Purpose
The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to ...summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS)
Methods
A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria.
Results
Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects.
Conclusion
Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.
Purpose
Low testosterone (T) in Klinefelter’s syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased ...cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls.
Methods
We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search.
Results
Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls.
Conclusion
TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.
Summary
This manuscript describes the role of low vitamin D in bone metabolism of Klinefelter subjects. Low vitamin D is frequent in this condition and seems to be more important than testosterone in ...inducing low bone mineral density (BMD) and osteoporosis. Supplementation with vitamin D restores BMD after 2 years of treatment, whereas testosterone alone seems to be ineffective.
Introduction
Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent, and it has been traditionally related to low testosterone (T) levels. However, low BMD can be observed also in patients with normal T levels and T replacement therapy does not necessarily increase bone mass in these patients. Nothing is known about vitamin D levels and supplementation in KS. In this study, we determine vitamin D status and bone mass in KS subjects and compare the efficacy of T therapy and vitamin D supplementation on BMD.
Methods
A total of 127 non-mosaic KS patients and 60 age-matched male controls were evaluated with reproductive hormones, 25-hydroxyvitamin D, PTH, and bone densitometry by dual-energy X-ray absorptiometry (DEXA). Patients with hypogonadism and/or 25-hydroxyvitamin D deficiency were treated with T-gel 2 % and/or calcifediol and re-evaluated after 24 months of treatment.
Results
25-hydroxyvitamin D levels were significantly lower in KS patients with respect to controls, and they had significantly lower lumbar and femoral BMD. The percentage of osteopenia/osteoporosis in subjects with 25-hydroxyvitamin D deficiency was higher with respect to subjects with normal 25-hydroxyvitamin D and was not related to the presence/absence of low T levels. Subjects treated with calcifediol or T + calcifediol had a significant increase in lumbar BMD after treatment. No difference was found in T-treated group.
Conclusions
These data highlight that low 25-hydroxyvitamin D levels seem to have a more critical role than low T levels in inducing low BMD in KS subjects. Furthermore, vitamin D supplementation seems to be more effective than T replacement therapy alone in increasing BMD.
ObjectiveKlinefelter syndrome (KS) is a chromosomal alteration characterized by increased risk of metabolic syndrome, mainly caused by visceral obesity. In the last years, obesity has been studied as ...a potential risk factor for prostate disease and recently a link has been demonstrated between visceral adiposity with prostate volume. The aim of this study was to analyze the relationship between obesity and prostate volume and growth during testosterone therapy in KS subjects.Design and methodsWe evaluated reproductive hormones, metabolic parameters, anthropometric measures, PSA, and prostate volume in 121 naïve non-mosaic KS patients and 60 age-matched healthy male controls. Fifty-six KS hypogonadic subjects were treated with testosterone-gel 2% and reevaluated after 18 months of treatment.ResultsProstate volume in KS was positively related to waist circumference (WC). The KS group with WC ≥94 cm had significantly higher prostate volume, BMI, insulin plasma levels, homeostasis model assessment index, total cholesterol, triglycerides, and glycemia with respect to the KS group with WC <94 cm. After testosterone replacement therapy, only hypogonadic KS men with WC ≥94 cm had a statistically significant increase in prostate volume. Furthermore, in untreated KS subjects, prostate volume showed a statistically significant increase after 18 months of follow-up only in subjects with WC ≥94 cm.ConclusionsThis study showed that visceral obesity, insulin resistance, and lipid and glucose metabolism alterations are associated with prostate volume and growth during testosterone replacement therapy in KS, independently from androgen or estrogen levels. These latter findings might provide the basis for a better management and follow-up of KS subjects.
