Effect of toremifene on clinical chemistry, hematology and hormone levels at different doses in healthy postmenopausal volunteers: phase I study.

Toremifene was given within the dose range of 3-680 mg as a single dose or on five consecutive days to 72 postmenopausal volunteers. Blood samples for clinical chemistry were taken hourly up to 7 h and 1, 2, 3, 7, 10 and 15 days after the last dose of toremifene. The concentrations of serum bilirubin, creatinine, amylase, free thyroxine, cortisol, prolactin, electrolytes and blood glucose remained unchanged at all dose levels. A statistically significant decrease was observed in liver enzymes (ASAT, ALAT, ALP) at the dose levels of 220-680 mg, whereas gamma-GT remained unchanged. A decrease in the concentration of LH and FSH was observed at the dose levels of 46 mg or higher and 220 mg or higher, respectively. These hormonal changes including the increase of SHBG at the dose levels of 220-680 mg and the decrease of antithrombin III (220-680 mg) may be attributed to a weak estrogen-like effect of toremifene. Side effects were minimal: pulse rate, blood pressure and ECG remained unchanged during the test period. Only two patients on 680 mg dose suffered from nausea and vertigo, and one of them discontinued the medication.