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ABSTRACT: Metabolic syndrome (MetS) is a diagnostic category which identifies subjects at high risk for diabetes and cardiovascular diseases, erectile dysfunction (ED) and male hypogonadism. However, MetS impact on male infertility has been poorly studied. We systematically evaluated possible associations between MetS and clinical characteristics in men with couple infertility. Out of 367 consecutive subjects, 351 men without genetic abnormalities were studied. MetS was defined according to the International Diabetes Federation&American Heart Association/National Heart,Lung, and Blood Institute classification. All men underwent physical, hormonal, seminal and scrotal ultrasound evaluation. Erectile and ejaculatory functions were assessed by International Index of Erectile Function-15 erectile function domain (IIEF-15-EFD) and Premature Ejaculation Diagnostic Tool (PEDT), respectively, while psychological symptoms by Middlesex Hospital Questionnaire. Out of 351 patients, 27 (7.7%) fulfilled MetS criteria. Among ultrasound features, in an age-adjusted logistic model, only testis inhomogeneity was significantly associated with increasing MetS factors (HR = 1.36 [1.09-1.70]; p < 0.01). In an age-adjusted model, MetS was associated with a stepwise decline in total testosterone (TT) (B = -1.25 ± 0.33; p < 0.0001), without a concomitant rise in gonadotropins. At univariate analysis, progressive motility and normal morphology were negatively related to the number of MetS components (both p < 0.0001), but when age and TT were introduced in a multivariate model, only sperm morphology retained a significant association (B = -1.418 ± 0.42; p = 0.001). The risk of ED (IIEF-15-EFD score <26) increased as a function of the number of MetS factors, even after adjusting for age and TT (HR = 1.45[1.08-1.95]; p < 0.02). No association between PEDT score and MetS was observed. Finally, after adjusting for age and TT, somatization and depressive symptoms were associated with increasing MetS components (B = 0.66 ± 0.03, p < 0.05; B = 0.69 ± 0.03, p < 0.02; respectively). In conclusion, in men with couple infertility, MetS is associated with hypogonadism, poor sperm morphology, testis ultrasound inhomogeneity, ED, somatization and depression. Recognizing MetS could help patients to improve not only fertility but also sexual and overall health.
Andrology. 01/2013;
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ABSTRACT: Oxidative stress (OS) is involved in many disoders including male infertility. Human spermatozoa are very sensitive targets of reactive oxygen species (ROS) and most sperm functions are impaired in the case of OS. In addition unbalanced production of ROS is considered one of the most important causes of sperm DNA fragmentation, a semen trait of infertile men. The relationship between oxidative damage and semen quality is partially controversial, probably due to the different methods and/or targets used to reveal the OS. In this study, by fluorescence microscopy and flow cytometry, we compared two methods to reveal 8-hydroxy,2-deoxyguanosine (8-OHdG), the hallmark of oxidative DNA damage: an immunofluorescence method and the commercial OxyDNA kit. We found that although both methods localized the labelling in sperm nuclei they yielded different measures, and only with the immunofluorescence method was the labelling specific for sperm 8-OHdG. The immunofluorescence method, coupled to flow cytometry, was thus selected to analyse the 8-OHdG content in semen samples from 94 subfertile patients and to investigate the relationship with semen quality. We found that the percentages of spermatozoa with 8-OHdG (mean±s.d., 11.4±6.9%) were related to sperm count (Pearson's correlation coefficient (r)=-0.27, P=0.04 (ANOVA and student's t-test)), motility (progressive: r=-0.22, P=0.04; non-progressive: r=0.25, P=0.01), and normal morphology (r=-0.27, P=0.01). In conclusion, we demonstrate that immunofluorescence/flow cytometry is a reliable and specific method to detect 8-OHdG at single-cell level and show that oxidative damage only partially overlaps poor semen quality, suggesting that it could provide additional information on male fertility with respect to routine semen analysis.
