Publications by authors named "Mario Maggi"

377 Publications

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

World J Mens Health 2021 Jun 1. Epub 2021 Jun 1.

Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy.

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 controls on several hormonal, reproductive 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 supraphysiological dosage of testosterone (T), performed in our laboratory. Available data clearly indicated that AAS negatively affect endogenous 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.
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http://dx.doi.org/10.5534/wjmh.210021DOI Listing
June 2021

Physical Activity and Female Sexual Dysfunction: A Lot Helps, But Not Too Much.

J Sex Med 2021 07 5;18(7):1217-1229. Epub 2021 Jun 5.

Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy; Andrology, Women's Endocrinology and Gender Incongruence Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy. Electronic address:

Background: Research on the relationship between physical activity (PA) and female sexual dysfunction (FSD) is lacking.

Aim: To investigate the clinical, psychological, and sexual correlates of PA in women with FSD.

Methods: A non-selected series of n = 322 pre- and post-menopausal patients consulting for FSD was retrospectively studied. Regular involvement in PA and its frequency (<1 hour/week: sedentary, 1-3 hours/week: active, 4-6 hours/week: very active, >6 hours/week: extremely active) were investigated with a specific question.

Outcomes: FSDs, including HSDD (Hypoactive sexual desire disorder) and FGAD (Female genital arousal disorder), were diagnosed according to a structured and clinical interview. Participants underwent a physical examination and a clitoral Doppler ultrasound, and were asked to complete the Female Sexual Function Index, Female Sexual Distress Scale-Revised, Body Uneasiness Test, and Middlesex Hospital Questionnaire.

Results: At multivariate analysis, women engaging in PA (67.4%, n = 217) scored significantly higher in several Female Sexual Function Index domains - including desire, arousal and lubrication - and showed lower sexual distress and lower resistance of clitoral arteries, as compared to sedentary women. A significant, inverse association between PA and HSDD was observed. Mediation analysis demonstrated that the negative association between PA and HSDD was partly mediated by body image concerns (Body Uneasiness Test Global severity index), psychopathological symptoms (Middlesex Hospital Questionnaire total score) and sexual distress (Female Sexual Distress Scale-Revised score). These latter 2 factors also partly mediated the association between PA and a reduced risk of FGAD, whilst a lower BMI was a full mediator in the relationship between PA and FGAD. Finally, extreme PA was associated with significantly worse scores in several psychosexual parameters (i,e, sexual satisfaction and histrionic/hysterical symptoms), even compared to a sedentary lifestyle.

Clinical Implications: Women consulting for FSD may gain benefits on desire, arousal, lubrication and sex-related distress from regular PA; however, physicians should remain alert to the downsides of excessive exercise.

Strengths & Limitations: The main strength lies in the novelty of the findings. The main limitations are the cross-sectional nature, the clinical setting, the small sample size of the different PA groups, and the use of self-reported instruments for the evaluation of PA.

Conclusion: In women with FSD, PA was associated with better sexual function and clitoral vascularization, lower sexual distress and reduced odds of HSDD and FGAD; the benefits of PA on sexuality were mediated by both psychological and organic determinants; excessive PA was related with a poor overall sexual function and with a low sexual satisfaction. Maseroli E, Rastrelli G, Di Stasi V, et al. Physical Activity and Female Sexual Dysfunction: A Lot Helps, But Not Too Much. J Sex Med 2021;18:1217-1229.
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http://dx.doi.org/10.1016/j.jsxm.2021.04.004DOI Listing
July 2021

Male Sexual Dysfunctions in the Infertile Couple-Recommendations From the European Society of Sexual Medicine (ESSM).

Sex Med 2021 Jun 2;9(3):100377. Epub 2021 Jun 2.

Endocrinology Unit, Medical Department, Azienda USL, Maggiore-Bellaria Hospital, Bologna, Italy.

Introduction: Sexual dysfunctions (SDs) have been frequently reported among male partners of infertile couples due to psychogenic, relational and/or organic issues related with the inability to conceive. Likewise, male infertility (MI) could be a consequence of sexual dysfunctions.

Aim: To review the evidence on the prevalence and treatment of male SDs in men of infertile couples and provide clinical recommendations on behalf of the European Society of Sexual Medicine (ESSM).

Methods: The MEDLINE database was searched in September 2019 for randomized clinical trials (RCTs), meta-analyses and open-label prospective or retrospective studies investigating the presence of erectile dysfunction (ED) and/or ejaculatory dysfunctions (EjDs) and/or low sexual desire (LSD) in conjunction with infertility.

Main Outcome Measure: The panel provided statements on: (i) Prevalence and association between SDs and MI; (ii) Treatment of male SDs in men of infertile couples.

Results: ED has been reported in 9% to 62% of male partners of infertile couples, with severe impairment observed in only 1% to 3% of ED cases. Moreover, worse semen parameters have been associated with greater ED severity. Phosphodiesterase type 5 inhibitors (PDE5is) can be safely used to treat ED among patients seeking fatherhood. Male partners of infertile couples are at higher risk of premature ejaculation (PE). Retrograde ejaculation (RE) and anejaculation are a cause of MI and can be managed with electroejaculation (EEJ) or penile vibratory stimulation (PVS) or, alternatively, with oral treatments, however the latter with limited documented success. Low sexual desire has been reported by one third of men of infertile couples.

