Outcomes of etonogestrel subdermal contraceptive implants: A single center cross-sectional study.

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.

Amenorrhea in adolescents using the etonogestrel contraceptive implant.

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.

An exploratory study on the possible association of serum etonogestrel concentrations with mood concerns and symptoms among contraceptive implant users.

OBJECTIVE: To evaluate if inter-individual variability in serum etonogestrel (ENG) concentrations accounts for variability in mood-related side effects among ENG implant users. STUDY DESIGN: Participants underwent a single-time blood draw for measurement of serum ENG concentrations using a liquid-chromatography mass-spectrometry assay, and completed a questionnaire at enrollment that retrospectively assessed mood-related side effects during the period of implant use. For a subset of participants, Patient Health Questionnaire-9 (PHQ-9) scores, obtained for other clinical purposes, were also compared. We used independent medians tests and linear regression to evaluate associations between mood symptoms and serum ENG concentrations as our primary outcome. RESULTS: Among 900 enrolled participants, 34% (306/900) reported mood changes on the baseline questionnaire. Of these, 31 (3.4%) participants also had documented PHQ-9 scores. Serum ENG concentrations (median 126.9 pg/mL [range 39.4-695.1]) were not associated with reported mood changes on the questionnaire (p = 0.19) or on the PHQ-9 (ß = 0.00, 95% CI -0.03, 0.03). CONCLUSION: Pharmacokinetic variability does not explain the inter-individual variability in mood-related side effects among ENG implant users. IMPLICATIONS: Mood-related side effects and altered mental health metrics are commonly reported by etonogestrel contraceptive implant users but demonstrate wide inter-individual variability. Individual differences in serum drug levels do not appear to account for this variability in mood-related side effects, and so future research should focus on novel personal factors.

Site necrosis at the insertion place of the single-rod subdermal contraceptive implant: report of five cases.

OBJECTIVE: Implant-site necrosis is a rare complication. We present a case-series of a necrosis as an adverse effect after the etonogestrel (ENG)-subdermal contraceptive implant placement. MATERIAL AND METHODS: Five women with site necrosis after the ENG-implant placement and their clinical manifestations and treatments. RESULTS: Local pain was the main symptom, appearing within 35 days of placement. Outpatient multidisciplinary treatment was undertaken. Local debridement and implant removal was performed in four out of the five women. Time to complete healing varied from 45 days to 12 months. CONCLUSION: Early diagnosis and multidisciplinary treatment are essential to avoid severe aesthetic or functional damages and major life-threatening complications.

We presented five cases with necrosis at the ENG-implant site of placement in which we proposed an early diagnosis and multidisciplinary treatment to avoid severe aesthetic or functional damages.

Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. RESULTS: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. CONCLUSION: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Experiences of women of childbearing age regarding Implanon provision in South Africa.

BACKGROUND: The World Health Organization has stated that millions of women of childbearing age in developing countries who are not planning to be pregnant are not utilising modern contraceptives such as long-term contraceptives, including Implanon. South Africa had a high rate of women of childbearing age who used Implanon as one of long-term contraception methods from its introduction in 2014. Familiar reasons for women to not use modern contraceptives involved a lack of healthcare facilities, supplies and trained healthcare workers in their area to provide effective contraceptive services in South Africa. AIM: This study aimed to explore and describe the experiences of women of childbearing age regarding Implanon provision. SETTING: The study was conducted in primary health care facilities of Ramotshere Moiloa subdistrict, South Africa. METHODS: Qualitative, descriptive phenomenological approach was used in this study. Twelve women of childbearing age were purposively sampled. Childbearing age refers to woman in their reproductive ages who will not be regarded as high risk for pregnancy. Semi-structured interviews were utilised to collect data and five Colaizzi's steps of data analysis were used. Data were collected from 12 of 15 selected women of childbearing age who had experience in utilising Implanon contraceptive device. Data saturation was reached after interviewing 12 participants as the information was coming out, repeatedly. RESULTS: Three themes with subthemes emerged from the study, namely period of Implanon use, experiences of obtaining information regarding Implanon and healthcare experiences related to Implanon. CONCLUSION: It was evident that a lack of effective pre- and post-counselling, eligibility screening and poor management of severe side effects are contributory factors that led to early removal and decline in uptake of the said method. There is also a lack of effective comprehensive Implanon training to some of reproductive service providers.Contribution: It may increase the number of women who still want to use Implanon as a reliable method.

Allergic and infectious complications of Etonogestrel implant placements: A case series.

