Infertility affects ∼7% of all men. Despite much progress, mainly in genetics, its etiology remains obscure in ∼50% of cases. To fill this gap, imaging of the male genital tract (MGT) has ...progressively expanded, providing useful information in the assessment of MGT abnormalities.
A critical, systematic review of the available literature was performed using Medline, with no restrictions regarding date of publication (i.e. from inception date until March 2014), along with analysis of previous reports in color Doppler ultrasound (CDUS) atlas textbooks. Normal anatomy and sonographic characteristics of the MGT have also been summarized.
Testicular volume (TV) is tightly associated with both sperm and hormonal parameters. Ultrasound (US) offers a greater accuracy in TV measurement than Prader orchidometer (PO). However US- and PO-derived TV are closely related, making PO-derived TV informative enough in the work-up of the infertile man in everyday clinical practice. US-derived TV might play an independent role in specific clinical conditions (i.e. large hydrocele, inguinal testis, enlarged epididymis). Scrotal US may detect signs of testicular dysgenesis, often related to an impaired spermatogenesis and to a higher risk of malignancy, or testicular lesions suggestive of malignancy. A decreased testis vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions (i.e. lymphoma, leukemia). The impact of varicocele detection and surgical correction on sperm parameters/fatherhood is debated. At present, the clinical management of varicocele is mainly based on physical examination. However, CDUS is useful in assessing venous reflux, when palpation is unreliable and/or in detecting recurrence/persistence after surgery. Epididymis head and/or tail dilation is suggestive of MGT obstruction or inflammation and both are related, along with echo-texture abnormalities, to impaired sperm parameters. Scrotal and transrectal US (TRUS) are useful in detecting congenital uni- or bilateral absence of vas deferens (CBAVD), which may be associated with epididymis, seminal vesicles (SV) or kidney abnormalities/agenesis. TRUS plays a key role in assessing obstructive azoospermia and detecting distal CBAVD or anomalies related to ejaculatory ducts obstruction, such as ejaculatory duct abnormalities, prostate median cysts or SV enlargement/emptying impairment. TRUS findings lead to operational decision-making, such as testicular sperm extraction in the case of CBAVD, cyst aspiration in the case of a large prostatic median cyst, and surgical treatment if ejaculatory duct abnormalities are observed. TRUS may reveal prostate volume reduction (suggestive of hypogonadism) or enlargement, which can be related to aging or even metabolic abnormalities. Finally, TRUS may reveal prostate and SV echo-texture abnormalities suggestive of inflammation or SV stasis.
MGT-CDUS is a useful tool in detecting abnormalities related to impaired male reproductive health. However, it suffers from a lack of standardization and often produces subjective/vague diagnoses. To fill this gap, the European Academy of Andrology has promoted an ongoing multicenter study aimed at defining the MGT-CDUS characteristics of healthy, fertile men.
How is the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?
Twenty-five percent of the men with recent SARS-Cov-2 ...infections and proven healing were oligo-crypto-azoospermic, despite the absence of virus RNA in semen.
The presence of SARS-CoV-2 in human semen and its role in virus contagion and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still unclear. So far, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and included a limited number of participants.
A prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV2 was performed. Four biological fluid samples, namely saliva, pre-ejaculation urine, semen, and post-ejaculation urine, were tested for the SARS-CoV-2 genome. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Routine semen analysis and quantification of semen leukocytes and interleukin-8 (IL-8) levels were performed.
Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. The occurrence of virus RNA was evaluated in all the biological fluids collected by RT-PCR. Semen parameters were evaluated according to the World Health Organization manual edition V. Semen IL-8 levels were evaluated by a two-step ELISA method.
After recovery from COVID-19, 25% of the men studied were oligo-crypto-azoospermic. Of the 11 men with semen impairment, 8 were azoospermic and 3 were oligospermic. A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (P < 0.001). Three patients (7%) tested positive for at least one sample (one saliva; one pre-ejaculation urine; one semen and one post-ejaculation urine), so the next day new nasopharyngeal swabs were collected. The results from these three patients and their partners were all negative for SARS-CoV-2.
Although crypto-azoospermia was found in a high percentage of men who had recovered from COVID-19, clearly exceeding the percentage found in the general population, the previous semen quality of these men was unknown nor is it known whether a recovery of testicular function was occurring. The low number of enrolled patients may limit the statistical power of study.
SARS-CoV-2 can be detected in saliva, urine, and semen in a small percentage of men who recovered from COVID-19. One-quarter of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia indicating that an assessment of semen quality should be recommended for men of reproductive age who are affected by COVID-19.
None.
N/A.
Late-onset hypogonadism (LOH) is a relatively common conditions affecting the aging male. The aim of this review is to summarize the available evidence regarding LOH and its interaction with general ...health. LOH is often comorbid to obesity and several chronic diseases. For this reason lifestyle modifications should be strongly encouraged in LOH subjects with obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and good treatment balance of chronic diseases. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. Available evidence seems to suggest that testosterone replacement therapy is able to improve central obesity (subjects with MetS) and glycometabolic control (patients with MetS and T2DM), as well as to increase lean body mass (HIV, chronic obstructive pulmonary disease), along with insulin resistance (MetS) and peripheral oxygenation (chronic kidney diseases). However, it should be recognized that the number of studies on benefits of T supplementation is too limited to draw final conclusions. Longer and larger studies are needed to better clarify the role of TRT in such chronic conditions.
The popularity of botanical products is on the rise in Europe, with consumers using them to complement their diets or to maintain health, and products are taken in many different forms (e.g. teas, ...juices, herbal medicinal products, plant food supplements (PFS)). However there is a scarcity of data on the usage of such products at European level.
To provide an overview of the characteristics and usage patterns of PFS consumers in six European countries.
Data on PFS usage were collected in a cross-sectional, retrospective survey of PFS consumers using a bespoke frequency of PFS usage questionnaire.
A total sample of 2359 adult PFS consumers from Finland, Germany, Italy, Romania, Spain and the United Kingdom.
Descriptive analyses were conducted, with all data stratified by gender, age, and country. Absolute frequencies, percentages and 95% confidence intervals are reported.
Overall, an estimated 18.8% of screened survey respondents used at least one PFS. Characteristics of PFS consumers included being older, well-educated, never having smoked and self-reporting health status as "good or very good". Across countries, 491 different botanicals were identified in the PFS products used, with Ginkgo biloba (Ginkgo), Oenothera biennis (Evening primrose) and Cynara scolymus (Artichoke) being most frequently reported; the most popular dose forms were capsules and pills/tablets. Most consumers used one product and half of all users took single-botanical products. Some results varied across countries.
The PlantLIBRA consumer survey is unique in reporting on usage patterns of PFS consumers in six European countries. The survey highlights the complexity of measuring the intake of such products, particularly at pan-European level. Incorporating measures of the intake of botanicals in national dietary surveys would provide much-needed data for comprehensive risk and benefit assessments at the European level.
Purpose
The use of opioids in patients with chronic non-cancer pain is common and can be associated with opioid-induced androgen deficiency (OPIAD) in men. This review aims to evaluate the current ...literature regarding the prevalence, clinical consequence and management of OPIAD.
Methods
A database search was performed in Medline, Embase and Cochrane using terms such as “analgesics”, “opioids” and “testosterone”. Relevant literature from January 1969 to March 2018 was evaluated.
Results
The prevalence of patients with OPIAD ranges from 19 to 86%, depending on the criteria for diagnosis of hypogonadism. The opioid-induced suppression of gonadotropin-releasing and luteinizing hormones represents the main important pathogenetic mechanisms. OPIAD has significant negative clinical consequences on sexual function, mood, bone density and body composition. In addition, OPIAD can also impair pain control leading to hyperalgesia, which can contribute to sexual dysfunction and mood impairment.
Conclusions
OPIAD is a common adverse effect of opioid treatment and contributes to sexual dysfunction, impairs pain relief and reduces overall quality of life. The evaluation of serum testosterone levels should be considered in male chronic opioid users and the decision to initiate testosterone treatment should be based on the clinical profile of individuals, in consultation with the patient.
Purpose
The concept of testosterone (T) supplementation (TS) as a new anti-obesity medication in men with testosterone deficiency syndrome (TDS) is emerging. Data from placebo-controlled trials are ...more conflicting. The aim of this study is to systematically review and meta-analyze available observational and register studies reporting data on body composition in studies on TS in TDS.
Methods
An extensive MEDLINE, Embase, and Cochrane search was performed including the following words: “testosterone” and “body composition.” All observational studies comparing the effect of TS on body weight and other body composition and metabolic endpoints were considered.
