Dataset Information

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

ABSTRACT:

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.

SUBMITTER: Lazorwitz A

PROVIDER: S-EPMC8496990 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

Lazorwitz Aaron A Sheeder Jeanelle J Teal Stephanie S

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception 20210217 4

<h4>Purpose</h4>To explore how diet and exercise habits associate with serum etonogestrel concentrations among contraceptive implant users.<h4>Materials and methods</h4>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 ...[more]

PMID: 33596152

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Project description:ObjectiveTo evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.MethodsWe 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.ResultsWe 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.ConclusionThough 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 sourceThis 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 registrationClinicalTrials.gov, NCT03335163.

Project description:ObjectiveTo determine whether serum etonogestrel concentrations in contraceptive implant users are associated with certain individual patient characteristics.Study designWe enrolled reproductive-age women using etonogestrel contraceptive implants between 12-36 months duration and measured a single serum etonogestrel concentration. Participants also completed a questionnaire about demographics.ResultsWe enrolled 350 participants; median age was 22.5 years (range 18.0-39.1), median months of implant use was 26.0 (range 12.0-36.0), and median body mass index was 25.7 kg/m2 (range 18.5-52.0). Our study population was primarily white/Caucasian (46.6% [163/350]) and Hispanic/Latina ethnicity (51.4% [180/350]). The median serum etonogestrel concentration was 137.4 pg/ml and etonogestrel concentrations varied 12.4 fold in the population (range 55.8-695.1 pg/ml). Using forward stepwise linear regression, months of implant use (β=-1.74, p<.001) and body mass index (β=-3.10, p<.001) were both significantly associated with decreased serum etonogestrel concentration with Black/African American race as a positive effect modifier (β=18.24, p=.099); R-squared for the model=0.13.ConclusionsIndividuals demonstrated a wide variability in serum etonogestrel concentrations, which can potentially affect side-effect profiles and efficacy. Increasing body mass index and longer duration of implant use were associated with small decreases in serum etonogestrel concentrations, while self-reported Black/African American race was associated with a non-significant increase. Despite these findings, most of etonogestrel variability was unaccounted for, suggesting that other clinical, pharmacologic, and genetic factors contributing to variability in etonogestrel concentrations remain to be determined.ImplicationsAlthough increases in body mass index are associated with lower etonogestrel levels in contraceptive implant users, the majority of women will maintain serum concentrations that consistently suppress ovulation. Furthermore, certain patient characteristics can only explain a small portion (13%) of the variability in serum etonogestrel levels among contraceptive implant users.

Project description:ObjectiveTo estimate whether serum etonogestrel concentrations influence bleeding patterns and related side effects in contraceptive implant users.MethodsWe conducted a prospective cross-sectional study with healthy, reproductive-aged women using etonogestrel implants for 12-36 months. Participants completed a brief questionnaire to assess their current bleeding pattern and any experience of abnormal bleeding with the implant. We then measured serum etonogestrel concentrations. We also reviewed the charts of participants to determine whether a prescription for oral contraceptive pills was ever given for treatment of implant-related bothersome bleeding. We performed multivariable logistic regression to test for associations between serum etonogestrel concentrations and both bleeding patterns and related side effects.ResultsWe enrolled 350 women, and 59.4% reported having experienced abnormal bleeding with the contraceptive implant. Only 14.9% of participants reported amenorrhea and 37.7% reported monthly periods. Among participants with reviewable medical records (n=253), roughly 20% had received a prescription for oral contraceptive pills during implant use. Increasing serum etonogestrel concentrations were significantly associated with increasing odds of reporting abnormal bleeding (adjusted odds ratio [aOR] 1.005, P=.015) and increasing odds of having received an oral contraceptive pill prescription (aOR 1.008, P=.002). For every 100 pg/mL increase in serum etonogestrel concentration, contraceptive implant users in this study had 1.6 times the odds of reporting abnormal bleeding and 2.3 times the odds of having received a prescription as treatment for bothersome bleeding.ConclusionWe found both objective and subjective evidence that higher levels of progestin from the contraceptive implant were associated with bleeding side effects experienced by women in this study. Pharmacologic variation may influence the side effects women experience with a variety of hormonal contraceptive methods, in turn affecting patient satisfaction and discontinuation rates.

