Absolute bioavailability of letrozole in healthy postmenopausal women

Simultaneous quantitative analysis of letrozole, its carbinol metabolite, and carbinol glucuronide in human plasma by LC-MS/MS

“…Fig. 1 Proposed metabolism of letrozole in humans [3][4][5] Accuracy as the deviation of the mean from the concentration added (given in %) and precision as the standard deviation (given in %) were determined by replicate analysis of low, medium, and high concentration quality controls. Six samples each were analyzed within one batch for intraday accuracy and precision and on six different days for inter-day accuracy and precision.…”

“…1) [3][4][5]. Urinary recovery of the latter accounts for 65% of the oral dose and represents the major pathway of clearance [5]. The initial step of letrozole metabolism as elucidated by in vitro experiments is mainly catalyzed by CYP2A6 and CYP3A4 [4].…”

Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination

“…Letrozole is readily absorbed after oral administration and it is mainly cleared by the liver with a mean half-life of approximately 45 hours. At doses of 1-5 mg/day letrozole has been shown to decrease circulating E to undetectable levels within 2-3 days of administration (22)(23)(24)(25).…”

Body mass index–associated differences in response to ovulation induction with letrozole

“…It is conceivable that a greater proportion of higher-BMI women are anovulatory due the increased circulating E 2 levels. Letrozole acts peripherally to decrease the aromatization of testosterone to estrogen, decreasing pituitary inhibition (2). The lower-BMI women likely have a greater range of infertility diagnoses, including diminished ovarian reserve and hypothalamic hypogonadism, which may not be alleviated by letrozole treatment.…”

“…Letrozole has a relatively short half-life ($45 hours) (2) and is thought to cause fewer antiestrogenic side effects than CC because estrogen receptors are not directly affected (1). A lower reported rate of multiple births compared with CC also makes letrozole an attractive option for oral OI (3).…”