While the efficacy of androgen replacement therapy (ART) has been widely investigated in Western countries, it remains controversial whether ART can improve health and prolong active lifestyles. A multicenter randomized controlled trial in Japan (EARTH Study) evaluated the efficacy of ART on late-onset hypogonadism (LOH) and prospectively assessed long-term effects on the physical and mental statuses of aging men. 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 was associated with significant decreases in waist circumstance and serum triglyceride (TG); with significant increases in whole-body and leg muscle mass volumes, serum hemoglobin, IPSS voiding subscore, and a positive effect on erectile function. There was no significant difference between the groups in terms of severe adverse events.

   Another study investigated the potential benefits of testosterone administration to elderly men (>65 years) with LOH in comparison with younger men and assessed the safety of testosterone administration in elderly men. A total of 561 hypogonadal men from two registry studies were divided into age groups of ≤65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with testosterone for up to 6 years.
   
   Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins.

   This study concluded: "The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH."

     Idiopathic hypogonadotropic hypogonadism is a rare disorder. A study of forty-three male patients (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and twenty controls (age and weight-matched) evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated.

   The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after androgen replacement therapy began, indicating significantly reduced atherosclerotic risk markers in these patients.

Clin Endocrinol (Oxf). 2015 Mar;82(3):422-8.