ABSTRACT
Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second question on IIEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.
ABSTRACT
PURPOSE: Although various attempts have been made and employed to restore normal testosterone levels in hypogonadal patients, it is still to be improved to achieve efficient hormone delivery. Recently a non-scrotal transdermal delivery system, Androderm patch, has been developed and proven to be of high efficacy and safety. We performed this study to examine the efficacy and safety of Androderm patch in Korean subjects. MATERIALS AND METHODS: A total of 26 hypogonadal men who met the inclusion and exclusion criteria enrolled this study Subjects who had been treated with intramuscular administration of tetosterone had a 6-week washout period. After baseline evaluations, placebo patch was administered for 4 weeks and reexamined. Then patients received therapy over a 24-week period and were evaluated at 4-week intervals. The following efficacy parameters were evaluated at various time points during the study; serum concentrations of testosterone, bioavailable testosterone and estradiol, nocturnal penile tumescence test using Rigiscan, sexual function questionnaires, and hypogonadism symptoms. Also evaluated were safety parameters including skin tolerability, laboratory parameters, prostate evaluation and adverse events. RESULTS: Fifteen patients were completed the study and included for data analysis. Most cause of drop-out cases(7/8) was local skin irritability. Testosterone level was increased from the pretreatment level of 91.5+/-83.3ng/dl to 503.1+/-177.6ng/dl during treatment. Bioavailable testosterone level was also increased significantly during treatment. Compared to baseline evaluations, significant improvements were shown in Rigiscan parameters(RAU & TAU values), sexual function scores and hypogonadism symptoms. No changes were found in safety parameters. However, it was also shown that a majority of patients(79.2%) experienced skin irritability with varying degree of reaction. CONCLUSIONS: In conclusion, non-scrotal testosterone transdermal delivery system can produce physiologic serum androgen levels, improve objective and subjective sexual functions and reduce hypogonadal symptoms without any serious adverse reactions. However, it is suggested that the frequent skin irritability remains to be overcome for further improvement.
Subject(s)
Humans , Male , Estradiol , Hypogonadism , Penile Erection , Prostate , Surveys and Questionnaires , Skin , Statistics as Topic , TestosteroneABSTRACT
To investigate the possibility of in vivo transplantation of Leydig cells as a new biologic androgen replacement therapy, the Leydig cells procured from 6 week-old male Sprague-Dawley rats were autotransplanted, and the level of testosterone secretion and histostructural changes were observed. The renal subcapsular and intraperitoneal transplant showed higher levels of testosterone compared to subcutaneous or scrotal counterparts, and the number of transplanted cells was correlated with the level of measured testosterone. Furthermore, if the Leydig cells were transplanted intraperitoneally after the uptake on synthetic collagen, testosterone levels were higher than the ones simply transplanted without synthetic collagen uptake, resulting in 27 fold increase at 3 months. The activity of 125I-hCG decreased 20 to 40% at each month after transplantation compared to the normal levels, but no statistical significance was noted among different periods. The histologic examination revealed neovascularized capillaries and well demarcated sheet-like group of eosinophilic Leydig cells were observed at 4 weeks. But the evidence of destructive changes such as a focal inflammation with central dystropic ossification could be noted after 3 month. On electron microscopy, the marked indentation of nucleus and presence of lipochrome pigment were seen, and the number and size of smooth endoplasmic reticulum and mitochondria were reduced after 3 month. In conclusion, testosterone output could be increased to the physiologic range by increasing the number of transplant cells or utilizing collagen uptake but further effort is necessary on delaying or preventing the structural and functional decrement of Leydig cells.