A retrospective analysis of factors associated with deep contraceptive implant removals compared to superficial removals.

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 23.2kg/m2 vs 26.6kg/m2, p = 0.024), BMI >40kg/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-OB/GYN (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.

Substance Use and Anxiety About Pain Among Patients Seeking Abortion Services.

OBJECTIVES: To evaluate how recent opioid, marijuana, and cannabidiol use affects pre-procedure pain-related anxiety for patients seeking abortion. METHODS: We conducted a prospective, cross-sectional anonymous survey of patients seeking abortion assessing recent substance use and anxiety about pain during and after abortion. We compared substance users' and non-users' anxiety scores. RESULTS: Among 217 participants, recent opioid users (5.3%) had higher median anxiety scores for pain during (7.0 vs 6.0; p=0.33) and after (8.0 vs 6.0; p=0.01) abortion than non-opioid users. Anxiety scores were similar for marijuana and cannabidiol users. CONCLUSIONS: Assessing recent opioid use may help guide counseling for anxiety about abortion.

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

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

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.

Herbal Supplement Use Among Adolescent and Young Adult Women in a Family Planning Clinic.

STUDY OBJECTIVE: We aimed to evaluate herbal medicine and supplement use patterns among adolescent and young adult women at a clinic focused on family planning. METHODS: We conducted a cross-sectional survey of patients (age 14-25) at an adolescent Title X clinic. Participants completed an electronic survey that assessed herbal medicine and supplement use, baseline demographic characteristics, and current contraceptive method. We evaluated supplement-drug interactions using the Natural Medicines database Interaction Checker. Quantitative analyses were performed using χ2 and independent medians tests. RESULTS: We enrolled 99 participants with a median age of 20 (15-24) years. Overall, 42.4% of patients reported ever having used supplements or herbal medicines, with 29.9% of patients reporting current supplement or herbal medicine use. Patients with higher education and private insurance were more likely to report a history of and current supplement use (P < .05). The most common herbal supplements reported were green tea (n = 26), cannabidiol (n = 17), and cranberry (n = 16), with 29.6% of participants reporting use to their general health care provider. The most common reasons for use were general health and wellness (29.1%), immune support (23.2%), stress (16.8%), and menstrual irregularities (6.0%). We found 62 moderate risk supplement-drug interactions, with 50 interactions attributed to hormonal contraceptive therapies. The most common interactions were via cytochrome P450 enzyme (CYP3A4 or CYP1A2) inhibition, decreased caffeine clearance, and potential hepatotoxicity. CONCLUSION: Adolescent and young adult women frequently reported past and current herbal medicine and supplement use, with high rates of moderate-risk supplement-drug interactions. Further research is needed to better elucidate these clinically relevant supplement-contraception interactions.

Feasibility and Utility of Posttraumatic Stress Disorder Screening Among Postpartum Patients at an Urban Safety-Net Institution.

Posttraumatic stress disorder (PTSD) is underdiagnosed peripartum. We administered a primary care screening tool and a pregnancy-related PTSD screening tool to postpartum patients presenting to our urban safety-net institution within 6 months of delivery, between August 2021 and February 2022. Our primary outcome was prevalence of positive PTSD screening results. Most patients (364/376, 96.8%) completed screening. Thirty (8.4%) had a positive score on at least one instrument, and seven of these 30 (23.3%) did not have a positive postpartum depression screening result. Among patients with a positive score, the majority (66.7%) obtained behavioral health follow-up. We found that routine PTSD screening for postpartum patients is feasible and identified patients at risk for PTSD. Obstetric practitioners should consider integrating PTSD screening into routine care.

Validation of 24-hour trough concentration as a proxy for intensive pharmacokinetic measurements for a combined oral contraceptive pill containing desogestrel.

