OHSU clinical researchers Alison Edelman, M.D., M.P.H., and Jeffrey Jensen, M.D., M.P.H., published a study that examined why emergency contraception isn’t as effective in obese women, and how to potentially increase its effectiveness in this population. The findings, published March 19 in the journal Contraception, show how obesity adversely impacts circulating levels of emergency contraception, and that doubling the dose appears to correct obesity-related interference in the drug’s efficacy.
Roughly half of all pregnancies in the U.S. are unintended. Single-dose emergency contraception (EC), commonly referred to as “the morning after pill,” has the potential to decrease the risk of pregnancy following unprotected sex by nearly 90%. The most commonly used EC is the progestin hormone levonorgestrel (LNG); now available over the counter to both adults and adolescents, its use is increasing. Unfortunately, the LNG-based method appears to be significantly less effective in obese women, failing 4 times as often as in non-obese women. The exact mechanism for this phenomenon remains unknown and no prior studies have compared this EC’s effectiveness between obese and women of normal weight.
In their paper, “Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: Single and double dosing,” the authors provide evidence of how obesity interferes with the pharmacokinetics (how the body responds to a drug’s movement into and out of the body) of LNG. Women enrolled in the study were given both a single and double dose of LNG, then free (pharmacologically active) and total LNG levels were measured in blood samples at various time intervals after administration. What the researchers found was the levels were significantly lower in obese women who had received a single dose vs. non-obese women, but LNG levels increased significantly with a double dose of the drug, nearly equal to the levels observed in normal BMI subjects receiving a single dose.
While the team was unable to determine a clear mechanism for obesity’s significant impact on LNG due to a limited sample, it does appear that binding proteins play a key role. Levels of sex hormone binding globulin (SHBG) are lower in the obese, and since LNG is bound to SHBG, unpredictable clearance of the hormone can occur. They conclude that doubling the LNG dose may be an effective strategy to improve its efficacy in obese women.
This work was made possible by the support of the Medical Research Foundation of Oregon (Grant 1501), the National Institutes of Health support of the OHSU Oregon Clinical & Translational Research Institute (NIH NCRR 1 UL1 RR024120), as well as the Oregon National Primate Reserach Center core grant (OD011092). Co-authors on this study: Ganesh Cherala, Ph.D., Steven Blue, and David Erickson, Ph.D.