Literature search identified only very few studies investigating the effects of menopause on pharmacokinetics of different drugs. We here provide some examples to showcase potential effects of menopause.
Clearance of alfentanil (a short-acting anesthetic) metabolized largely by CYP3A4, was studied in 21 women and found to be more than double as high at premenopausal age compared to menopausal age, with no such effect in age-matched men [3]. Clearance of tirilazad, a neuroprotective steroid, metabolized by CYP3A4, was one third higher in 10 premenopausal women compared to 10 menopausal women [4]. The same study showed a similar difference in the clearance of midazolam (a short acting tranquilizer), which is considered a marker of CYP3A4 activity [4]. Zijp et al. [5] analyzed the effect of menopausal status on metabolism of tacrolimus, an immunosuppressant metabolized by CYP3A4 in 818 patients. Metabolism in women of premenopausal age was 43% higher than in women of menopausal age, while there was a non-significantly (12%) higher metabolism in men of comparable age groups.
Castberg et al. [6] analyzed age and sex effects in 7626 users of quetiapine, an antipsychotic, metabolized by CYP3A4. They found a sex-by-age interaction and showed that male and female serum concentrations are similar until age 50, after which women develop significantly higher values than men, inducing a 33% sex difference.
Rosuvastatin, a competitive hydroxymethylglutaryl-coenzyme A inhibitor, partly metabolized by CYP2C9, was studied in 40 women [7]. Three hours after administration of a single dose of 40 mg, more than fourfold higher plasma levels were found in premenopausal women, compared to menopausal women.
Olanzapine, an antipsychotic drug metabolized by CYP1A2, was studied in 248 patients, finding a sex-by-age interaction, with higher blood levels in young women and lower blood levels in older women [8]. While the dose-corrected concentration (C:D ratio) of olanzapine increased with age in men, it decreased in women; an effect that may be attributable to menopause. Finally, a study including over 3000 men and women using lamotrigine (an anti-epileptic drug metabolized by UGT) demonstrated a significant drop in clearance in women aged 51–55 [9], but not in male peers, again suggesting interaction between menopausal status and pharmacokinetics.