OBJECTIVES: To confirm that 24-hour steady-state trough measurements (C24) are high-quality proxies for gold standard pharmacokinetic measurements (area under the curve [AUC]) of a combined oral contraceptive pill (COCP). STUDY DESIGN: We conducted a 12-sample, 24-hour pharmacokinetic study in healthy reproductive-age females taking a COCP containing 0.15-mg desogestrel (DSG) and 30-µg ethinyl estradiol (EE). As DSG is a pro-drug for etonogestrel (ENG), we calculated correlations between steady-state C24 and 24-hour AUC values for both ENG and EE. RESULTS: Among 19 participants at steady state, C24 measurements were highly correlated with AUC for both ENG (r = 0.93; 95% CI 0.83-0.98) and EE (r = 0.87; 95% CI 0.68-0.95). CONCLUSIONS: Steady-state 24-hour trough concentrations are high-quality proxies for gold standard pharmacokinetics of a DSG-containing COCP. IMPLICATIONS: Use of single-time trough concentration measurements at steady state provides excellent surrogate results for gold standard AUC values for both DSG and EE among COCP users. These findings support that large studies exploring interindividual variability in COCP pharmacokinetics can avoid the time- and resource-intensive costs associated with measuring AUC. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT05002738.

The effect of rifampin on serum etonogestrel concentrations and biomarkers of ovulation among contraceptive implant users: A pharmacokinetic and pharmacodynamic study.

OBJECTIVES: Rifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic effects of a short course (2 weeks) of rifampin on serum etonogestrel (ENG) concentrations and serologic measures of ovarian activity (endogenous estradiol [E2] and progesterone [P4]) among ENG implant users. STUDY DESIGN: We enrolled healthy females using ENG implants for 12 to 36 months. We measured baseline serum ENG concentrations using a validated liquid chromatography mass-spectrometry assay and baseline E2 and P4 concentrations using chemiluminescent immunoassays. After 2 weeks of rifampin 600 mg daily, we repeated ENG, E2, and P4 measurements. We compared pre- and post-rifampin serum measurements using paired Wilcoxon signed-rank tests. RESULTS: Fifteen participants completed all study procedures. Participants' median age was 28.2 years (range 21.8-34.1), median body-mass index was 25.2 kg/m2 (range 18.9-37.3), and median duration of implant use was 22 months (range 12-32). All participants experienced significant decreases from baseline ENG concentrations (median 164.0 pg/mL [range 94.4-265.0]) to post-rifampin measurements (median 47.8 pg/mL [range 24.7-82.8]) (p < 0.001). Serum E2 concentrations also significantly increased with rifampin exposure (median 73 pg/mL vs 202 pg/mL, p = 0.003); increases in serum P4 concentrations were not statistically significant (p = 0.19). Three participants (20%) experienced increased luteal activity, with one presumptively ovulating post-rifampin (P4 = 15.8 ng/mL). CONCLUSIONS: With only short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant decreases in serum ENG concentrations that led to changes in biomarkers indicative of waning suppression of ovulation. IMPLICATIONS: Even a short, 2-week course of treatment with rifampin places etonogestrel contraceptive implant users at risk for decreased contraceptive efficacy. Clinicians should counsel patients using etonogestrel implants considering any duration of rifampin therapy on the need for backup nonhormonal contraception or the use of an intrauterine device to avoid unintended pregnancies.

Herbal supplement use among reproductive-aged women in an academic infertility practice.

