ABSTRACT
A woman in her 20s was referred to a tertiary hospital emergency department for management of a migrating Implanon NXT. The Implanon was inserted 1 week prior by the patient's general practitioner who was unable to palpate the Implanon after insertion and hence, ordered an ultrasound scan which showed an actively migrating Implanon in the left basilic vein. She had mild chest pain, and her physical examination, ECG and blood tests were unremarkable. A CT chest showed a 31 mm foreign body within the right lower lobar artery. The foreign body was removed by interventional radiology by accessing the right internal jugular vein under ultrasound guidance and inserting a 6 FR pig catheter into the pulmonary trunk. The position was confirmed with angiogram and the foreign body was removed using a goose neck snare. The patient was discharged the same day with no complications, and fell pregnant a few months afterwards.
Subject(s)
Desogestrel , Foreign-Body Migration , Pulmonary Artery , Humans , Female , Foreign-Body Migration/surgery , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/complications , Pulmonary Artery/diagnostic imaging , Desogestrel/adverse effects , Desogestrel/administration & dosage , Contraceptive Agents, Female/adverse effects , Contraceptive Agents, Female/administration & dosage , Device Removal , Endovascular Procedures , Young Adult , Tomography, X-Ray ComputedABSTRACT
This case report details a rare case of contraceptive implant migration in a young woman. The migration was discovered three years post-insertion during a routine replacement visit. Despite the absence of pulmonary symptoms, a CT scan revealed the implant in the inferior lobe of the right lung. The patient was referred for further evaluation, but immediate surgical removal was deferred. This case report highlights the importance of healthcare providers recognising migration as a rare complication during implantation and suggests self-examination as a potential preventive strategy.
Subject(s)
Contraceptive Agents, Female , Drug Implants , Foreign-Body Migration , Tomography, X-Ray Computed , Humans , Female , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/surgery , Drug Implants/adverse effects , Contraceptive Agents, Female/adverse effects , Contraceptive Agents, Female/administration & dosage , Lung/diagnostic imaging , Lung/surgery , Adult , Desogestrel/adverse effects , Desogestrel/administration & dosageABSTRACT
A 17-year-old previously healthy female developed posterior reversible encephalopathy syndrome 1 week after etonogestrel implantation. She had a previous etonogestrel implant removed 4 months prior after unrelenting abdominal pain and hyponatremia with a negative workup for other etiologies, including hypercoagulable disorders and malignancy. This second insertion and resulting hospitalization allowed for the diagnosis of acute intermittent porphyria (AIP) to be confirmed. Progesterone can induce enzymatic activity upstream of porphobilinogen deaminase, the enzyme implicated in AIP, resulting in build-up of toxic metabolites. AIP requires high clinical suspicion for diagnosis but should be considered when hormonal triggers lead to unexplained neurovisceral symptoms.
Subject(s)
Desogestrel , Porphyria, Acute Intermittent , Humans , Female , Porphyria, Acute Intermittent/diagnosis , Porphyria, Acute Intermittent/chemically induced , Adolescent , Desogestrel/adverse effects , Desogestrel/administration & dosage , Contraceptive Agents, Female/adverse effects , Contraceptive Agents, Female/administration & dosage , Drug Implants/adverse effectsABSTRACT
Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1ß, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1ß) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.
Subject(s)
Biomarkers , Desogestrel , HIV Infections , Levonorgestrel , Medroxyprogesterone Acetate , Microbiota , Vagina , Humans , Female , Adolescent , Vagina/microbiology , Vagina/immunology , Vagina/drug effects , HIV Infections/immunology , Microbiota/drug effects , Biomarkers/metabolism , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/adverse effects , Medroxyprogesterone Acetate/pharmacology , Young Adult , Levonorgestrel/pharmacology , Levonorgestrel/administration & dosage , Desogestrel/administration & dosage , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/pharmacology , Longitudinal Studies , Progestins/pharmacology , Progestins/administration & dosage , ElafinABSTRACT
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.
