Change in serum dehydroepiandrosterone, testosterone, insulin-like growth factor-1, and osteocalcin levels with the third generation selective estrogen receptor modulator arzoxifene (LY353381·HCI)

Phase I trials of arzoxifene, a third generation SERM lacking uterine agoninst actvity, have reported reductions in serum IGF-1 or IGF-1/IGFBP-3 ratio. Little information is available on serum levels of DHEA and free testosterone, known risk factors for postmenopausal breast cancer. As part of an ongoing Phase II chemoprevention trial of arzoxifene in high risk women, serum for a variety of biomarkers was obtained and frozen at baseline, after six months of arzoxifene 20 mg/day vs placebo, and again following six months of open label arzoxifene. A vanguard group of 24 subjects has completed study and results at baseline and study completion are available for the initial 14 subjects. Both pre- and post-menopausal subjects were eligible, with hormone replacement allowed providing women had been on continuously for ≥6 months prior to entry. No changes in hormonal treatment were allowed during the study. Serum was obtained (during the follicular portion of the cycle, D1-14, for premenopausal women) and stored frozen until analysis. Median age was 49.5 years (range 43-61) and median baseline estradiol level was 68 pg/ml (