Original research article| Volume 94, ISSUE 1, P52-57, July 2016

Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing



      To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations.

      Study design

      Healthy, reproductive-age women with obese and normal BMIs received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3 mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group.


      A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8 kg/m2, range 20.8–23.7; obese BMI=5, 39.5 kg/m2, range 35.9–46.7). The total LNG Cmax for obese subjects following ECx1 (5.57±2.48 ng/mL) was significantly lower than the level observed in normal BMI women (10.30±2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52±2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern.


      Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity-related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women.


      This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women.


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        • Finer L.B.
        • Henshaw S.K.
        Disparities in rates of unintended pregnancy in the United States, 1994 and 2001.
        Perspect Sex Reprod Health. 2006; 38: 90-96
        • Grimes D.
        • Von Hertzen H.
        • Piaggio G.
        • Van Look D.F.A.
        Randomized controlled trial of levonorgestrel versus the yuzpe regimen of combined oral contraceptives for emergency contraception.
        Lancet. 1998; 352: 428-433
        • Kavanaugh M.L.
        • Williams S.
        • Schwarz E.B.
        Emergenecy contraception use and counseling after changes in United States prescription status.
        Fertil Steril. 2001; 95: 2578-2581
        • Glasier A.
        • Cameron S.T.
        • Blithe D.
        • Scherrer B.
        • Mathe H.
        • Levy D.
        • et al.
        Can we identify women at risk of pregnancy despite using emergency contraception? data from randomized trials of ulipristal acetate and levonorgestrel.
        Contraception. 2011; 84: 363-367
        • Piaggio G.
        • Von Hertzen H.
        • Grimes D.A.
        • Van Look P.F.A.
        Timing of emergency contraception with levonorgestrel or the yuzpe regimen.
        Lancet. 1999; 353: 721
        • Piaggio G.
        • Kapp N.
        • Von Hertzen H.
        Effect on pregnancy rates of the delay in the administration of levonorgestrel for emergency contraception: a combined analysis of four WHO trials.
        Contraception. 2011; 84: 35-39
        • Johansson E.
        • Brache V.
        • Alvarez F.
        • Faundes A.
        • Cochon L.
        • Ranta S.
        • et al.
        Pharmacokinetic study of different dosing regimens of levornorgestrel for emergency contraception in healthy women.
        Hum Reprod. 2002; 17: 1472-1476
        • Edelman A.B.
        • Carlson N.E.
        • Cherala G.
        • Munar M.Y.
        • Stouffer R.L.
        • Cameron J.L.
        • et al.
        Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic–pituitary-ovarian activity.
        Contraception. 2009; 80: 119-127
        • Edelman A.
        • Cherala G.
        • Munar M.Y.
        • Dubois B.
        • McInnis M.
        • Stanczyk F.Z.
        • et al.
        Prolonged monitoring of ethinyl estradiol and levonorgestrel levels confirms an alterered pharmacokinetic profile in obese oral contraceptive users.
        Contraception. 2013; 87: 220-226
        • Edelman A.
        • Cherala G.
        • Munar M.Y.
        • McInnis M.
        • Stanczyk F.Z.
        • Jensen J.T.
        Correcting oral contraceptive pharmacokinetic alterations due to obesity. A randomized controlled trial.
        Contraception. 2014; 90: 550-556
        • Westhoff C.L.
        • Torgal A.H.
        • Mayeda E.R.
        • Pike M.C.
        • Stanczyk F.Z.
        Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women.
        Contraception. 2010; 81: 474-480
        • Croxatto H.B.
        • Diaz S.
        • Pavez M.
        • Cardenas H.
        • Larsson M.
        • Johansson E.D.B.
        Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.
        Contraception. 1988; 38: 509-523
        • Johannsson E.
        • Brache V.
        • Alvarez F.
        • Faundes A.
        • Cochon L.
        • Ranta S.
        • et al.
        Pharmacokinetic study of different dosing regimens of levnorgestrel for emergency contraception in healthy women.
        Hum Reprod. 2002; 17: 1472-1476
        • Rowland M.
        Protein binding and drug clearance.
        Clin Pharmacokinet. 1994; 1 ([Suppl]): 10-17
        • Edelman A.
        • Cherala G.
        • Stanczyk F.
        Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review.
        Contraception. 2010; 82: 314-232
        • Stanczyk F.
        All progestins are not created equal.
        Steriods. 2003; 68: 879-890
        • Lindstedt G.
        • Lundberg P.
        • Lapidus L.
        • Lundgren H.
        • Bengtsson C.
        • Bjorntorp P.
        Low sex-hormone-binding globulin concentration as independent risk factor for development of NIDDM.
        Diab. 1991; 40: 123-128
        • Edwards D.J.
        Beneficial pharmacokinetic drug interactions.
        Adv Pharmacoepidem Drug Saf. 2012; S1-002
      1. FDA prescribing information, Plan B one-step. Available at: [Accessed November 2, 2015].

        • Cherala G.
        • Edelman A.
        • Thornburg K.
        Traditional assay methodology, drug species, and perinatal growth: a perfect storm for oral contraceptive failure among obese women.
        J Womens Health. 2014; 23: 855
        • Callahan R.
        • Stanczyk F.
        • Taylor D.
        • Steiner M.
        • Kopf G.
        • Dorflinger L.
        Measuring total plasma levonorgestrel (LNG) levels among users of contraceptive implants: a comparison of radioimmunoassay and mass spectrometry methods.
        in: Meeting of the Fertility Control Club. 2015 ([Barcelona, Spain])
        • Ohshima T.
        • Hasegawa T.
        • Johno I.
        • Kitazawa S.
        Variations in protein binding of drugs in plasma and serum.
        Clin Chem. 1989; 35: 1722-1725
        • El-Migdadi F.
        • Qaw F.
        Serum and plasma levels of total and free testosterone and of sex hormone binding globulins in rats growing in the below sea level environment of the Jordan Valley.
        Internet J Endocrinol. 2009;