Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

The challenge of weight loss maintenance in obesity: a review of the evidence on the best strategies available.

Long-term weight loss maintenance represents a big challenge for the management of obesity. This narrative review aims to provide an overview of the main endocrine mechanisms involved in weight regain in subjects with obesity and to review the current evidence on the best lifestyle approaches, including diet and physical activity. Weight regain after weight loss occurs in about 50% of subjects with obesity in the absence of lifestyle changes. The primary endocrine mechanism responsible for weight regain involves the brain-gut axis, which encourages food intake and thus weight regain through the secretion and action of several gastrointestinal hormones, such as ghrelin, leptin and cholecystokinin. Several evidence reported changes of secretion of these hormones during weight loss and weight loss maintenance programs. Endurance training is the most effective physical activity to lose and keep weight loss; the association of endurance with resistance training is recommended for remodelling body shape.

Possible Adrenal Involvement in Long COVID Syndrome.

Background: A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. The most frequent symptoms are fatigue and cognitive dysfunction. We describe a patient suffering from Long COVID in whom adrenal involvement was highlighted. Methods: The patient described Long COVID symptoms that persist 3 months after the negativization of the molecular swab test. The main symptoms were weakness, brain fog, dizziness, and muscular and joint pain. All routine lab panels for inflammation, anemia, and thyroid and liver function were conducted. Moreover, salivary cortisol and DHEA-S determinations were used to compute the adrenal stress index (ASI). Results: All tests were negative, except the ASI that showed very low levels of free cortisol. The patient started hydrocortisone acetate supplementation. Conclusion: Long COVID symptoms could be explained by an adrenal involvement, due to a COVID-19 action on adrenal glands and by a iatrogenic side effect of high glucocorticoid therapy during the COVID-19 infection. Salivary cortisol determination is effective for establishing a correct recovery plan.

Resolution of Disseminated Intravascular Coagulation in a Patient with COVID-19 and Associated Sepsis-Induced Neutropenia.

COVID-19 has been associated with a hypercoagulable state and thrombotic events. Venous thromboembolism has been the most commonly reported type of thrombosis but also arterial thrombosis and disseminated intravascular coagulation in inpatients have been described frequently in several clinical experiences. Patients with COVID-19, because of its tendency to induce leucopenia and overlapping of bacterial infection, may experience sudden disseminated intravascular coagulation (DIC), as in the case that we report here. However, early diagnosis and treatment may be associated with positive resolution of these severe complications.

What is the best diet for cardiovascular wellness? A comparison of different nutritional models.

Cardiovascular diseases (CVD) represent to date the leading cause of mortality in both genders in the developed countries. In this context, a strong need for CVD prevention is emerging through lifestyle modification and nutrition. In fact, several studies linked CVD with unhealthy nutrition, alcohol consumption, stress, and smoking, together with a low level of physical activity. Thus, the primary aim is to prevent and reduce CVD risk factors, such as impaired lipid and glycemic profiles, high blood pressure and obesity. Different types of diet have been, therefore, established to optimize the approach regarding this issue such as the Mediterranean diet, Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. Depending on the diet type, recommendations generally emphasize subjects to increase vegetables, fruits, whole grains, and pulses consumption, but discourage or recommend eliminating red meat, sweets, and sugar-sweetened beverages, along with processed foods that are high in sugar, salt, fat, or low in dietary fiber. In particular, we evaluated and compared the peculiar aspects of these well-known dietary patterns and, thus, this review evaluates the critical factors that increase CVD risk and the potential application and benefits of nutritional protocols to ameliorate dietary and lifestyle patterns for CVD prevention.

Blood Targets of Adjuvant Drugs Against COVID19.

While waiting for the vaccine and/or the best treatment for COVID19, several drugs have been identified as potential adjuvant drugs to counteract the viral action. Several drugs, in fact, have been suggested for their ancillary antiviral role. Viral proteases and peptidases, may interact with well-known drugs such as anticoagulants, antihypertensives, antiserotoninergics and immunomodulants. We here report a basic list of these drugs that include bioflavonoids, heparinoids, ACE inhibitors, angiotensin receptor blockers, antiserotoninergics, and monoclonal antibodies against cytokines that may interact with the viral cycle.