Conclusion: ED could significantly affect male partners of infertile couple; PDE5is should be suggested to ensure an effective and satisfactory sexual relationship of the couple. Anejaculation and RE should be considered as a possible cause of MI and treated accordingly. Low sexual desire is frequently reported among men of infertile couple and could be a symptom of other systemic conditions or psychological distress. Capogrosso P, Jensen CFS, Rastrelli G, et al. Male Sexual Dysfunctions in the Infertile Couple-Recommendations From the European Society of Sexual Medicine (ESSM). J Sex Med 2021;9:100377.
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http://dx.doi.org/10.1016/j.esxm.2021.100377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240351PMC
June 2021

Historical trends for the standards in scrotal ultrasonography: What was, what is and what will be normal.

Andrology 2021 Jun 4. Epub 2021 Jun 4.

Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy.

Background: Ultrasonography is the gold standard imaging method for scrotal investigation. Colour Doppler ultrasonography, contrast-enhanced ultrasonography and sonoelastography allow sonographers to assess size, echotexture, vascular features and stiffness of the scrotal organs and abnormalities. Scrotal ultrasonography has been used to investigate male reproductive health, scrotal pain, masses and trauma. However, ultrasonography thresholds/classifications used to distinguish normal and pathologic features of the scrotal organs have changed over time, and have not yet been fully standardized.

Objectives: To evaluate historical trends for the standards in scrotal ultrasonography: what was, what is and what will be normal.

Methods: An extensive Medline search was performed identifying the most relevant studies in the English language from inception to date.

Results: We provide here (i) a brief overview of the history of ultrasonography, (ii) current indications for scrotal ultrasonography and (iii) previous and current normal values, cut-offs and classifications of the main colour-Doppler ultrasonography parameters/characteristics of the scrotal organs, as derived from recent guidelines and evidence-based studies. In addition, we report recommendations and the clinical utility of contrast-enhanced ultrasonography and sonoelastography. Finally, we discuss critical issues needing further evidence and future directions to fill in the current gaps.

Discussion: Several studies on scrotal ultrasonography are available. However, guidelines/recommendations dealing with specific ultrasonography applications have been published only in recent years. More recently, the European Academy of Andrology published evidence-based scrotal colour-Doppler ultrasonography reference ranges/normative parameters derived from a cohort of healthy, fertile men. In addition, a standardization of the methodology to evaluate qualitative and quantitative colour-Doppler ultrasonography parameters was reported. Other international societies reported indications, methodological standards, clinical utility and limitations of contrast-enhanced ultrasonography and sonoelastography.

Conclusions: To date, colour-Doppler ultrasonography normative values for the scrotal organs are available. However, a wide international consensus on assessment and classification of several ultrasonography parameters is still lacking. An alignment of the world societies on these issues is advocated.
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http://dx.doi.org/10.1111/andr.13062DOI Listing
June 2021

The Role of testosterone treatment in patients with metabolic disorders.

Expert Rev Clin Pharmacol 2021 Jun 21:1-13. Epub 2021 Jun 21.

Endocrinology Unit, Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

Introduction: The specific role of testosterone [T] replacement therapy [TRT] on glycometabolic profile and body composition, particularly in patients with metabolic syndrome [MetS] and/or type 2 diabetes mellitus [T2DM], is still the object of an intense debate.

Areas Covered: To discuss available evidence on the association between T and metabolic diseases and on the possible effect of T administration on metabolic disorder-associated hypogonadism. Both preclinical and clinical data have been considered. In addition, a meta-analysis of the available placebo and non-placebo-controlled randomized clinical trials [RCTs] investigating the effects of TRT in T2DM or MetS in several outcomes has been also performed.

Expert Opinion: Data derived from preclinical and clinical studies suggest that T administration, by reducing fat mass, can improve body composition and ameliorate some aspects of glucose metabolism. The effects of TRT on sexual function in patients with established metabolic derangements are inconsistent, whereas better results were observed in preclinical conditions or in patients with newly diagnosed T2DM.
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http://dx.doi.org/10.1080/17512433.2021.1938548DOI Listing
June 2021

Erectile Dysfunction Is a Hallmark of Cardiovascular Disease: Unavoidable Matter of Fact or Opportunity to Improve Men's Health?

J Clin Med 2021 May 20;10(10). Epub 2021 May 20.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50121-50145 Florence, Italy.

Erectile dysfunction (ED) is an early manifestation of cardiovascular (CV) disease. For this reason, men with ED should be carefully assessed for CV risk factors in order to prevent future major adverse CV events (MACE). Traditional risk factors are not found in all subjects at high CV risk. In fact, a relevant proportion of MACE occurs in men who are apparently risk factor free. In men with ED, it is important to take into account not only traditional risk factors but also unconventional ones. Several parameters that derive from good clinical assessment of subjects with ED have proven to be valuable predictors of MACE. These include family history of cardiometabolic events, alcohol abuse, fatherhood, decreased partner's sexual interest, severe impairment in erection during intercourse or during masturbation, impaired fasting glucose, increased triglycerides, obesity even without metabolic complications, decreased penile blood flows or impaired response to an intra-cavernosal injection test. Recognizing these risk factors may help in identifying, among subjects with ED, those who merit stricter lifestyle or pharmacological interventions to minimize their CV risk. Effective correction of risk factors in ED men considered as high risk, besides reducing CV risk, is also able to improve erectile function.
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http://dx.doi.org/10.3390/jcm10102221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161068PMC
May 2021

Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy.

