Francesco Pallotti

Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action

In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

Androgenetic alopecia: a review

PurposeAndrogenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia.MethodsUsing the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016.ResultsThe occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome AR⁄EDA2R locus and the chromosome 20p11 locus.ConclusionsCandidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.

Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients.

Various microRNAs from the miR-371-3 and miR-302a–d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a–d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.

Effects of a dietary supplement on cholesterol in subjects with moderate hypercholesterolemia.

BACKGROUND AND AIMS Prospective studies have demonstrated that the risk of death due to ischaemic heart disease is strongly correlated with blood cholesterol (TC) levels. Diet is the basic treatment for all dyslipidaemia. If diet alone proves inadequate, supplements can be used to try to reduce cholesterol levels. These substances are indicated in moderate dyslipidaemia, as they are able to induce a moderate reduction in blood cholesterol. The objective of our study was to investigate the effects of a dietary supplement containing Omega-3, Policosanol, Resveratrol, L-carnitine, Monascus purpureus, Coenzyme Q10, Vitamin B6 and Vitamin B12 on TC (primary end point) and LDL, triglycerides and HDL (secondary endpoints). PATIENTS AND METHODS The study involved 40 men and 40 women recruited from the outpatient section of our Department randomly assigned to the treatment group (A) or the control group (B). RESULTS There was a statistically significant reduction in TC 6 months after the end of treatment in both groups. In Group A, there was also a statistically significant change in HDL, LDL and TG, while in group B, there was no statistically significant change in HDL, LDL or TG. CONCLUSIONS The dietary supplement used in our study, in combination with a balanced diet and physical exercise, was found to induce a significant reduction in TC and LDL-C and an improvement in HDL-C. In contrast, while a balanced diet together with physical exercise but without the dietary supplement produced a significant reduction in TC, it had no significant effect on the other lipid parameters tested.

Le nuove frontiere del laboratorio endocrinologico: la LC-MS/MS

Sono trascorsi più di dieci anni dalle prime applicazioni della cromatografia liquida abbinata alla spettrometria di massa tandem (LC-MS/MS) in endocrinologia. Tale tecnica ha rappresentato, in particolare nel campo della steroidologia, una svolta decisiva rispetto alla più nota, ma poco praticabile, gas cromatografia-MS (GC-MS), nonché rispetto ai metodi immunometrici (immunoassays, IA), che ancora oggi dominano i laboratori clinici italiani. I vantaggi della LC-MS/MS sono sostanzialmente tre: (i) la soluzione del problema della similarità strutturale tra composti della stessa famiglia, il maggior limite degli IA; (ii) l’ampliamento del pannello delle molecole misurabili ad ormoni, intermedi e precursori della biosintesi attualmente non dosabili con IA; (iii) livelli di sensibilità e selettività tali da permettere la rivalutazione di fluidi alternativi ai derivati ematici, quali la saliva, contenente concentrazioni ormonali estremamente basse, e l’urina, matrice ricca di molecole potenzialmente interferenti. Tali vantaggi si traducono in una migliore efficacia diagnostica dei marcatori già noti, nell’individuazione di nuovi marcatori, o di profili di marcatori. Inoltre, l’elevato potere informativo della LC-MS/MS sta determinando una riconsiderazione dell’assetto steroideo in patologie complesse quali l’iperandrogenismo femminile, le iperplasie, gli adenomi e i carcinomi surrenalici, aprendo nuovi scenari per

La gestione clinica dei maschi 46,XX

Il riscontro di un cariotipo 46,XX in un soggetto fenotipicamente maschile è una condizione rara, con prevalenza stimata intorno a 1:20000, che frequentemente può essere riscontrata dallo specialista endocrinologo-andrologo chiamato a definire le cause dell’infertilità del paziente. La diagnosi è molto spesso tardiva: i soggetti affetti presentano difatti genitali esterni maschili alla nascita, raramente ambigui (< 20% dei casi), e solo durante lo sviluppo il riscontro di severa ipotrofia testicolare bilaterale consente di ipotizzare un disturbo dello sviluppo sessuale.

