Lack of interaction between orlistat and oral contraceptives

Objectives: Orlistat, a potent and selective inhibitor of gastrointestinal lipases, is designed for the treatment of obesity. A double-blind, randomised, placebo-controlled, 2-way crossover study investigated the possible influence of orlistat on the ovulation-suppressing action of combination oral contraceptives (OC). Methods: After an 8-day run-in prior to the first of two consecutive menstrual cycles (Day 1 was the first day of menstruation), two groups of 10 healthy women, 20-27 years of age and on a stable regimen with OCs, received either 120 mg orlistat t.i.d. or placebo t.i.d. on Days 1-23 of the first cycle, and, separated by a placebo washout period on Days 24-28, the alternative treatment on Days 1-23 of the second cycle. In both cycles, serum luteinizing hormone (LH) was measured on Days 12-16 and progesterone on Days 12, 16, 19-23. Results: The geometric means of time-averaged concentrations (Days 12-16 for LH and Days 19-23 for progesterone) in the cycles with orlistat and placebo, respectively, and the one-sided 95% confidence region for the mean in the cycle with orlistat were 1.92, 2.03 and < 2.23 IU l(-1) for LH and 0.147, 0.145 and < 0.176 mu g l(-1) for progesterone. The one-sided 95% confidence region for the ratio (orlistat/placebo) of geometric means was < 1.06 for LH and < 1.11 for progesterone. Conclusion: During normal ovulation the peak serum concentration of LH is above 30 IU l(-1) around Day 14 of the cycle, and that of progesterone exceeds 3 mu g l(-1) around day 21. The 95% confidence regions for the means, as well as all individual concentrations, were below these limits. It was concluded that orlistat did not influence the ovulation suppressing action of oral contraceptives.