Subject(s)
Desogestrel , Implementation Science , Qualitative Research , Humans , Female , Desogestrel/administration & dosage , Adult , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/therapeutic use , United States , Interviews as Topic , Drug Implants , Male , Attitude of Health Personnel , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data , Time FactorsABSTRACT
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.
Subject(s)
Desogestrel , Levonorgestrel , Progestins , Rats, Wistar , Thyroid Gland , Animals , Female , Rats , Progestins/pharmacology , Progestins/adverse effects , Thyroid Gland/drug effects , Thyroid Gland/metabolism , Levonorgestrel/pharmacology , Desogestrel/administration & dosage , Desogestrel/pharmacology , Thyroxine/blood , Thyroid Hormones/blood , Thyroid Function TestsABSTRACT
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.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Drug Implants , Foreign-Body Migration , Humans , Desogestrel/administration & dosage , Desogestrel/adverse effects , Female , Drug Implants/adverse effects , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/adverse effects , Device Removal , Contraceptive Agents, Hormonal/adverse effects , Contraceptive Agents, Hormonal/administration & dosageABSTRACT
OBJECTIVE: To identify factors associated with the need for a deep etonogestrel contraceptive implant removal as compared to superficial removal. STUDY DESIGN: We conducted a retrospective cohort study of patients undergoing contraceptive implant removal from January 2014 to January 2023. We extracted key patient characteristics from electronic health record review and compared patients requiring deep removal versus routine superficial removal using Chi-squared, Fischer's exact, and Mann-Whitney U test. A multivariate logistic regression identified variables associated with increased odds of requiring a deep implant removal. RESULTS: The deep and superficial removal groups included 162 and 585 patients, respectively. Deep removal was associated with younger age at removal (median 25.0 vs 26.0 years, p = 0.005), lower body mass index (BMI) at insertion (median 23.2 kg/m2 vs 26.6 kg/m2, p = 0.024), BMI≥ 40 kg/m2 at removal (15.2% vs 7.0%, p = 0.007), weight gain during implant use (median 6.6 vs 1.8 kg, p ≤ 0.001), longer duration of use (median 36.0 vs 27.5 months, p < 0.001), implant exchange (37.3% vs 17.4%, p < 0.001), and insertion by non-physician (43.3% vs 19.3%, p < 0.001) or non-obstetrican and gynecologist (31.4% vs 11.8%, p < 0.001). Lower BMI at insertion (aOR 0.92, [95% CI 0.87-0.98]), weight gain during use (aOR 1.06 [95% CI 1.02-1.10]), and longer duration of use (aOR 1.05 [95% CI 1.02-1.07]) remained significantly associated with deep removal in regression analysis. CONCLUSION(S): We identified lower BMI at insertion, weight gain during use, and longer duration of use as independent factors associated with increased likelihood of needing a deep contraceptive implant removal. IMPLICATIONS: Clinicians should utilize proper technique when inserting contraceptive implants, especially in patients at risk for deep insertion, and ensure immediate referral to Centers of Experience for patients with non-palpable implants.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Device Removal , Drug Implants , Humans , Retrospective Studies , Female , Device Removal/statistics & numerical data , Adult , Desogestrel/administration & dosage , Contraceptive Agents, Female/administration & dosage , Young Adult , Body Mass Index , Logistic ModelsABSTRACT
PURPOSE OF THE ARTICLE: The main aim of the study was to analyze the population of women who used etonogestrel implant, the reason that led them to this type of contraception, and the degree of compliance with it. Materials and methods: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. MATERIALS AND METHODS: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. RESULTS: The average age of placement of etonogestrel implant was 33.8 ± 3.45 years. As regards level of education, 16/47 (34%) of the women had a university degree, 21/47 (44%) had a high school diploma and 10/47 (21%) had a secondary school diploma. The 12/47 (25%) of the women were, at the time of the counselling, unemployed and only 8% did not use in the past contraceptive methods other than etonogestrel implant. The 92% of women choose etonogestrel implant because it offered safe, comfortable and long-lasting contraception. Among the main side effects evaluated, we reported spotting in 24 out of 47 (51%), headache in 4 out of 47 (8.5%). The 85% of the women recommended etonogestrel implant to their friends as a contraceptive method, with an approval rating for the implant, expressed a rating from 1 to 10 with the mean that was 7.79, the median 8. CONCLUSIONS: Our results are of interest because they derive from a region of Italy in which the Long acting reversible contraception (LARC) is strongly underused. Etonogestrel implant was a safe and effective, long-acting, reversible hormonal contraception (LARC) and majority of women recommended the etonogestrel implant to their friends as a contraceptive method.