Patients rarely experience complications at the time of Etonogestrel subdermal contraceptive implant placement. Few case reports describe infection or allergy as a complication at the time of implant insertion. In this case series, we discuss three infections and one allergic reaction following Etonogestrel implant placement, review six previous case reports of eight cases of infection or allergy, and discuss management of these complications. We highlight differential diagnosis when encountering a placement complication, considerations of dermatologic conditions when placing Etonogestrel implants, and discuss when to consider removal of the implant when a complication occurs.

Management of Etonogestrel implant migration into the pulmonary artery.

OBJECTIVES: To evaluate the relationship between time since contraceptive implant placement and retrieval outcomes in patients with implant migration into the pulmonary artery. STUDY DESIGN: We reviewed all cases of pulmonary artery implant migration referred to the Marie Lannelongue hospital from 2015 through 2020. Using our hospital database, we collected patients' clinical data and removal information to assess the success of therapeutic management according to the delay between implant insertion and removal. RESULTS: We identified 8 cases. Physicians located 2 in the upper and 6 in the lower lobe. Five patients had associated pulmonary symptoms, most commonly, chest pain and dyspnea. Physicians attempted an endovascular procedure in all cases with successful removal in 3 patients. In the 5 failures, angiography displayed arterial thrombosis distal to the implant. These patients had successful removal with an open mini-thoracotomy (< 5 cm). None of the 8 patients had serious post-operative complications. For the 3 patients with successful endovascular retrieval, 2 had early diagnosis (≤ 3 months). CONCLUSION: Endovascular approach with angiography should be performed as a first line treatment modality. Endothelialization and fibrosis within the vessel represent the principal limitations of endovascular strategy, but a retrieval could be attempted anyway with caution. In case of failure, an open approach is required. IMPLICATIONS STATEMENT: When a migration into the pulmonary artery is diagnosed, health care professionals should refer patients as soon as possible to a tertiary center with a vascular surgery and/or interventional radiology and thoracic surgery departments.

Bleeding profile of women with cardiovascular risk factors using a drospirenone only pill with 4 mg over nine cycles compared to desogestrel 0.075 mg.

OBJECTIVE: Progestin-only pills are associated with irregular bleeding patterns, including amenorrhea. Desogestrel (DSG) 75 mcg, a pill that inhibits ovulation, shows poor cycle control that may harm acceptability and compliance. A Drospirenone (DRSP)-only pill was developed with 24 & 4 days of active & placebo days every 28-day cycle to improve cycle control. STUDY DESIGN: A phase III study in healthy women aged 18 to 45 years was performed to compare the bleeding profile of women taking a DRSP versus DSG over nine cycles. 249 women were older > 35 years: 173 using DRSP and 73 DSG. 259 women had a BMI > 25 kg/m2: 189 using DRSP and 70 DSG and 340 women were smokers: 237 using DRSP and 103 DSG. The amount of unscheduled bleeding/spotting days was analyzed in each of these sub-groups and compared statistically. RESULTS: Age: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 8.1 (SD10.53) for DRSP and 20.1 (19.41) for DSG; p = .0089. BMI > 25 kg/m2: During cycles 2-4 the mean number of unscheduled bleeding days and spotting was 7.8 (SD 12.18) for DRSP and 17.7 for DSG (SD 19.39); p = .0001. Smokers: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 9.6 (SD 11.69) for DRSP and 17.4 for DSG (SD 17.47); p = .0016. CONCLUSIONS: These analyses show the improvement in the bleeding profile of women with specific cardiovascular risk factors using the DRSP only oral contraceptive product compared to DSG.ImplicationsAn improvement in the bleeding profile of women with specific cardiovascular risk factors like age > 35 years, BMI > 25kg/m2, and smokers using the DRSP only oral contraceptive product is described.Herby a higher contraceptive efficacy in these patients that additionally benefit from estrogen-free contraceptive methods is expected.

Long-term treatment of endometriosis-related pain among women seeking hormonal contraception.

OBJECTIVE: To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. METHODS: An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. RESULTS: No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. CONCLUSIONS: A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

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).

Comparative evaluation of low-level light therapy and ethinyl estradiol and desogestrel combined oral contraceptive for clinical efficacy and regulation of serum biochemical parameters in primary dysmenorrhoea: a prospective randomised multicentre trial.

