Which Androgen for the Andropause—DHT or Testosterone?

Abstracts & Commentary

Synopsis: Transdermal DHT improves sexual function and may be a useful alternative for androgen replacement.

Sources: Kunelius P, et al. J Clin Endocrinol Metab. 2002; 87:1467-1472; Wang C, Swerdloff R. J Clin Endocrinol Metab. 2002;87:1462-1466.

Bioavailable testosterone (T) declines approximately 1% per year in men between 40 and 70 years of age. Kunelius and colleagues note that "in contrast to menopausal symptoms in women the age-related changes in testicular function in men are gradual and may be difficult to recognize. However, a number of changes typically experienced by ageing males have been attributed to a decline in circulating T levels." Diminished virility, fertility, energy, and depression as well as a decrease in bone and muscle mass and an increase in adiposity have been attributed to the decrease in T.

The objective of the study was to investigate the effects of DHT gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in a randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had serum T levels of 15 nmol/L or less (normal range, 10-35 nmol/L), and/or sex hormone binding globulin (SHBG) greater than 30 nmol/L. The mean age was 58 years (range, 58-70). A total of 114 men completed the study. DHT was administered transdermally for 6 months, and the doses varied between 125-250 mg/d.

Early morning erections improved in the DHT group at 3 months (P = 0.003) and the ability to maintain erections improved in the DHT group compared with the placebo group (P = 0.04). No significant changes were observed in well-being between the DHT and the placebo group (significant placebo effects were noted in the area of well-being). Serum concentrations of LH, FSH, estrogen (E2), T, and SHBG decreased significantly during the DHT treatment. Treatment with DHT did not effect liver function or the lipid profile. The hemoglobin and hematocrit both increased significantly. Prostate weight and prostate specific antigen did not change during treatment.

Kunelius et al concluded that 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.

Comment by Ralph R. Hall, MD, FACP

This interesting study is complicated by several factors. First, this is a small number of patients treated for a short period of time. Second, the level of T in this group was relatively high. The normal range of T in men is 10-35 nmol/L. Using the range of up to 15 nmol/L, this study may have decreased the apparent effectiveness of the DHT treatment.

In the accompanying editorial, Wang and Swerdloff note that the decrease in E2 that occurs in nonaromatizing androgens may have several potentially negative effects. Estrogens are thought to have beneficial effects on bone mineral density, dementia, and possibly cardiovascular disease. Studies documenting bone mineral markers during DHT treatment have not been done. The lack of adverse effects of DHT in this study is encouraging but better outcome measures are needed.

There were no changes in prostate size or increases in PSA determinations to indicate unfavorable effects on the prostate. Again, E2 is thought to contribute to increases in prostate hyperplasia and at least one study has reported decreases in prostate size during treatment with DHA.1

Studies are needed that compare T with DHT and placebo. In order to measure the effects of T and DHT on muscle strength, groups who are sedentary need to be compared with those in a structured exercise program. These early reports on both T and DHT certainly justify longer and more comprehensive trials of both T and DHT.

There are now extensive data supporting the safety of transdermal T in men with andropause and other forms of hypogonadism. There is not enough evidence supporting the safety of long-term DHT treatment to justify its use. Before starting T, however, rectal prostate examination should be carried out and if nodules are found, prostatic biopsy carried out.

The 4-page editorial by Wang and Swerdloff, (they have vast clinical and investigative experience in this area), is a brief, up-to-date, but comprehensive review of the present status of androgen replacement in older men. 

Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.

Reference

1. de Lignieres B. Ann Med. 1993;25:235-241.