Objective: To address the knowledge gap surrounding herbal medicine and supplement usage patterns and supplement-prescription medication interactions among patients seeking treatment for infertility. Design: Cross-sectional survey study. Setting: Academic infertility practice. Patients: Ninety-five reproductive-aged patients. Interventions: Not applicable. Main Outcome Measures: Use of herbal medications and supplements, baseline demographics, history of infertility treatments, and potential supplement-medication interactions. Results: We surveyed 95 participants with a median age of 35 years. Overall, 68.4% of patients reported ever having used supplements or herbal medicines in the past. Current use of herbal supplements and vitamins was reported by 53.7% and 93.7% of participants, respectively, with a median of 2 (range 19) supplements used per person. There were no significant associations between patient demographics, comorbidities, or infertility treatments with increased rates of supplement use. The most commonly used herbal supplements were: green tea (n = 14), chamomile (n = 12), peppermint (n = 9), turmeric (n = 8), elderberry (n = 7), ginger (n = 7), maca (6) with the most common modalities being pills/capsules (23.8%) and tea (42.3%). The most common reasons for use were: general health and wellness (24.5%), immune support (16.2%), stress (14.0%), and fertility (15.0%). Patients used maca (n = 5), chasteberry (n = 3), goji berry (n = 2), ginger (n = 2), yam-based progesterone (n = 2), and combination product (n = 2) for fertility purposes. A total of 7.9% of patients learned about these products from their general health care provider, and 33.3% of supplements were disclosed by patients to their provider. We identified 41 moderate-risk supplement-drug interactions, with 12 of these interactions attributed to infertility therapies. Based on the interaction checker, the most commonly proposed mechanisms of interaction were CYP3A4 and CYP2C19 inhibition. In terms of safety in pregnancy, cannabidiol and chasteberry were suggested to be "possibly unsafe in pregnancy," and red raspberry leaf "likely unsafe in pregnancy" without direct medical supervision. Conclusions: We found over two thirds of women seeking treatment for infertility reported past and over half reported current herbal medicine and supplement use. Notably, the Natural Medicines Interaction Checker suggested high rates of moderate-risk supplement-drug interactions and possible harmful effects in early pregnancy. Our results call for further investigation of clinically relevant supplement interactions with infertility therapies.

Short-notice cancellations of laparoscopic permanent contraception.

OBJECTIVE: Permanent contraception through tubal sterilization is the preferred contraceptive method for 25% of women in the United States. Laparoscopic permanent contraception has an anecdotally high cancellation rate. Cancellations affect operating room utilization and may reflect barriers to care. We aimed to identify the short-notice cancellation (≤7 days from scheduled surgery) rate for laparoscopic permanent contraception, reasons for cancellation, and postcancellation outcomes. STUDY DESIGN: We performed a retrospective chart review of patients aged 18 to 50 who canceled or no-showed a scheduled laparoscopic permanent contraception surgery between May 2016 and May 2019 at an academic tertiary care hospital and academic county hospital in Denver, Colorado. We reviewed electronic health records to determine the time between cancellation and surgery date and documented reasons for cancellation. We evaluated contraceptive methods used and pregnancies within a year after the canceled surgery. RESULTS: The overall surgery cancellation rate for scheduled laparoscopic permanent contraception was 22% (123 of 558). Short-notice cancellation occurred for 71.5% of patients and 32.5% (40 of 123) canceled same day. The most common reason for cancellation was patient choice (74%) followed by financial/insurance issues (11.4%). In the year after their canceled surgery, 22% (27 of 123) of patients obtained permanent contraception and 5.7% (7 of 123) had a subsequent pregnancy. CONCLUSIONS: Among patients who canceled their laparoscopic permanent contraception, the vast majority canceled their surgery a week or less from their scheduled date. These short-notice cancellations may adversely affect both patients and the health care system. More research is needed on institutional policies to reduce laparoscopic permanent contraception cancellations while helping patients who want effective contraception find an option that works best for them. IMPLICATIONS: Our retrospective cohort study found that laparoscopic permanent contraception surgeries have an overall high cancellation rate at both an academic tertiary and an academic county hospital, with most cancellations occurring less than 7 days prior to surgery. Future research will be used to reduce barriers to permanent contraception while developing clinical tools to reduce surgery cancellation rates.

Effect of Topiramate on Serum Etonogestrel Concentrations Among Contraceptive Implant Users.