Reproduction 01/2013; 145(3):227-35. · 2.58 Impact Factor
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ABSTRACT: STUDY QUESTION: What are the associations between semen apoptotic M540 bodies and other parameters of semen quality and sonographic alterations of the male genital tract in a cohort of infertile subjects? SUMMARY ANSWER: In infertile subjects, semen M450 bodies are highly correlated with ultrasound and clinical signs of testis abnormalities but not with alterations of other parts of the male genital tract, suggesting a testicular origin of M540 bodies. WHAT IS KNOWN ALREADY: We have reported the presence in semen of round anucleate elements, named 'M540 bodies', resembling apoptotic bodies as they contain several apoptotic markers. STUDY DESIGN AND SIZE: A consecutive series of 130 males with couple infertility were evaluated, during the same day session, for clinical, scrotal and transrectal color-Doppler ultrasound characteristics, and hormonal and semen parameters, including interleukin 8 (sIL-8) and M540 body levels. PARTICIPANTS/MATERIALS, SETTING METHODS: Semen parameters were analyzed by WHO recommended procedures. CDU was performed using the ultrasonographic console Hitachi H21. sIL-8 and serum hormones were evaluated by ELISA methods. MAIN RESULTS AND THE ROLE OF CHANCE: The average percentage value of M540 bodies was 24.6 ± 18.3. After adjusting for possible confounders (age, waist, calculated free testosterone and smoking habit), M450 body levels negatively correlated with sperm number/ejaculate, progressive motility, normal morphology and sIL-8 levels (adj.r = -0.455, P < 0.0001; adj.r = -0.464, P < 0.0001; adj.r = -0.430, P < 0.001; adj.r = -0.236, P < 0.05, respectively). In a subset of patients with a history of cryptorchidism (n = 8), M540 bodies were higher than in non-cryptorchid men (40.5 ± 14.8 versus 23.6 ± 18.2%; P < 0.02). A negative correlation was found between M540 and ultrasound testis volume (adj.r = -0.241, P < 0.05), whereas a positive association was found with testis inhomogeneity [HR = 1.06 (1.02-1.09); P = 0.002], hypoechogenicity [HR = 1.05 (1.01-1.08); P < 0.02] and FSH levels (adj.r = 0.309, P < 0.01). No relationships were found with CDU characteristic of the prostate, seminal vesicles, epididymis and vas deferens. In a multivariate model, testis inhomogeneity and history of cryptorchidism were independently associated with M540 body levels (adj.r = 0.355, P < 0.01 and adj.r = 0.223, P < 0.05, respectively). Receiver operating characteristic analysis demonstrated that at the threshold of 27%, M540 bodies discriminate subjects with testis inhomogeneity with a sensitivity of 72% and specificity of 73%. LIMITATIONS, REASONS FOR CAUTION: The increased M540 body semen levels in men with a history of cryptorchidism should be confirmed in a larger number of patients. WIDER IMPLICATIONS OF THE FINDINGS: M540 bodies may be considered a semen marker of altered testis function and thus their evaluation may be helpful in the diagnosis of male infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from Ministry of University and Scientific Research (Prin project to E.B. and FIRB project to S.M.) and Regione Toscana (to G.F.).
Human Reproduction 09/2012; · 4.47 Impact Factor
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ABSTRACT: Previous studies concerning ultrasound evaluation of the seminal vesicles (SV) were performed on a limited series of subjects, and considered few parameters, often only before ejaculation and without assessing the patients' sexual abstinence. The aim of this study was to evaluate the volume and the emptying characteristics of the SV and their possible correlations with scrotal and transrectal ultrasound features.
The SV of 368 men seeking medical care for couple infertility were evaluated by ultrasound. All patients underwent, during the same ultrasound session, scrotal and transrectal evaluation, before and after ejaculation, and the ejaculate was subjected to semen analysis. A new parameter, SV ejection fraction, calculated as: [(SV volume before ejaculation - SV volume after ejaculation)/SV volume before ejaculation] × 100, was evaluated.
After adjusting for sexual abstinence and age, both pre-ejaculatory SV volume and SV ejection fraction were positively associated with ejaculate volume. As assessed by receiver operating characteristic curve, a cut-off for SV ejection fraction of 21.6% discriminates subjects with normal ejaculate volume (≥1.5 ml) and pH (≥7.2 ml) with both sensitivity and specificity equal to 75%. Subjects with SV ejection fraction of <21.6% more often had a higher post-ejaculatory SV volume and ejaculatory duct abnormalities. Furthermore, a higher post-ejaculatory SV volume was associated with a higher prostate volume and SV abnormalities. Higher epididymal and deferential diameters were also detected in subjects with a higher post-ejaculatory SV volume or reduced SV ejection fraction. No association between SV and testis ultrasound features or sperm parameters was observed. Associations with SV ejection fraction were confirmed in nested 1:1 case-control analysis.
