Testosterone Replacement Therapy and Cardiovascular Risk: A Review

Recent reports in the scientific and lay press have suggested that testosterone (T) replacement therapy (TRT) is likely to increase cardiovascular (CV) risk. In a final report released in 2015, the Food and Drug Administration (FDA) cautioned that prescribing T products is approved only for men who have low T levels due to primary or secondary hypogonadism resulting from problems within the testis, pituitary, or hypothalamus (e.g., genetic problems or damage from surgery, chemotherapy, or infection). In this report, the FDA emphasized that the benefits and safety of T medications have not been established for the treatment of low T levels due to aging, even if a man's symptoms seem to be related to low T. In this paper, we reviewed the available evidence on the association between TRT and CV risk. In particular, data from randomized controlled studies and information derived from observational and pharmacoepidemiological investigations were scrutinized. The data meta-analyzed here do not support any causal role between TRT and adverse CV events. This is especially true when hypogonadism is properly diagnosed and replacement therapy is correctly performed. Elevated hematocrit represents the most common adverse event related to TRT. Hence, it is important to monitor hematocrit at regular intervals in T-treated subjects in order to avoid potentially serious adverse events

The impact of male factors and their correct and early diagnosis in the infertile couple's pathway: 2021 perspectives

Purpose: The current clinical practice in reproductive medicine should pose the couple at the centre of the diagnostic-therapeutic management of infertility and requires intense collaboration between the andrologist, the gynaecologist and the embryologist. The andrologist, in particular, to adequately support the infertile couple, must undertake important biological, psychological, economical and ethical task. Thus, this paper aims to provide a comprehensive overview of the multifaceted role of the andrologist in the study of male factor infertility. Methods: A comprehensive Medline, Embase and Cochrane search was performed including publications between 1969 and 2021. Results: Available evidence indicates that a careful medical history and physical examination, followed by semen analysis, always represent the basic starting points of the diagnostic work up in male partner of an infertile couple. Regarding treatment, gonadotropins are an effective treatment in case of hypogonadotropic hypogonadism and FSH may be used in men with idiopathic infertility, while evidence supporting other hormonal and nonhormonal treatments is either limited or conflicting. In the future, pharmacogenomics of FSHR and FSHB as well as innovative compounds may be considered to develop new therapeutic strategies in the management of infertility. Conclusion: To provide a high-level of care, the andrologist must face several critical diagnostical and therapeutical steps. Even though ART may be the final and decisive stage of this decisional network, neglecting to treat the male partner may ultimately increase the risks of negative outcome, as well as costs and psychological burden for the couple itself

Magnetic resonance imaging assessment of lipomatous soft-tissue tumors

Aim: To establish the accuracy of magnetic resonance imaging (MRI) in distinguishing between benign and malignant lipomatous tumors; to evaluate the reproducibility of the MRI interpretation assessing the agreement between judgments of two radiologists with the same experience in soft-tissue sarcomas; to identify an association among MRI findings (size, depth, septa, nodules, signal homogeneity) and nature of the lesion. Materials and Methods: A total of 54 patients (28 men and 26 women), with a mean age of 56 (range=27-84) were included years. All subjects followed-up by the Multidisciplinary Sarcoma Group. The following MRI findings were judged in a blind study by two radiologists: Size, localization, septa, nodules and signal homogeneity. A diagnostic indication was then given from among lipoma, atypical lipomatous tumour (ALT) and liposarcoma. Accuracy in distinguishing between benign and malignant lesions, and between lipoma and ALT (Fisher's exact test), inter-operator agreement (Cohen's kappa), association of MRI findings and malignancy of the lesion (Fisher's exact test and odds ratio) were evaluated. Results: The inter-operator agreement was complete (100%). The agreement between diagnostic hypothesis and histological diagnosis was statistically significant (p<0.05). Among the radiological findings taken into account, only septa and signal homogeneity were significantly associated with the malignancy of the lesion (p<0.05). Conclusion: MRI could be helpful in distinguishing lipomatous tumors, allowing biopsy to be avoided in some cases (negative predictive value=100%)

Nutritional characterization of Cicer arietinum L. cultivars with respect to morphological and agronomic parameters

Chickpea (Cicer arietinum L.) is one of the grain legumes more interesting for its nutritional value and genetic improvement in order to resistance to Aschochyta rabiei, seeds weight and adaptation to mechanical harvesting. The aim of this research was the agronomic and qualitative characterization of 15 cultivars of chickpea. During the cultural cycle resistance and sensitiveness to Aschochyta rabiei were analyzed. At harvesting, grain yield and yields components were registered. Moreover, proximate composition, fatty acids content and saturated/unsaturated ratio of grain samples were determined. Cultivars with high 1000 seeds weight showed a more favourable oleic acid content and unsaturated/saturated ratio but those with smooth seeds had a higher content in linolenic acid. All cultivars showed high values of polyunsaturated fatty acids (42.9-56.2%), inferior of monounsaturated (29.5-36.1%) and low of saturated (10.0-22.9%). Black chickpea (2.9) had the lowest unsaturated/saturated ratio, while the highest was noticed for cv. Visir (7.46). Cultivars with small and smooth seeds showed a better proteins content. These results showed availability of seeds with favourable characteristics useful for different utilization. In particular, the cultivars with small and smooth seeds, usually not preferred by consumers, seem to be interesting for processing in nutritional foods and dietetics

