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.

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.

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.

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.

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.

Use of effective contraception following provision of the progestogen-only pill for women presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic cluster-randomised crossover trial.

BACKGROUND: Unless women start effective contraception after oral emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies. We hypothesised that pharmacist provision of the progestogen-only pill as a bridging interim method of contraception with emergency contraception plus an invitation to a sexual and reproductive health clinic, in which all methods of contraception are available, would result in increased subsequent use of effective contraception. METHODS: We did a pragmatic cluster-randomised crossover trial in 29 UK pharmacies among women receiving levonorgestrel emergency contraception. Women aged 16 years or older, not already using hormonal contraception, not on medication that could interfere with the progestogen-only pill, and willing to give contact details for follow-up were invited to participate. In the intervention group, women received a 3-month supply of the progestogen-only pill (75 µg desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In the control group, pharmacists advised women to attend their usual contraceptive provider. The order in which each pharmacy provided the intervention or control was randomly assigned using a computer software algorithm. The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4 months. This study is registered, ISRCTN70616901 (complete). FINDINGS: Between Dec 19, 2017, and June 26, 2019, 636 women were recruited to the intervention group (316 [49·6%], mean age 22·7 years [SD 5·7]) or the control group (320 [50·3%], 22·6 years [5·1]). Three women (one in the intervention group and two in the control group) were excluded after randomisation. 4-month follow-up data were available for 406 (64%) participants, 25 were lost to follow-up, and two participants no longer wanted to participate in the study. The proportion of women using effective contraception was 20·1% greater (95% CI 5·2-35·0) in the intervention group (mean 58·4%, 48·6-68·2), than in the control group (mean 40·5%, 29·7-51·3 [adjusted for recruitment period, treatment group, and centre]; p=0·011).The difference remained significant after adjusting for age, current sexual relationship, and history of effective contraception use, and was robust to the effect of missing data (assuming missingness at random). No serious adverse events occurred. INTERPRETATION: Provision of a supply of the progestogen-only pill with emergency contraception from a community pharmacist, along with an invitation to a sexual and reproductive health clinic, results in a clinically meaningful increase in subsequent use of effective contraception. Widely implemented, this practice could prevent unintended pregnancies after use of emergency contraception. FUNDING: National Institute for Health Research (Health Technology Assessment Programme project 15/113/01).

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.

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.

Ovarian stimulation for fertility preservation in an oncology patient with etonogestrel implant in place.

PURPOSE: To describe a case of a young woman who presented for fertility preservation and underwent ovarian stimulation with an etonogestrel implant in place. METHODS: A 24-year old, gravida 0, with an etonogestrel implant and newly diagnosed lower extremity sarcoma and DVT desiring oocyte cryopreservation prior to adjuvant chemotherapy and radiation. To avoid delay in her oncologic care and allow for continued use of contraception post-retrieval, the patient underwent controlled ovarian hyperstimulation (COH) without removal of the etonogestrel implant. RESULTS: Baseline labs included follicle-stimulating hormone 9 mIU/mL, luteinizing hormone 4.9 mIU/mL, estradiol 42 pg/mL, anti-Müllerian hormone 5.1 ng/mL, and antral follicle count greater than 40. The patient was placed on an antagonist protocol and stimulated with 125 IU Gonal-F and 75 IU Menopur. She received a total of 12 days of gonadotropin stimulation. On the day of trigger, her estradiol was 1472 pg/mL, lead follicle 21.5 mm with a total of 25 follicles measured > 12 mm. She was triggered with 5000 U hCG. She had a total of 23 oocytes retrieved, 17 of which were metaphase II and vitrified. CONCLUSIONS: COH and successful oocyte cryopreservation can be achieved in patients with an etonogestrel implant in situ without apparent detrimental effects to oocyte yield or maturity. Due to the etonogestrel implant's inhibitory effects on LH, it is recommended to use an hCG trigger for final oocyte maturation.

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 prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression.