The SV contribute significantly to the ejaculate volume. A new parameter, SV ejection fraction, could be useful in assessing SV emptying. A SV ejection fraction of <21.6% was associated with prostate-vesicular and epididymal ultrasound abnormalities.
Human Reproduction 02/2012; 27(4):974-82. · 4.47 Impact Factor
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S. Marchiani,
L. Tamburrino,
L. Giuliano,
D. Nosi,
� V. Sarli,
L. Gandini,
� P. Piomboni,
§ G. Belmonte, § G. Forti,
E. Baldi,
M. Muratori
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ABSTRACT: Sumoylation is a post-translational modification involved in the regulation of
several cell functions. Recent studies suggest its involvement in spermatogenesis,
but occurrence and function of SUMO (small ubiquitin-like modifier) in
mature spermatozoa remain unknown. We report the occurrence of several
SUMO1-conjugated proteins, in a range of 20–85 kDa, in ejaculated spermatozoa.
By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive
spermatozoa in 58 subjects undergoing semen analysis in our laboratory
and correlated the obtained values with semen parameters. We found that the
percentage of SUMO1-positive spermatozoa was inversely correlated with total
(r = )0.35, p < 0.01) and progressive motility (r = )0.29, p < 0.05). Such correlations
become stricter when only asthenospermic subjects were included in
the analysis (r = )0.58, p = 0.01 for progressive motility, n = 17) and were lost
in non-asthenospermic subjects. By immunofluorescence and immunoconfocal
fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus
and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy
as well as a long permeabilization protocol demonstrated a massive localization
of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish
dead ⁄ live cells, we show that SUMO1 is mainly present in live spermatozoa. In
conclusion, sumoylation of human spermatozoa may be involved in the regulation
of motility.Sumoylation is a post-translational modification involved in the regulation of
several cell functions. Recent studies suggest its involvement in spermatogenesis,
but occurrence and function of SUMO (small ubiquitin-like modifier) in
mature spermatozoa remain unknown. We report the occurrence of several
SUMO1-conjugated proteins, in a range of 20–85 kDa, in ejaculated spermatozoa.
By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive
spermatozoa in 58 subjects undergoing semen analysis in our laboratory
and correlated the obtained values with semen parameters. We found that the
percentage of SUMO1-positive spermatozoa was inversely correlated with total
(r = )0.35, p < 0.01) and progressive motility (r = )0.29, p < 0.05). Such correlations
become stricter when only asthenospermic subjects were included in
the analysis (r = )0.58, p = 0.01 for progressive motility, n = 17) and were lost
in non-asthenospermic subjects. By immunofluorescence and immunoconfocal
fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus
and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy
as well as a long permeabilization protocol demonstrated a massive localization
of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish
dead ⁄ live cells, we show that SUMO1 is mainly present in live spermatozoa. In
conclusion, sumoylation of human spermatozoa may be involved in the regulation
of motility.
International Journal of Andrology 12/2011; · 3.59 Impact Factor
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S. Marchiani,
L. Tamburrino,
L. Giuliano,
D. Nosi,
V. Sarli,
L. Gandini,
P. Piomboni,
G. Belmonte, G. Forti,
E. Baldi,
M. Muratori
[show abstract]
[hide abstract]
ABSTRACT: Sumoylation is a post-translational modification involved in the regulation of several cell functions. Recent studies suggest its involvement in spermatogenesis, but occurrence and function of SUMO (small ubiquitin-like modifier) in mature spermatozoa remain unknown. We report the occurrence of several SUMO1-conjugated proteins, in a range of 20–85 kDa, in ejaculated spermatozoa. By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive spermatozoa in 58 subjects undergoing semen analysis in our laboratory and correlated the obtained values with semen parameters. We found that the percentage of SUMO1-positive spermatozoa was inversely correlated with total (r = −0.35, p < 0.01) and progressive motility (r = −0.29, p < 0.05). Such correlations become stricter when only asthenospermic subjects were included in the analysis (r = −0.58, p = 0.01 for progressive motility, n = 17) and were lost in non-asthenospermic subjects. By immunofluorescence and immunoconfocal fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy as well as a long permeabilization protocol demonstrated a massive localization of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish dead/live cells, we show that SUMO1 is mainly present in live spermatozoa. In conclusion, sumoylation of human spermatozoa may be involved in the regulation of motility.