Endocrine 2021 May 25. Epub 2021 May 25.

Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, AOU Careggi, Florence, Italy.

Purpose: Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome.

Methods: A retrospective and multicentre study was designed, which involved a total of 251 patients affected by different tumors (mostly non-small cell lung cancer, 68.92% and melanoma, 24.30%) and treated with the PD-1 inhibitors nivolumab (61.35%) or pembrolizumab (38.65%) for up to 60 months. Clinical and biochemical data were recorded until July 31, 2020.

Results: Endocrine toxicity occurred in 70 out of 251 patients (27.89%). It was mostly related to thyroid dysfunction and in 75% of cases occurred within 6 months from the beginning of therapy. A previous endocrine morbidity and female gender were predictors of endocrine toxicity. There was no association between endocrine dysfunction and patient outcome. However, when all toxicities (i.e., endocrine and non endocrine) were considered, a significant association with progression-free survival and overall survival was found.

Conclusions: Thyroid alterations are frequently observed in cancer patients treated with anti PD-1 drugs, particularly in women and in the presence of a previous endocrinopathy. We suggest that regular thyroid assessment should be performed in these patients, especially in the first months of therapy. Finally, the onset of side effects, related to anti PD-1 agents, appears to be associated with a better outcome.
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http://dx.doi.org/10.1007/s12020-021-02750-wDOI Listing
May 2021

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study.

J Sex Med 2021 06 20;18(6):1053-1064. Epub 2021 May 20.

Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Bologna, Italy.

Background: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS).

Aim: To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS.

Methods: A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane's Q and I. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg's rank correlation and trim-and-fill test were used to assess publication bias.

Main Outcome Measure: The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models.

Results: Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age.

Clinical Implications: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels.

Strength & Limitations: This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis.

Conclusions: ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status. A Barbonetti, S D'Andrea, W Vena, et al. Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study. J Sex Med 2021;18:1054-1064.
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http://dx.doi.org/10.1016/j.jsxm.2021.03.078DOI Listing
June 2021

Outdoor light pollution and COVID-19: The Italian case.

Environ Impact Assess Rev 2021 Sep 9;90:106602. Epub 2021 May 9.

University of Pavia, Department of Economics and Management, Italy.

There is a wide debate on the connections between pollution and COVID-19 propagation. This note faces this problem by exploring the peculiar case of the correlation between outdoor light pollution and the ratio between infected people and population. We discuss the empirical case of Italian provinces (NUTS-3 level), which represent an interesting context for the noticeable entity of contagions and for the relevant level of outdoor light pollution. The empirical results, based on a multivariate cross section model controlling for income, density, population ageing and environmental pollution, show that there is a positive relation between outdoor light pollution per capita and the strength of COVID-19 infection. This effect is statistically more robust in a non linear specification than in a linear one. We interpret our findings as a piece of evidence related to the impact of outdoor light pollution on human health, thus suggesting policies aimed at reducing this important source of pollution.
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http://dx.doi.org/10.1016/j.eiar.2021.106602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106897PMC
September 2021

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

Eur J Endocrinol 2021 May 28;185(1):137-144. Epub 2021 May 28.

Endocrinology Unit, Careggi University Hospital, Florence, Italy.

Objective: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients.

Design And Methods: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed.

Results: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death.

Conclusions: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.
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http://dx.doi.org/10.1530/EJE-20-1447DOI Listing
May 2021

Ghrelin as a possible biomarker and maintaining factor in patients with eating disorders reporting childhood traumatic experiences.

Eur Eat Disord Rev 2021 Jul 3;29(4):588-599. Epub 2021 May 3.

Psychiatry Unit, Department of Health Sciences, University of Florence, Florence, Italy.

Objective: The recent conceptualization of ghrelin as a stress hormone suggested that its chronic alterations may have a role in maintaining overeating behaviors in subjects with eating disorders (EDs) reporting childhood traumatic experiences. The aim of this study was to investigate the alterations of ghrelin levels in patients with EDs, their associations with early trauma, binge and emotional eating, and possible moderation/mediation models.

Method: Sixty-four patients with EDs and 42 healthy controls (HCs) had their plasma ghrelin levels measured and completed questionnaires evaluating general and ED-specific psychopathology, emotional eating, and childhood traumatic experiences.

Results: Participants with anorexia nervosa had higher ghrelin levels than HCs in body mass index (BMI)-adjusted comparisons. Moreover, patients reporting a history of childhood trauma had higher ghrelin levels. Childhood sexual abuse (CSA), BMI, and self-induced vomiting were independent predictors of ghrelin levels. Moderation analyses showed that ghrelin levels were associated with binge and emotional eating only for higher levels of childhood trauma. Elevated ghrelin was a significant mediator for the association of CSA with binge eating.

