Center for Reproductive Medicine and Andrology

Münster, Germany

Center for Reproductive Medicine and Andrology

Münster, Germany
SEARCH FILTERS
Time filter
Source Type

PubMed | University of Rome La Sapienza, Bayer Pharma, Diabetes Agency, AziendaUsl Bologna Maggiore Bellaria Hospital and 3 more.
Type: Journal Article | Journal: Journal of endocrinological investigation | Year: 2016

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.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.Out of 824 retrieved articles, 32 were included in the study enrolling 4513 patients (mean age 51.76.1years). TS was associated with a time-dependent reduction in body weight and waist circumference (WC). The estimated weight loss and WC reduction at 24months 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.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.


PubMed | University of Marburg, Center for Reproductive Medicine and Andrology, Justus Liebig University and Childrens Hospital Boston
Type: Journal Article | Journal: Histochemistry and cell biology | Year: 2016

Within the human testis, large amounts of sulfated steroid hormones are produced. As shown in breast tissue and placenta, these might not only be excretion intermediates, but re-activated in target cells by steroid sulfatase (STS). This process is called sulfatase pathway and may play a pivotal role in para- and/or intracrine regulation by creating a local supply for steroid hormones. This requires a facilitated transport via uptake carriers and efflux transporters as these hydrophilic molecules cannot pass the cell membrane. Moreover, blood-testis barrier formation in the testis requires a transport through Sertoli cells (SCs) to reach germ cells (GCs). Sertoli cells are therefore expected to play a key role as gate-keepers for sulfatase pathway in human seminiferous epithelium. We analyzed the mRNA and protein expression of uptake carriers and efflux transporters like organic anion-transporting polypeptides (OATP2B1, OATP3A1) and multidrug resistance-related proteins (MRP1, MRP4) in testicular tissue and cultured Sertoli cells (FS1, HSEC). Additionally, expression pattern of STS as well as sulfonating enzymes (SULTs) were assessed. OATP2B1, OATP3A1 and STS were detected in SCs as well as GCs, whereas MRP1 is only expressed in SCs, and SULT1E1 only in Leydig cells, respectively. By transcellular transport of [H


Aponte P.M.,Federal University of Minas Gerais | Aponte P.M.,Central University of Venezuela | Schlatt S.,Center for Reproductive Medicine and Andrology | de Franca L.R.,Federal University of Minas Gerais
Clinics | Year: 2013

Aspermatogenesis is a severe impairment of spermatogenesis in which germ cells are completely lacking or present in an immature form, which results in sterility in approximately 25% of patients. Because assisted reproduction techniques require mature germ cells, biotechnology is a valuable tool for rescuing fertility while maintaining biological fatherhood. However, this process involves, for instance, the differentiation of preexisting immature germ cells or the production/derivation of sperm from somatic cells. This review critically addresses four potential techniques: sperm derivation in vitro, germ stem cell transplantation, xenologous systems, and haploidization. Sperm derivation in vitro is already feasible in fish and mammals through organ culture or 3D systems, and it is very useful in conditions of germ cell arrest or in type II Sertoli-cell-only syndrome. Patients afflicted by type I Sertoli-cell-only syndrome could also benefit from gamete derivation from induced pluripotent stem cells of somatic origin, and human haploid-like cells have already been obtained by using this novel methodology. In the absence of alternative strategies to generate sperm in vitro, in germ cells transplantation fertility is restored by placing donor cells in the recipient germ-cell-free seminiferous epithelium, which has proven effective in conditions of spermatogonial arrest. Grafting also provides an approach for ex-vivo generation of mature sperm, particularly using prepubertal testis tissue. Although less feasible, haploidization is an option for creating gametes based on biological cloning technology. In conclusion, the aforementioned promising techniques remain largely experimental and still require extensive research, which should address, among other concerns, ethical and biosafety issues, such as gamete epigenetic status, ploidy, and chromatin integrity. © 2013 CLINICS.


