High Plasma Levels of Dihydrotestosterone Decline in Hypogonadal Men Following Testosterone Substitution
Gooren, L(1); Saad, F(2, 3); Haider, A(4); Yassin, A(3, 5)
(1)VUmc, Amsterdam, Netherlands (2)Bayer-Schering, Berlin, Germany (3)Gulf Medical College, Ajman, UAE (4)Bremerhaven, Germany (5)Segeberger Kliniken, Norderstedt, Germany
Introduction: Dihydrotestosterone (DHT), the most potent natural androgen, is formed through 5alpha-reduction of testosterone (T) and is 4-6 times more potent than T. Production of DHT is regarded as a means of amplification of the androgenic signal. Circulating DHT levels are approximately 10% of the blood T levels, mostly produced by non-gonadal tissues which express 5 alpha-reductase. The aim of this study was to monitor plasma levels of DHT in hypogonadal men receiving T substitution. Methods: Male patients with late onset hypogonadism underwent T substitution either via transdermal testosterone gel (50 mg/day, n=25) or intra-muscular long-acting testosterone undecanoate (TU, 1000 mg / 12 weeks, n=30). Plasma levels of T and DHT were measured at baseline and at study end. Results: At baseline the mean plasma levels of DHT was 275 ± 169 ng/L (range: 39 - 540 ng/L) and this fell significantly following T substitution to 162 ± 89 ng/L (p<0.05). In all patients who had a plasma level of DHT > 200 ng/L at baseline (n=21), DHT fell following T substitution from 376 ± 156 to 226 ± 103 ng/L (p<0.01). However, in patients who had a plasma level of DHT < 200 ng/L at baseline (n=34), plasma levels of DHT did not significantly alter following T substitution; 108 ± 45 to 104 ± 67 ng/L. Conclusion: Hypogonadal men exhibit a wide variance in plasma levels of DHT, and there would appear to be marked differences in how individuals respond to testosterone therapy based their DHT level. Some men with moderate degrees of T deficiency exhibit high levels of DHT which fall upon T administration. This occurs more prominently in individuals with a DHT level > 200 ng/L. In men with DHT < 200ng/L, T administration had little effect on DHT. It is hypothesized that the high levels of DHT in some hypogonadal men might protect these men from androgen deficiency through its greater potency. This protection may then no longer be needed when T levels are restored so DHT levels decline.