Summary
In the last years, follice‐stimulating hormone (FSH) receptor (FSHR) gene polymorphisms have been studied as potential risk factors for spermatogenetic failure. In this study, we have ...evaluated the response of FSH treatment in terms of sperm production on the basis of Ala307Thr‐Asn680Ser polymorphisms in the FSHR gene in a group of oligozoospermic subjects with hypospermatogenesis and normal FSH levels. Patients were randomized into two groups: 70 treated with recombinant FSH (150 IU thrice per week for 3 months) and 35 without treatment. After 3 months of treatment, we observed significant increase in total sperm count, sperm concentration, forward motility, percentage of normal morphology forms and total motile sperm. When 70 treated subjects were subdivided based on FSHR genotype, only subjects with at least one serine in position 680 showed a statistically significant increase in these sperm parameters, whereas subjects with homozygote Thr307‐Asn680 showed no difference in any seminal parameters evaluated. Non‐treated subjects showed no differences in any parameter evaluated. This study suggests that the analysis of this gene represents a valid pharmacogenetic approach to the treatment of male infertility, confirming also the importance of strict criteria for the selection of patients to be treated with FSH.
Background:
Recent data suggest a potential role of testis in vitamin D activation, where Leydig cells could represent key players in this process since they express the highest amount of CYP2R1, a ...key enzyme involved in vitamin D 25 hydroxylation.
Aim:
To evaluate bone status in unilateral orchiectomy and to assess
in vivo
and
in vitro
LH-dependency of Vitamin D 25 hydroxylation.
Subjects and methods:
125 normotestosteronemic patients with testicular cancer (TC), featured by unilateral orchiectomy and 41 age-matched healthy male controls were studied in the Center for Human Reproduction Pathology at the University of Padova. To evaluate LH-dependency of Vitamin D 25 hydroxylation
in vitro
, Leydig cell cultures were stimulated with hCG and assessed for CYP2R1 expression, whereas
in vivo
10 hypogonadotropic hypogonadal (HH) patients were evaluated before and after treatment with gonadotropins for bone metabolism markers. Hormonal pattern and bone metabolism markers were measured in all subjects, whereas 105 patients and 41 controls underwent bone densitometry by DEXA.
Results:
In TC patients 25-hydroxyvitamin D levels were significantly lower compared to controls. Furthermore, 23.8% of patients with TC displayed low bone density (Z-score <−2 SD). None of the 41 control subjects showed any significant alteration of BMD.
In vitro
and
in vivo
studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent.
Conclusion:
Our data show an association between TC and alteration of the bone status, despite unvaried androgen and estrogen levels, suggesting the evaluation of bone status and possible vitamin D deficiency in TC survivors.
Summary
The Klinefelter syndrome (KS) is the most frequent sex chromosomal disorder in males, characterized by at least one supernumerary X chromosome (most frequent karyotype 47,XXY). This syndrome ...presents with a broad range of phenotypes. The common characteristics include small testes and infertility, but KS subjects are at increased risk of hypogonadism, cognitive dysfunction, obesity, diabetes, metabolic syndrome, osteoporosis, and autoimmune disorders, which are present in variable proportion. Although part of the clinical variability might be linked to a different degree of testicular function observed in KS patients, genetic mechanisms of the supernumerary X chromosome might contribute. Gene‐dosage effects and parental origin of the supernumerary X chromosome have been suggested to this regard. No study has been performed analyzing the genetic constitution of the X chromosome in terms of copy number variations (CNVs) and their possible involvement in phenotype of KS. To this aim, we performed a SNP arrays analysis on 94 KS and 85 controls. We found that KS subjects have more frequently than controls X‐linked CNVs (39/94, 41.5% with respect to 12/42, 28.6% of females, and 8/43, 18.6% of males, p < 0.01). The number of X‐linked CNVs in KS patients was 4.58 ± 1.92 CNVs/subject, significantly higher with respect to that found in control females (1.50 ± 1.29 CNVs/subject) and males (1.14 ± 0.37 CNVs/subject). Importantly, 94.4% X‐linked CNVs in KS subjects were duplications, higher with respect to control males (50.0%, p < 0.001) and females (83.3%, p = 0.1). Half of the X‐linked CNVs fell within regions encompassing genes and most of them (90%) included genes escaping X‐inactivation in the regions of X–Y homology, particularly in the pseudoautosomal region 1 (PAR1) and Xq21.31. This study described for the first time the genetic properties of the X chromosome in KS and suggests that X‐linked CNVs (especially duplications) might contribute to the clinical phenotype.
