Reproductive toxicity of exemestane, an antitumoral aromatase inactivator, in rats and rabbits

Impaired reproduction in adult male, but not female, rats following juvenile treatment with the aromatase inhibitor, exemestane

“…Male body weights were similar among groups during the treatment period; however, a transient decrease in male body weight was noted following the end of dosing that resolved by PND 66. This is consistent with the observation in adult male rats treated with exemestane (Beltrame et al, 2001) and adult male rats treated with the aromatase inhibitor anastrozole (Turner et al, 2000) where body weight were unaltered by chronic administration. However, peripubertal rats treated with exemestane (100 mg/kg/week slow release from PND 26 to 68) or with the aromatase inhibitor letrozole (1 mg/kg/day from PND 30 to 90) had reduced body weight gain (Bajpai et al, 2010; van Gool et al, 2010a), whereas prepubertal male mice treated letrozole (2 mg/kg/day from PND 21 to 31) showed increased body weight gain (Eshet et al, 2004).…”

“…Increased female body weights were noted beginning on PND 31 that persisted through the end of the study. Similar increases in weight gain have been noted in peripubertal and adult female rats treated with exemestane and were attributed to an anabolic effect secondary to the intended pharmacological effect of exemestane (Beltrame et al, 2001; van Gool et al, 2010b).…”

“…Fadrozole suppressed estrous cyclicity during the treatment period, but normal cycling initiated within several days after treatment was discontinued. Although not monitored during the treatment period in our study, it is also likely that exemestane treatment suppressed estrous cyclicity as has been previously shown in adult females (Beltrame et al, 2001). Exemestane‐treated female rats (100 mg/kg/week slow release formulation from PND 26 to 47) showed decreased ovarian weight and an increased incidence of ovarian cysts (van Gool et al, 2010b).…”

“…Lack of such safety concerns may lead to widespread and indiscriminate use in children. Previous reproductive toxicology studies with exemestane in adult rats showed effects consistent with the intended pharmacological effects of the drug, that is, inhibition of aromatase resulting in an increase in circulating androgens and a decrease in circulating estrogens (Beltrame et al, 2001). In adult male rats these effects included compromised mating behavior (decreased copulation rate) as indicated by a marked inability of the rats to produce copulatory plugs when mated with untreated females.…”

Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial

“…The teratogenic potential of aromatase inhibitor was shown in animal studies (25). However, compared with other ovulationinduction agents, Mitwally et al (26) reported similar miscarriage, ectopic-pregnancy, and cycle-cancellation rates as well as pregnancy outcome in letrozole-treated patients.…”