five participants (as prespecified), their median age was 26.0 years (range: 19.6-30.3), and median body mass index was 25.0 kg/m2 (range: 22.0-28.0). All serum ENG concentrations remained >90 pg/mL and were within the range of published data for arm insertion of ENG implant at all time points. The mean serum ENG level was 511.7 pg/mL (±168.2) at 1 week and 136.6 pg/mL (±21.8) at 12 months. During the first week after insertion, four of five participants noted insertion site pain with a median pain score of 2 (range 1-3), but all noted resolution by week two. Participants reported variable bleeding patterns consistent with standard ENG implant placement. At the end of the study, all participants reported satisfaction with the implant and would recommend scapular insertion to a friend. CONCLUSIONS: Scapular insertion of the ENG contraceptive implant has similar pharmacokinetics to arm insertion over 1 year of use. This novel, alternative site was well tolerated and demonstrated similar bleeding side effects to standard arm insertion. IMPLICATIONS: Subdermal scapular insertion of the etonogestrel contraceptive implant demonstrated similar pharmacokinetics to arm insertion over 1 year of use. Our pilot data support scapular insertion as an alternative site for ENG contraceptive implants, which could be beneficial for certain patient populations.

Effectiveness and continuation rates of the etonogestrel-subdermal contraceptive implant versus short-acting contraceptive methods offered at no cost in Campinas, Brazil.

OBJECTIVES: To compare the efficacy, reasons for discontinuation and continuation rates of the etonogestrel (ENG)-subdermal contraceptive implant when offered at no cost, and the basis of free choice versus short-acting reversible contraceptive (SARC) methods including combined oral contraceptives (COCs), once-a-month injectables, vaginal ring, and patch. METHODS: We conducted a prospective study at the University of Campinas, Brazil, involving women aged 18 to 40 years. They were counseled on various contraceptive methods before entering the study and followed up every 3 months for up to 24 months. Satisfaction was assessed using a Likert scale. Survival rates were estimated using the Kaplan-Meier test, and curve comparisons were performed using the log-rank test. RESULTS: We enrolled 609 women including 358/609 women (58.8%) who chose the ENG-implant and 251/609 (41.2%) who chose SARC methods. Contraceptive failure and all other reasons for discontinuation were significantly higher in SARC users compared to the ENG-implant users (P < 0.001 and P = 0.002, respectively). The continuation rate was higher among ENG-implant users (89.9% and 75.4%) compared to SARC methods users (27.2% and 15.9%) up to 1 and 2 years after study initiation, respectively. Satisfaction was high in both groups (>82%). CONCLUSIONS: The ENG-implant showed higher contraceptive effectiveness and higher continuation rates than SARC methods up to 2 years after study initiation. Furthermore, users from both groups were highly satisfied with their contraceptive. The main reason for discontinuing use of the ENG-implant was bothersome uterine bleeding, while for SARC methods it was for personal reasons.

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.

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.

Female sexual function in women using LARC methods.

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

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

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

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.