OBJECTIVE: To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users. METHODS: We conducted a prospective, noninferiority study with healthy women using etonogestrel implants continuously for 12-36 months. We measured baseline serum etonogestrel concentrations and then began a 6-week titrated topiramate regimen to standard migraine (100 mg/day) and epilepsy (400 mg/day) dosages. We repeated serum etonogestrel concentrations at 3 weeks (100 mg/day), 4 weeks (200 mg/day), and 6 weeks (400 mg/day) of topiramate therapy. We measured etonogestrel using a validated liquid chromatography-tandem, mass-spectrometry assay and tested for noninferiority (less than 30% decrease) in serum etonogestrel concentrations from baseline. RESULTS: We enrolled 48 total participants; 32 completed 3 weeks, 31 completed 4 weeks, and 27 completed all follow-up visits. Participants' median age was 25.3 years (range 18.3-37.2), median body mass index (BMI) was 25.5 kg/m2 (range 18.7-42.2), and median duration of implant use was 24 months (range 12-36). Median etonogestrel concentrations were 142 pg/mL (range 76.2-771) at baseline, 126 pg/mL (range 72.4-585) at 3 weeks, 119 pg/mL (range 65.6-542) at 4 weeks, and 105 pg/mL (46.2-859) at 6 weeks. The 95% CIs for mean percent change in serum etonogestrel concentrations from baseline were [-37.3%+16.9%], [-45.4%+5.2%], and [-66.8%+24.8%] at 3 weeks, 4 weeks, and 6 weeks, respectively. Excluding one participant who had a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of participants (8/26, 95% CI 14.3-51.8%) had a serum etonogestrel concentration less than 90 pg/mL at 6 weeks. CONCLUSION: Though only a mild enzyme-inducing antiepileptic drug, concomitant topiramate use led to inferior serum etonogestrel concentrations among implant users, with a significant proportion reaching etonogestrel concentrations below the threshold for ovulatory suppression when taking antiepileptic dosages of topiramate. FUNDING SOURCE: This study was primarily funded through an Investigator-Initiated Study grant from Merck Sharp & Dohme Corp [MISP#57073]. This work was also supported by NIH/NCATS CTSA Grant Number UL1 TR001082 and NICHD K12 Women's Reproductive Health Research Scholar Program (grant number 5K12HD001271-18). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03335163.

Concordance of Desired and Administered Postpartum Contraceptives among Emergency and Full Scope Medicaid Patients.

OBJECTIVE: To determine if concordance of contraceptive preference and uptake differ between postpartum recipients of emergency versus full scope Medicaid. STUDY DESIGN: We performed a historical cohort study of patients who delivered at a safety-net hospital in Denver, Colorado in 2016. In our public system, all patients had access to immediate postpartum tubal ligation and all forms of reversible contraception in outpatient clinics. We used data from electronic health records to compare contraceptive preferences and uptake between patients with full scope and emergency Medicaid at hospital discharge and by 12 weeks postpartum. We then compared contraceptive concordance (use of the same method as desired during delivery admission) between the groups at time of postpartum discharge and by 12 weeks postpartum. RESULTS: We examined 693 women; 349 (50.1%) had emergency Medicaid and 344 (49.9%) had full scope Medicaid. The mean age at delivery was 27.9 years, and most patients were Hispanic (74%). Women with emergency Medicaid were less likely to receive their desired method of postpartum contraception before hospital discharge (53.6% vs. 66.9%; p < .01). One-half of the patients with emergency Medicaid who did not receive their desired method of immediate postpartum contraception were unable to obtain it based on insurance ineligibility. By 12 weeks postpartum, the rates of concordance did not differ by insurance status: 52.4% of patients with emergency Medicaid and 55.2% of patients with full scope Medicaid received their desired method of contraception (p = .46). CONCLUSIONS: Emergency Medicaid recipients, largely recent and/or unauthorized immigrants, have high demand for highly effective postpartum contraceptives. Although emergency Medicaid recipients initially had lower rates of receipt of their desired contraceptive during the hospital stay compared with those with full scope Medicaid, they ultimately had similar concordance rates by 12 weeks postpartum. We suspect this finding was in part due to free access to all methods of contraception in our outpatient clinics during the postpartum course. Systemic barriers should be reduced to ensure better access to postpartum contraceptives for all patients, regardless of insurance coverage, to improve reproductive equity.

Discontinuation of hormonal contraception due to changes in mood and decreases in sexual desire: the role of adverse childhood experiences.

