The Effects of Transdermal Dihydrotestosterone in the Aging Male: A Prospective, Randomized, Double Blind Study

Abstract

The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal penile tumescence once per week or less, andropause symptoms, and a serum T level of 15 nmol/liter or less and/or a serum SHBG level greater than 30 nmol/liter. The mean age was 58 yr (range, 50-70 yr). Of these subjects, 114 men completed the study. DHT was administered transdermally for 6 months, and the dose varied from 125-250 mg/d. General well-being symptoms and sexual function were evaluated using a questionnaire, and prostate symptoms were evaluated using the International Prostate Symptoms Score, transrectal ultrasonography, and assay of serum prostate-specific antigen. Early morning erections improved transiently in the DHT group at 3 months of treatment (P< 0.003), and the ability to maintain erection improved in the DHT group compared with the placebo group (P < 0.04). No significant changes were observed in general well-being between the placebo and the DHT group. Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment. Treatment with DHT did not affect liver function or the lipid profile. Hemoglobin concentrations increased from 146.0 +/- 8.2 to 154.8 +/- 11.4 g/liter, and hematocrit from 43.5 +/- 2.5% to 45.8 +/- 3.4% (P < 0.001). Prostate weight and prostate-specific antigen levels did not change during the treatment. No major adverse events were observed. Transdermal administration of DHT improves sexual function and may be a useful alternative for androgen replacement. As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia, DHT may be beneficial, compared with aromatizing androgens, in the treatment of aging men.

Testosterone Deficiency in Men: Systematic Review and Standard Operating Procedures for Diagnosis and Treatment

“…However, the lack of estrogenic activity of DHT could be regarded as an advantage in particular situations, such as gynecomastia, where estrogenic activity of T should be avoided. Concerns on the use of DHT for Tth derives also from its putative prostate‐stimulating effect, which however was not confirmed in the few trials published so far ([136], EBMl1a). DHT is available in some countries as a 2.5% transdermal preparation and in others as an orally active 1‐methyl derivative, mesterolone, which is converted by the liver to DHT.…”

Plasma levels of dihydrotestosterone remain in the normal range in men treated with long-acting parenteral testosterone undecanoate

“…As DHT is implicated in the development of benign prostatic hyperplasia (BPH) and prostate cancer, high DHT blood levels have traditionally been regarded as undesirable. Furthermore, three DHT gel studies did not report any increase in PSA levels, prostate volume or symptoms (de Lignieres, 1993;Ly et al, 2001;Kunelius et al, 2002). Studies with scrotal testosterone patches providing a long-term outcome with high DHT blood levels over a period of several years, do not indicate any risk of prostatic hyperplasia or cancer, although they involve only a small number of patients (Behre et al, 1999).…”

“…Furthermore, three DHT gel studies did not report any increase in PSA levels, prostate volume or symptoms (de Lignieres, 1993;Ly et al, 2001;Kunelius et al, 2002). Further, the androgen physiological mechanisms of the prostate are geared to maximise androgen effects, first by its high density of T receptors, and second by its high degree of conversion of T to DHT (Wilson, 1996), resulting in higher intraprostatic DHT levels than serum DHT levels and higher levels of intraprostatic DHT than levels of intraprostatic T. This could potentially explain why an elevation of peripheral DHT levels has no impact on the prostate itself, also apparent from studies that used DHT itself for androgen treatment which found no effect on the prostate (de Lignieres, 1993;Ly et al, 2001;Kunelius et al, 2002). In one study, even a 15% decrease of prostate volume was detected (de Lignieres, 1993), and this is possibly due to the following mechanism: DHT suppresses LH and FSH levels, resulting in lower endogenous T production which in turn leads to diminished aromatisation of testosterone to oestradiol.…”

Erratum

“…40Y42 Mood enhancement and improved well-being figure prominently in anecdotal reports and uncontrolled clinical trials, 16,41 but these have not been consistently demonstrated in placebo-controlled studies of either hypogonadal 17,40,43 or eugonadal 42,44,45 men. The body of evidence suggests that administration of exogenous testosterone has consistent positive effects on libido and energy, which seem to be greatest in the setting of hypogonadism (ie, testosterone replacement).…”