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 1-1 for LH and 0.147, 0.145 and < 0.176 micrograms 1-1 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 1-1 around Day 14 of the cycle, and that of progesterone exceeds 3 micrograms 1-1 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.
PIP: In the Netherlands, a double-blind, randomized, placebo-controlled, two-way crossover study was conducted to determine whether administration of the inhibitor of gastrointestinal lipases, Orlistat, concomitantly with combined oral contraceptives (OCs) inhibits the ovulation-suppressing action of OCs. The 20 subjects, 20-27 years old, were healthy and had a body mass index between 22 and 27 kg m-2. All subjects completed the study. Most adverse events were mild and related to the pharmacological effect of Orlistat (fatty or oily stool, flatus with discharge, or abdominal pain). The geometric means of time-averaged serum concentrations in the cycles with Orlistat and the placebo and the 1-sided 95% confidence region for the mean in the cycle with Orlistat were 0.147, 0.145, and less than 0.176 mcg l-1 for progesterone and 1.92, 2.03, and less than 2.23 IU l-1 for luteinizing hormone (LH), respectively. These figures were well below the peak concentrations during normal ovulation (3 mcg l-1 for progesterone and 30 IU l-1 for LH). The plasma concentration of Orlistat was either close to the limit of quantification (1 mcg l-1) or below this limit. These findings suggest that Orlistat had no effect on the ovulation-suppression capabilities of the OCs.