PubMed | Eli Lilly and Company, University of Manchester and Center for Reproductive Medicine and Andrology
Type: Journal Article | Journal: The journal of sexual medicine | Year: 2016

Evidence from well-designed studies documenting the benefit of testosterone replacement therapy as a function of patient demographic and clinical characteristics is lacking.To determine demographic and clinical predictors of treatment outcomes in hypogonadal men with low sex drive, low energy, and/or erectile dysfunction.Post hoc analysis of a randomized, multicenter, double-blinded, placebo-controlled, 16-week study of 715 hypogonadal men (mean age= 55.3 years, age range= 19-92 years) presenting with low sex drive and/or low energy who received placebo or testosterone solution 2% for 12 weeks.Two levels defined patient-reported improvement (PRI) in sex drive or energy: level 1 was at least a little better and level 2 was at least much better in energy or sex drive on the Patient Global Impression of Improvement at study end point. PRI in erectile function was stratified by erectile dysfunction severity at baseline as measured by the erectile function domain of the International Index for Erectile Function: mild at baseline (change of 2), moderate at baseline (change of 5), and severe at baseline (change of 7). Associations of demographic and clinical characteristics with PRI were calculated with stepwise forward multiple logistic regression analysis. Odds ratios represented the likelihood of PRI in symptoms among variable categories.Higher levels of end-point testosterone were associated with higher rates of PRI (at levels 1 and 2) in sex drive and energy (P < .001 for the two comparisons). Lower baseline testosterone levels wereassociated with higher rates of level 1 PRI in sex drive (P= .028); and classic hypogonadism (vs non-classic hypogonadism) was associated with higher rates of level 2 PRI in sex drive (P= .005) and energy (P= .006).When assessing the potential for improvements in men with testosterone deficiency using patient-reported outcome questionnaires, possible predictors of treatment outcomes to consider include the etiology of hypogonadism and testosterone levels (baseline and end point).


Arnold S.L.,University of Washington | Kent T.,Washington State University | Hogarth C.A.,Washington State University | Schlatt S.,Center for Reproductive Medicine and Andrology | And 7 more authors.
Journal of Lipid Research | Year: 2015

Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern and relative contribution of these enzymes to RA formation in the testis is unknown. In this study, novel methods tomeasure ALDH1A protein levels and intrinsic RA formation were used to accurately predict RA formation velocities in individual human testis samples and an association between RA formation and intratesticular RA concentrations was observed. The distinct localization of ALDH1A in the testis suggests a specifi c role for each enzyme in controlling RA formation. ALDH1A1 was found in Sertoli cells,while only ALDH1A2 was found in spermatogonia, spermatids, and spermatocytes. in theabsence of cellular retinol binding protein (CRBP)1, ALDH1A1 was predicted to be the main contributor to intratesticular RA formation, but when CRBP1 was present, ALDH1A2 was predicted to be equally important in RA formation as ALDH1A1. This study provides a comprehensive novel methodology to evaluate RA homeostasis in human tissues and provides insight to how the individual ALDH1A enzymes mediate RA concentrations in specifi c cell types. - Arnold, S. L., T. Kent, C. A. Hogarth, S. Schlatt, B. Prasad, M. Haenisch, T. Walsh, C. H. Muller, M. D. Griswold, J. K. Amory,and N. Isoherranen. Importance of ALDH1A enzymes in determining human testicular retinoic acid concentrations. J. Lipid Res. 2015. 56:342-357. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.