Etonogestrel implant is a safe and effective, long-acting, reversible hormonal contraception (LARC). The majority of women in our study choose the etonogestrel implant for its characteristics; among the main side effects evaluated we reported spotting and headache. The majority of women recommended the etonogestrel implant to their friends as a contraceptive method.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Drug Implants , Patient Satisfaction , Humans , Desogestrel/administration & dosage , Desogestrel/adverse effects , Female , Adult , Italy , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/adverse effects , Retrospective Studies , Patient Satisfaction/statistics & numerical data , Surveys and Questionnaires , Patient Compliance/statistics & numerical dataABSTRACT
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.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Uterine Hemorrhage , Humans , Female , Desogestrel/administration & dosage , Desogestrel/adverse effects , Adult , Prospective Studies , Uterine Hemorrhage/genetics , Contraceptive Agents, Female/adverse effects , Contraceptive Agents, Female/administration & dosage , Endometrium/metabolism , Endometrium/drug effects , Endometrium/pathology , Drug Implants , Chemokine CXCL1/genetics , Chemokine CXCL1/metabolism , Young AdultABSTRACT
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.
Subject(s)
Desogestrel , Device Removal , Foreign-Body Migration , Humans , Female , Device Removal/methods , Desogestrel/administration & dosage , Foreign-Body Migration/surgery , Foreign-Body Migration/diagnostic imaging , Young Adult , Contraceptive Agents, Female/administration & dosage , Drug Implants , Pulmonary Artery/surgery , Pulmonary Artery/diagnostic imaging , Tomography, X-Ray Computed , Pulmonary Embolism/etiology , Treatment Outcome , PneumonectomyABSTRACT
High rates of unplanned pregnancies persist despite pharmacological developments and advancements in contraceptive methods. Here, we demonstrate that the etonogestrel-releasing subdermal contraceptive implant (IMP-ETN) may be an appropriate and cost-effective alternative to levonorgestrel-releasing intrauterine systems (LNG-IUSs) for women in Brazil. For our pharmacoeconomic analysis, we reviewed the literature on IMP-ETN regarding its acceptance, eligibility criteria, choice, relations with age, adverse events and, finally, the unmet need in the fee-for-service private healthcare sector. We considered qualitative observations in combination with quantitative analysis and performed a deterministic sensitivity analysis to investigate whether this technology can be self-sustainable over a period of five years. The target population for this analysis comprised 158,696 women. Compared with the continued use of LNG-IUSs, adopting the IMP-ETN can result in a cost avoidance of $ 7.640.804,02 in the first year and $ 82,455,254.43 in five years. Disseminating information among physicians will promote this change and strengthen the potential cost avoided by private health system payers. These savings can be used to improve other healthcare programs and strategies. Moreover, the principles of care can be promoted by improving and adapting healthcare systems and expanding treatment and follow-up strategies. This would also provide support to women's reproductive rights and improve their quality of life. Our results suggest that the IMP-ETN has a favorable cost-effectiveness profile. Given all its advantages and negative incremental cost impact over a period of five years, the IMP-ETN may be a more favorable alternative to LNG-IUSs. Therefore, it should be offered to beneficiaries with a private healthcare plan. This analysis overcomes previous barriers to the use of cost-benefit models, and our results may help balance decision-making by policymakers, technical consultants, and researchers.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Intrauterine Devices, Medicated , Pregnancy , Female , Humans , Levonorgestrel/therapeutic use , Contraceptive Agents, Female/therapeutic use , Brazil , Quality of Life , Intrauterine Devices, Medicated/adverse effects , Delivery of Health CareABSTRACT
OBJECTIVES: To examine the prevalence of menstrual irregularities, side effects, and discontinuation rates of etonogestrel subdermal implants (ESI) in women attending King Abdulaziz Medical City, Jeddah, Saudi Arabia. METHODS: This cross-sectional was carried out based on electronic medical records and a phone-based questionnaire administered to women who underwent ESI insertion in a single tertiary care hospital in Jeddah, Saudi Arabia, between 2019 and 2022. The primary objective was the prevalence of menstrual abnormalities. The secondary study objective included the discontinuation rate, reasons for discontinuation, and ESI side effects. RESULTS: In total, 345 women with ESI were included in this study. The prevalence of any type of menstrual abnormalities was 88%. Other side effects included skin and mood changes, arm pain, and numbness. The discontinuation rate was 11% in the first year and 22% before the completion of 36 months. CONCLUSION: Although menstrual abnormalities are a common side effect of ESI, only 22% of users discontinued this method of contraception.