Project description:ObjectiveTo identify genetic variants that influence steady-state etonogestrel concentrations among contraceptive implant users.MethodsWe enrolled healthy, reproductive-age women in our pharmacogenomic study using etonogestrel implants for 12-36 months without concomitant use of hepatic enzyme inducers or inhibitors. We collected participant characteristics, measured serum etonogestrel concentrations, and genotyped each participant for 120 single nucleotide variants in 14 genes encoding proteins involved in steroid hormone (ie, estrogens, progestins) metabolism, regulation, or function. We performed generalized linear modeling to identify genetic variants associated with steady-state etonogestrel concentrations.ResultsWe enrolled 350 women, who had a median serum etonogestrel concentration of 137.4 pg/mL (range 55.8-695.1). Our final generalized linear model contained three genetic variants associated with serum etonogestrel concentrations: NR1I2(PXR) rs2461817 (β=13.36, P=.005), PGR rs537681 (β=-29.77, P=.007), and CYP3A7*1C (β=-35.06, P=.025). Variant allele frequencies were 69.4%, 84.9%, and 5.1%, respectively. Our linear model also contained two nongenetic factors associated with etonogestrel concentrations: body mass index (BMI) (β=-3.08, P=7.0×10) and duration of implant use (β=-1.60, P=5.8×10); R for the model =0.17.ConclusionOnly BMI and duration of implant use remained significantly associated with steady-state etonogestrel concentrations. Of the three novel genetic associations found, one variant associated with increased etonogestrel metabolism (CYP3A7*1C) causes adult expression of fetal CYP3A7 proteins and can consequently alter steroid hormone metabolism. Women with this variant may potentially have increased metabolism of all steroid hormones, as 27.8% (5/18) of CYP3A7*1C carriers had serum etonogestrel concentrations that fell below the threshold for consistent ovulatory suppression (less than 90 pg/mL). More pharmacogenomic investigations are needed to advance our understanding of how genetic variation can influence the effectiveness and safety of hormonal contraception, and lay the groundwork for personalized medicine approaches in women's health.Clinical trial registrationClinicalTrials.gov, NCT03092037.

Project description:ObjectiveTo identify genetic variants associated with weight gain related to etonogestrel contraceptive implant use.Study designWe 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.ResultsAmong 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 (β = 0.54, p = 9.4 × 10-12).ConclusionGenetic 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.ImplicationsGenetic 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.

Project description:ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrel concentrations between antiretroviral regimens. We considered a minimum serum etonogestrel concentration of 90 pg/mL adequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

Project description:OBJECTIVE:To evaluate whether ulipristal acetate reduces the number of bleeding days in etonogestrel implant users in a 30-day period as compared with placebo. METHODS:We performed a single-center, randomized, double-blind, placebo-controlled trial. Eligible participants were women aged 18-45 years with an etonogestrel implant in place for greater than 90 days and less than 3 years who reported greater than one bleeding episode in a 24-day period. Enrolled participants were randomized to receive 15 mg ulipristal acetate compared with an identical-appearing placebo daily for 7 days. Participants completed daily bleeding diaries using automated text messaging to evaluate whether ulipristal acetate reduces the number of bleeding days as compared with placebo. Secondary outcomes included participant satisfaction with bleeding and the effect of ulipristal acetate on ovulation status. A sample size of 52 per group (n=104) was planned, calculated with an effect size of a 30% reduction in bleeding days, SD of 10 days, and dropout of 15%. Our study was terminated early (N=65) as a result of a U.S. Food and Drug Administration hold, but power was sufficient for analysis. The effect of ulipristal acetate on ovulatory potential was evaluated in a subset with weekly serum progesterone. RESULTS:From May 2017 to January 2018, 65 women were allocated to receive 15 mg ulipristal acetate (n=32) or placebo (n=33) daily for 7 days. Demographic characteristics were similar between groups. Women randomized to ulipristal acetate reported 5 fewer days of bleeding over a 30-day reference period after treatment (P=.002). At the conclusion of the 30-day follow-up period, women in the ulipristal acetate group were more satisfied with their bleeding profile than the placebo group (87.5% vs 60%, respectively; P<.001). Serum progesterone levels were nonovulatory in a subset of each group (placebo group range: less than 0.2-1.3 ng/mL; ulipristal acetate group range: less than 0.2-4.4 ng/mL). CONCLUSION:Ulipristal acetate is well-tolerated and reduced the number of bleeding days in etonogestrel implant users in our study. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03118297.

Dataset Information

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

Purpose

Materials and methods

Results

Conclusion

Clinical trial registration

Publications

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

Similar Datasets

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