International Journal of Andrology 11/2011; 34(6pt1):581 - 593. · 3.59 Impact Factor
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E Bandini,
A D Fisher,
V Ricca,
J Ristori,
M C Meriggiola,
E A Jannini,
C Manieri,
G Corona,
M Monami,
E Fanni,
A Galleni, G Forti,
E Mannucci,
M Maggi
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ABSTRACT: Childhood maltreatment (CM) is quite common and constitutes a nonspecific risk factor for a range of different psychiatric symptoms during lifespan. It has been demonstrated that sexual minorities are at higher risk of maltreatment and abuse, and a high proportion of transsexual subjects report CM. The aim of this study is to evaluate the prevalence of reported CM in a clinical sample of patients with male-to-female Gender Identity Disorder (MtF GID), and to explore the relationship between these early life events, body image and different psychopathological and clinical variables. A consecutive series of 162 patients with male genotype was evaluated from July 2008 to May 2010. A total of 109 subjects (mean age 36 ± 10 years) meeting the criteria for MtF GID and giving their informed consent were considered. The occurrence of CM experiences was evaluated through a face-to-face clinical interview. Patients were asked to complete the Body Uneasiness Test and Symptom Checklist-90 Revised. More than one-fourth of patients reported CM. Maltreated subjects reported a higher body dissatisfaction and display a worse lifetime mental health. The presence of reported CM in these patients has relevant psychopathological implications, and therefore should be carefully investigated.
International journal of impotence research 08/2011; 23(6):276-85. · 2.73 Impact Factor
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F Lotti,
G Corona,
G M Colpi,
E Filimberti,
S Degli Innocenti,
M Mancini,
E Baldi,
I Noci, G Forti,
L Adorini,
M Maggi
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ABSTRACT: Obesity is associated with a systemic, low-grade inflammatory state. Although the relationship between obesity and semen parameters or prostate diseases has been previously investigated, the association between body mass index (BMI), prostate inflammatory diseases and color- Doppler ultrasound (CDU) of the male genital tract (MGT) has been poorly studied.
To evaluate the association between BMI and CDU features of the MGT, signs and symptoms of prostate inflammation, semen parameters. MATERIALS/SUBJECTS AND METHODS: We studied 222 men seeking medical care for couple infertility. According to the World Health Organization classification, subjects were divided into 3 groups: normal weight (no.=131, BMI=18.5-24.9 kg/m2), overweight (no.=71, BMI=25.0-29.9 kg/m2), obese (no.=20, BMI≥30.0 kg/m2). All patients underwent simultaneous testosterone evaluation and seminal analysis, including interleukin 8 (sIL-8), along with scrotal and transrectal CDU, before and after ejaculation. Prostatitis symptoms were evaluated by National Institutes of Health- Chronic Prostatitis Symptom Index questionnaire.
After adjusting for age and testosterone levels, higher BMI was significantly related to higher prostate volume and several CDU features of the prostate, including macro-calcifications, inhomogeneity, higher arterial peak systolic velocity (the latter adjusted also for blood pressure), but not with abnormalities of testis, epididymis, seminal vesicles. Furthermore, higher BMI and BMI class were significantly related to higher sIL-8, a reliable surrogate marker of prostate inflammatory diseases, even after adjustment for age. Conversely, no associations among BMI, clinical symptoms of prostatitis or semen parameters were observed.
Subjects with higher BMI might develop CDU and biochemical signs suggestive of prostate inflammation, although not clinically overt.