FSH treatment improves sperm DNA damage in men with idiopathic infertility carriers of the FSH receptor p.N680S homozygous N genotype: an interim analysis

Study question: To assess whether in men with idiopathic infertility, the sperm DNA fragmentation (sDF) improves depending on the FSH receptor (FSHR) genotype as assessed by the non-synonymous polymorphisms (SNP) rs6166 (wild type or p.N680S). Summary answer: FSH treatment improves sDF in a subgroup of idiopathic infertile men, although 40% of these men do not show any significant improve- ment. The response of sDF, a surrogate marker of sperm quality, together with the evaluation of FSHR SNP p.N680S might be useful to predict the response to FSH treatment. What is known already: FSH is fundamental for spermatogenesis and is em- pirically used to treat male idiopathic infertility. Several studies suggest that sDF could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is widely accepted that the FSHR SNP p.N680S influences ovarian response in women and testicular volume in men. Study design, size, duration: Multicenter, longitudinal, prospective, open-la- bel, two-arms clinical trial. Subjects enrolled were idiopathic infertile men and received 150 IU of recombinant FSH (Gonal f®) every other day for 12 weeks and were then followed-up for further 12 weeks after FSH-withdrawal. Patients were evaluated at baseline and at the end of the two phases. Participants/materials, setting, methods: Eighty-eight men with idiopathic male infertility carrier of the homozygous FSHR p.N680S N or S genotype, FSH 15%, were enrolled. 66 patients completed the sDF analysis. sDF was centrally evaluated by TUNEL/PI assay coupled to flow cy- tometry, resolving two different sperm populations, namely: PIbrighter and PIdimmer. Main results and the role of chance: Thirty-seven men (56%) were carriers of the p.N680S homozygous-N and 29 (44%) of the homozygous-S genotype, respectively. Total sDF (PIbrighter + PIdimmer) was significantly lower at the end of the study in patients carriers of the p.N680S-N allele than patients carri- ers of p.N680S-S allele (p = 0.008). Only in patients carriers of the p.N680S-N allele, total sDF decreased significantly from baseline to the end of the study (p = 0.021) and this decrease was entirely sustained by the sperm population containing vital sperms (i.e., PIbrighter fraction) (p = 0.008). PIdimmer frac- tion, including only non-vital sperms, was significantly higher in patients car- riers of the p.N680S-S allele than in carriers of N allele (p = 0.018). Total sDF was inversely related to total sperm number (p = 0.020) and progressive sperm motility (p = 0.014). Limitations, reason for caution: The statistical power of the results obtained so far is 86.9%, with alpha-error 0.05. This is an interim-analysis. Wider implications of the findings: The study suggests that FSH treatment induces a significant improvement of total sDF in men carriers of the p.N680S homozygous N allele. This sDF decrease awaits confirmation, since the study will be completed by June 2015. Study funding/competing interest(s): Funding by commercial/corporate company(ies) – The study was supported by unrestricted grant by Merck Serono. Trial registration number: EudraCT number 2010-020240-35. Keywords: FSH treatment, male infertility, Sperm-DNA fragmentatio

Low Testosterone Levels Predict Clinical Adverse Outcomes in SARS-CoV-2 Pneumonia Patients

Background: The pandemic of new severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has stressed the importance of effective diagnostic and prognostic biomarkers of clinical worsening and mortality. Epidemiological data showing a differential impact of SARS-CoV-2 infection on women and men have suggested a potential role for testosterone (T) in determining gender disparity in the SARS-CoV-2 clinical outcomes. Objectives: To estimate the association between T level and SARS-CoV-2 clinical outcomes (defined as conditions requiring transfer to higher or lower intensity of care or death) in a cohort of patients admitted in the respiratory intensive care unit (RICU). Materials and methods: A consecutive series of 31 male patients affected by SARS-CoV-2 pneumonia and recovered in the respiratory intensive care unit (RICU) of the “Carlo Poma” Hospital in Mantua were analyzed. Several biochemical risk factors (ie, blood count and leukocyte formula, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, D-dimer, fibrinogen, interleukin 6 (IL-6)) as well as total testosterone (TT), calculated free T (cFT), sex hormone–binding globulin (SHBG), and luteinizing hormone (LH) were determined. Results: Lower TT and cFT were found in the transferred to ICU/deceased in RICU group vs groups of patients transferred to IM or maintained in the RICU in stable condition. Both TT and cFT showed a negative significant correlation with biochemical risk factors (ie, the neutrophil count, LDH, and PCT) but a positive association with the lymphocyte count. Likewise, TT was also negatively associated with CRP and ferritin levels. A steep increase in both ICU transfer and mortality risk was observed in men with TT&nbsp;&lt;&nbsp;5&nbsp;nmol/L or cFT&nbsp;&lt;&nbsp;100&nbsp;pmol/L. Discussion and conclusion: Our study demonstrates for the first time that lower baseline levels of TT and cFT levels predict poor prognosis and mortality in SARS-CoV-2-infected men admitted to RICU

Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems

PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization