Risks and Benefits of Late Onset Hypogonadism Treatment: An Expert Opinion

Giovanni Corona,Linda Vignozzi,Alessandra Sforza,Mario Maggi 대한남성과학회 2013 The World Journal of Men's Health Vol.31 No.2

Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized association with sexual and reproductive failure. LOH is frequently associated with chronic conditions including cardiovascular diseases (CVD), obesity, osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases. Despite this evidence, in patients with these conditions, LOH is still only rarely investigated and testosterone replacement therapy (TRT) rarely considered. In this paper, we critically reviewed the available evidence on LOH treatment focusing on possible risks and benefits. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient’s expectations. The fear of prostate cancer and the risk of erythrocytosis probably represent the main limitations of TRT in aging men. However, TRT in healthy older men in near physiological doses does not appear to incur serious adverse events, although regular monitoring of prostate-specific antigen and hematocrit levels is required. Available evidence also suggests that TRT might ameliorate central obesity and glycometabolic control in patients with metabolic syndrome and type 2 diabetes. In addition, TRT has been associated with an increase in bone mineral density in men with osteoporosis, with an improvement in lean body mass in subjects with human immunodeficiency virus infection or chronic obstructive pulmonary disease, as well as with peripheral oxygenation in patients with chronic kidney diseases. Despite this evidence, however, it should be recognized that the results of these trials were heterogeneous and limited by small sample sizes. Hence, further research is required regarding the long-term benefits and adverse effects of TRT in LOH.

Testosterone Replacement Therapy and Cardiovascular Risk: A Review

Giovanni Corona,Giulia Rastrelli,Elisa Maseroli,Alessandra Sforza,Mario Maggi 대한남성과학회 2016 The World Journal of Men's Health Vol.34 No.2

Recent reports in the scientific and lay press have suggested that testosterone (T) replacement therapy (TRT) is likely to increase cardiovascular (CV) risk. In a final report released in 2015, the Food and Drug Administration (FDA) cautioned that prescribing T products is approved only for men who have low T levels due to primary or secondary hypogonadism resulting from problems within the testis, pituitary, or hypothalamus (e.g., genetic problems or damage from surgery, chemotherapy, or infection). In this report, the FDA emphasized that the benefits and safety of T medications have not been established for the treatment of low T levels due to aging, even if a man's symptoms seem to be related to low T. In this paper, we reviewed the available evidence on the association between TRT and CV risk. In particular, data from randomized controlled studies and information derived from observational and pharmacoepidemiological investigations were scrutinized. The data meta-analyzed here do not support any causal role between TRT and adverse CV events. This is especially true when hypogonadism is properly diagnosed and replacement therapy is correctly performed. Elevated hematocrit represents the most common adverse event related to TRT. Hence, it is important to monitor hematocrit at regular intervals in T-treated subjects in order to avoid potentially serious adverse events.

Testosterone Deficiency and Risk of Cognitive Disorders in Aging Males

Corona Giovanni,Guaraldi Federica,Rastrelli Giulia,Sforza Alessandra,Maggi Mario 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.1

Cognitive impairment and dementia are predicted to undergo a dramatic increase in the following years with more than 131.5 million people being affected by 2030. Although vascular diseases play the most important role in the pathogenesis of memory impairment in aging men, some pre-clinical and clinical evidence has suggested a possible contribution of the age-dependent reduction of testosterone (T). In this paper we have summarized and discussed all the information derived from available animal and experimental studies. In addition, we meta-analyzed data rising from all randomized placebo controlled trials (RCTs) published so far. Only limited preclinical and clinical evidence can support a possible contribution of T in the pathogenesis of the age-dependent impairment of cognitive functions. In addition, our meta-analysis did not support the use of T replacement therapy for the improvement of several cognitive domains analyzed including attention/working memory, executive function, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability. However, it is important to recognize that the vast majority of available RCTs included mixed populations of subjects with eugonadism and hypogonadism preventing any final conclusion being drawn on these issues.

Testosterone Replacement Therapy and Cardiovascular Risk: A Review

Giovanni Corona G,Giulia Rastrelli,Elisa Maseroli,Alessandra Sforza,Mario Maggi 대한남성과학회 2015 The World Journal of Men's Health Vol.33 No.3

Recent reports in the scientific and lay press have suggested that testosterone (T) replacement therapy (TRT) is likely to increase cardiovascular (CV) risk. In a final report released in 2015, the Food and Drug Administration (FDA) cautioned that prescribing T products is approved only for men who have low T levels due to primary or secondary hypogonadism resulting from problems within the testis, pituitary, or hypothalamus (e.g., genetic problems or damage from surgery, chemotherapy, or infection). In this report, the FDA emphasized that the benefits and safety of T medications have not been established for the treatment of low T levels due to aging, even if a man’s symptoms seem to be related to low T. In this paper, we reviewed the available evidence on the association between TRT and CV risk. In particular, data from randomized controlled studies and information derived from observational and pharmacoepidemiological investigations were scrutinized. The data meta-analyzed here do not support any causal role between TRT and adverse CV events. This is especially true when hypogonadism is properly diagnosed and replacement therapy is correctly performed. Elevated hematocrit represents the most common adverse event related to TRT. Hence, it is important to monitor hematocrit at regular intervals in T-treated subjects in order to avoid potentially serious adverse events.

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer

Corona Giovanni,Filippi Sandra,Bianchi Nicola,Dicuio Mauro,Rastrelli Giulia,Concetti Sergio,Sforza Alessandra,Maggi Mario 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.3

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with meta-bolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the avail-able evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned con-siderations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.

Consequences of Anabolic-Androgenic Steroid Abuse in Males; Sexual and Reproductive Perspective

Corona Giovanni,Rastrelli Giulia,Marchiani Sara,Filippi Sandra,Morelli Annamaria,Sarchielli Erica,Sforza Alessandra,Vignozzi Linda,Maggi Mario 대한남성과학회 2022 The World Journal of Men's Health Vol.40 No.2

The real epidemiology and the possible consequences of anabolic-androgenic steroids (AAS) use still represent a very tricky task due to the difficulties in the quantification and detection of these drugs. Chronic use of AAS, frequently combined with other illicit substances, can induce tremendous negative effects on the reproductive system, but it is also associated with an increased overall and cardiovascular mortality risk. In the present review we summarize and discuss the available evidence regarding the negative impact of AAS on the male reproductive system, providing practical suggestions to manage these problems. For this purpose a meta-analysis evaluating the effects of AAS abusers vs. controls on several hormonal, reproduc-tive and metabolic parameters was performed. In addition, in order to overcome possible limitations related to the combined use of different AAS preparations, we also retrospectively re-analyzed data on animal models treated with supraphysiologi-cal dosage of testosterone (T), performed in our laboratory. Available data clearly indicated that AAS negatively affect en-dogenous T production. In addition, increased T and estradiol circulating levels were also observed according to the type of preparations used. The latter leads to an impairment of sperm production and to the development of side effects such as acne, hair loss and gynecomastia. Furthermore, a worse metabolic profile, characterized by reduced high density lipoprotein and increased low density lipoprotein cholesterol levels along with an increased risk of hypertension has been also detected. Finally sexual dysfunctions, often observed upon doping, represent one the most probable unfavorable effects of AAS abuse.