Androgen Replacement Therapy in Late-Onset Hypogonadism: Current Concepts and Controversies – A Mini-Review

Abstract

Background: Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. Objective: The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1–2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. Methods: A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Results: Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Conclusions: Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental.

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

“…Because testosterone deficiency plays a key role in LOH, testosterone replacement therapy has been used to alleviate the symptoms of LOH. 5,8,9,32 To reveal the mechanism of decreased testosterone production in aged Leydig cells and possibly identify new therapies, we studied the effect of autophagic alteration on steroidogenesis in young and aged rat Leydig cells and TM3 mouse Leydig cells.…”

“…3 And testosterone replacement therapy can alleviate the symptoms and signs with a wide range of benefits that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. 2,[4][5][6][7][8] Serum testosterone levels decrease in aged males, and dysfunction of the aged Leydig cells might plays a key role in this process. [9][10][11] Androgen is mainly produced by Leydig cells and many enzymes, such as steroidogenic acute regulatory (StAR) protein, cholesterol sidechain cleavage enzyme (P450scc) and 3b-hydroxysteroid dehydrogenase, are involved in regulation of testosterone production.…”

The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism

“…In opposition to the abrupt cessation of ovarian estrogen 13 production, the decline in testicular endocrine function begins 14 slowly around the age of 40 years [1]. In men aged between 40 and 15 70 years, total testosterone level falls by about 1.6% per year, while 16 free and bioavailable testosterone by about 2-3% per year [2].…”

Comprehensive evaluation of androgen replacement therapy in aging Japanese men with late-onset hypogonadism

“…While female menopause is well studied, androgen deficiency of the aging male remains poorly understood [1]. Serum total testosterone and free testosterone levels decline with age in males by 0.8% and about 2% per year, respectively [2].…”

“…Although all modern guidelines assess testosterone replacement therapy (TRT) as safe if recommendations are followed properly, there may not be yet conclusive evidence as to the safety of TRT [1]. In this study, we investigated the efficacy and safety of TRT given for at least six months in 50 consecutively enrolled Japanese men with LOH.…”