Sleep Apnea, Obesity, and Disturbed Glucose Homeostasis: Epidemiologic Evidence, Biologic Insights, and Therapeutic Strategies.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA), obesity, and disturbed glucose homeostasis are usually considered distinct clinical condition, although they are tightly related to each other. The aim of our manuscript is to provide an overview of the current evidence on OSA, obesity, and disturbed glucose homeostasis providing epidemiologic evidence, biological insights, and therapeutic strategies. RECENT FINDINGS: The mechanisms hypothesized to be involved in this complex interplay are the following: (1) "direct weight-dependent" mechanisms, according to which fat excess compromises respiratory mechanics, and (2) "indirect weight-dependent" mechanisms such as hyperglycemia, insulin resistance and secondary hyperinsulinemia, leptin resistance and other hormonal dysregulations frequently found in subjects with obesity, type 2 diabetes, and/or sleep disorders. Moreover, the treatment of each of these clinical conditions, through weight loss induced by diet or bariatric surgery, the use of anti-obesity or antidiabetic drugs, and continuous positive airway pressure (CPAP), seems to positively influence the others. These recent data suggest not only that there are multiple connections among these diseases but also that treating one of them may result in an improvement of the others.

Effect of treatment with testosterone on endothelial function in hypogonadal men: a systematic review and meta-analysis.

Despite several studies showing an inverse correlation of total testosterone with endothelial damage, the effect of testosterone replacement therapy (TTh) on endothelial function has been scarcely investigated. In order to systematically assess the relationship between endothelial dysfunction and TTh, we performed a review and meta-analysis of available prospective and cross-sectional studies. A thorough research was performed on MEDLINE for hypogonadism and endothelial dysfunction. We retrieved 28 papers, among which 23 were excluded for different reasons: five papers accounting for six studies (two crossover randomized clinical trial (RCT), three observational, one placebo controlled RCT) were therefore included in analysis. Overall, 86 patients with hypogonadism were included in analysis (mean age 49.57 ± 8.85 years). Baseline total testosterone serum levels were 8.11 ± 2.42 nmol/L and significantly increased while undergoing TTh (standard mean difference (SMD) 2.93 nmol/L, 95% confidence interval (CI) 1.89:3.97, p < 0.001). Due to the paucity of studies available, flow-mediated dilation (FMD) was chosen as the best surrogate marker of endothelial dysfunction. FMD did not significantly change after testosterone administration (SMD -0.22, 95% CI -1.29:0.84, I2 = 90%); acute testosterone administration was associated with an increase in FMD, whereas a reduction in FMD emerged following chronic treatment, but statistical significance was not reached for both effects. This is the first meta-analysis study assessing the influence of TTh on endothelial function; however, results are far from conclusive, as proven by the high heterogeneity.

Sex Differences of Vitamin D Status across BMI Classes: An Observational Prospective Cohort Study.

Growing evidence reported that vitamin D deficiency is a common finding in obesity. Vitamin D status also seems to be sex-related, although little is known regarding this association. Therefore, the aim of this study was to investigate the sex-related differences of serum 25OH vitamin D (25OHD) concentrations across body mass index (BMI) classes and, if there were any differences, whether they could be explained by sex-related differences in body composition. We enrolled 500 subjects (250 males, age 37.4 ± 11.8 years; 250 females, age 36.6 ± 11.8 years). Body composition was assessed by bioelectrical impedance analysis (BIA) phase-sensitive system. Serum 25OHD concentration was quantified by a direct, competitive chemiluminescence immunoassay. Vitamin D deficiency was defined as a serum 25OHD concentrations < 20 ng/mL (50 nmol/L). Stratifying the sample population according to sex and BMI categories, 25OHD concentrations were significantly higher in males compared to females in all BMI classes and decreased along with the increase of BMI values. Females with vitamin D deficiency had higher fat mass (FM) % compared to males with vitamin D deficiency. The 25OHD concentrations inversely correlated with FM % in both sexes. In a multiple regression analysis model, sex, FM %, and BMI were predictive factors of 25OHD concentration. In conclusion, our study suggests that 25OHD concentrations were lower in females than males across all BMI categories. Given the tight correlation between 25OHD concentrations and FM %, it can be hypothesized that the lower 25OHD concentrations in females than males can be explained by the fact that females have a higher amount of fat than males.