PURPOSE: To evaluate if adverse childhood experiences are associated with hormonal contraception discontinuation due to mood and sexual side effects. MATERIALS AND METHODS: Women, ages 18-40 (N = 826), with current and/or previous hormonal contraceptive use completed surveys on demographics, contraceptive history, and the Adverse Childhood Experiences Questionnaire. We characterised women into high (≥2 adverse experiences) and low (0 or 1) adverse childhood experience groups. We calculated risk ratios for associations between adverse childhood experiences and outcomes of interest using log binomial generalised linear models, and adjusted for relevant demographic variables. RESULTS: Women in the high adverse childhood experiences group (n = 355) were more likely to report having discontinued hormonal contraception due to decreases in sexual desire (adjusted risk ratio 1.44, 1.03-2.00, p = .030). Covariates included age, current hormonal contraception use, and various demographic variables associated with discontinuation. Adverse childhood experiences were not associated with mood or sexual side effects among current (n = 541) hormonal contraceptive users. CONCLUSIONS: Self-reported adverse childhood experiences were associated with greater likelihood of discontinuing hormonal contraception due to behavioural side effects, particularly decreases in sexual desire. Identification of risk factors for behavioural side effects can assist patients and clinicians in making informed choices on contraception that minimise risk of early discontinuation.

Variability in repeat serum etonogestrel concentrations among contraceptive implant users during the steady-release pharmacokinetic period.

OBJECTIVE: To assess the variability of repeated measurements of serum etonogestrel concentration among contraceptive implant users. STUDY DESIGN: We measured 3 consecutive serum etonogestrel concentrations, drawn weekly, in women using etonogestrel implants for 12 to 36 months. We used a repeated measures test to evaluate differences. RESULTS: Among 20 participants, repeat serum etonogestrel concentrations did not differ from initial measurements (Friedman's test, p = 0.95). Mean serum etonogestrel concentrations had similar 95% confidence intervals at each time point: (134.09, 201.46), (135.08, 237.46), and (132.66, 192.45). CONCLUSION: We confirm that single-time measurements of serum etonogestrel concentration are acceptable pharmacokinetic outcomes for etonogestrel implant studies. IMPLICATIONS: Pharmacokinetic studies of the etonogestrel contraceptive implant assume single-time measurements are stable steady-state estimates based on small studies using older analysis methods. Our repeated measures study using modern liquid-chromatography mass-spectrometry analysis methods provides updated support for single-time pharmacokinetic measurements among etonogestrel implant users.

Etonogestrel contraceptive implant uptake and safety among solid organ transplant recipients.

OBJECTIVES: To determine the safety of etonogestrel contraceptive implant use among reproductive-age women who are solid organ transplant recipients. STUDY DESIGN: We conducted a retrospective cohort study with matching of reproductive-age women (14-45 years) who were solid organ transplant recipients and received care at a tertiary medical center in Denver, Colorado between 2011 and 2019. We identified cases who used an etonogestrel contraceptive implant post-transplant and then matched controls (no hormonal contraceptive use) in a 1:1 ratio according to age, transplant type, and institution. We compared pregnancy patterns, post-transplant infections, immunosuppressant therapy adjustments, and graft complications between cases and controls. We also evaluated implant-related side effect profiles and continuation rates among cases only. RESULTS: We identified 24 cases and 24 matched controls. When compared to age and transplant organ-matched controls, contraceptive implant users were not at increased risk for adverse transplant-related outcomes. Graft rejection was the most common transplant-related complication in both groups (n = 11, 45.8% cases; n = 10, 41.7% controls). Additionally, outcomes concerning pregnancies, infections and immunosuppressant therapy changes showed no statistically significant difference between either group. CONCLUSIONS: This study provides the first data that the etonogestrel contraceptive implant is likely a safe contraceptive option for reproductive-age women who are solid organ transplant recipients. Given the solid organ transplant recommendations to avoid pregnancy during the first 1 to 2 years post-transplant, healthcare providers should continue to counsel solid organ transplant recipients at risk of pregnancy on the etonogestrel contraceptive implant as an effective and safe method of pregnancy prevention. IMPLICATIONS: Reproductive age women who are solid organ transplant recipients face additional health risks with unintended pregnancies. The etonogestrel contraceptive implant remains a safe and effective method of contraception for this specific population, with no increase in graft-related complications among contraceptive implant users.

Applicability of ancestral genotyping in pharmacogenomic research with hormonal contraception.

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

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.

An exploratory analysis on the influence of genetic variants on weight gain among etonogestrel contraceptive implant users.

OBJECTIVE: To identify genetic variants associated with weight gain related to etonogestrel contraceptive implant use. STUDY DESIGN: We conducted a retrospective analysis from a parent pharmacogenomic study of healthy, reproductive-aged women using etonogestrel implants. We reviewed medical records to calculate objective weight changes from implant insertion to study enrollment and asked participants about subjective weight gain (yes/no) during contraceptive implant use. We used genotyping data (99 genetic variants) from the parent study to conduct backward-stepwise generalized linear modeling to identify genetic variants associated with objective weight changes. RESULTS: Among 276 ethnically diverse participants, median body-mass index (BMI) was 25.8 kg/m2 (range 18.5-48.1). We found a median weight change of +3.2 kg (range -27.6 to +26.5) from implant insertion to study enrollment. Report of subjective weight gain had minimal agreement with measured weight gain during implant use (Cohen's kappa = 0.21). Our final generalized linear model contained two variables associated with objective weight change that met conservative statistical significance (p < 5.0 × 10-4). Participants with two copies (homozygous) of the ESR1 rs9340799 variant on average gained 14.1 kg more than all other participants (p = 1.4 × 10-4). Higher enrollment BMI was also associated with objective weight gain (ß = 0.54, p = 9.4 × 10-12). CONCLUSION: Genetic variants in the estrogen receptor 1 (ESR1) do not have known associations with obesity or metabolic syndrome, but there is physiologic plausibility for a progestin-mediated genetic association between ESR1 and weight gain. Additional genetic research is needed to substantiate our findings and elucidate further advances in individualized counseling on the risk of weight gain with exogenous steroid hormones. IMPLICATIONS: Genetic variation in the estrogen receptor 1 gene may account for variability in weight gain among etonogestrel contraceptive implant users. If these findings can be replicated with other progestin-containing medications, we may be able to better individualize contraceptive counseling.

Satisfaction with medication abortion and marijuana use: A prospective cohort study.

OBJECTIVES: This exploratory study compared self-reported satisfaction rates and pain scores between patients who used marijuana during their medication abortion versus non-users. STUDY DESIGN: We recruited medication abortion patients at a University-affiliated abortion clinic in Denver, Colorado. Participants completed a pre-abortion questionnaire, pain diary, and follow-up survey that assessed satisfaction with pain control, symptoms, and abortion experience. Using medians test, we compared the sums of median satisfaction scores between patients who used marijuana versus non-users. Based on diary entries, we also compared reported pain over 24 h after misoprostol (area under the curve [AUC]) between cohorts. RESULTS: We enrolled 51 participants; 16 marijuana users and 35 non-marijuana users. Marijuana users and non-users had similar sums of median satisfaction scores (22 vs. 20 out of 30, p = 0.90) and median question-specific satisfaction scores (range 7-8 vs. 6.5-8, p = 0.6-1.0). Sixteen marijuana users (100%) and 20 (57%) non-users completed their pain diary; median AUCs for pain were similar (65.0 vs. 59.5, p = 0.73). Thirteen (81%) patients subjectively correlated marijuana use with pain reduction, seven (44%) with anxiety reduction, and six (38%) with nausea/vomiting improvement. CONCLUSIONS: We found no significant difference in measures of medication abortion satisfaction and pain when comparing marijuana users to non-users. However, marijuana users often attributed symptom improvement during their medication abortion to marijuana use. IMPLICATIONS: Until randomized studies are available, clinicians can counsel patients that marijuana use may not necessarily affect satisfaction or pain with medication abortion. It remains unknown whether marijuana has potential benefits in a marijuana-naïve population undergoing medication abortion. Future studies should explore the role that marijuana and its derivatives may play for pain and side effect management during medication abortion among marijuana-naïve patients.