Estimating the Contribution of the Prostate to Blood Dihydrotestosterone

The prostate strongly expresses type 2 5α-reductase, which avidly converts on entry most testosterone (T) to 5α-dihydrotestosterone (DHT). However, the quantitative contribution of the prostate to blood DHT is uncertain. We evaluated prostatic contribution to blood DHT by comparing the blood DHT concentrations in androgen-deficient patients with or without a prostate while they were receiving standard dose of T replacement. Androgen-deficient males (ADM) and female to male (F2M) transsexuals were studied in 2 centers, with both groups receiving either testosterone ester injections (250 mg mixed T esters) every 1 wk (Amsterdam) or 800 mg subdermal T implantation (Sydney). Among 39 Dutch patients, F2M (n = 21) were younger and smaller in physique than ADM (n = 18). One week (±1 d) after an injection, plasma DHT concentrations were 1.6 ± 0.2 (F2M) vs. 1.4 ± 0.2 (ADM) nmol/liter (P = 0.47), but the postinjection time interval to blood sampling was shorter in F2M (5.9 ± 0.4 vs. 7.2 ± 0.3 d; P = 0.01). Covariance adjustment for time since last injection, age, and physique did not change the lack of significant difference in postinjection plasma DHT concentration. The rapid and wide excursions in plasma T concentrations after an im T ester injection make the timing of blood sampling critical. To remove confounding by this variable, the experiment was repeated at a second site in similar patients, but using a depot T that achieves steady-state delivery for prolonged periods. Among 29 Australian patients, before and 1 month after subdermal implantation of 800 mg T, plasma DHT concentrations were not significantly different between groups [F2M, 1.1 ± 0.1 (n = 14); ADM, 1.3 ± 0.1 (n = 15); P = 0.28]. Correction for covariates, including age, height, weight, body surface area, and body mass index, did not influence the lack of significant difference between treated groups. As both modes of T administration yielded similar plasma DHT concentrations regardless of the presence of a prostate, this study indicates that the normal human prostate is not a major contributor to circulating blood DHT concentrations.

New injectable testosterone ester maintains serum testosterone of castrated monkeys in the normal range for four months

Two groups of four long-term orchidectomized cynomolgus monkeys, Macaca fascicularis, weighing 2.8–4.6 kg received either a single intramuscular injection of 40 mg of a new testosterone ester, testosterone-trans-4-n-butylcyclohexyl-carboxylate (20 Aet-1) in an aqueous suspension or 32.8 mg testosterone oenanthate dissolved in sesame oil. Both preparations contained equal amounts of testosterone, namely 23.6 mg. Testosterone oenenthate injections resulted in supraphysiological serum testosterone levels for eight days followed by a rapid decline so that the lower physiological limit was reached after three weeks. In contrast, 20 Aet-1 produced a moderate increase of serum testosterone levels into the physiological range. Serum testosterone remained in this range for a period of 18 weeks. Thus it appears that the 20 Aet-1 may provide a long desired, new modality of testosterone substitution for hypogonadal men as well as for methods of male fertility control.

Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue ifself seems to effect no additional increase of testosterone in the tissue.