Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women

Abstract

Background This study was conducted to compare oral contraceptive (OC) pharmacokinetics (PK) in normal weight (BMI 19.0-24.9) and obese (BMI 30.0-39.9) women. Study Design During the third week of the third cycle of OC use, we admitted 15 normal weight and 15 obese women for collection of 12 venous specimens over 24 h. Using RIA techniques, we measured levels of ethinyl estradiol (EE) and levonorgestrel (LNG). During the same cycle, women underwent twice-weekly sonography to assess ovarian follicular development and blood draws to measure endogenous estradiol (E2) and progesterone levels. Results Obese women had a lower area under the curve (AUC; 1077.2 pg*h/mL vs 1413.7 pg*h/mL) and lower maximum values (85.7 pg/mL vs 129.5 pg/mL) for EE than normal weight women (p = 0.04 and 0.01, respectively); EE trough levels were similar between BMI groups. The similar, but smaller, differences in their LNG levels for AUC and maximum values (Cmax) were not statistically significant. While peak values differed somewhat, the LNG trough levels were similar for obese and normal weight women (2.6 ng/mL and 2.5 ng/mL, respectively). Women with greater EE AUC had smaller follicular diameters (p = 0.05) and lower E2 levels (p = 0.04). While follicular diameters tended to be larger among obese women, these differences were not statistically significant. Conclusion OC hormone peak levels are lower among obese women compared to normal weight women, but their trough levels are similar. In this small study, the observed PK differences did not translate into more ovarian follicular activity among obese OC users.

Inhibition of Human Liver Aldehyde Oxidase: Implications for Potential Drug-Drug Interactions

“…The traditional model for mixed inhibition involves one inhibitor binding site that is removed from the active site. This site may have its conformation altered by the presence or absence of substrate at the active site, such that the affinity for (Westhoff et al, 2010). b In pregnant women (Piwowarska et al, 2010).…”

Obesity and contraception: controversy?

“…21 Another study demonstrated lower serum concentrations of both EE and LNG in obese women, but trough levels were not significantly different. 22 The implication of these findings on the contraceptive efficacy of oral contraceptives may be small or negligible, as the minimum concentrations of LNG were sufficient to suppress ovulation. Again, there was evidence of more follicular activity in obese patients.…”

“…A body of literature has emerged focusing on the unique metabolic changes observed in obesity, pharmacokinetic alterations, and their effect on contraceptive efficacy. [20][21][22]24,25 Studies overall have been conflicting, but concern exists about increased rates of failure of hormonal contraceptives in this subset of women. The etiology of this finding is not well understood but is thought to be a result of alterations in the pharmacokinetics and metabolism of steroid hormone contraceptives.…”

“…Although not statistically significant, there was a trend toward larger follicular size with sonographic imaging as well as higher estradiol concentrations in obese subjects than in normal weight subjects. 22 There is less data about the pharmacokinetics of non-oral routes. Only one study looked at injectable contraception in obese women.…”

“…The etiology of this finding is not well understood but is thought to be a result of alterations in the pharmacokinetics and metabolism of steroid hormone contraceptives. [20][21][22]24,25 Metabolism/Pharmacokinetics in obese women and contraception…”