Conclusions: These results support the hypothesis that chronic alterations in ghrelin levels following childhood traumatic experiences could represent a neurobiological maintaining factor of pathological overeating behaviors in EDs.
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http://dx.doi.org/10.1002/erv.2831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251850PMC
July 2021

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

Front Endocrinol (Lausanne) 2021 29;12:641446. Epub 2021 Mar 29.

Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio," University of Florence, Florence, Italy.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.
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http://dx.doi.org/10.3389/fendo.2021.641446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040974PMC
March 2021

Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study.

J Sex Med 2021 05 2;18(5):908-919. Epub 2021 Apr 2.

Endocrinology Unit, Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy. Electronic address:

Background: Few data have looked at the occurrence and clinical correlates of self-reported shorter than desired ejaculation latency (rapid ejaculation, RE) and its related distress in the general population.

Aim: To determine the prevalence and clinical correlates of self-reported RE and RE- related distress in middle age and older European men.

Methods: Subjects were recruited from population samples of men aged 40-79 years across 8 European centers.

Outcomes: Self-reported RE and its related distress were derived from the European male Aging Study (EMAS) sexual function questionnaire (EMAS-SFQ). Beck's depression Inventory (BDI) was used for the quantification of depressive symptoms, the Short Form 36 health survey (SF-36) for the assessment of the quality of life, the International Prostate Symptom Score (IPSS) for the evaluation of lower urinary tract symptoms.

Results: About 2,888 community dwelling men aged 40-79 years old (mean 58.9 ± 10.8 years) were included in the analysis. Among the subjects included, 889 (30.8%) self-reported RE. Among them, 211 (7.3%) claimed to be distressed (5.9% and 1.4% reported mild or moderate-severe distress, respectively). Increasing levels of RE-related distress were associated with a progressive worse sexual functioning, higher risk of ED and with couple impairment, along with a higher prevalence of depressive symptoms (all P < 0.05). Furthermore, a worse quality of life and higher IPSS score were associated with RE-related distress (all P < 0.05). The aforementioned results were confirmed even when patients using drugs possibly interfering with ejaculation or those without a stable relationship were excluded from the analysis.

Clinical Implications: RE is a frequent condition in men from the general population; however, its related distress is relatively modest. Nonetheless, men with any degree of self-reported RE show increasing levels of depression, worse quality of life and worse couple satisfaction.

Strengths & Limitations: This is the first study estimating the prevalence of self-reported RE and its related distress, along with their biological and psychological correlates, in a population sample of European middle age and older men. However, is should be recognized that the diagnosis of RE was derived from patient reports and not supported by Intra-ejaculatory-Latency-Time (IELT) measurements.

Conclusion: Self-reported RE is relatively common in European men aged more than 40 years. The reported limited RE-related distress may explain the relatively low number of medical consultations for RE. RE-related distress is associated with worse sexual function, couple impairment, and more LUTS resulting in a worse quality of life and mood disturbances. Corona G, Rastrelli G, Bartfai G, et al. Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study. J Sex Med Rev 2021;18:908-919.
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http://dx.doi.org/10.1016/j.jsxm.2021.01.187DOI Listing
May 2021

Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI).

J Sex Med 2021 04 18;18(4):821-829. Epub 2021 Mar 18.

Andrology, Women's Endocrinology and Gender Incongruence Unit, Florence University Hospital, Florence, Italy. Electronic address:

Background: Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown.

Aim: To evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT.

Methods: In a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate.

Main Outcome Measure: Changes in CV risk factors and 30-year Framingham CVD risk during GAHT.

Clinical Implications: In transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk.

Strengths & Limitations: The strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT.

Results: In transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes - such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time.

Conclusions: Our findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk. Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;18:821-829.
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http://dx.doi.org/10.1016/j.jsxm.2021.01.185DOI Listing
April 2021

Sexual habits among Italian transgender adolescents: a cross-sectional study.

Int J Impot Res 2021 Mar 16. Epub 2021 Mar 16.

Andrology, Women's Endocrinology and Gender Incongruence Unit, Florence University Hospital, Florence, Italy.

Recent studies showed that transgender (TGN) adolescents are more at risk of negative sexual outcomes than their peers. However, little is known about the psychopathological and sociodemographic correlates of sexual-related experiences in TGN adolescents. This cross-sectional study aimed at overcoming this limitation describing this association in a sample of 18 transgirls and 32 transboys recruited at the Gender Clinic of the University of Florence between 2015 and 2020. Clinical, sociodemographic, and sexual-related features were collected through a face-to-face interview and anamnestic forms. Self-report questionnaires were administered to evaluate gender dysphoria (Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults), emotional and behavioral problems (Youth Self Report), and body uneasiness (Body Uneasiness Test). The percentage of subjects reporting to have had at least one romantic relationship in life was 62.5% among transboys and 16.7% in transgirls (OR = 8.65, p < 0.01), whereas 28.1% of transboys and 5.6% of transgirls were sexually active (OR = 6.63, p > 0.05). A worse psychological functioning and risk-taking behaviors were associated with being sexually active (p < 0.05). These results underline the deep interconnection between psychological vulnerability and sexual-related features in TGN adolescents, confirming the importance of developing gender inclusive sex education programs to prevent negative sexual outcomes in this population.
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http://dx.doi.org/10.1038/s41443-021-00427-6DOI Listing
March 2021

Metabolic Syndrome and Reproduction.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, 50139 Florence, Italy.