The management of very low-calorie ketogenic diet in obesity outpatient clinic: a practical guide.

The epidemic of obesity is growing steadily across the whole world. Obesity is not only a merely aesthetic disease but is the "mother" of most chronic diseases such as associated with a range of type 2 diabetes, cardiovascular disease, obstructive sleep apnea, and cancer. However, although there is a need to find a strategy to stop this epidemic disease, most of the times the current nutritional strategies are not effective in weight loss and in long term weight maintenance. Very low-calorie ketogenic diets (VLCKD) is increasingly establishing as a successful nutritional pattern to manage obesity; this is due to rapid weight loss that gives rise to a positive psychological cycle which in turn increases the compliance to diet. Another important key point of VLCKD is the ability to preserve fatty free mass which is known to play a role of paramount importance in glucose metabolism. Despite the clinical evidence of VLCKD there are paucity of data regarding to its management. Therefore, we will provide a useful guide to be used by nutrition experts taking care of subjects with obesity. In particular, we will report recommendations on the correct use of this therapeutic approach for weight loss and management of side effects.

Somatotropic Axis and Obesity: Is There Any Role for the Mediterranean Diet?

Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels-which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index-BMI of 45.19 ± 6.30 kg/m2). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance-HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet-and in particular protein intake-was associated with a better GH status.

Adherence to the Mediterranean Diet, Dietary Patterns and Body Composition in Women with Polycystic Ovary Syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and is characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Obesity, low-grade chronic inflammatory status, and insulin-resistance (IR) often coexist in PCOS. The Mediterranean diet (MD) is an anti-inflammatory dietary pattern, which is rich in complex carbohydrates and fiber, and high in monounsaturated fat. There is a close association among obesity, low-grade chronic inflammation, IR, and hormonal derangements in PCOS. The main aim of the present study was to evaluate the adherence to MD, the dietary intake, and the body composition and their association with PCOS clinical severity in a cohort of treatment-naïve women with PCOS when compared with a control group of healthy women matched for age and body mass index (BMI). In this case-controlled, cross-sectional study, we enrolled 112 patients with PCOS and 112 controls. PREvención con DIetaMEDiterránea (PREDIMED) and seven-day food records were used to evaluate the degree of adherence to the MD and dietary pattern, respectively. Body composition was evaluated by bioelectrical impedance analysis (BIA) phase-sensitive system. Testosterone levels and Ferriman-Gallwey score assessed the clinical severity of PCOS. C-reactive protein (CRP) levels were determined with a nephelometric assay with CardioPhase high sensitivity. PCOS women showed higher testosterone levels, Ferriman-Gallwey score, fasting insulin and glucose levels, and Homeostatic Model Assessment (HoMA)-IR when compared with the control group (p < 0.001). In addition, we found that the PCOS women consumed less extra-virgin olive oil, legumes, fish/seafood, and nuts compared with control group. Despite no differences in energy intake between the two groups, the PCOS women consumed a lower quantity of complex carbohydrate, fiber, monounsaturated fatty acids (MUFA), and n-3 polyunsaturated fatty acid (PUFA), and higher quantity of simple carbohydrate, total fat, saturated fatty acid (SFA), PUFA and n-6 PUFA than the control group. The PCOS women have an adverse body composition when compared with controls, with the lowest values of phase angle (PhA) and fat-free mass (p < 0.001). Additionally, after adjusting for BMI and total energy intake, testosterone levels showed significant negative correlations with PREDIMED score (p < 0.001) and consumption of protein (p = 0.005), complex carbohydrate (p < 0.001), fiber (p < 0.001), MUFA (p < 0.001), n-3 PUFA (p = 0.001), and positive associations with CRP levels, simple carbohydrate, SFA, n-6 PUFA (p < 0.001, respectively), and PUFA (p = 0.002). The cut-off for PREDIMED score ≤ 6 (p < 0.001, area under the curve (AUC) 0.848, standard error 0.036, 95% confidence interval (CI) 0.768 to 0.909) could serve as a threshold for significantly increased risk of high value of testosterone levels. In conclusion, a novel direct association between the adherence to MD and the clinical severity of the disease was reported in women with PCOS. This association could support a therapeutic role of foods and nutrients of the Mediterranean dietary pattern in the PCOS pathogenesis likely involving their inflammatory status, IR, and hyperandrogenemia. In addition, we reported a different body composition that is characterized by lower PhA and fat-free mass than controls. These data suggested a role of PhA as a useful marker of the clinical severity of this syndrome and provided strong evidence regarding the strategic relevance of the nutritional assessment in the management of women with PCOS.

Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI (p < 0.001). Stratifying the sample population according to the BMI classes, 25(OH)D levels decreased significantly along with the increase in BMI (p < 0.001), with the lowest 25(OH)D levels in the class III obesity. In addition, stratifying the sample population according to 25(OH)D categories, BMI and fat mass (FM) decreased, while PhA increased significantly along with the 25(OH)D categories (p < 0.001). The 25(OH)D levels showed significant positive associations with PhA (r = -0.59, p < 0.001), and this association remained significant also after adjusting for BMI and FM (r = 0.60, p < 0.001). The lowest values of PhA were significantly associated with the severity of obesity (OR 0.3, p < 0.001) and of 25(OH)D deficiency (OR 0.2, p < 0.001). To compare the relative predictive power of body composition parameters associated with the 25(OH)D levels, we performed a multiple linear regression analysis. The most sensitive and specific cut-off for 25(OH)D levels to predict the PhA above the median was >14 ng/mL (p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation.

From gut microbiota dysfunction to obesity: could short-chain fatty acids stop this dangerous course?

Study of the interactions between the gut microbiota and brain-gut axis represents a very appealing approach to increasing our knowledge about the mechanisms leading to obesity and obesity-related diseases. The aim of this review is to focus on the effects of short-chain fatty acids (SCFAs), which are the main products of gut microbial fermentation from non-digestible carbohydrates in the colon, on the gut-brain axis. Evidence is accumulating regarding the role of SCFAs in the fine-tuning of the gut-brain axis, a feedback system which is vital not only for the proper maintenance of gastrointestinal and metabolic functions, but also for the regulation of food intake and energy expenditure. SCFAs are thought to play a key role in increasing the host capacity to harvest excess energy from the diet. SCFAs, however, can exert their effects on the host metabolism via multiple complementary pathways. Metabolic, inflammatory, and neural pathways can be regulated by SCFAs, which can act by sensing nutritional status, thereby maintaining body energy homeostasis. SCFA production from prebiotic consumption is the rationale for targeting intestinal mechanisms to increase energy expenditure and thereby reduce obesity risk.

Neuropsychiatric Aspects in Men with Klinefelter Syndrome.