PubMed | Center for Reproductive Medicine and Andrology, University of Washington and Washington State University
Type: Journal Article | Journal: Journal of lipid research | Year: 2015

Retinoic acid (RA), the active metabolite of vitamin A, is required for spermatogenesis and many other biological processes. RA formation requires irreversible oxidation of retinal to RA by aldehyde dehydrogenase enzymes of the 1A family (ALDH1A). While ALDH1A1, ALDH1A2, and ALDH1A3 all form RA, the expression pattern and relative contribution of these enzymes to RA formation in the testis is unknown. In this study, novel methods to measure ALDH1A protein levels and intrinsic RA formation were used to accurately predict RA formation velocities in individual human testis samples and an association between RA formation and intratesticular RA concentrations was observed. The distinct localization of ALDH1A in the testis suggests a specific role for each enzyme in controlling RA formation. ALDH1A1 was found in Sertoli cells, while only ALDH1A2 was found in spermatogonia, spermatids, and spermatocytes. In the absence of cellular retinol binding protein (CRBP)1, ALDH1A1 was predicted to be the main contributor to intratesticular RA formation, but when CRBP1 was present, ALDH1A2 was predicted to be equally important in RA formation as ALDH1A1. This study provides a comprehensive novel methodology to evaluate RA homeostasis in human tissues and provides insight to how the individual ALDH1A enzymes mediate RA concentrations in specific cell types.


Traish A.M.,Boston University | Guay A.T.,Tufts University | Zitzmann M.,Center for Reproductive Medicine and Andrology
Hormone Molecular Biology and Clinical Investigation | Year: 2014

5α-reductases, a unique family of enzymes with a wide host of substrates and tissue distributions, play a key role in the metabolism of androgens, progestins, mineralocorticoids and glucocorticoids. These enzymes are the rate-limiting step in the synthesis of a host of neurosteroids, which are critical for central nervous system function. Androgens and glucocorticoids modulate mitochondrial function, carbohydrate, protein and lipid metabolism and energy balance. Thus, the inhibition of these regulatory enzymes results in an imbalance in steroid metabolism and clearance rates, which leads to altered physiological processes. In this report, we advance the hypothesis that inhibition of 5α-reductases by finasteride and dutasteride alters not only steroid metabolism but also interferes with the downstream actions and signaling of these hormones. We suggest that finasteride and dutasteride inhibit 5α-reductase activities and reduce the clearance of glucocorticoids and mineralocorticoids, potentiating insulin resistance, diabetes and vascular disease. © 2014 by De Gruyter 2014.


Traish A.M.,Boston University | Zitzmann M.,Center for Reproductive Medicine and Andrology
Reviews in Endocrine and Metabolic Disorders | Year: 2015

Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this intervention may evolve as a novel approach to treatment of obesity in men with TD. © 2015, Springer Science+Business Media New York.


Muller T.,Stem Cell Biology Unit | Muller T.,Hannover Medical School | Hupfeld T.,Stem Cell Biology Unit | Roessler J.,Hannover Medical School | And 3 more authors.
Journal of Medical Primatology | Year: 2011

Background Common marmoset monkeys (Callithrix jacchus) are readily used in biomedical research. However, superovulation for embryonic stem cell production and developmental research still remain difficult. Inexplicably, follicle-stimulating hormone (FSH) as key player in superovulation has to be administered in extremely high dosages in this non-human primate compared to human. Methods To evaluate whether marmoset FSH (cjFSH) is functionally more competent than its human homologue on the marmoset FSH receptor (cjFSHR), we established in vitro a homologous system characterizing homologous and recombinantly produced cjFSH. Results Upon stimulation of two cell lines stably expressing either the marmoset or the human FSH receptor (cj/hFSHR), respectively, the second messenger signaling of the activated receptor displayed no significant difference in ED50 values. Thermostability of cjFSH was significantly prolonged by roughly 20% on both FSHRs. Conclusion High FSH dosage in marmoset superovulation cannot be explained by enhanced biopotency of the natural animal's gonadotropin. © 2010 John Wiley & Sons A/S.


PubMed | Boston University and Center for Reproductive Medicine and Andrology
Type: Journal Article | Journal: Reviews in endocrine & metabolic disorders | Year: 2015

Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle,which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this interventionmay evolve as a novel approach to treatment of obesity in men with TD .

Loading Center for Reproductive Medicine and Andrology collaborators
Loading Center for Reproductive Medicine and Andrology collaborators