Metabolic syndrome (MetS) and infertility are two afflictions with a high prevalence in the general population. MetS is a global health problem increasing worldwide, while infertility affects up to 12% of men. Despite the high prevalence of these conditions, the possible impact of MetS on male fertility has been investigated by a few authors only in the last decade. In addition, underlying mechanism(s) connecting the two conditions have been investigated in few preclinical studies. The aim of this review is to summarize and critically discuss available clinical and preclinical studies on the role of MetS (and its treatment) in male fertility. An extensive Medline search was performed identifying studies in the English language. While several studies support an association between MetS and hypogonadism, contrasting results have been reported on the relationship between MetS and semen parameters/male infertility, and the available studies considered heterogeneous MetS definitions and populations. So far, only two meta-analyses in clinical and preclinical studies, respectively, evaluated this topic, reporting a negative association between MetS and sperm parameters, testosterone and FSH levels, advocating, however, larger prospective investigations. In conclusion, a possible negative impact of MetS on male reproductive potential was reported; however, larger studies are needed.
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http://dx.doi.org/10.3390/ijms22041988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922007PMC
February 2021

Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis.

Rev Endocr Metab Disord 2021 06 22;22(2):275-296. Epub 2021 Feb 22.

Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy.

The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9 ± 8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p < 0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.
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http://dx.doi.org/10.1007/s11154-021-09630-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899074PMC
June 2021

Choosing the best algorithm among five thyroid nodule ultrasound scores: from performance to cytology sparing-a single-center retrospective study in a large cohort.

Eur Radiol 2021 Aug 18;31(8):5689-5698. Epub 2021 Feb 18.

Endocrinology Unit, Medical-Geriatric Department, Azienda Ospedaliero-Universitaria Careggi, Viale Pieraccini 18, 50139, Florence, Italy.

Objective: Incidental diagnosis of thyroid nodules, and therefore of thyroid cancer, has definitely increased in recent years, but the mortality rate for thyroid malignancies remains very low. Within this landscape of overdiagnosis, several nodule ultrasound scores (NUS) have been proposed to reduce unnecessary diagnostic procedures. Our aim was to verify the suitability of five main NUS.

Methods: This single-center, retrospective, observational study analyzed a total number of 6474 valid cytologies. A full clinical and US description of the thyroid gland and nodules was performed. We retrospectively applied five available NUS: KTIRADS, ATA, AACE/ACE-AME, EUTIRADS, and ACRTIRADS. Thereafter, we calculated the sensitivity, specificity, PPV, and NPV, along with the number of possible fine-needle aspiration (FNA) sparing, according to each NUS algorithm and to clustering risk classes within three macro-groups (low, intermediate, and high risk).

Results: In a real-life setting of thyroid nodule management, available NUS scoring systems show good accuracy at ROC analysis (AUC up to 0.647) and higher NPV (up to 96%). The ability in FNA sparing ranges from 10 to 38% and reaches 44.2% of potential FNA economization in the low-risk macro-group. Considering our cohort, ACRTIRADS and AACE/ACE-AME scores provide the best compromise in terms of accuracy and spared cytology.

Conclusions: Despite several limitations, available NUS do appear to assist physicians in clinical practice. In the context of a common disease, such as thyroid nodules, higher accuracy and NPV are desirable NUS features. Further improvements in NUS sensitivity and specificity are attainable future goals to optimize nodule management.

Key Points: • Thyroid nodule ultrasound scores do assist clinicians in real practice. • Ultrasound scores reduce unnecessary diagnostic procedures, containing indolent thyroid microcarcinoma overdiagnosis. • The variable malignancy risk of the "indeterminate" category negatively influences score's performance in real-life management of thyroid lesions.
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http://dx.doi.org/10.1007/s00330-021-07703-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270877PMC
August 2021

Management of hypoactive sexual desire disorder in transgender women: a guide for clinicians.

Int J Impot Res 2021 Feb 8. Epub 2021 Feb 8.

Andrology, Women's Endocrinology and Gender Incongruence Unit, Florence University Hospital, Viale Pieraccini 6, 50139, Florence, Italy.

Hypoactive sexual desire disorder (HSDD) represents a common condition among transgender women. However, to date no specific guidelines for the management of HSDD in transgender persons are available. The aim of the present narrative Review is to evaluate evidence-based treatment for HSDD and to suggest treatment options for HSDD in transgender women. Clinically relevant publications on the management of HSDD (from 1985 to 2020) were searched in PubMed and Medline databases, using the following terms: "sexual desire", "sexual health", "HSDD", "transgender", "gender-affirming treatment", "sexual therapy", "testosterone treatment", "Central nervous system-active medications", and variants. Since sexual desire could be affected by several factors, a comprehensive assessment of HSDD- exploring biological, psychological, and social domains- is recommended, in order to identify possible predisposing, precipitating and maintaining factors. Among treatment options, transgender women may benefit of different sex therapy strategies and/or central nervous system-active medications-such as flibanserin, bremelanotide, bupropion and buspirone-and transdermal testosterone, bearing in mind that this option could be poorly accepted by patients due to the risk of virilizing effects. The lack of data regarding the efficacy of HSDD treatment options in transgender women emphasize the need for literature to focus more on this topic in the future.
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http://dx.doi.org/10.1038/s41443-021-00409-8DOI Listing
February 2021

Neuroprotective Effects of Testosterone in the Hypothalamus of an Animal Model of Metabolic Syndrome.

