The effect of the menstrual cycle on the pharmacokinetics of caffeine in normal, healthy eumenorrheic females

Eur J Clin Pharmacol. 1999 Aug;55(6):445-9. doi: 10.1007/s002280050654.


Objective: Hormonal fluctuations of estrogen and progesterone in eumenorrheic women may be capable of altering the pharmacokinetics of certain agents. The objective of this study was to determine the effect of the luteal, ovulatory and follicular phases of the menstrual cycle on the pharmacokinetics of caffeine, a low clearance, flow-independent drug.

Methods: Subjects were ten healthy, non-smoking, eumenorrheic females who were not pregnant and had not used oral contraceptives for a minimum of 3 months prior to the study. Blood samples were collected during one menstrual cycle for the determination of estradiol and progesterone concentrations during the follicular (days 2-6 post-onset of menses), ovulatory (days 13-16 post-onset of menses) and luteal (days 22-26 post-onset of menses) phases. Caffeine was administered over a single menstrual cycle during the follicular, ovulatory and luteal phases. Each subject was administered a single oral dose of caffeine (300 mg) in 100 ml of lemonade during each phase of the menstrual cycle. A venous catheter was used to collect blood samples at pre-dose and at the following time points: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 and 24 h. Plasma caffeine concentrations were determined using a validated ultraviolet high-performance liquid chromatography method.

Results: There were no significant (P < 0.05) differences in the pharmacokinetic parameters of caffeine across the menstrual cycle phases. The average area under the plasma concentration-time curve (AUCinf) was 93.01 mg 1(-1) x h and the absorption rate constant (ka) was 2.88 h(-1) during the ovulatory phase, 83.0 mg 1(-1) h and 2.06 h(-1), respectively, during the luteal phase and 84.7 mg 1(-1) x h and 1.84 h(-1), respectively, during the follicular phase.

Conclusions: These findings suggest that the menstrual cycle does not significantly alter the pharmacokinetics of caffeine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Caffeine / pharmacokinetics*
  • Central Nervous System Stimulants / pharmacokinetics*
  • Cross-Over Studies
  • Female
  • Follicular Phase / metabolism
  • Humans
  • Luteal Phase / metabolism
  • Menstrual Cycle / metabolism*
  • Ovulation / metabolism


  • Central Nervous System Stimulants
  • Caffeine