A PHASE II, PLACEBO-CONTROLLED, DOUBLE-BLIND, DOSE-RANGING (35MG/D OR 70MG/D)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an investigator initiated, industry sponsored protocol which was conceived with significant input by the investigators at Harbor. This is a multi-center study in male subjects ages 60-80 who have low serum testosterone and symptoms of hypogonadism. There will be approximately 120 patients (40 in each treatment group). They will be given 35 mg/d, 70 mg/d dihydrotestosterone (DHT) gel, or a placebo gel. All subjects will apply the gel once daily. The primary efficacy endpoint in this study is an increase in Lean Body Mass (LBM) as determined by the DEXA (a machine used to measure bone mineral density and total body composition). Secondary endpoints in this study include changes in Libido, muscle strength, sexual function, aging male symptom scale, quality of life, normal testosterone levels, cognition, mood, and clinician's global impression of change. The study will occur over a six-month period. Before the subject is randomized to receive study medications, he will undergo a screening phase, which includes the consent process, physical exam, blood tests, urine tests, and an electrocardiogram (EKG). If all results of the screening are found to be within the normal range, the subject will be randomized to receive either 35 mg/d, 70 mg/d DHT or placebo gel. They will also undergo a prostate ultrasound, blood test, DEXA, muscle strength testing and a six-minute walk test, at the baseline visit. Subjects will return to the GCRC on months 1, 3, and 6, for blood tests (to measure hormone levels), completion of questionnaires, vital sign assessment, and assessment of gel application areas. A seven-day diary will be completed prior to each visit to record sexual desire, erections, and alcohol intake. Physical exam will be done at months 3 and 6. An prostate ultrasound will be repeated at month 6 (end of study). At months 2, 4, and 5, subjects will be telephoned to inquire about their daily gel treatment and any changes in their health and medications. The total amount of blood drawn for the study will be less than a pint. The patient may benefit from the effects of androgen replacement therapy including improvement in sexual function and an increase of lean body mass and bone thickness. The anticipated total male hormone (DHT plus testosterone) levels achieved after DHT application will be within the physiologic range of the total androgen level in adult men. It is unlikely that the subjects will experience any clinically significant side effects, except for mild weight gain, oiliness of skin, acne, and skin irritation. Other possible side effects include: increase in red blood cells, breast tenderness, leg swelling, changes in cholesterol levels, increase in prostate size and symptoms of obstruction to urine flow. There is no clear evidence that shows that male hormones cause cancer of the prostate. Men will be followed with serum PSA levels and prostate ultrasound will be done at baseline and end of study. Men with pre-study symptoms of difficulty in urinating will not be eligible to participate. Prolonged skin contact by the female partner where DHT is applied may result in some slight increase of facial hair in the partner. Patients will wear protective clothing or showered before close contact with females and children. It must be kept out of reach from women, children, and persons with inability to read and understand. As mentioned above, we anticipate screening and enrolling 120 subjects and randomizing no more than 40 subjects here at Harbor-UCLA. However, this study will be done at two other centers, besides Harbor-UCLA, and all hormone assays from the 120 subjects randomized from all three centers will be done at the GCRC or the Endocrine Research Laboratory of the investigators. This study will help develop a new transdermal method for androgen replacement for aging, hypogonadal men. Although DHT is the most abundant male hormone within the prostate, there is no evidence that administration of exogenous DHT will increase the DHT levels in the prostate. On the contrary there have been suggestions that as DHT cannot be converted to the female hormone and as both male and female hormones are required for the development of prostate enlargement in older men, DHT has been suggested to have less prostate growth promoting effect than testosterone itself.