Int J Mol Sci 2021 Feb 4;22(4). Epub 2021 Feb 4.

I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), 00136 Rome, Italy.

Metabolic syndrome (MetS) is known to be associated to inflammation and alteration in the hypothalamus, a brain region implicated in the control of several physiological functions, including energy homeostasis and reproduction. Previous studies demonstrated the beneficial effects of testosterone treatment (TTh) in counteracting some MetS symptoms in both animal models and clinical studies. This study investigated the effect of TTh (30 mg/kg/week for 12 weeks) on the hypothalamus in a high-fat diet (HFD)-induced animal model of MetS, utilizing quantitative RT-PCR and immunohistochemical analyses. The animal model recapitulates the human MetS features, including low testosterone/gonadotropin plasma levels. TTh significantly improved MetS-induced hypertension, visceral adipose tissue accumulation, and glucose homeostasis derangements. Within hypothalamus, TTh significantly counteracted HFD-induced inflammation, as detected in terms of expression of inflammatory markers and microglial activation. Moreover, TTh remarkably reverted the HFD-associated alterations in the expression of important regulators of energy status and reproduction, such as the melanocortin and the GnRH-controlling network. Our results suggest that TTh may exert neuroprotective effects on the HFD-related hypothalamic alterations, with positive outcomes on the circuits implicated in the control of energy metabolism and reproductive tasks, thus supporting a possible role of TTh in the clinical management of MetS.
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http://dx.doi.org/10.3390/ijms22041589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914611PMC
February 2021

Pheochromocytoma/paraganglioma preclinical models: which to use and why?

Endocr Connect 2020 Dec;9(12):R251-R260

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Pheochromocytomas/paragangliomas (PPGLs) are rare neuroendocrine tumours linked to more than 15 susceptibility genes. PPGLs present with very different genotype/phenotype correlations. Certainly, depending on the mutated gene, and the activated intracellular signalling pathways, as well as their metastatic potential, each tumour is immensely different. One of the major challenges in in vitro research, whatever the study field, is to choose the best cellular model for that study. Unfortunately, most of the time there is not 'a best' cell model. Thus, in order to avoid observations that could be related to and/or dependent on a specific cell line, researchers often perform the same experiments using different cell lines simultaneously. The situation is even more complicated when there are only very few cell models obtained in different species for a disease. This is the case for PPGLs. In this review, we will describe the characteristics of the different cell lines and of mouse models, trying to understand if there is one that is more appropriate to use, depending on which aspect of the tumours one is trying to investigate.
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http://dx.doi.org/10.1530/EC-20-0472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774759PMC
December 2020

Insight on the Intracrinology of Menopause: Androgen Production within the Human Vagina.

Endocrinology 2021 02;162(2)

Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio," University of Florence, Florence, Italy.

In this study, we investigated steroidogenic gene mRNA expression in human vaginas and verified the ability of human vagina smooth muscle cells (hvSMCs) to synthesize androgens from upstream precursor dehydroepiandrosterone (DHEA). As a readout for androgen receptor (AR) activation, we evaluated the mRNA expression of various androgen-dependent markers. hvSMCs were isolated from vagina tissues of women undergoing surgery for benign gynecological diseases. In these cells, we evaluated mRNA expression of several steroidogenic enzymes and sex steroid receptors using real time reverse transcription-polymerase chain reaction. Androgen production was quantified with liquid chromatography tandem-mass spectrometry (LC-MS/MS). In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α, whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of proandrogenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfotransferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short-term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone and DHT secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. This study confirmed that the human vagina is an androgen-target organ with the ability to synthesize androgens, thus providing support for the use of androgens for local symptoms of genitourinary syndrome in menopause.
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http://dx.doi.org/10.1210/endocr/bqaa219DOI Listing
February 2021

Outcomes of combination therapy with daily Tadalafil 5mg plus Tamsulosin 0.4mg to treat lower urinary tract symptoms and erectile dysfunction in men with or without metabolic syndrome.

Minerva Urol Nefrol 2020 Nov 17. Epub 2020 Nov 17.

Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Careggi Hospital, Florence, Italy.

Background: To assess the impact of Tadalafil 5mg/die plus Tamsulosin 0.4mg/die combination therapy on LUTS and ED, according to presence vs. absence of Mets.

Methods: 75 consecutive men presenting with ED and LUTS were enrolled. Patients were divided into two groups according to MetS presence. All subjects were treated with combination therapy for 12 weeks. Patients were re-evaluated after treatment with Uroflowmetry and PVR, IPSS, IPSS QoL, OAB-q and IIEF-5.

Results: After enrollment, 50 patients were included: 31(62.0%) with MetS and 19(38.0%) without MetS. At baseline, patients without MetS showed a significantly better IPSS, IIEF and OAB-q, as compared to those with MetS. After 12 weeks of combination therapy LUTS, ED and flowmetry significantly improved in both groups(p<0.001). The improvement after 12 weeks was similar between groups in all parameters(p>0.05), except for ΔOAB-q that was significantly better for patients with MetS(p=0.028). Nevertheless, total IPSS, all IPSS subscores and OAB-q were significantly better at 12 weeks in men without MetS(p<0.05). Despite IIEF-5 was significantly different at baseline, after 12 weeks of combination therapy, erectile function was similar in men with or without METS:16.3±3.8 vs 7.7±4.7(p=0.238). No serious AE was reported and complications were comparable between groups(p>0.05).