OBJECTIVES: To assess the feasibility of comparing the rates of positive depression screens at 6 weeks and 3 months postpartum in women using immediate postpartum etonogestrel implant (ENG-implant) and women using non-hormonal contraception or sterilisation. METHODS: This was a pilot prospective cohort study performed to test the design adequacy of comparing the rates of positive postpartum PHQ-9 screens (≥10) in women using immediate postpartum ENG-implant and women using non-hormonal contraception or sterilisation. Participants were recruited during the third trimester of pregnancy or during delivery hospitalisation. They self-allocated to one of the two comparison groups. PHQ-9 surveys were administered during the third trimester of pregnancy, immediately postpartum, and at 6 weeks and 3 months postpartum. RESULTS: Between June 2017 and March 2018, 91 patients were recruited. Of these patients, 11 were excluded and the remaining 80 were split evenly into each cohort. The women in the ENG-implant group were younger, less educated, and more often publicly insured. The percentage of participants with positive PHQ-9 screens were: 3% during the postpartum hospitalisation, 6.2% at 6 weeks postpartum, and 10.2% at 3 months postpartum. PHQ-9 scores were similar between groups at both postpartum time points. CONCLUSION: The rates of positive PHQ-9 screens at 6 weeks postpartum were similar between groups. These preliminary data suggest that immediate postpartum placement of the ENG-implant does not negatively impact the risk for a positive depression screen. Larger-scale, adequately powered studies are warranted to further investigate this finding.

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.

Does LH suppression by progesterone-primed ovarian stimulation compared with GnRH antagonist affect live birth rate among oocyte recipients?

RESEARCH QUESTION: Is live birth rate among recipients of donated oocytes different depending on mode of treatment for endogenous LH suppression administered to oocyte donors during ovarian stimulation? DESIGN: A retrospective cohort study of recipients of freshly donated oocytes from oocyte donors who underwent ovarian stimulation with gonadotrophins at a private, university-based infertility clinic between January 2017 and March 2018. For endogenous LH suppression, oocyte donors received daily injections of gonadotrophin releasing hormone antagonist ganirelix (GNR) or daily oral 75 µg desogestrel (DSG) until triggering with 0.2 mg of triptorelin. Three hundred recipient cycles of freshly donated oocytes were included: 154 from oocyte donor DSG cycles and 146 from oocyte donor GNR cycles. RESULTS: Comparison of basal characteristics of oocyte donors showed no differences in mean age, anti-Müllerian hormone levels and body mass index between the oocyte donor DSG p and oocyte donor GNR groups, respectively. Similarly, no differences were observed among mean age of recipients and body mass index. Out of 300 fresh embryo transfers, 190 clinical pregnancies (63.3%) and 150 live births (50%) were achieved. Per embryo transfer clinical pregnancy rate was 66.2% in the DSG recipient group and 60.3% in the GNR recipient group (P = 0.338). Live birth rates were not significantly different between both groups (48.7% among DSG recipient group and 51.4% among GNR recipient group; P = 0.729). CONCLUSIONS: Live birth rate among recipients of donated oocytes does not differ depending on the mode of treatment for endogenous LH suppression administered to the oocyte donors during ovarian stimulation. This information is reassuring and will be of interest to teams using these kinds of protocols, although further research is needed.

Low dose combined oral contraceptives induced thrombotic anterior wall myocardial infarction: a case report.

BACKGROUND: Combined oral contraceptive pills are associated with an established risk for venous thrombosis; however, their risk for arterial thrombosis remains uncertain, especially with the development of low dose new generations of combined oral contraceptive. Arterial thrombosis is less likely to occur with the use of oral contraceptive pills in the absence of cardiovascular risk factors. CASE PRESENTATION: We report a 35-year old female with no cardiovascular risk factors who presented with thrombotic anterior wall myocardial infarction 6 months after using a third generation low dose combined oral contraceptive pills (Marvelon; ethinylestradiol 30 mcg and desogestrel 150 mcg). CONCLUSION: Third generation low dose combined oral contraceptives may lead to myocardial infarction in young women, even in the absence of other cardiovascular risk factors.

Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy).

BACKGROUND: Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013. OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials. SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size. AUTHORS' CONCLUSIONS: Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Feasibility and acceptability of using medical and nursing students to provide Implanon NXT at the community level in Kinshasa, Democratic Republic of Congo.

BACKGROUND: The use of implants has steadily increased in Kinshasa since 2013 but clinic-based access to this family planning method is limited due to distance and costs barriers. The objective of this study was to examine the feasibility and acceptability of providing Implanon NXT at the community level using medical and nursing students (M/N) as distributors, as part of a strategy to improve contraceptive uptake in the Democratic Republic of Congo. METHODS: A cohort of 531 women who chose to receive Implanon NXT from a M/N student during community-based campaign days participated in three rounds of a quantitative survey administered at the time of insertion of the method, and at 6 and 12 months later. We conducted descriptive analysis to assess the feasibility and acceptability of providing the method through M/N students in terms of method choice, user profiles, contraceptive history, experience with insertion and side effects, continuation / discontinuation of the method, and overall satisfaction with FP services as well as students' preparedness and capacity to safely offer the method, and their satisfaction with the experience.. RESULTS: The study demonstrated the feasibility of training students for community-based provision of Implanon NXT and 95% of them were satisfied with their experience. Acceptability of both the method and the service delivery strategy was high among participants, including among young and first-time contraceptive users. Out of the 441 women with a known outcome at 12 months, 92% still had Implanon NXT inserted, despite some of them reporting experiencing side effects. The vast majority (79%) would "strongly recommend" obtaining NXT from a M/N student if a friend wanted to avoid pregnancies. CONCLUSIONS: The provision of Implanon NXT at the community-level is a promising solution to address some of the barriers to accessing this method for women living in Kinshasa. However, strengthening pre-insertion counseling, particularly on expected side-effects and the possibility of early removal, is necessary to increase informed choice for the women and potentially limit method discontinuation.

Analysis and new contraception frontiers with combined vaginal rings.

Combined vaginal rings (ethinylestradiol (EE)/desogestrel), indicated for contraception, are highly effective, comparable to other combined hormonal contraceptives, such as pills. In addition to this benefit, vaginal rings are easy to use, with a probable lower risk of forgetting, due to their non-daily, monthly schedule. Besides, for users with poor gastric tolerance to oral formulations, they represent a method with safety and comparable extraconceptive benefits. The latest generation rings have a novel polymeric structure, do not need special storage methods and do not generate accelerated initial release of EE, reducing the early increased systemic exposure to the synthetic steroids they contain. This review describes main aspects related to its use, efficacy, and safety for contraceptive purposes.

Metformin metabolic and vascular effects in normal weight hyperinsulinemic polycystic ovary syndrome patients treated with contraceptive vaginal ring. A pilot study.

PURPOSE: The aim of this longitudinal, controlled, and retrospective pilot study was to assess how metformin, associated with a contraceptive vaginal ring, may influence lipid and carbohydrate metabolism, and surrogate markers of arterial function in normal weight polycystic ovary syndrome patients. MATERIAL AND METHODS: Among 28 lean patients, 15 were treated with vaginal ring plus metformin and 13 women with only vaginal ring. The effects were assessed after six months. The patients were submitted to evaluation of lipid and carbohydrate metabolism; Doppler analysis of ophthalmic artery; brachial artery flow-mediated vasodilatation; and oral glucose tolerance test. RESULTS: After six months, the fasting insulin, glucose/insulin ratio, and homeostatic model assessment estimates for insulin resistance were significantly improved in metformin group. The ophthalmic artery pulsatility index did not significantly improve in either group. The brachial artery vasodilation was better in metformin treated patients. CONCLUSION: Metformin, associated with vaginal ring, improves the insulin and carbohydrate metabolism. This, associated with the significant improvements of surrogate markers of arterial function, may be responsible of a slight possible cardiovascular and cerebrovascular protective effect.