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Pharmacokinetics of Hormonal Contraception in Individuals with Obesity: a Review

  • Family Planning (A Burke, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

A Correction to this article was published on 10 December 2020

This article has been updated

Abstract

Purpose of Review

Obesity continues to affect many women globally. In the USA, almost 40% of all women are obese and many of these women use hormonal contraception for pregnancy prevention. How well hormonal contraceptive works for these individuals has been an area of ongoing research. Pharmacokinetics (PK), the study of drug passage through the body, can shed light on how differences in physiology between obese and non-obese populations can impact drug disposition and subsequent efficacy. This review aims to reflect on these types of studies and empower clinicians with information to help tackle the challenges of the obesity epidemic and help them provide the best contraceptive options to their patients. Here, we present the basics of the mechanisms of action of hormonal contraception, fundamental pharmacokinetic principles, and the latest research into pharmacokinetics, obesity, and hormonal contraception.

Recent Findings

New studies focused on the PK of hormonal contraception in women with obesity have shown that while there are distinct differences in how steroid hormones are processed in women with different body mass indices, contraceptive efficacy is likely the same. This is replicated in studies involving a variety of hormonal contraceptive methods.

Summary

PK studies allow for a detailed analysis of steroid hormone processing in individuals with obesity. Observing PK parameters at each stage of the passage of these hormones through the body, researchers have drilled down on physiologic differences that accompany obesity. In reviewing these PK parameter differences, however, it appears that while processes are different, the end result of pregnancy prevention is likely not compromised in the setting of obesity. Emergency contraception, which functions by a different mechanism from that of continuous hormonal contraception, is the one area in which obesity has been demonstrated to impact efficacy.

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Change history

  • 10 December 2020

    A Correction to this paper has been published: <ExternalRef><RefSource>https://doi.org/10.1007/s13669-020-00301-0</RefSource><RefTarget Address="10.1007/s13669-020-00301-0" TargetType="DOI"/></ExternalRef>

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Prevalence of obesity among adults and youth: United States, 2015–2016. In: Statistics CfDCaPNCfH, editor.: U.S. Department of Health and Human Services; 2017.

  2. Kavanaugh ML, Jerman J. Contraceptive method use in the United States: trends and characteristics between 2008, 2012 and 2014. Contraception. 2018;97(1):14–21.

    Article  Google Scholar 

  3. Establishing effectiveness and safety for hormonal drug products intended to prevent pregnancy guidance for industry. Office of Medical Products and Tobacco, Center for Drug Evaluation and Research, Food and Drug Administration. 2019.

  4. Jensen J, Creinin M. Speroff & Darney’s clinical guide to contraception: Wolters Kluwer Health; 2019.

  5. Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth. 2000;85(1):91–108.

    Article  CAS  Google Scholar 

  6. Wisen O, Johansson C. Gastrointestinal function in obesity: motility, secretion, and absorption following a liquid test meal. Metabolism. 1992;41(4):390–5.

    Article  CAS  Google Scholar 

  7. Geier A, Dietrich CG, Grote T, Beuers U, Prüfer T, Fraunberger P, et al. Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat. J Hepatol. 2005;43(6):1021–30.

    Article  CAS  Google Scholar 

  8. Lesser GT, Deutsch S. Measurement of adipose tissue blood flow and perfusion in man by uptake of 85Kr. J Appl Physiol. 1967;23(5):621–30.

    Article  CAS  Google Scholar 

  9. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39(3):215–31.

    Article  CAS  Google Scholar 

  10. Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004;58(2):119–33.

    Article  Google Scholar 

  11. Nisbet AC. Intramuscular gluteal injections in the increasingly obese population: retrospective study. Bmj. 2006;332(7542):637–8.

    Article  Google Scholar 

  12. Edelman AB, Cherala G, Stanczyk FZ. Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception. 2010;82(4):314–23.

    Article  CAS  Google Scholar 

  13. Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord. 2000;24(Suppl 2):S64–70.