FATHERHOOD AND SPERM DNA DAMAGE IN TESTICULAR CANCER PATIENTS

Testicular cancer (TC) is one of the most treatable of all malignancies and the management of the quality of life of these patients is increasingly important, especially with regard to their sexuality and fertility. Survivors must overcome anxiety and fears about reduced fertility and possible pregnancy-related risks as well as health effects in offspring. There is thus a growing awareness of the need for reproductive counseling of cancer survivors. Studies found a high level of sperm DNA damage in TC patients in comparison with healthy, fertile controls, but no significant difference between these patients and infertile patients. Sperm DNA alterations due to cancer treatment persist from 2 to 5 years after the end of the treatment and may be influenced by both the type of therapy and the stage of the disease. Population studies reported a slightly reduced overall fertility of TC survivors and a more frequent use of ART than the general population, with a success rate of around 50%. Paternity after a diagnosis of cancer is an important issue and reproductive potential is becoming a major quality of life factor. Sperm chromatin instability associated with genome instability is the most important reproductive side effect related to the malignancy or its treatment. Studies investigating the magnitude of this damage could have a considerable translational importance in the management of cancer patients, as they could identify the time needed for the germ cell line to repair nuclear damage and thus produce gametes with a reduced risk for the offspring.

Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial

Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets. Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test. Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis. Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function. Trial Registration: EUDRACT Number 2010-020196-23. Registred 14 April 2011.

Terapia della eiaculazione precoce

L’eiaculazione precoce (EP) è il più frequente disturbo sessuale riferito nel maschio, ed è a tutti gli effetti un sintomo auto-identificato, auto-riportato e auto-valutato da chi ne soffre. Attualmente la International Society for Sexual Medicine ha definito l’EP come un’eiaculazione che avviene sempre o quasi sempre entro 1 minuto (EP life-long) o 3 minuti (EP acquisita) dalla penetrazione, con incapacità di ritardare l’eiaculazione e conseguenze negative sul piano personale come frustrazione, sofferenza e/o condotte di rifiuto dell’atto sessuale [1]. Dal punto di vista tassonomico, possiamo riconoscere forme assolute e relazionali, organiche e psicogene (o meglio non-organiche), acquisite o life-long. Il corretto approccio all’EP consiste nel non considerarla esclusivamente una patologia a sé stante, ma un possibile sintomo di una condizione latente [2, 3]. Misure di prevenzione. Valgono come utili misure preventive tutte le strategie volte a limitare la comparsa di condizioni che vedano l’EP come sintomo, come ad esempio la tireotossicosi e le infezioni del tratto genito-urinario come le prostatiti. Procedure clinico-diagnostiche. La diagnosi di EP è come detto auto-riportata: questionari validati (PEDT: Premature Ejaculation Diagnostic Tool; PEP: Premature Ejaculation Profile) contribuiscono a facilitare la diagnosi che comunque richiede un attento colloquio clinico, volto ad investigare altri eventuali sintomi sessuali (in particolare la

Marcatori tumorali di neoplasia testicolare: presente e futuro

La neoplasia testicolare è la patologia tumorale più frequente negli uomini in fascia di età riproduttiva. Nonostante negli ultimi anni si sia verificato un incremento in tutta Europa (in Italia circa +1.9% annuo), la sopravvivenza di questi pazienti è notevolmente migliorata (>90% a 5 anni), garantendo ai sopravvissuti un’aspettativa di vita sovrapponibile a quella della popolazione generale. Gli istotipi più rappresentati sono il seminoma e le forme non seminomatose, anche se le forme miste sono di frequente riscontro [1]. I tumori testicolari possono produrre proteine, dosabili nel sangue, che vengono utilizzate ai fini diagnostici (anche di diagnosi precoce) e nel monitoraggio della patologia tumorale testicolare.