Clinical Concerns on Sex Steroids Variability in Cisgender and Transgender Women Athletes.

In the female athletic community, there are several endogenous and exogenous variables that influence the status of the hypothalamus-pituitary-ovarian axis and serum sex steroid hormones concentrations (e. g., 17ß-estradiol, progesterone, androgens) and their effects. Moreover, female athletes with different sex chromosome abnormalities exist (e. g., 46XX, 46XY, and mosaicism). Due to the high variability of sex steroid hormones serum concentrations and responsiveness, female athletes may have different intra- and inter-individual biological and functional characteristics, health conditions, and sports-related health risks that can influence sports performance and eligibility. Consequently, biological, functional, and/or sex steroid differences may exist in the same and in between 46XX female athletes (e. g., ovarian rhythms, treated or untreated hypogonadism and hyperandrogenism), between 46XX and 46XY female athletes (e. g., treated or untreated hyperandrogenism/disorders of sexual differentiation), and between transgender women and eugonadal cisgender athletes. From a healthcare perspective, dedicated physicians need awareness, knowledge, and an understanding of sex steroid hormones' variability and related health concerns in female athletes to support physiologically healthy, safe, fair, and inclusive sports participation. In this narrative overview, we focus on the main clinical relationships between hypothalamus-pituitary-ovarian axis function, endogenous sex steroids and health status, health risks, and sports performance in the heterogeneous female athletic community.

Redundant modulatory effects of proinflammatory cytokines in human osteoblastic cells in vitro.

OBJECTIVES: The aim of our study was to investigate possible interaction of IL-17, TRAIL, and TNF-α in the modulation of osteoblast homeostasis in vitro, using human differentiated osteoblastic Saos-2 cells as in vitro model. METHODS: The effects of these cytokines on osteoblastic cell viability were assessed, by MTT assay, alone or in combination, at different times and concentrations. The effects of IL-17 and TNF-α on the regulatory system of osteoclast activity RANK/RANKL/ OPG were evaluated by Western blot and ELISA techniques in cell culture media. Quantitative expression of RANKL, OPG and pro-inflammatory factors were analysed at the mRNA level by quantitative real time RT-PCR. RESULTS: Effects of IL-17, TNF-α and TRAIL on osteoblastic cell viability indicated that IL-17 alone, or in combination with TNF-α did not alter Saos-2 cell viability. On the other hand, TRAIL, as expected, exhibited time- and concentration-dependent cytotoxicity. The expression both RANKL and OPG were increased at the mRNA level and protein release by IL-17 and TNF-α, either alone or in combination. The analysis of IL-17 and TNF-α on pro-inflammatory molecules mRNA expression, such as CXC family chemokines CXCL-1 and CXCL-5, COX-2 and IL-6 demonstrated an increase in these pro-inflammatory cytokines with cooperative effects of the combination. CONCLUSIONS: Overall, these results suggest that IL-17, TRAIL and TNF-α sustain bone tissue inflammation associated with decrease of calcified component. To do so, they act redundantly each other, to amplify the inflammatory response in the bone. In conclusion, unravelling novel molecular targets within the bone-cytokine network represents a platform for innovative treatment of bone diseases due to immunological diseases such as psoriatic arthritis.

Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects.

PURPOSE: Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals. METHODS: The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers. RESULTS: In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r 2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r 2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r 2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r 2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r 2 = 0.03) and femoral site (p < 0.04, r 2 = 0.03). CONCLUSIONS: In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.

CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism?

INTRODUCTION: It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. AIM: To describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. METHODS: A systematic Medline search was conducted using several terms related to and including the terms "androgen receptor," "CAG-repeat polymorphism," "male hypogonadism," "female hypogonadism," and "neurodegenerative disease." MAIN OUTCOME MEASURES: Clinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. RESULTS: A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. CONCLUSIONS: The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women.

Weight loss by multidisciplinary intervention improves endothelial and sexual function in obese fertile women.