Results
Out of 824 retrieved articles, 32 were included in the study enrolling 4513 patients (mean age 51.7 ± 6.1 years). TS was associated with a time-dependent reduction in body weight and waist circumference (WC). The estimated weight loss and WC reduction at 24 months were −3.50 −5.21; −1.80 kg and −6.23 −7.94; −4.76 cm, respectively. TS was also associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction in fasting glycemia and insulin resistance. In addition, an improvement of lipid profile (reduction in total cholesterol as well as of triglyceride levels and an improvement in HDL cholesterol levels) and in both systolic and diastolic blood pressure was observed.
Conclusions
Present data support the view of a positive effect of TS on body composition and on glucose and lipid metabolism. In addition, a significant effect on body weight loss was observed, which should be confirmed by a specifically designed RCT.
Obesity and late-onset hypogonadism Corona, G.; Vignozzi, L.; Sforza, A. ...
Molecular and cellular endocrinology,
12/2015, Letnik:
418
Journal Article
Recenzirano
Obesity and male hypogonadism (HG) are often associated, as demonstrated in all cross-sectional studies. Prospective studies have indicated that i) having HG at baseline increases the risk of ...visceral obesity (and metabolic syndrome) and that ii) obesity induces incident HG. Hence, there is a bidirectional relationship between the two conditions. This is the main topic of this review, along with some pathogenic considerations. Meta-analysis of intervention studies indicates that treating obesity is a very efficient treatment for obesity-induced HG. The mechanism by which obesity induces HG has not yet been completely understood, but dietary-induced hypothalamic inflammation, along with a decreased GnRH release, is plausible. Among patients seeking medical care for obesity, the proportion of HG is relatively high. The prevalence of obesity among patients referring for sexual dysfunction is also elevated. Hence, in symptomatic, obese, hypogonadal subjects, testosterone supplementation (TS) can be considered. Whereas long-term uncontrolled register studies suggest that TS could decrease weight, analysis of controlled studies only support a parallel increase in lean mass and decrease in fat mass, with a resulting null effect on weight. Considering that T induces an increase in muscle mass, it is conceivable that the amount of activity obese people can undertake after TS will increase, allowing a closer adherence to physical exercise programs. Some studies, here meta-analyzed, support this concept.
•Obesity and male hypogonadism (HG) are associated with a bidirectional link.•Hypothalamic inflammation, and GnRH release impairment represent the most important supposed pathogenetic mechanisms.•Weight loss induces body weight reduction-dependent increase in testosterone (T) levels.•In hypogonadal, obese men, testosterone substitution (TS) with lifestyle modifications could result in better outcomes.
Abstract
STUDY QUESTION
What is the diagnostic potential of next generation sequencing (NGS) based on a ‘mouse azoospermia’ gene panel in human non-obstructive azoospermia (NOA)?
SUMMARY ANSWER
The ...diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and allowed the discovery of two novel genes involved in NOA due to meiotic arrest.
WHAT IS KNOWN ALREADY
NOA is a largely heterogeneous clinical entity, which includes different histological pictures. In a large proportion of NOA, the aetiology remains unknown (idiopathic NOA) and yet, unknown genetic factors are likely to play be involved. The mouse is the most broadly used mammalian model for studying human disease because of its usefulness for genetic manipulation and its genetic and physiological similarities to man. Mouse azoospermia models are available in the Mouse Genome Informatics database (MGI: http://www.informatics.jax.org/).
STUDY DESIGN, SIZE, DURATION
The first step was to design of a ‘mouse azoospermia’ gene panel through the consultation of MGI. The second step was NGS analysis of 175 genes in a group of highly selected NOA patients (n = 33). The third step was characterization of the discovered gene defects in human testis tissue, through meiotic studies using surplus testicular biopsy material from the carriers of the RNF212 and STAG3 pathogenic variants. The final step was RNF212 and STAG3 expression analysis in a collection of testis biopsies.
PARTICIPANTS/MATERIALS, SETTING, METHODS
From a total of 1300 infertile patients, 33 idiopathic NOA patients were analysed in this study, including 31 unrelated men and 2 brothers from a consanguineous family. The testis histology of the 31 unrelated NOA patients was as follows: 20 Sertoli cell-only syndrome (SCOS), 11 spermatogenic arrest (6 spermatogonial arrest and 5 spermatocytic arrest). The two brothers were affected by spermatocytic arrest. DNA extracted from blood was used for NGS on Illumina NextSeq500 platform. Generated sequence data was filtered for rare and potentially pathogenic variants. Functional studies in surplus testicular tissue from the carriers included the investigation of meiotic entry, XY body formation and metaphases by performing fluorescent immunohistochemical staining and immunocytochemistry. mRNA expression analysis through RT-qPCR of RNF212 and STAG3 was carried out in a collection of testis biopsies with different histology.