Subject(s)
Desogestrel , Electronic Health Records , Humans , Female , Cross-Sectional Studies , Desogestrel/adverse effects , Contraceptive AgentsABSTRACT
BACKGROUND: Concomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant led to 82% lower etonogestrel exposure when compared with women who do not receive antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations that demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of 2 etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. OBJECTIVE: This study compared the rate of ovulation and etonogestrel pharmacokinetics among women on efavirenz-based antiretroviral therapy who received 2 etonogestrel implants (136 mg; double implant group) in comparison with those who received 1 etonogestrel implant (68 mg; control group). STUDY DESIGN: This randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for the treatment of HIV. Participants were randomized 1:1 to the double implant or control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9-12), 6 (weeks 21-24), and 12 (weeks 45-48). Progesterone concentrations >3 ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher's exact tests for each month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36, and 48 after implant placement and analyzed using a validated liquid chromatography-triple quadrupole mass spectrometry method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range) and compared between groups by geometric mean ratio with 90% confidence intervals. RESULTS: All participants (n=72) were cisgender Ugandan women with a median age of 31 years (interquartile range, 29-36), and 36 participants were enrolled in each study group. Two participants in the control group discontinued the trial; 1 at week 1 because of undetected pregnancy at entry and another at week 45 because of clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the control group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the double implant group (month 3: 11 [31%] vs 0 [0%]; month 6: 17 [49%] vs 0 [0%]; month 12: 19 [56%] vs 2 [6%], respectively; all P<.001). The odds of ovulation were reduced by 97.7% (95% confidence interval, 90.1-99.5) in the double implant group over 48 weeks. At each time point, etonogestrel concentration was more than 2-fold higher in the double implant group than in the controls (geometric mean ratio, 2.30-2.83) with a geometric mean ratio of 2.83 (90% confidence interval, 1.89-3.35) at week 48. There were no differences in the adverse events between groups and no participant discontinued because of adverse events. CONCLUSION: Over 48 weeks of combined use, placing 2 etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure when compared with 1 etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel during efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.
Subject(s)
Alkynes , Benzoxazines , Contraceptive Agents, Female , Cyclopropanes , Desogestrel , Drug Implants , HIV Infections , Humans , Desogestrel/administration & dosage , Female , Cyclopropanes/administration & dosage , Benzoxazines/administration & dosage , Adult , Contraceptive Agents, Female/administration & dosage , HIV Infections/drug therapy , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Pregnancy , Ovulation/drug effects , Drug Interactions , Young Adult , Contraceptive Agents, Hormonal/administration & dosage , UgandaABSTRACT
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.
Subject(s)
Computer Simulation , Contraceptive Devices, Female , Models, Biological , Tenofovir , Vagina , Vaginal Absorption , Vaginal Creams, Foams, and Jellies , Female , Humans , Vaginal Creams, Foams, and Jellies/administration & dosage , Vaginal Creams, Foams, and Jellies/pharmacokinetics , Tenofovir/pharmacokinetics , Tenofovir/administration & dosage , Vagina/metabolism , Vagina/drug effects , Administration, Intravaginal , Ethinyl Estradiol/pharmacokinetics , Ethinyl Estradiol/administration & dosage , Desogestrel/administration & dosage , Desogestrel/pharmacokinetics , Pyrimidines/pharmacokinetics , Pyrimidines/administration & dosage , Adult , Area Under Curve , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/administration & dosageABSTRACT
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.