Journal of endocrinological investigation 07/2011; 34(10):e336-42. · 1.57 Impact Factor
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ABSTRACT: The relationship between extramarital affairs and cardiovascular risk is still not completely clarified. The aim of this study was to investigate whether extramarital affairs have a protective effect on cardiovascular risk or, conversely, a deleterious one. Among patients studied, 91.8% of the whole sample reported no or occasional extramarital affairs, while 8.2% declared a stable secondary relationship. During a median follow-up of 4 [0-8] years, 95 major adverse cardiovascular events (MACE), eight of which were fatal, were observed. Cox analysis, after adjustment for confounding factors, showed that presence of stable extramarital affair was associated with a higher incidence of MACE (HR = 2.13 [1.12; 4.07], p = 0.023). The introduction in the Cox model of patient perceived partner's hypoactive sexual desire (PPPHSD) attenuates the association (HR 1.86 [0.93; 3.70], p = 0.078). The sample was therefore divided according to PPPHSD. We observed that unadjusted incidence of MACE was significantly associated with presence of extramarital affairs only in men reporting a primal partner without PPPHSD. This association was also confirmed in a Cox regression model, after adjusting for confounders (HR = 2.87 [1.81; 6.98], p = 0.020). We can conclude that to be unfaithful represents an independent risk factor for MACE. Therefore, infidelity induces not only heart trouble in the betrayed partners, but seems to be also able to increase the betrayer's heart-related events.
International Journal of Andrology 06/2011; 35(1):11-7. · 3.59 Impact Factor
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ABSTRACT: The physiological role of prolactin (PRL) in men is not completely clarified. We previously reported that in subjects consulting for sexual dysfunction, lower PRL plasma levels were associated with worse lipid and glycaemic profile, as well as with a higher prevalence of metabolic syndrome and arteriogenic erectile dysfunction (ED). The aim of this study was to assess possible associations between PRL levels and incident major cardiovascular events (MACE) in subjects with ED. When only subjects without pathological hyperprolactinaemia (PRL < 735 mU/L or 35 ng/mL) and pituitary diseases were considered, both unadjusted and adjusted analyses showed a significantly lower incidence of MACE in subjects with PRL levels in the highest PRL quintile (246-735 mU/L or 12-35 ng/mL) when compared with the rest of the sample. In particular, the risk of MACE was reduced by 5% (1-9%; p = 0.03) for each 10 ng/mL increment of PRL. Conversely, comparing patients with hyperprolactinaemia with matched controls, no significant difference was detected between cases and controls in MACE. In subjects at high risk for cardiovascular diseases, such as those with ED, a relatively high PRL plasma level is associated with an overall decreased chance of MACE, independently from other known risk factors.
International Journal of Andrology 06/2011; 34(3):217-24. · 3.59 Impact Factor
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G Parenti,
P C Cecchi,
B Ragghianti,
A Schwarz,
F Ammannati,
P Mennonna,
A Di Rita,
P Gallina,
N Di Lorenzo,
P Innocenti, G Forti,
A Peri
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[hide abstract]
ABSTRACT: Subarachnoid hemorrhage (SAH) is a potential cause of hypopituitarism. Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH.
To prospectively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters.
Pituitary function was tested in 60 patients within 72 h after spontaneous SAH.
56.9% of the patients showed at least one anterior pituitary hormone deficiency: gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies (33.3 and 22.0%, respectively), whereas ACTH and TSH deficiency was less frequent (7.1 and 1.8%, respectively). With the exception of secondary hypogonadism, the prevalence of other pituitary hormone deficiencies is in agreement with previous studies, which evaluated pituitary function on longterm follow up after SAH. No correlation was found between hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma Scales. Moreover, no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher's scale.
We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself, the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism. Therefore, an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow-up.