We aimed to compare low-level light therapy with oral contraceptive pills for pain relief and serum levels of nitric oxide and prostaglandin E2 in patients with primary dysmenorrhoea. This was a randomised, active comparator-controlled, multicentre study. In total, 156 patients were randomised to receive either low-level light therapy with light-emitting diodes (LED) applying on two acupoints, namely, conception vessel 4 (CV4) and CV6 or conventional treatment with oral Marvelon, 30 µg of ethinyl estradiol and 150 µg of desogestrel (DSG/EE), for three consecutive menstrual cycles. The main outcome was the proportion of patients who achieved 33% or more decrease in pain scores measured using the visual analogue scale, which was deemed as efficient rate. Absolute changes in visual analogue scale scores, serum levels of nitric oxide (assessed by nitrites and nitrates reflecting nitric oxide metabolism) and prostaglandin E2 (measured by enzyme-linked immunosorbent assay) were the secondary outcomes. A total of 135 patients completed the study (73 in the light therapy group and 62 in the DSG/EE group). The efficient rate at the end of treatment was comparable between the groups (73.6% vs. 85.7%, χ2 = 2.994, p = 0.084). A more significant reduction in pain scores was observed in the DSG/EE group (39.25% vs. 59.52%, p < 0.001). Serum levels of prostaglandin E2 significantly decreased from baseline but did not differ between groups (- 109.57 ± 3.99 pg/mL vs. - 118.11 ± 12.93 pg/mL, p = 0.51). Nitric oxide concentration remained stable in both groups. Low-level light therapy with LED-based device applied on acupuncture points CV4 and CV6 demonstrated a similar level of dysmenorrhoea pain reduction to DSG/EE combined contraceptive. Both treatment modalities achieved clinically meaningful levels of pain reduction. Registration on ClinicalTrials.gov: TRN: NCT03953716, Date: April 04, 2019.

Tamoxifen for the Treatment of Etonogestrel Implant-Associated Bleeding in an Adolescent Gynecology Practice.

OBJECTIVE: To describe clinical outcomes in a cohort of adolescent female patients using tamoxifen for the treatment of bothersome etonogestrel (ENG) implant-associated bleeding. DESIGN: Retrospective chart review SETTING: A tertiary children's hospital PARTICIPANTS: Adolescent female patients ages 12-21 seen between August 2016 and August 2019 with an ENG implant in place who received a tamoxifen prescription for the indication of implant-associated bleeding. INTERVENTIONS: None MAIN OUTCOME MEASURES: Main outcome measures were implant continuation rates, average time to implant discontinuation after tamoxifen prescription, reasons for implant removal, number of doses and timing of tamoxifen use, bleeding patterns, and adverse effects. RESULTS: A total of 67 patients met the inclusion criteria. The mean age of patients was 16.7 years old. Of the patients with available follow-up data, 49 out of 60 (81.7%) were still using the implant at 12 months, 29 out of 53 (54.7%) at 24 months, and 9 out of 40 (22.5%) at 36 months. The average time from tamoxifen prescription to implant removal was 12.1 months. Bothersome bleeding was the primary reason for ENG implant discontinuation (68.6%). No side effects from tamoxifen use were reported. CONCLUSION: Tamoxifen was well-tolerated among this cohort of patients and can be considered a treatment option to manage bothersome implant bleeding in adolescents.

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.

Manejo farmacológico del sangrado irregular no menstrual asociado al uso de implantes anticonceptivos subdérmicos / Pharmacological management of irregular non-menstrual bleeding associated with the use of subdermal contraceptive implants

El spottingo sangrado irregular no menstrual es uno de los principales efectos secundarios de los implantes anticonceptivos, situación que se recomienda discutir con la usuaria previo a la colocación, para evitar falsas expectativas o temores que lleven a la extracción temprana del dispositivo. A propósito de una paciente sin antecedentes relevantes que consultó al centro de salud por spotting desde la colocación del implante cuatro meses antes, decidimos revisar la evidencia sobre la efectividad de los distintos esquemas farmacológicos disponibles para el manejo de este evento adverso. Luego de realizar una búsqueda bibliográfica concluimos que, si bien existe sustento para indicar algunos de los esquemas farmacológicos, este es aún débil y son necesarios estudios clínicos adicionales que brinden evidencia sólida sobre qué esquema en particular utilizar, evaluando sus riesgos y beneficios. (AU)

Spotting or irregular non-menstrual bleeding is one of the main side effects of contraceptive implants, a situation that health professionals must discuss with the user prior to its placement in order to avoid false expectations or fears that lead to early removal of the implant. Regarding a patient with no relevant history who consulted the health center due to spotting four months after implant placement, we decided to review the evidence onthe effectiveness on different pharmacological schemes available for the management of this adverse event. After performing a literature search, we concluded that, although there is support for indicating some of the pharmacological schemes, this is still weak, and further clinical studies are needed to provide solid evidence on which particular scheme touse, assessing its risks and benefits. (AU)

Ectopic pregnancy with etonogestrel implant.

The etonogestrel implant is the most effective contraceptive available. We report a case of ectopic pregnancy in a woman who had an etonogestrel implant inserted 15 months ago and the effective concentration of the implant was within normal limits.