INTRODUCTION: Weight loss in sexually active women improves their quality of life. At present, no studies have investigated whether weight loss may affect female sexual function in severe obese women. AIM: The aim of this study was to investigate the effects of different programs of weight loss on female sexual dysfunction complaints and on endothelial function in premenopausal obese females. METHODS: Forty-four out of overall 80 obese fertile women (age 18-49 years; mean 36 years) were enrolled because of sexual complaints at Female Sexual Function Index-6 (FSFI-6 score ≤19). Patients were then allocated to different treatments of 8 weeks duration each: an intensive residential program with hypocaloric diet plus controlled physical exercise along with lifestyle modifications at a specialized clinic (Group A, N = 23) and a non-intensive outpatient clinic program consisting of hypocaloric diet and physical exercise at home (Group B, N = 21). Afterward, overall patients were allocated to an extended 8-week follow-up period consisting of outpatient clinic controlled diet plus physical exercise at home. MAIN OUTCOME MEASURES: Primary end points were modifications of FSFI-6 scores and endothelial function as measured by reactive hyperemia (RHI) with EndoPat-2000. Secondary end points were modifications in body composition as measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: After 16 weeks, FSFI-6 score and the frequency of sexual activity were significantly higher in Group A compared with Group B (P < 0.01), and significant improvements in arousal, lubrication, and satisfaction sub-domain scores were also found (P < 0.01). Group A showed improvements in RHI (P < 0.01) and marked improvement in homeostasis model assessment of insulin resistance (P < 0.001), anthropometric parameters as weight (P < 0.01), body mass index (P < 0.01), fat mass (P < 0.0001), and percentage of fat mass (P < 0.005) compared with Group B. A relationship between peak insulin (P < 0.0001) and RHI (P < 0.001) vs. FSFI-6 scores was found, respectively. CONCLUSIONS: A multidisciplinary approach to female obesity appears to be superior to conventional outpatient clinic to produce weight loss and to improve several aspects of sexual dysfunction in obese women. Such changes might be related to persistent improvements in endothelial function and in insulin resistance.

New therapeutical horizons in the management of postmenopausal osteoporosis.

Osteoporosis is a bone metabolic disease characterized by a compromised skeletal fragility, leading to an increased risk of developing spontaneous and traumatic fractures. This disease is the consequence of an imbalance of the physiological process of bone turnover (or coupling), with the lost of the equilibrium between the activity of osteoblasts and osteoclasts. Therapy has been aimed mainly at the correction of the imbalance between bone resorption and bone formation, to protect skeletal integrity and reduce the risk of fractures. Thus, pharmacological treatments have been aimed at modulating the activity of bone cells.

Skeletal alterations in women affected by obesity.

Obesity has always been considered a protective factor for the skeleton and for osteoporosis. However, new epidemiologic and clinical data have shown that high level of fat mass might be a risk factor for osteoporosis and fragility fractures. Further, increasing evidences seem to indicate that the different components of metabolic syndrome (i.e. hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol) are also potential risk factors for the development of low bone mineral density and osteoporosis.

Effects of tadalafil on skeletal muscle tissue: exploring interactions and novel mechanisms of action.

Beside its mechanical roles in controlling posture and locomotion, skeletal muscle system, the largest insulin and steroid hormones target tissue, plays a key role in influencing thermoregulation, secondary sexual characteristics, hormones metabolism, and glucose uptake and storage, as well as energetic metabolism. Indeed, in addition to insulin, several hormones influence the skeletal muscle metabolism/function and/or are influenced by skeletal muscles activity (i.e., physical exercise). Particularly, steroid hormones play a key role in modulating many biological processes in muscles, essential for overall muscle's function and homeostasis, both at rest and during all physical activities (i.e., physical exercise, muscular work). Phosphodiesterase type 5 (PDE5) is the enzyme engaged to hydrolyze cyclic guanosine monophosphate (cGMP) in inactive 5'-GMP form. Therefore, through the inhibition of this enzyme, the intracellular level of cGMP increases, and the cGMP-related cellular responses are prolonged. Different drugs inhibiting PDE5 (PDE5i) exist, and the commercially available PDE5i are sildenafil, vardenafil, tadalafil, and avanafil. The PDE5i tadalafil may influence cellular physiology and endocrine-metabolic pathways in skeletal muscles and exerts its functions both by activating the cell signaling linked to the insulin-related metabolic pathways and modulating the endocrine responses, protein catabolism and hormone-related anabolism/catabolism during and after physical exercise-related stress. Based on recent in-vivo and in-vitro findings, in this narrative review the aim was to summarize the available evidence describing the interactions between the PDE5i tadalafil and steroid hormones in skeletal muscle tissue and physical exercise adaptation, focusing our interest on their possible synergistic or competitive action(s) on muscle metabolism and function.

Global olfactory function correlates with global sexual functioning in men and women.