Journal of endocrinological investigation 05/2011; 34(5):361-5. · 1.57 Impact Factor
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ABSTRACT: Since the first definition of the AZoospermia Factor (AZF) regions, the Y chromosome has become an important target for studies aimed to identify genetic factors involved in male infertility. This chromosome is enriched with genes expressed exclusively or prevalently in the testis and their absence or reduction of their dosage is associated with spermatogenic impairment. Due to its peculiar structure, full of repeated homologous sequences, the Y chromosome is predisposed to structural rearrangements, especially deletions/ duplications. This review discusses what is currently known about clinically relevant Y chromosome structural variations in male fertility, mainly focusing on copy number variations (CNVs). These CNVs include classical AZF deletions, gr/gr deletion and TSPY1 CNV. AZF deletions are in a clear-cut causeeffect relationship with spermatogenic failure and they also have a prognostic value for testis biopsy. gr/gr deletion represents the unique example in andrology of a proven genetic risk factor, providing an eight-fold increased risk for oligozoospermia in the Italian population. Studies on TSPY1 CNV have opened new perspectives on the role of this gene in spermatogenic efficiency. Although studies on the Y chromosome have importantly contributed to the identification of new genetic causes and thus to the improvement of the diagnostic work-up for severe male factor infertility, there is still about 50% of infertile men in whom the etiology remains unknown. While searching for new genetic factors on other chromosomes, our work on the Y chromosome still needs to be completed, with special focus on the biological function of the Y genes.
Journal of endocrinological investigation 03/2011; 34(5):376-82. · 1.57 Impact Factor
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Journal of endocrinological investigation 01/2011; 34(1):1-2. · 1.57 Impact Factor
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ABSTRACT: The treatment of advanced prostate cancer (CaP) with androgen deprivation therapy inevitably renders the tumours castration resistant and incurable. Under these conditions, neuroendocrine differentiation (NED) of CaP cells occurs and neuropeptides released by neuroendocrine cells facilitate tumour progression. Pharmacological strategies aiming to prevent or delay NED during androgen ablation could, therefore, increase the effectiveness of the therapy. Mechanisms and pathways inducing NED in CaP are poorly understood and data are often discordant. In the present study, we used several CaP cell lines (androgen-responsive: LNCaP, PC3-AR, 22RV1 and -irresponsive: DU145 and PC3) to evaluate NED after androgen deprivation or treatment with epidermal growth factor (EGF). NED was determined by neuron-specific enolase and chromogranin A expression and by the occurrence of morphological changes in the cells. Androgen-deprivation conditions induced NED in LNCaP and PC3-AR, but not in 22Rv1, PC3 and DU145 cells. LNCaP and PC3-AR cells also became resistant to thapsigargin-induced apoptosis. In all the AR-positive cell lines, androgen deprivation caused a decrease in androgen receptor expression indicating that it is downregulated irrespective of NED induction. Treatment with EGF induced NED in DU145 cells and the EGF receptor inhibitor gefinitib prevented the process. On the contrary, no effect of EGF was demonstrated in LNCaP or 22Rv1 cells. CaP cell lines did not respond univocally to treatments inducing NED, suggesting that studies on this topic should be performed in a wide spectrum of cell models which can be more indicative of the tumour variability in vivo.
International Journal of Andrology 12/2010; 33(6):784-93. · 3.59 Impact Factor
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ABSTRACT: Several studies suggest that type 2 diabetes mellitus (T2DM) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone replacement therapy (TRT) in T2DM has not been completely clarified. The aim of the present study was to analyse systematically the relationship between androgen levels and T2DM by reviewing and meta-analysing available prospective and cross-sectional studies. In addition, a specific meta-analysis on the metabolic effects of TRT in available randomized clinical trials (RCTs) was performed. An extensive Medline search was performed including the following words: 'testosterone', 'type 2 diabetes mellitus' and 'males'. Of 742 retrieved articles, 37 were included in the study. In particular 28, 5 and 3 were cross-sectional, longitudinal and interventional studies, respectively. A further unpublished RCT was retrieved from http://www.clinicaltrials.gov. T2DM patients showed significantly lower testosterone plasma levels in comparison with non-diabetic individuals. Similar results were obtained when T2DM subjects with and without erectile dysfunction were analysed separately. Meta-regression analysis demonstrated that ageing reduced, while obesity increased, these differences. However, in a multiple regression model, after adjusting for age and body mass index (BMI), T2DM was still associated with lower total testosterone (TT) levels (adjusted r = -0.568; p < 0.0001). Analysis of longitudinal studies demonstrated that baseline TT was significantly lower among patients with incident diabetes in comparison with controls (HR = -2.08[-3.57;-0.59]; p < 0.001). Combining the results of RCTs, TRT was associated with a significant reduction in fasting plasma glucose, HbA1c, fat mass and triglycerides. Conversely, no significant difference was observed for total and high-density lipoprotein cholesterol, blood pressure and BMI. The meta-analysis of the available cross-sectional data suggests that T2DM can be considered independently associated with male hypogonadism. Although only few RCTs have been reported, TRT seems to improve glycometabolic control as well as fat mass in T2DM subjects.
