Obese women may need a double dose of levonorgestrel-based emergency contraception (LNG EC), a new study hints.

“We found that obesity lowers the dose of LNG EC by about 50% and that we can reverse this by doubling the dose,” Dr. Alison Edelman from Oregon Health & Science University in Portland told Reuters Health by email.

Studies have suggested that LNG EC is less effective in obese women, failing four times as often as in non-obese women. The mechanism behind this is unknown but likely due to differences in LNG pharmacokinetics (PK), Dr. Edelman and colleagues note in their paper published online in Contraception.

To investigate, they studied five obese and five normal weight women who were healthy and of reproductive age. During the follicular phase, the women received 1.5 mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received double that dose (3 mg, ECx2).

The researchers obtained serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5 hours to assess total and free LNG PK parameters. The difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group was the primary outcome.

Following ECx1, the total LNG Cmax was significantly lower in obese women than normal weight women (5.57 vs. 10.30 ng/mL), the researchers found.

“Notably,” they say, ECx2 increased the Cmax significantly (10.52 ng/ml, p=0.002), approximating the level in normal weight women receiving ECx1. Free LNG Cmax followed a similar pattern.

This study shows that obesity “adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women,” they conclude.

Dr. Edelman told Reuters Health, “Our study did not focus on more-clinical outcomes like ovulation or pregnancy. It’s too early to know if doubling the dose of LNG EC would result in providing women of higher weights better protection. As obesity has the capacity to impact any point of the pathways that drugs follow it may not be as simple as changing the amount of drug in the system. On the other hand, LNG is extremely safe with no upper limit of toxicity known. We hope to conduct more research on the impact of this double dose and if it’s a viable option for women.”