Summary
Klinefelter syndrome is a frequent cause of hypogonadism, but despite hundreds of publications on different aspects of Klinefelter syndrome, only a few studies dealt with sexual dysfunction. ...In particular, testosterone is critical for various aspects of sexual response, but its role on sexuality in Klinefelter syndrome patients is debatable and no studies have evaluated the efficacy of testosterone treatment on sexual dysfunction in these subjects. Furthermore, the impact of psychological and relational aspects on sexual function of Klinefelter syndrome subjects is poorly defined. In this study, we aimed to determine the presence and type of sexual dysfunctions in Klinefelter syndrome subjects; to correlate them with testosterone levels and psychosexological and relational domains; and to evaluate the effects of testosterone therapy. We studied 62 non‐mosaic naïve Klinefelter syndrome patients and 60 age‐matched controls by means of medical history, psychosexological history, 15‐item International Index of Erectile Function questionnaire, endocrine assessment, and dynamic penile color Doppler ultrasound. Twenty‐five hypogonadal Klinefelter syndrome patients were studied after 6 months of testosterone replacement therapy. Klinefelter syndrome subjects have reduced 15‐item International Index of Erectile Function scores regarding sexual desire, intercourse satisfaction, and overall satisfaction with respect to controls, and these aspects were significantly associated with testosterone levels. Klinefelter syndrome subjects had also higher prevalence of erectile dysfunction, but no relation with testosterone levels was evident. A high prevalence of a range of psychological disturbances was present in Klinefelter syndrome subjects with erectile dysfunction with respect to those without erectile dysfunction. No statistical difference in the prevalence of premature and delayed ejaculation was observed between Klinefelter syndrome and control subjects. Testosterone replacement therapy improved sexual desire, intercourse satisfaction, and overall satisfaction scores, but had no effect on erectile function. Penile color Doppler ultrasound was normal in all subjects. This study shows that sexual dysfunction in Klinefelter syndrome is multifactorial and related only in part to hypogonadism and largely to psychological disturbances. Evaluation and therapy of sexual dysfunction should include a combined andrological and psychosexological approach.
Spermatogenesis in Klinefelter syndrome Selice, R.; Di Mambro, A.; Garolla, A. ...
Journal of endocrinological investigation,
12/2010, Letnik:
33, Številka:
11
Journal Article
Recenzirano
Background
: Klinefelter syndrome (KS) (47,XXY) is the most common sex chromosomal disorder, and it is a frequent form of male hypogonadism and infertility. Although the majority of these patients ...are azoospermic, they might have severe oligozoospermia or residual single-residual foci with spermatogenesis in the testis.
Aim
: We report our experience on sperm retrieval in the ejaculate and testis, and evaluate the frequency of chromosome abnormalities in sperm of KS.
Subjects and methods
: Eighty-four 47,XXY KS were evaluated with seminal analysis, body hair distribution, reproductive hormones, ultrasonographic scanning of the testis and prostate, bilateral testicular sperm extraction (TESE), sperm or testicular cells sex chromosomes aneuploidies.
Results
: Out of 84 patients, 7 (7/84; 8.3%) had sperm in the ejaculate. Out of the 77 azoospermic patients, 24 underwent TESE and 9 (9/24; 37.5%) had successful sperm recovery. The comparison of reproductive hormones, age and testicular volume did not show significant differencesbetween patients with and without successful sperm recovery in semen or TESE. Patients without successful sperm recovery in semen analysis or TESE had signs of hypoandrogenism more evident than patients with successful sperm recovery. Patients with KS produced a higher number of sperm aneuploidy with respect to normozoospermic fertile controls and non-genetic severely oligozoospermic men.
Conclusions
: Men with KS are not always sterile. In some of these patients sperm can be found in semen or in the testis, but the proportion of sperm aneuploidy is high. Signs of hypoandrogenism seem to be associated with low sperm recovery rate.
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