International Journal of Andrology 10/2010; 34(6 Pt 1):528-40. · 3.59 Impact Factor
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F Lotti,
G Corona,
M Mancini,
E Filimberti,
S Degli Innocenti,
G M Colpi,
E Baldi,
I Noci, G Forti,
L Adorini,
M Maggi
[show abstract]
[hide abstract]
ABSTRACT: This study was aimed at evaluating the association between seminal plasma interleukin-8 (sIL-8) and colour-Doppler ultrasound (CDU) characteristics of the male genital tract in a series of patients fulfilling the criteria of male accessory gland infections (MAGI). Of 250 subjects seeking medical care for couple infertility, 79 (mean age: 36.4 ± 7.5 years) met the criteria of MAGI and scored higher than the rest of the sample on the National Institutes of Health-Chronic Prostatitis Symptom Index score. All patients underwent simultaneous hormone evaluation and seminal analysis (including sIL-8), along with scrotal and transrectal CDU before and after ejaculation. After adjusting for age, sIL-8 in patients with MAGI was significantly related to several abnormal semen and CDU parameters. In particular, leucocytospermia was closely associated with sIL-8. Ejaculate volume, unlike other semen or hormonal parameters, was negatively associated with sIL-8. When scrotal CDU was performed, sIL-8 was positively related to CDU inhomogeneous, hypo-echoic, hyper-echoic epididymis and to epididymal calcifications. In addition, a positive correlation among sIL-8, hyperaemic epididymis and an increased size of epididymal tail was found. When transrectal CDU was performed, an association among sIL-8 and hyper-echoic seminal vesicles, dilated ejaculatory ducts and duct calcifications was also observed. Finally, sIL-8 was positively related to prostate CDU abnormalities such as calcifications, inhomogeneous/hypo-echoic texture, hyperaemia and high arterial blood flow. No association was found with testis parameters. In conclusion, sIL-8 levels in patients with MAGI are associated with several parameters and CDU abnormalities of epididymis, seminal vesicles, ejaculatory ducts and prostate, but not of the testis. Furthermore, sIL-8 positively correlates with CDU signs of ejaculatory duct inflammatory subobstruction.
International Journal of Andrology 10/2010; 34(6 Pt 1):600-13. · 3.59 Impact Factor
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S Marchiani,
L Tamburrino,
L Giuliano,
D Nosi,
V Sarli,
L Gandini,
P Piomboni,
G Belmonte, G Forti,
E Baldi,
M Muratori
[show abstract]
[hide abstract]
ABSTRACT: Sumoylation is a post-translational modification involved in the regulation of several cell functions. Recent studies suggest its involvement in spermatogenesis, but occurrence and function of SUMO (small ubiquitin-like modifier) in mature spermatozoa remain unknown. We report the occurrence of several SUMO1-conjugated proteins, in a range of 20-85 kDa, in ejaculated spermatozoa. By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive spermatozoa in 58 subjects undergoing semen analysis in our laboratory and correlated the obtained values with semen parameters. We found that the percentage of SUMO1-positive spermatozoa was inversely correlated with total (r = -0.35, p < 0.01) and progressive motility (r = -0.29, p < 0.05). Such correlations become stricter when only asthenospermic subjects were included in the analysis (r = -0.58, p = 0.01 for progressive motility, n = 17) and were lost in non-asthenospermic subjects. By immunofluorescence and immunoconfocal fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy as well as a long permeabilization protocol demonstrated a massive localization of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish dead/live cells, we show that SUMO1 is mainly present in live spermatozoa. In conclusion, sumoylation of human spermatozoa may be involved in the regulation of motility.