MAIN RESULTS AND THE ROLE OF CHANCE
Our approach was relatively successful, leading to the genetic diagnosis of one sporadic NOA patient and two NOA brothers. This relatively high diagnostic performance is likely to be related to the stringent patient selection criteria i.e. all known causes of azoospermia were excluded and to the relatively high number of patients with rare testis histology (spermatocytic arrest). All three mutation carriers presented meiotic arrest, leading to the genetic diagnosis of three out of seven cases with this specific testicular phenotype. For the first time, we report biallelic variants in STAG3, in one sporadic patient, and a homozygous RNF212 variant, in the two brothers, as the genetic cause of NOA. Meiotic studies allowed the detection of the functional consequences of the mutations and provided information on the role of STAG3 and RNF212 in human male meiosis.
LIMITATIONS, REASONS FOR CAUTION
All genes, with the exception of 5 out of 175, included in the panel cause azoospermia in mice only in the homozygous or hemizygous state. Consequently, apart from the five known dominant genes, heterozygous variants (except compound heterozygosity) in the remaining genes were not taken into consideration as causes of NOA. We identified the genetic cause in approximately half of the patients with spermatocytic arrest. The low number of analysed patients can be considered as a limitation, but it is a very rare testis phenotype. Due to the low frequency of this specific phenotype among infertile men, our finding may be considered of low clinical impact. However, at an individual level, it does have relevance for prognostic purposes prior testicular sperm extraction.
WIDER IMPLICATIONS OF THE FINDINGS
Our study represents an additional step towards elucidating the genetic bases of early spermatogenic failure, since we discovered two new genes involved in human male meiotic arrest. We propose the inclusion of RNF212 and STAG3 in a future male infertility diagnostic gene panel. Based on the associated testis phenotype, the identification of pathogenic mutations in these genes also confers a negative predictive value for testicular sperm retrieval. Our meiotic studies provide novel insights into the role of these proteins in human male meiosis. Mutations in STAG3 were first described as a cause of female infertility and ovarian cancer, and Rnf212 knock out in mice leads to male and female infertility. Hence, our results stimulate further research on shared genetic factors causing infertility in both sexes and indicate that genetic counselling should involve not only male but also female relatives of NOA patients.
STUDY FUNDING/COMPETING INTEREST(S)
This work was funded by the Spanish Ministry of Health Instituto Carlos III-FIS (grant number: FIS/FEDER-PI14/01250; PI17/01822) awarded to CK and AR-E, and by the European Commission, Reproductive Biology Early Research Training (REPROTRAIN, EU-FP7-PEOPLE-2011-ITN289880), awarded to CK, WB, and AE-M. The authors have no conflict of interest.
Background
Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) are conditions extremely prevalent in the aging male. Although androgens are involved in prostate growth during ...developmental age, their role in the pathogenesis of BPH/LUTS is debated. Recent data indicate that low testosterone and high estradiol favor disease progression. In addition, the role of other determinants, such as metabolic syndrome or prostate inflammation, is emerging.
Aim
We reviewed the evidence regarding the pathogenesis of BPH/LUTS with particular attention to metabolic influence.
Materials and methods
A review of published evidence was performed using Medline.
Results
Available evidence shows that a three-hit hypothesis can be drawn. An overt, or even a subclinical, bacterial or viral infection could induce prostatic inflammation (first hit) that could be autosustained or exacerbated by the presence of an altered metabolism and in particular by hypercholesterolemia (second hit). Hypogonadism and/or hyperestrogenism could act as a third hit, favoring the maintenance of this inflammatory state. The combined action of all three hits, or even two of them, may result in overexpression of Toll-like receptors (TLRs), transformation of prostatic cells into antigen-presenting cells and activation of resident human prostate-associated lymphoid tissue ending in overproduction of growth factors which, in turn, will induce prostate remodeling and further prostate enlargement. The mechanical obstruction, along with the direct action of the unfavorable metabolic and hormonal milieu on the bladder neck, helps in generating LUTS.
Conclusion
Inflammation, dyslipidemia and altered sex-steroid milieu mutually concur in determining BPH/LUTS.
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