PMID- 32407811 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20211015 IS - 1879-0518 (Electronic) IS - 0010-7824 (Print) IS - 0010-7824 (Linking) VI - 102 IP - 3 DP - 2020 Sep TI - An exploratory analysis on the influence of genetic variants on weight gain among etonogestrel contraceptive implant users. PG - 180-185 LID - S0010-7824(20)30150-5 [pii] LID - 10.1016/j.contraception.2020.05.002 [doi] AB - 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/m(2) (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 x 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 x 10(-4)). Higher enrollment BMI was also associated with objective weight gain (beta = 0.54, p = 9.4 x 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. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Lazorwitz, Aaron AU - Lazorwitz A AD - University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Family Planning, 12631 E 17th Ave, B198-2, Aurora, CO 80045, USA. Electronic address: aaron.lazorwitz@cuanschutz.edu. FAU - Dindinger, Eva AU - Dindinger E AD - University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Family Planning, 12631 E 17th Ave, B198-2, Aurora, CO 80045, USA. Electronic address: eva.dinginder@cuanschutz.edu. FAU - Harrison, Margaret AU - Harrison M AD - University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Family Planning, 12631 E 17th Ave, B198-2, Aurora, CO 80045, USA. Electronic address: Margaret.harrison@cuanschutz.edu. FAU - Aquilante, Christina L AU - Aquilante CL AD - University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, 12850 E Montview Blvd, Aurora, CO 80045, USA. Electronic address: Christina.aquilante@cuanschutz.edu. FAU - Sheeder, Jeanelle AU - Sheeder J AD - University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Family Planning, 12631 E 17th Ave, B198-2, Aurora, CO 80045, USA. Electronic address: jeanelle.sheeder@cuanschutz.edu. FAU - Teal, Stephanie AU - Teal S AD - University of Colorado Anschutz Medical Campus, Department of Obstetrics and Gynecology, Division of Family Planning, 12631 E 17th Ave, B198-2, Aurora, CO 80045, USA. Electronic address: Stephanie.teal@cuanschutz.edu. LA - eng GR - K12 HD001271/HD/NICHD NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States GR - UL1 TR002535/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200512 PL - United States TA - Contraception JT - Contraception JID - 0234361 RN - 0 (Contraceptive Agents, Female) RN - 0 (Drug Implants) RN - 304GTH6RNH (etonogestrel) RN - 81K9V7M3A3 (Desogestrel) SB - IM MH - Adult MH - *Contraceptive Agents, Female/adverse effects MH - Desogestrel/adverse effects MH - Drug Implants MH - Female MH - Humans MH - Retrospective Studies MH - Weight Gain/genetics PMC - PMC7483263 MID - NIHMS1594424 OTO - NOTNLM OT - Contraception OT - Estrogen receptor OT - Etonogestrel OT - Obesity OT - Pharmacogenomics OT - Weight gain COIS- Financial Disclosure: Dr. Teal serves on a Data Monitoring Board for a study funded by Merck and Co. and has served as a consultant for Bayer Healthcare. The University of Colorado Department of Obstetrics and Gynecology has received research funding from Bayer, Agile Therapeutics, Merck and Co, and Medicines360. The other authors did not report any potential conflicts of interest. EDAT- 2020/05/15 06:00 MHDA- 2021/10/16 06:00 PMCR- 2021/09/01 CRDT- 2020/05/15 06:00 PHST- 2020/01/30 00:00 [received] PHST- 2020/04/30 00:00 [revised] PHST- 2020/05/01 00:00 [accepted] PHST- 2020/05/15 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2020/05/15 06:00 [entrez] PHST- 2021/09/01 00:00 [pmc-release] AID - S0010-7824(20)30150-5 [pii] AID - 10.1016/j.contraception.2020.05.002 [doi] PST - ppublish SO - Contraception. 2020 Sep;102(3):180-185. doi: 10.1016/j.contraception.2020.05.002. Epub 2020 May 12.