International Journal of Andrology 10/2010; 34(6 Pt 1):581-93. · 3.59 Impact Factor
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ABSTRACT: Although it is well established that all the aspects of male reproduction are hormonally regulated, the endocrine control of the ejaculatory reflex is still not completely clarified. Sex steroids, thyroid and pituitary hormones (oxytocin and prolactin) have been proposed to control the ejaculatory process at various levels; however, only a few reports are currently available. The aim of this study was to evaluate the contribution of testosterone, thyrotropin (TSH) and prolactin (PRL) in the pathogenesis of ejaculatory dysfunction in a large series of subjects consulting for sexual dysfunction. Among the 2652 patients studied, 674 (25.2%) and 194 (7.3%) reported premature and delayed ejaculation (PE and DE), respectively. Categorizing ejaculatory difficulties on an eight-point scale starting from severe PE and ending with anejaculation (0 = severe PE, 1 = moderate PE, 2 = mild PE, 3 = no difficulties, 4 = mild DE, 5 = moderate DE, 6 = severe DE and 7 = anejaculation), PRL as well as TSH levels progressively increased from patients with severe PE towards those with anejaculation. Conversely, the opposite was observed for testosterone levels. All of these associations were confirmed after adjustment for age (adjusted r = 0.050, 0.053 and -0.038 for PRL, TSH and testosterone, respectively; all p < 0.05). When all hormonal parameters were introduced in the same regression model, adjusting for age, ΣMHQ (an index of general psychopathology) and use of selective serotonin reuptake inhibitor antidepressants, they were independently associated with ejaculatory problems (adjusted r = 0.056, 0.047 and -0.059 for PRL, TSH and testosterone, respectively; all p < 0.05). This study indicates endocrine system is involved in the control of ejaculatory function and that PRL, TSH and testosterone play an independent role.
International Journal of Andrology 03/2010; 34(1):41-8. · 3.59 Impact Factor
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ABSTRACT: Klinefelter's syndrome (KS) is the most common sex chromosomal aberration among men, with estimated prevalence of about 1 in 500 newborn males. The classical phenotype of KS is widely recognized, but many affected subjects present only very mild signs. While the association between KS and infertility has been well documented, few studies have investigated sexual function in the KS patients. In the present paper we reviewed studies addressed to emotional processing and sexual function in KS. We searched the following databases Medline, Pubmed, Embase, for Klinefelter's syndrome, sexuality. We focus on the peculiar contribution of genetic and hormonal background, which characterizes sexual dysfunction in KS. Abnormal structure and function of the emotional brain circuits have been described in KS. These alterations were less pronounced when the patients underwent to testosterone replacement therapy suggesting that they were mediated by testosterone deficiency. Accordingly, clinical studies indicate that sexual dysfunctions, eventually present in KS, are not specifically associated with the syndrome but are related to the underlying hypogonadism. In conclusion, androgen deficiency more than chromosomal abnormality is the major pathogenic factor of sexual dysfunction in KS.
Molecular Human Reproduction 03/2010; 16(6):418-24. · 3.85 Impact Factor
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ABSTRACT: Puberty is the developmental period during which rapid somatic changes and attainment of reproductive capacity take place. The sine qua non event for the onset of puberty is the increase in pulsatile GnRH release from GnRH neurons. GnRH neurons originate in the nasal placode and migrate, from the nasal compartment through the basal forebrain, before they attain their positions in the hypothalamus. Failure of GnRH neurons to migrate, mainly due to genetic alterations, leads to a clinical condition defined congenital hypogonadotropic hypogonadism. Other important factors demonstrated a permissive role for GnRH secretion at time of puberty, such as the kisspeptin G-protein-coupled receptor 54 (GPR54, now called KISS-1R) and its ligand, as well as neurokinin B (NKB) and the neurokinin 3 (NK3) receptor. Kisspeptin and neurokinin B colocalized in a subset of hypothalamic neurons that regulate GnRH secretion by GnRH neurons. Indeed, loss of function mutations in the above-mentioned and other genes result in hypogonadotrophic hypogonadism with absence of pubertal development. In males, pubertal increase of androgens levels seems to be required for the attainment of a normal bone density and male-specific body composition. However, also genetic variants of genes involved in bone metabolism as well as in osteoblast/osteoclast activation are associated to bone mineral density.
Journal of endocrinological investigation 01/2010; 33(7 Suppl):27-32. · 1.57 Impact Factor
