Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

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

Late-onset hypogonadism （LOH） is closely related to secondary androgen deficiency in aged males, but the mechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone （LH）-stimulated steroidogenic acute regulatory （STAR） protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species （ROS） levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H2O2, resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.

Hypogonadism and erectile dysfunction： an overview

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases （eNOS and nNOS）, and phosphodiesterase type-5 （PDE-5）, which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men.

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population

Background Late onset hypogonadism negatively impacts on men＇s psychological well-being This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life.Methods Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6： aging male＇s symptoms （AMS） rating scale,