Tamoxifen as a therapeutic agent in acromegaly

Abstract

Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males. We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20-40 mg daily for 2-11 months (median of 4 months). IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2-4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men. Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82%) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47%). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated. Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.