    Article  CAS  Google Scholar 

  14. Natavio M, Stanczyk FZ, Molins EAG, Nelson A, Jusko WJ. Pharmacokinetics of the 1.5 mg levonorgestrel emergency contraceptive in women with normal, obese and extremely obese body mass index. Contraception. 2019;99(5):306–11.

    Article  CAS  Google Scholar 

  15. Reinecke I, Hofmann B, Mesic E, Drenth HJ, Garmann D. An integrated population pharmacokinetic analysis to characterize levonorgestrel pharmacokinetics after different administration routes. J Clin Pharmacol. 2018;58(12):1639–54.

    Article  CAS  Google Scholar 

  16. Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15(11):2792–800.

    Article  CAS  Google Scholar 

  17. Lee YH, Pratley RE. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep. 2005;5(1):70–5.

    Article  CAS  Google Scholar 

  18. Cheng Q, Aleksunes LM, Manautou JE, Cherrington NJ, Scheffer GL, Yamasaki H, et al. Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity. Mol Pharm. 2008;5(1):77–91.

    Article  CAS  Google Scholar 

  19. Henegar JR, Bigler SA, Henegar LK, Tyagi SC, Hall JE. Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol. 2001;12(6):1211–7.

    CAS  Google Scholar 

  20. Bauer LA, Edwards WA, Dellinger EP, Simonowitz DA. Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients. Eur J Clin Pharmacol. 1983;24(5):643–7.

    Article  CAS  Google Scholar 

  21. Korsager S. Administration of gentamicin to obese patients. Int J Clin Pharmacol Ther Toxicol. 1980;18(12):549–53.

    CAS  Google Scholar 

  22. Sketris I, Lesar T, Zaske DE, Cipolle RJ. Effect of obesity on gentamicin pharmacokinetics. J Clin Pharmacol. 1981;21(7):288–93.

    Article  CAS  Google Scholar 

  23. Li WM, Chou YH, Li CC, Liu CC, Huang SP, Wu WJ, et al. Association of body mass index and urine pH in patients with urolithiasis. Urol Res. 2009;37(4):193–6.

    Article  Google Scholar 

  24. Lopez LM, Bernholc A, Chen M, Grey TW, Otterness C, Westhoff C, et al. Hormonal contraceptives for contraception in overweight or obese women. Cochrane Database Syst Rev. 2016;8:CD008452.

    Google Scholar 

  25. Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL, Daling JR. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol. 2005;105(1):46–52.

    Article  Google Scholar 

  26. Brunnerhuber L, Hogue C, Stein A, Drews C, Zieman M. Body mass index and risk for oral contraceptive failure: a case–cohort study in South Carolina. Ann Epidemiol. 2006;16(8):637–43.

    Article  Google Scholar 

  27. Doose DR, Wang SS, Padmanabhan M, Schwabe S, Jacobs D, Bialer M. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia. 2003;44(4):540–9.

  28. Edelman AB, Carlson NE, Cherala G, Munar MY, Stouffer RL, Cameron JL, et al. Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic–pituitary–ovarian activity. Contraception. 2009;80(2):119–27.

  29. Westhoff CL, Torgal AH, Mayeda ER, Pike MC, Stanczyk FZ. Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 2010;81(6):474–80.

  30. Edelman AB, Cherala G, Munar MY, Dubois B, McInnis M, Stanczyk FZ, et al. Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an altered pharmacokinetic profile in obese oral contraceptives users. Contraception. 2013;87(2):220–6.

  31. Foegh M, Archer DF, Stanczyk FZ, Rubin A, Mishell DR. Ovarian activity in obese and nonobese women treated with three transdermal contraceptive patches delivering three different doses of ethinyl estradiol and levonorgestrel. Contraception. 2013;87(2):201–11.

  32. Westhoff CL, Torgal AH, Mayeda ER, Petrie K, Thomas T, Dragoman M, et al. Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women. American Journal of Obstetrics and Gynecology. 2012;207(1):39.e1–.e6.

