Late Onset Hypogonadism

Hypogonadism is known as late-onset hypogonadism (LOH), age-related hypogonadism, PADAM (Partial Androgen Deficiency in Aging Male), ADAM (Androgen Decline in the Aging Male), or TDS (Testosterone Deficiency Syndrome)

According to the literature it has been reported that three different factors are responsible for changes in serum testosterone levels in older men. LOH is a consequence of the aging process, deterioration of hypothalamic-pituitary function, and Leydig cell function in the testes The aging of males leads to disorders of pulsed secretion of GnRH by dysregulation of the hypothalamic pulse generator and reduction of the frequency and amplitude of LH pulses. The amount and activity of Leydig cells decreases mainly by progression of atherosclerosis and degenerative changes in Leydig cells. Only the free, unbound testosterone is biologically active. SHBG levels increase with age, so the proportion of bioactive free testosterone decreases. In older men, it often leads to an increase in aromatase activity, which metabolises testosterone to estradiol. This phenomenon is compounded by the co-occurrence of obesity, diabetes mellitus, cardiovascular disease, and cancer

Age-related hypogonadismis a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of the quality of life and harmful effects on multiple organ systems. In middle-aged men, the incidence of biochemical hypogonadism varies from 2.1% to 12.8%. The incidence of low testosterone and symptoms of hypogonadism in men aged 40-79 years varies from 2% to 6%. Hypogonadism is more prevalent in older men, in obesity, in those with co-morbidities, and in men with a poor health status. There are no pathognomonic symptoms of LOH. However, the most characteristic symptoms are erectile dysfunction, decreased sexual activity and loss of libido, decreased muscle strength, decreased vital energy, hot flashes, gynaecomastia and decreased testicular volume, and low-energy conditions. Non-specific symptoms include: decreased self-confidence, motivation, depression and irritability, memory and concentration impairment, sleep disorders or insomnia, and decreased psychomotor activity. There is a higher prevalence of type 2 diabetes, obesity, cardiovascular disease, osteoporosis, and anaemia in men with decreased testosterone levels. The clinical consequences of hypogonadism are determined by the age of onset and the severity of hypogonadism. In LOH, the severity of many clinical symptoms is much lower than in pre-pubertal onset of androgen deficiency. The mortality of patients with testosterone deficiency is significantly higher than among men with normal serum testosterone level. Pye et al. estimated that severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the testosterone level and the presence of sexual symptoms contribute independently. Compared with eugonadal men, the multivariable-adjusted risk of mortality was two fold higher in those with testosterone level less than 2.5 ng/ml (irrespective of symptoms; HR 2.3; 95% CI: 1.2-4.2) and three fold higher in those with three sexual symptoms (irrespective of serum testosterone; compared with asymptomatic men; HR 3.2; 95% CI: 1.8-5.8). Similar risks were observed for cardiovascular mortality.

Hypogonadism is a generally acknowledged risk factor for osteoporosis, and testosterone substitution is an accepted therapeutic measure for prevention of osteoporosis as well as for improving bone mass in patients with manifest hypogonadism. According to the latest guidelines on osteoporosis from the Endocrine Society, total testosterone measurement is suggested in all men evaluated for osteoporosis or considered for pharmacological treatment with bone-active agents.

In older men with LOH, testosterone replacement therapy (TRT) may present several benefits regarding body composition, metabolic control, and psychological and sexual parameters.

TRT has a beneficial effect on health, manifested by improvement in mood, concentration, sleep quality, physical and mental fitness, increased libido, increased frequency of morning erections and erotic dreams, and improvement of erectile dysfunction and satisfaction with sex life. Randomised trials show a correlation between restored physiological testosterone levels, muscle mass, and strength measured as leg-press strength and quadriceps muscle volüme. TRT improves bone mineral density at the lumbar spine and femoral neck. Body composition is influenced by TRT in hypogonadal men, with a consequent decrease of fat mass and an increase in lean body mass. TRT has positive effects on glycaemia and lipid profile, and it decreases insulin resistance and visceral adiposity in hypogonadal men with impaired glucose tolerance and lipid profile, with a consequent decrease of mortality.