Letrozole is an aromatase inhibitor, used to treat post-menopausal women with hormone receptor-positive or advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In case of adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair testing, this study aims at investigating the incorporation into hair of single or repeated doses of letrozole.

Four subjects were recruited to investigate the incorporation in hair after ingestion of letrozole. Hair samples were obtained from: (i) 2 subjects (A and B) in chronic therapy with 2.5mg of letrozole/day and (ii) 2 subjects (C and D) who ingested one dosage of 2.5mg and 0.62mg of letrozole, respectively. From subject A and B a whole length hair sample was collected, and segmental analysis was performed on 1cm long segments. From subjects C and D, beard hair was sampled by shaving before administration (t=0), 3 days after administration, and 6 days after administration. Head hairs were cut close to the scalp 10 and 90 days after administration. Analysis were performed through HPLC–HRMS.

Letrozole was present in concentration higher than 160pg/mg in all segments from subjects A and B. In subject C a detectable amount of the analyte in beard of the first 3 days (160pg/mg in 0–3 days), up to the 6th day (130pg/mg in 3–6 days) after ingestion and in head hair collected 10 days after ingestion (60pg/mg) were found. In subject D, a lower amount of letrozole both in beard (100 and 85pg/mg) and in head hair (30pg/mg) was determined. Letrozole was detected also in head hair collected 90 days after the drug administration (30pg/mg in C and 17pg/mg in subject D).

This preliminary study shows that a single administration of a therapeutic dose (2.5mg) or less than a dose (0.62mg) of the drug produces a positive hair sample. Moreover, the results highlight large differences between concentrations in hair of subjects who consumed a single dose and hair of subjects in chronic therapy and suggest a positive correlation between frequency and/or dose ingested and hair concentration. The relatively higher amount identified in beard when compared to head hair suggests a mixed mode of incorporation in beard through sweat and blood.