Conclusions: Patients with MetS have worse LUTS and ED profiles. However, tadalafil plus tamsulosin combination treatment provided them a similar ED profile and a greater relief of OAB symptoms at the end of the trial. Combination therapy had the same safety profile in men besides MetS. Further randomized controlled trials are needed.
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http://dx.doi.org/10.23736/S0393-2249.20.04099-0DOI Listing
November 2020

Prognostic and Monitoring Value of Circulating Tumor Cells in Adrenocortical Carcinoma: A Preliminary Monocentric Study.

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Florence, Italy.

Adrenocortical carcinoma (ACC), a rare and aggressive neoplasia, presents poor prognosis when metastatic at diagnosis and limited therapies are available. Specific and sensitive markers for early diagnosis and a monitoring system of therapy and tumor evolution are urgently needed. The liquid biopsy represents a source of tumor material within a minimally invasive blood draw that allows the recovery of circulating tumor cells (CTCs). CTCs have been recently shown to be detectable in ACC. In the present paper, we evaluated the prognostic value of CTCs obtained by size-filtration in a small pilot cohort of 19 ACC patients. We found CTCs in 68% of pre-surgery and in 38% of post-surgery blood samples. In addition, CTC clusters (CTMs) and cancer associated macrophages (CAMLs) were detectable in some ACC patients. The median number of CTCs significantly decreased after the mass removal. Finally, stratifying patients in high and low pre-surgery CTC number groups, assuming the 75th percentile CTC value as cut-off, CTCs significantly predicted patients' overall survival (log rank = 0.005), also in a multivariate analysis adjusted for age and tumor stage. In conclusion, though preliminary and performed in a small cohort of patients, our study suggests that CTC number may represent a promising marker for prognosis and disease monitoring in ACC.
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http://dx.doi.org/10.3390/cancers12113176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693770PMC
October 2020

and Non-Chromaffin Tumors: A Mediastinal Germ Cell Tumor Occurring in a Young Man with Germline Mutation.

Medicina (Kaunas) 2020 Oct 25;56(11). Epub 2020 Oct 25.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139 Florence, Italy.

Mutations in genes encoding one of the subunits of succinate dehydrogenase (SDH) are involved in pheochromocytoma (PHEO) and paraganglioma (PGL) development. Over the last few years, such mutations have also been associated with non-chromaffin tumors. However, immunohistochemistry (IHC) on the tumor tissue and a study on the loss of heterozygosity (LOH) aimed at demonstrating the pathogenic role of genes have only been employed in a few cases. We describe the case of a 19-year-old Caucasian man with a germline mutation, who presented with acne resistant to medical treatment. His follow-up for chromaffin tumors was negative, while hormonal tests revealed suppressed gonadotropins with testosterone in the upper range of normality and elevated β-human chorionic gonadotropin (β-hCG). At the whole-body enhanced CT scan, a mediastinal lesion suggestive of a germ cell tumor (GCT) was detected. FDG-PET (fluorodeoxyglucose-positron emission tomography) imaging showed low glucose metabolism at the mediastinal site. Surgical removal of the mass was uneventful. Pathology confirmed the diagnosis of GCT consisting of cystic teratoma (95%) and seminoma (5%). IHC for SDHB showed normal protein expression, and genetic analysis of the tumor tissue revealed the absence of LOH. Normalization of the hormonal tests and acne attenuation were achieved after surgery. We report an incidental association of a germinal mutation and mediastinal GCT in a young Caucasian man. Our paper highlights the importance of IHC and genetic analysis in confirming the etiologic role of genes in nonchromaffin tumors, thus excluding incidental associations.
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http://dx.doi.org/10.3390/medicina56110561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693473PMC
October 2020

Subclinical male hypogonadism.

Minerva Endocrinol 2020 Sep 24. Epub 2020 Sep 24.

Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy.

Introduction: The concept of subclinical or compensated male hypogonadism (SHG), characterized by increased gonadotropins and normal testosterone levels is emerging. However, its real clinical significance is still conflicting. The aim of the present study is to summarize and discuss the available evidence related to the possible definition of SHG and the possible advantages of testosterone replacement therapy (TRT).

Evidence Acquisition: A comprehensive systematic Medline, Embase and Cochrane search was performed. Publications from January 1, 1969 up to February 29th, 2020 were included. The search was restricted to English-language articles and studies of human participants.

Evidence Synthesis: Two main clinical forms of SHG can be described. The first identifies young patients who have a positive medical history for testis damage occurring before puberty onset. The second form can occur as a consequence of an age-dependent decline of T. Whereas the former can be the consequence of several congenital or acquired diseases, also possible causes of primary hypogonadism, the real significance of the latter is still debatable. Available evidence indicates that age-related SHG is quite a common phenomenon, occurring in 9.4% of aging men from the general population. Cross-sectional and longitudinal data have documented that it is associated with poor health and can be a sign of forthcoming increased cardiovascular mortality and morbidity.