BACKGROUND AND OBJECTIVE: Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy (47, XXY) and cause of male hypergonadotropic hypogonadism. It is characterized by an extreme clinical heterogeneity in presentation, including infertility, hypogonadism, language delay, metabolic comorbidities, and neurocognitive and psychiatric disorders. Since testosterone is known to have organizational, neurotrophic and neuroprotective effects on brain, the condition of primary hypogonadism could play a role. Moreover, given that KS subjects have an additional X, genes on the extra-chromosome could also exert a significant impact. The aim of this narrative review is to analyze the available literature on the relationship between KS and neuropsychiatric disorders. METHODS: To extend to the best of published literature on the topic, appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. RESULTS: Both morphological and functional studies focusing on the brain showed that there were important differences in brain structure of KS subjects. Different psychiatric disorders such as Schizophrenia, autism, attention deficit hyperactivity disorder, depression and anxiety were frequently reported in KS patients according to a broad spectrum of phenotypes. T supplementation (TRT) was not able to improve the psychotic disorders in KS men with or without overt hypogonadism. CONCLUSION: Although the risk of psychosis, depression and autism is increased in subjects with KS, no definitive evidence has been found in studies aiming at identifying the relationship between aneuploidy, T deficit and the risk of psychiatric and cognitive disorders in subjects affected by KS.

Sport, doping and male fertility.

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being "fit" does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength - both excessive intensity and duration of exercise training - are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility.

The environment and male reproduction: The effect of cadmium exposure on reproductive function and its implication in fertility.

Cadmium is an environmental pollutant known as endocrine disruptor. Testis is particularly susceptible to cadmium, and testis injury occurs at high but even low levels of exposure. Cadmium reproductive toxicity is mediated by multiple mechanisms, including structural damage to testis vasculature and blood-testis barrier, inflammation, cytotoxicity on Sertoli and Leydig cells, oxidative stress mainly by means of mimicry and interference with essential ions, apoptosis, interference with selected signaling pathways and epigenetic regulation of genes involved in the regulation of reproductive function, and disturbance of the hypothalamus-pituitary-gonadal axis. The current review outlines epidemiological observational findings from environmental and occupational exposure in humans, and reports experimental studies in humans and animals. Lastly, a focus on the pathogenetic mechanisms of cadmium toxicity and on the specific mechanisms of cadmium sensitivity and resistance, particularly assessed in animal models, is included. Despite convincing experimental findings in animals and supporting evidences in humans identifying cadmium as reproductive toxicant, observational findings are controversial, suffering from heterogeneity of study design and pattern of exposure, and from co-exposure to multiple pollutants.

The role of vitamin D in male fertility: A focus on the testis.

In the last decade, vitamin D has emerged as a pleiotropic molecule with a multitude of autocrine, paracrine and endocrine functions, mediated by classical genomic as well as non-classical non-genomic actions, on multiple target organs and systems. The expression of vitamin D receptor and vitamin D metabolizing enzymes in male reproductive system, particularly in the testis, suggests the occurrence of vitamin D synthesis and regulation as well as function in the testis. The role of vitamin D in the modulation of testis functions, including hormone production and spermatogenesis, has been investigated in animals and humans. Experimental studies support a beneficial effect of vitamin D on male fertility, by modulating hormone production through genomic and non-genomic actions, and, particularly, by improving semen quality essentially through non-genomic actions. However, clinical studies in humans are controversial. Indeed, vitamin D seems to contribute to the modulation of the bioavailable rather than total testosterone. Moreover, although an increased prevalence or risk for testosterone deficiency was reported in men with vitamin D deficiency in observational studies, the majority of interventional studies demonstrated the lack of effect of vitamin D supplementation on circulating levels of testosterone. The most consistent effect of vitamin D was reported on semen quality. Indeed, vitamin D was shown to be positively associated to sperm motility, and to exert direct actions on spermatozoa, including non-genomic driven modulation of intracellular calcium homeostasis and activation of molecular pathways involved in sperm motility, capacitation and acrosome reaction. The current review provides a summary of current knowledge on the role of vitamin D in male fertility, by reporting clinical and experimental studies in humans and animals addressing the relationship between vitamin D and testis function.

Effect of chronic cabergoline treatment and testosterone replacement on metabolism in male patients with prolactinomas.

INTRODUCTION: Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. PATIENTS AND METHODS: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8 nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. RESULTS: Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI0), homeostatic model assessment of insulin secretion (HOMA-ß) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-ß. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI0, HOMA-ß and HOMA-IR significantly improved compared to baseline, with FI, ISI0, HOMA-ß and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. CONCLUSIONS: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.