  33. Segall-Gutierrez P, Taylor D, Liu X, Stanzcyk F, Azen S, Mishell DR. Follicular development and ovulation in extremely obese women receiving depo-medroxyprogesterone acetate subcutaneously. Contraception. 2010;81(6):487–95.

  34. Sivin I, Lähteenmäki P, Ranta S, Darney P, Klaisle C, Wan L, et al. Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants. Contraception. 1997;55(2):81–5.

  35. Sivin I, Wan L, Ranta S, Alvarez F, Brache V, Mishell DR, et al. Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants. Contraception. 2001;64(1):43–9.

  36. Mornar S, Chan L-N, Mistretta S, Neustadt A, Martins S, Gilliam M. Pharmacokinetics of the etonogestrel contraceptive implant in obese women. AJOG. 2012;207(2):110.e1–.e6.

  37. Hidalgo MM, Hidalgo-Regina C, Bahamondes MV, Monteiro I, Petta CA, Bahamondes L. Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. Contraception. 2009. July;80(1):84–9.

  38. Seeber B, Ziehr SC, Gschlieβer A, Moser C, Mattle V, Seger C, et al.  Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system. Contraception. 2012;86(4):345–9.

  39. • Westhoff CL, Reinecke I, Bangerter K, Merz M. Impact of body mass index on suppression of follicular development and ovulation using a transdermal patch containing 0.55-mg ethinyl estradiol/2.1-mg gestodene: a multicenter, open-label, uncontrolled study over three treatment cycles. Contraception. 2014;90(3):272–9 A study investigating PK parameters for the steroid hormone components of a transdermal contraceptive patch, demonstrating that even in individuals with obesity, ovulation was consistently inhibited with the patch.

    Article  CAS  Google Scholar 

  40. Creinin MD, Baker JB, Eisenberg DL, Ginde S, Turok DK, Westhoff CL. Levonorgestrel levels in nonobese and obese women using LNG20, a new intrauterine contraceptive. Obstet Gynecol. 2015;125:84S–5S.

  41. •• Luo D, Westhoff CL, Edelman AB, Natavio M, Stanczyk FZ, Jusko WJ. Altered pharmacokinetics of combined oral contraceptives in obesity - multistudy assessment. Contraception. 2019;99(4):256–63 A study aggregating data from multiple PK studies demonstrating minor changes in PK parameters for the steroid hormones in oral contraceptive pills. Trough levels for hormones were found to be the same in individuals with and without obesity.

    Article  CAS  Google Scholar 

  42. • Edelman AB, Cherala G, Blue SW, Erikson DW, Jensen JT. Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. Contraception. 2016;94(1):52–7 This study shows that double dosing of LNG emergency contraception in individuals with obesity may remedy the lack of efficacy of single LNG EC doses in this population.

    Article  CAS  Google Scholar 

  43. Edelman AB, Cherala G, Munar MY, McInnis M, Stanczyk FZ, Jensen JT. Correcting oral contraceptive pharmacokinetic alterations due to obesity: a randomized controlled trial. Contraception. 2014;90(5):550–6.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Oregon Health & Science University, Portland, OR, 97239, USA

    Shaalini Ramanadhan & Alison Edelman

  2. Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, 14214, USA

    William J. Jusko

Authors
  1. Shaalini Ramanadhan
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  2. William J. Jusko
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  3. Alison Edelman
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Corresponding author

Correspondence to Shaalini Ramanadhan.

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Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Conflict of Interest

Dr. Edelman reports grants from the National Institutes of Health and Merck, along with contract work for Up To Date and HRA Pharma outside the submitted work. Drs. Ramanadhan and Jusko have nothing to disclose.

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The original version of this article was revised: In Table 2 and Table 3, complete and correct bibliographical information were added.

This article is part of the Topical Collection on Family Planning

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Ramanadhan, S., Jusko, W.J. & Edelman, A. Pharmacokinetics of Hormonal Contraception in Individuals with Obesity: a Review. Curr Obstet Gynecol Rep 9, 72–78 (2020). https://doi.org/10.1007/s13669-020-00284-y

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