Conclusions: Although available evidence suggests that in aging populations SHG can be considered a particular condition associated with an increased CV risk, it is still unknown if treatment with T can improve any outcomes in these subjects. Hence, further interventional studies are advisable in order to better understand the characteristics of SHG and the possible advantages of an early TRT.
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http://dx.doi.org/10.23736/S0391-1977.20.03208-3DOI Listing
September 2020

Family History for Cardio-Metabolic Diseases: A Predictor of Major Adverse Cardiovascular Events in Men With Erectile Dysfunction.

J Sex Med 2020 12 18;17(12):2370-2381. Epub 2020 Sep 18.

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; I.N.B.B. - Istituto Nazionale Biostrutture e Biosistemi, Rome, Italy.

Background: Family history (FH) of cardiovascular (CV) disease is a known CV risk factor. However, it is rarely considered for CV risk stratification. Furthermore, FH for metabolic diseases is generally overlooked.

Aim: To evaluate, in a population of men with erectile dysfunction (ED), whether FH for cardio-metabolic diseases could provide insights into metabolic and sexual features and predict the occurrence of forthcoming major adverse CV events (MACE).

Methods: A consecutive series of 4,693 individuals (aged 51.3 ± 13.3 years) attending an Andrology outpatient clinic for ED was studied. A subset of these (n = 1,595) was evaluated retrospectively for MACE occurrence.

Outcomes: Several metabolic and sexual function-related parameters were studied. For the retrospective study, information on an incident MACE was collected over a mean follow-up of 4.2 ± 2.5 years.

Results: A greater number of cardio-metabolic FH factors were associated with a worse metabolic profile, including higher waist circumference, triglycerides, glucose, glycosylated hemoglobin, and diastolic blood pressure, as well as lower high-density lipoprotein cholesterol. An increased number of FH factors were associated with worse erectile function (odds ratio = 1.14[1.07;1.23], P < .0001), impaired penile dynamic peak systolic velocity, and lower testosterone levels. In the retrospective study, a positive cardiometabolic FH was associated with a significantly higher incidence of MACEs, even after adjusting for age and comorbidities (hazard ratio = 1.51[1.06-2.16], P = .023). Interestingly, when dividing the sample into high- and low-risk categories according to several CV risk factors (age, previous MACEs, high-density lipoprotein cholesterol, and comorbidities), FH was confirmed as a predictor of incident MACE only among the low-risk individuals.

Clinical Implications: Investigating FH for cardio-metabolic diseases is a quick and easy task that could help clinicians in identifying, among individuals with ED, those who deserve careful evaluation of CV and metabolic risk factors. Moreover, considering FH for CV risk stratification could predict MACEs in individuals who, according to conventional CV risk factors, would be erroneously considered at low risk.

Strengths & Limitations: The large sample size and the systematic collection of MACEs through an administrative database, with no risk of loss at follow-up, represent strengths. The use of administrative database for MACE collection may lead to some misclassifications. The specific population of the study limits the generalizability of the results.

Conclusion: FH is simple and inexpensive information that should be part of the CV risk assessment in all men with ED because it helps in the identification of those who need lifestyle and risk factor modifications and whose risk would otherwise be overlooked. Rastrelli G, Yannas D, Mucci B, et al. Family History for Cardio-Metabolic Diseases: A Predictor of Major Adverse Cardiovascular Events in Men With Erectile Dysfunction. J Sex Med 2020;17:2370-2381.
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http://dx.doi.org/10.1016/j.jsxm.2020.08.012DOI Listing
December 2020

Circadian rhythm and erectile function: is there a penile clock?

Nat Rev Urol 2020 Nov;17(11):603-604

Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1038/s41585-020-00376-7DOI Listing
November 2020

Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts.

Int J Mol Sci 2020 Aug 25;21(17). Epub 2020 Aug 25.

Section of Human Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

TNFα is the main proinflammatory cytokine implicated in the pathogenesis of neurodegenerative disorders, but it also modulates physiological functions in both the developing and adult brain. In this study, we investigated a potential direct role of TNFα in determining phenotypic changes of a recently established cellular model of human basal forebrain cholinergic neuroblasts isolated from the nucleus basalis of Meynert (hfNBMs). Exposing hfNBMs to TNFα reduced the expression of immature markers, such as nestin and β-tubulin III, and inhibited primary cilium formation. On the contrary, TNFα increased the expression of TNFα receptor TNFR2 and the mature neuron marker MAP2, also promoting neurite elongation. Moreover, TNFα affected nerve growth factor receptor expression. We also found that TNFα induced the expression of DNA-methylation enzymes and, accordingly, downregulated genes involved in neuronal development through epigenetic mechanisms, as demonstrated by methylome analysis. In summary, TNFα showed a dual role on hfNBMs phenotypic plasticity, exerting a negative influence on neurogenesis despite a positive effect on differentiation, through mechanisms that remain to be elucidated. Our results help to clarify the complexity of TNFα effects in human neurons and suggest that manipulation of TNFα signaling could provide a potential therapeutic approach against neurodegenerative disorders.
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http://dx.doi.org/10.3390/ijms21176128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504606PMC
August 2020
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