Subject(s)
Contraceptive Agents, Female , Desogestrel , Drug Implants , Scapula , Humans , Female , Desogestrel/administration & dosage , Desogestrel/pharmacokinetics , Pilot Projects , Adult , Contraceptive Agents, Female/pharmacokinetics , Contraceptive Agents, Female/administration & dosage , Young Adult , Contraceptive Agents, Hormonal/administration & dosage , Contraceptive Agents, Hormonal/pharmacokineticsABSTRACT
After a fortuitous observation of two cases of chemosensitivity recovery in women with congenital central hypoventilation syndrome (CCHS) who took desogestrel, we aimed to evaluate the ventilatory response to hypercapnia of five CCHS patients with or without treatment consisting of desogestrel (DESO) or levonorgestrel (LEVO). Only two patients became responsive to hypercapnia under treatment, according to their basal vagal heart rate variability. These results suggest that heart rate variability may be promising tool to discriminate patients susceptible to become responsive to hypercapnia under DESO-LEVO treatment.Clinical Trials Identifier NCT01243697.
Subject(s)
Hypoventilation/congenital , Progestins , Sleep Apnea, Central , Humans , Female , Progestins/therapeutic use , Hypercapnia/diagnosis , Hypercapnia/drug therapy , Desogestrel/therapeutic use , Heart Rate , Homeodomain Proteins/therapeutic useABSTRACT
OBJECTIVE: Clinical factors related to development of amenorrhea in adolescents with the etonogestrel contraceptive implant are not well-understood. The purpose of this study is to describe what baseline clinical characteristics are associated with amenorrhea in adolescents with a contraceptive implant 12 months after placement. STUDY DESIGN: This retrospective cohort study included 252 post-menarchal individuals aged 12-22 years with a contraceptive implant placed between 2016-2020. Data abstracted at insertion, three months post-insertion, and 12 months post-insertion included demographics, baseline bleeding pattern, prior contraception use, post-insertion bleeding pattern, and method discontinuation. We assessed possible predictive characteristics of our outcomes using bivariate and multivariable logistic regression analyses. RESULTS: Twenty nine percent of patients were amenorrheic 12 months after placement. Patients who were amenorrheic at 12 months were more likely to be obese (41.1% vs 24.6%, p = 0.01), to have been amenorrheic prior to implant insertion (16.9% vs 5.4%, p < 0.01, to have used hormonal contraception immediately prior to insertion (42.5% vs 26.3%, p = 0.01), to have had the most recent contraceptive method being another implant (12.3% vs 3.6%, p = 0.02), and to have developed amenorrhea within three months after placement (22.2% vs 12.6%, p < 0.01). After multivariable regression analysis, only obesity (adjusted odds ratio [aOR] 2.2 95% CI 1.1-4.2) and amenorrhea at three months (aOR 3.6, CI 1.1-11.5) were associated with amenorrhea at 12 months. CONCLUSION: Obesity and early amenorrhea were associated with 12-month amenorrhea in adolescents using the etonogestrel subdermal implant. Understanding this can help with contraceptive method selection and counseling for patients and providers. IMPLICATIONS: Obesity and early amenorrhea with the etonogestrel contraceptive implant are associated with longer-term amenorrhea in adolescents using this method. These findings can aid providers with method selection and pre-insertion decision-making for adolescents considering contraceptive implant use, as well as continued counseling after placement.
Subject(s)
Contraceptive Agents, Female , Female , Humans , Adolescent , Contraceptive Agents, Female/adverse effects , Amenorrhea/chemically induced , Retrospective Studies , Desogestrel/adverse effects , Obesity , Drug Implants/adverse effectsABSTRACT
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.