Aging and sex hormones in males

Several large cohort studies have disclosed the trajectories of sex steroids changes overtime in men and their clinical significance. In men the slow, physiological decline of serum testosterone (T) with advancing age overlaps with the clinical condition of overt, pathological hypogonadism. In addition, the increasing number of comorbidities, together with the high prevalence of chronic diseases, all further contribute to the decrease of serum T concentrations in the aging male. For all these reasons both the diagnosis of late-onset hypogonadism (LOH) in men and the decision about starting or not T replacement treatment remain challenging. At present, the biochemical finding of T deficiency alone is not sufficient for diagnosing hypogonadism in older men. Coupling hypogonadal symptoms with documented low serum T represents the best strategy to refine the diagnosis of hypogonadism in older men and to avoid unnecessary treatments

The endocrine role of estrogens on human male skeleton

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men

Estrogens and male reproduction

The chapter deals with the study of estrogen role in male reproduction, in particulare the role on hypothalamic-pituitary-gonadal axi

Update on acquired hypogonadism in men living with HIV: pathogenesis, clinic, and treatment

Hypogonadism is a frequent finding among men living with HIV (MLWH) and it seems to occur earlier in comparison with the general male population. Although the prevalence of hypogonadism in MLWH has significantly lowered thanks to advancements in medical management, it remains high if compared with age-matched HIV-uninfected men, ranging from 13% to 40% in the age group of 20-60 years. Signs and symptoms of low serum testosterone (T) in MLWH are cause of concern since they are non-specific, of mild-to-moderate degree, and often overlapping with those of infection per se. For these reasons, hypogonadism can be underestimated in the absence of targeted laboratory blood examinations. With regard to the etiological factors involved in the T decrease, emerging evidence has suggested the functional nature of hypogonadism in MLWH, pointing out the mutual relationship between sex steroids, health status, comorbidities, and HIV-related factors. In agreement with this hypothesis, a therapeutic approach aiming at improving or reversing concomitant diseases through lifestyle changes (e.g. physical activity) rather than pharmacological T treatment should be theoretically considered. However, considering both patient’s barriers to lifestyle changes to be maintained overtime and the lack of evidence-based data on the efficacy of lifestyle changes in normalizing serum T in MLWH, T therapy remains an option when other non-pharmacological interventions are ineffective as well as for all other functional forms of hypogonadism. From this perspective, the traditional therapeutic management of male hypogonadism in MLWH, especially the role of T supplementation, should be revised in the light of the probable functional nature of hypogonadism by considering a good balance between benefits and harmful. This narrative review presents an overview of current knowledge on hypogonadism in MLWH, deepening the factors driving and taking part in T decrease, providing advice for the clinical approach, and underlining the importance of individualized treatment aiming at optimizing non-gonadal comorbidities and thus avoiding over-, or even unnecessary, treatment with T

Male hypogonadism and pre-diabetes interplay: association or causal interaction? A systematic review

Aim: The association between type 2 diabetes mellitus (T2DM) and male hypogonadism has been largely demonstrated. Testosterone (T) serum levels are often lower in men with T2DM compared to the general population, and, conversely, men with higher T serum levels have shown lower risk of T2DM. On the contrary, the association between pre-diabetes and male hypogonadism has been less investigated thus far. Pre-diabetes is a common clinical condition preceding T2DM and has been recognized as a potential risk factor for other metabolic disorders and cardiovascular diseases. Therefore, the aims of this review are to investigate the association between pre-diabetes and male hypogonadism and to evaluate the potential effect of T treatment on glucose metabolism and anti-diabetic therapy on T serum levels. Methods: We conducted this systematic review developing different literature searches, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol. Results: In our analysis, male hypogonadism has a prevalence of around 24%-35% in pre-diabetic men. Moreover, we observed improvement of metabolic parameters in pre-diabetes with T treatment. On the contrary, antidiabetic therapy seems to have no particular effects on T serum levels. Conclusion: Overall, we demonstrated that, although T administration could be considered in pre-diabetic men, pre-diabetes-related treatments should be confined to the control glucose metabolism, since no evidence for a positive effect on total T serum levels is available. Future research should be oriented to study the role of new antidiabetic drugs in the sex hormonal status in hypogonadal men

Estrogens in males: what have we learned in the last 10 years?

This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications

The osteoporotic male: Overlooked and undermanaged?

Age-related bone loss in men is a poorly understood phenomenon, although increasing data on the pathophysiology of bone in men is becoming available. Most of what we know on bone pathophysiology derives from studies on women. The well-known association between menopause and osteoporosis is far from been disproven. However, male osteoporosis is a relatively new phenomenon. Its novelty is in part compensated for by the number of studies on female osteoporosis and bone pathophysiology. On the other hand, the deeper understanding of female osteoporosis could lead to an underestimation of this condition in the male counterpart. The longer life-span exposes a number of men to the risk of mild-to-severe hypogonadism which in turn we know to be one of the pathogenetic steps toward the loss of bone mineral content in men and in women. Hypogonadism might therefore be one among many corrigible risk factors such as cigarette smoking and alcohol abuse against which clinicians should act in order to prevent osteoporosis and its complications. Treatments with calcium plus vitamin D and bisphophonates are widely used in men, when osteoporosis is documented and hypogonadism has been excluded. The poor knowledge on male osteoporosis accounts for the lack of well shared protocols for the clinical management of the disease. This review focuses on the clinical approach and treatment strategy for osteoporosis in men with particular attention to its relationship with male hypogonadism