BACKGROUND: Olfaction is intimately involved in reproductive behaviors. However, there is limited evidence about the relationship between olfactory and sexual functioning, and whether this relationship is modulated by gender. This study aimed to investigate the correlates between olfactory and sexual functioning in a cohort of young healthy individuals; secondary outcomes were the possible correlates between disgust and perceived vulnerability to illness, with particular relation to sexual attitudes. METHODS: Between January 2019 and December 2022, we enrolled 125 participants (51 males and 74 females) without known sexual disorders. The mean age was 28.47±8.6, and the mean Body Mass Index (BMI) was 23.86±3.3 without major disease or concomitant drug assumption, except for nutraceutical use. Olfactory sensitivity was tested with the Sniffin' Sticks Test (SST). Body Odor Disgust Scale (BODS) and Perceived Vulnerability to Disease (PVD) questionnaires were administered for the evaluation of perceived susceptibility to illness along with the Sexual Attitude Scale (SAS) for the evaluation of sexual attitudes. Sexual function was evaluated by the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) questionnaires, respectively. RESULTS: Overall, a close relationship between sexual function and olfaction in both sexes (P<0.05) was found. In the male sample, better olfactive scores were positively correlated to all IIEF sub-domains but negatively with BMI and age, respectively (P<0.05). Moreover, olfaction was negatively correlated with a restrictive attitude towards sexuality (SAS) (P<0.05). The latter was also positively correlated with PVD (P<0.01). In the female sample, all FSFI subscales but sexual desire was positively correlated with olfaction (P<0.05). CONCLUSIONS: We herein confirm that olfactory capacities positively correlate with sexual behavior in both sexes. In males, these findings were mostly dependent upon increasing age and BMI. In females all domains of sexual function but sexual desire correlated with olfactory capacity, thus suggesting independent neural pathway activation for sexual desire. Finally, better olfactory capacities seem to determine sexual attitudes and disease avoidance behaviors irrespective of gender.

Positive effects of dietary supplementation with nutraceuticals on male subclinical hypogonadism: a pilot study.

BACKGROUND: Lifestyle modifications (i.e., physical activity [PA] and lower dietary intake) often are not sufficient to improve testosterone (TE) levels and promote weight loss in men with metabolic hypogonadism. The aim of the study was to investigate the effects of a nutraceutical formulation containing myoinositol, alpha lipoic acid, folic acid and SelectSIEVE® as add-on treatment to lifestyle modifications in improving obesity-related subclinical hypogonadism. METHODS: Body composition, insulin resistance, testicular and erectile function were investigated in 15 males (age=39.5±14.5 years; Body Mass Index [BMI]=30.2±3.8 kg/m2, with subclinical hypogonadism (TE levels <14 and normal luteinizing hormone [LH]). After a run-in three months unsupervised PA period (T1), the nutraceutical supplement was administered two-times per day for three additional months (T2). RESULTS: BMI, the percentage fat mass, insulinemia and Homeostasis Model Assessment Index (P<0.01) along with glycemia (P<0.05) were significantly reduced at T2 compared to T1, respectively; fat free mass (FFM) was significantly higher at T2 compared to T1 (P<0.01). Also, TE, LH and 5-item international index of erectile function score were significantly increased at T2 compared to T1 (P<0.01), respectively. CONCLUSIONS: The combination of unsupervised PA and nutraceutical supplement improves body composition, insulin sensitivity and TE production in overweight-obese men with metabolic hypogonadism. Further controlled studies in the long-term are warranted to elucidate potential changes in fertility.

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study.

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm(2); femoral BMD= 0.847 ± 0.117 g/cm(2)). TU induced a significant improvement of bone mass after 36 months (lumbar BMD=1.053 ± 0.145 g/cm(2); p < 0.002; femoral BMD=0.989 ± 0.109; p < 0.003 g/cm(2)) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r(2) = 0.66, p < 0.0001) and femoral (r(2) =0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.

NLRP3-inflammasome activation in male reproductive system diseases.

The nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) inflammasome, a multiprotein complex belonging to the innate immune system, plays a key role in the chronic inflammatory response, through the production of proinflammatory cytokines, IL-1ß and IL-18, which can elicit their effects through receptor activation, both locally and systemically. Furthermore, it has been demonstrated the interaction of NLRP3 inflammasome components with redox signaling, endoplasmic reticulum stress, and mitochondrial function. A growing literature reported the involvement of NLRP3 platform dysregulation in the pathophysiology of different chronic diseases so it has been proposed that the inhibition of NLRP3 inflammasome could represent a new potential therapeutic target in the management of autoimmune and chronic inflammatory diseases, including cancer. In addition, it has been demonstrated that Sars-CoV2 preferentially activates NLRP3 inflammasome, strongly contributing to the hyperinflammatory state responsible for COVID-19. Recently, in vitro and animal models of both infectious and non-infectious male genital tract diseases affecting fertility, demonstrated the activation of the innate immune system, leading to increased levels of pro-inflammatory cytokines, as well as apoptosis and pyroptosis and that it was likely mediated by activation of the NLRP3 inflammasome. The objective of this review was to analyze the evidence on the role and the mechanisms by which NLRP3-inflammasome pathway activation may exert detrimental effects on the male reproductive system. Furthermore, although the literature data are still discordant, this review also highlighted the possible connection between SARS-CoV-2 infection/NLRP3 activation/oxidative stress and male infertility.

Predicting the response to SGLT-2 inhibitors as add-on therapy to multiple day injection insulin with glycated albumin: a pilot study.

BACKGROUND: Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin. METHODS: Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers. RESULTS: At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days. CONCLUSIONS: Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.

Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression in human adipocytes in vitro.

INTRODUCTION: Prolonged tadalafil administration in men with erectile dysfunction is associated with increased testosterone (T): estradiol (E(2)) ratio mainly related to reduction of E(2) levels. AIM: To investigate the presence of phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase (ARO) expression in differentiated human visceral adipocytes in culture. MAIN OUTCOME MEASURES: PDE5 mRNA and protein expression in primary human visceral adipocytes as well as mRNA and protein expression of ARO, with functional activity after selective PDE5 blockade by tadalafil and sildenafil. METHODS: Purified primary human visceral pre-adipocytes were differentiated ex vivo and were exposed to tadalafil or sildenafil (1 µM) for different intervals of time (6-12-24-96 hours). ARO mRNA content and expression were measured by Western Blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. T and E(2) in supernatants were measured by ELISA also in the presence of letrozole. RESULTS: Differentiated adipocytes were found to express detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold, respectively (P < 0.001). ARO mRNA and protein levels were increased by the treatment with PDE5i in a time- and dose-dependent manner. Such effect was mimicked by 8-bromo-cGMP but was lost after 24 and 96 hours; differently, the PDE3B specific inhibitor milrinone (1 µM), displayed no effect. Accordingly, long-term exposure (24 and 96 hours) to PDE5i caused a significant increase in E(2) concentrations in the supernatant (1.7 and 2 fold, respectively; P < 0.001), with a parallel reduction of T (15% and 30%, respectively; P < 0.001). Such effect was reversed by the co-incubation with the specific ARO-inhibitor letrozole. CONCLUSIONS: Our results demonstrate that PDE5 is expressed in human visceral adipocytes and that acute exposure to PDE5i selectively stimulates ARO expression, which is related to a specific PDE5 blockade. We speculate that modulation of ARO activity by PDE5i could be one of the mechanisms responsible, at least in part, for the beneficial effects of PDE5i on endothelial and metabolic functions.

The Burden of Hormonal Disorders: A Worldwide Overview With a Particular Look in Italy.

Endocrine diseases have a considerable impact on public health from an epidemiological point of view and because they may cause long-term disability, alteration of the quality-of-life of the affected patients, and are the fifth leading cause of death. In this extensive review of the literature, we have evaluated the prevalence of the different disorders of endocrine interest in the world and Italy, highlighting their epidemiological, clinical, and economic impact.

Estrogen-Receptor-Positive Breast Cancer in Postmenopausal Women: The Role of Body Composition and Physical Exercise.

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer-related death. To date, it is still a challenge to estimate the magnitude of the clinical impact of physical activity (PA) on those parameters producing significative changes in future BC risk and disease progression. However, studies conducted in recent years highlight the role of PA not only as a protective factor for the development of ER+ breast cancer but, more generally, as a useful tool in the management of BC treatment as an adjuvant to traditional therapies. In this review, we focused our attention on data obtained from human studies analyzing, at each level of disease prevention (i.e., primary, secondary, tertiary and quaternary), the positive impact of PA/exercise in ER+ BC, a subtype representing approximately 70% of all BC diagnoses. Moreover, given the importance of estrogen receptors and body composition (i.e., adipose tissue) in this subtype of BC, an overview of their role will also be made throughout this review.

