Comparison of effects of the rise in serum testosterone by raloxifene and oral testosterone on serum insulin-like growth factor-1 and insulin-like growth factor binding protein-3

Abstract

Objective: In aging men serum levels of testosterone and insulin-like growth factor-1 (IGF-1) decline, potential factors in the reduced muscle strength, abdominal obesity, sexual dysfunction and impaired general well being of aging. The partial oestrogen agonist and antagonist raloxifene increase serum testosterone levels in aging men, but the effect of raloxifene on serum IGF-1 levels in men is unknown. In this study the effects of raloxifene on IGF-1 levels and the associated increase in serum testosterone were compared to the effects of oral testosterone supplementation. Design and patients: Thirty healthy elderly men between 60 and 70 years received raloxifene 120 mg/day or placebo in a randomised double blind fashion for 3 months. Secondly, seven female to male (F to M) transsexuals undergoing hormonal sex reassignment received testosterone undecanoate 160 mg/day. Measurement: At baseline and after three months serum levels of testosterone, IGF-1 and its most important binding protein, IFGBP-3 was measured. In the group transsexuals also serum gonadotrophins and 17β-oestradiol was measured. Results: Compared to placebo raloxifene increased serum testosterone by 20% but it decreased serum IGF-1 levels by 24.5% (95% confidence interval (CI): −13.0 to −36.1%). No significant change in serum IGFBP-3 levels was found. The effect of raloxifene on serum IGF-1 has been observed with other oral oestrogens, and, therefore, is likely to be ascribed to the partial oestrogen agonist activity of raloxifene. In the F to M transsexuals, serum testosterone levels increased from median <1.0 nmol/l to 6.2 nmol/l, without significant changes in serum gonadotrophins and 17β-oestradiol levels. Serum IGF-1 levels increased by 12.1% (95% CI: 1.9–22.3%) versus baseline. No effect was observed on serum IGFBP-3 levels. Conclusion: Both raloxifene and oral testosterone increased serum testosterone, but raloxifene significantly decreased serum IGF-1 levels without affecting IGFBP-3. By contrast, oral testosterone supplementation in F to M transsexuals increased IGF-1 levels. In both treatment groups no significant change in serum IGFBP-3 was found.