Effect of aromatizable and unaromatizable androgen replacement in hypogonadal men on GH responsiveness

Although studies have clearly demonstrated that oestrogen replacement affects GH responsiveness by causing relative GH resistance, the effect of androgen replacement is unknown. Circumstantial evidence only suggests that androgen replacement may increase GH sensitivity and/or responsiveness. To examine the impact of androgens on GH responsiveness, hypogonadal men underwent the IGF-1 generation test in the unreplaced state, replaced with testosterone (T) and also replaced with dihydrotestosterone (DHT), its nonaromatizable metabolite.

Twelve hypogonadal men with a normal GH axis were recruited. Each subject in random order had 4 weeks off T (NoRx), 4 weeks on T gel (TG) and 4 weeks on DHT gel (DHTG) applied daily, with 1 week washout between each preparation. An IGF-1 generation test using a subcutaneous injection of 7 mg of GH was performed at the end of each of these 4-week phases.

Serum GHBP, total and free IGF-1, IGFBP-3 and acid-labile subunit (ALS) levels were measured at baseline and 24 h (peak) after GH administration.

Despite a decrease in GHBP during the TG and DHTG phases, there were no observed differences in baseline, peak or increment (peak - baseline) total or free IGF-1 between the NoRx, TG or DHTG phases.

There is no evidence of fluctuation in GH responsiveness in hypogonadal men, untreated or replaced with T or DHT alone. This implies that the increased level of oestradiol as a consequence of T replacement in hypogonadal men does not impact significantly on GH responsiveness, nor is there evidence of an androgen effect with elevated DHT levels as a consequence of either T or DHT replacement.