Effects of Selenium Supplementation on Sperm Parameters and DNA-Fragmentation Rate in Patients with Chronic Autoimmune Thyroiditis.

BACKGROUND: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. AIM: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. PATIENTS AND METHODS: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. RESULTS: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. CONCLUSION: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified.

Is there a role for glucagon-like peptide-1 receptor agonists in the treatment of male infertility?

Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are novel anti-hyperglycemic drugs efficacious on glucose control, weight loss, and cardiovascular prevention. These drugs may also be effective in modulating testicular function. In fact, they increase serum testosterone levels in diabetic and/or obese patients with functional hypogonadism on a dysmetabolic basis. Although part of this effect can be ascribed to weight loss, some evidence suggests that there is a direct effect at the testicular level. Indeed, human Leydig, Sertoli, and germ cells express GLP1 receptors. GLP1-RAs improve sperm metabolism, motility, and insulin secretion in vitro. Likewise, GLP1-RAs exert positive effects on the metabolism of human Sertoli cells in vitro. Finally, GLP1 is secreted by mouse Leydig cells and this suggests the presence of a paracrine mechanism by which these cells could support the metabolism of Sertoli cells. Therefore, the widespread use of GLP1-RAs in clinical practice may reveal an important role in the management of male infertility in obese and/or diabetic patients given the negative impact of these diseases on testicular steroidogenesis and spermatogenesis. This should suggest the design of randomized controlled studies aimed at evaluating the effects of these drugs on testicular function.

Effects of Acute Whole-Body Vibration Practice on Maximal Fat Oxidation in Adult Obese Males: A Pilot Study.

OBJECTIVE: Whole-body vibration (WBV) training has been established as a useful method to improve physical fitness in obese individuals. However, the effects of WBV exercise on maximal fat oxidation (MFO) have not been examined in obese subjects yet. METHOD: MFO was eval-uated during a cardiopulmonary exercise test (CPET) on a treadmill in 12 adult obese males (BMI = 34.9 ± 3.3 kg/m2) after three different warm-up conditions: static half squat plus WBV (HSV), static half squat without WBV (HSWV), and rest (REST). Cortisol levels were evaluated before and after the warm-up, and 1 min (T1), 10 min (T10), and 30 min (T30) of the recovery phase. RESULTS: MFO was significantly higher in HSV (p = 0.013; 569.4 ± 117.9 mg/min) and HSWV (p = 0.033; 563.8 ± 142.9 mg/min) than REST (445.5 ± 117.9 mg/min). Cortisol concentrations at T1 were significantly higher in HSV (p = 0.023) and HSWV (p = 0.015) than REST. Moreover, cortisol concentrations were significantly lower at T30 than T1 in HSWV (p = 0.04). No differences were found between T30 and T1 in HSV. CONCLUSIONS: Active warm-up increases MFO; however, vibration stimulus during half squatting does not increase MFO during a CPET in obese subjects. The lack of significant differences of cortisol concentrations in HSV during the recovery phase might suggest a long-term effect of WBV on the endocrine system.

Osteoporosis and Sarcopenia Increase Frailty Syndrome in the Elderly.

Musculoskeletal aging is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Bone and muscle tissues were increasingly recognized, as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. During growth, bone mineral content closely correlates with muscle mass, and several evidences suggest that osteoporosis and sarcopenia present common pathophysiological factors and show the correlation between low bone mineral density and sarcopenia in both men and women. Then, sarcopenia and osteoporosis, typical features of aging, are often associated with each other and with the frailty syndrome. In particular, sarcopenia and osteoporosis are major contributors to disability and frailty and the common denominators are age-related chronic inflammation, changes in body composition and hormonal imbalance. Frailty syndrome is characterized by a reduced response to stress, triggering the decline of the physiological functioning of the various systems. Frailty syndrome, typical of the older people, is frequently associated with a reduction in the quality of life and mobility. Falls often are the basis of reduced mobility and ability to perform the common functions of daily life and the increase in the number of institutionalizations. Moreover, the reduction of muscle mass, associated with altered muscle composition, fat and fibrous infiltration and alterations in innervations, and the increase in fat mass, have a synergistic effect on the increase in cardiovascular risk. The aim of this review is to analyze the pathophysiological mechanisms underlying the frailty syndrome and its association with sarcopenia and osteoporosis, and investigate possible intervention measures.