Michael Zitzmann

Universitätsklinikum Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (115)357.83 Total impact

  • Michael Zitzmann
    Nature Reviews Urology 04/2015; DOI:10.1038/nrurol.2015.73 · 4.52 Impact Factor
  • Experimental and Clinical Endocrinology & Diabetes; 03/2015
  • Experimental and Clinical Endocrinology & Diabetes; 03/2015
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    Dataset: EJE 2011
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    ABSTRACT: Abstract Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.
    The Aging Male 02/2015; DOI:10.3109/13685538.2015.1004049 · 1.85 Impact Factor
  • Michael Zitzmann
  • Michael Zitzmann, Sabine Kliesch
    Diabetes aktuell 01/2015; 12(08):359-365. DOI:10.1055/s-0034-1543992
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    ABSTRACT: Context: Klinefelter Syndrome (KS) is the most common chromosome disorder in men (47,XXY), exhibiting a phenotype with marked variation and increased morbidity. The pathophysiological link between the supernumerary X chromosome and the clinical phenotype remains unknown. Objective: To elucidate whether differential gene expression patterns can be detected in KS patients and whether these are related to inherent clinical features. Design, Setting, Participants: EXAKT (Epigenetics, X-chromosomal features and Clinical Applications in Klinefelter syndrome Trial) is a Münster-based prospective project involving 132 Klinefelter men and their parents. A range of cardiovascular, inflammatory and metabolic factors in comparison to age-matched male (n=50)/female controls (n=50) and in relation to genetic features is assessed. Main outcomes, measures: Predefined hypothesis: differential gene expression patterns in blood cells exist in KS patients vs male controls and are related to the clinical phenotype. Results: Differential expression of 36 X-chromosomal and autosomal genes put KS patients into a unique genetic setting vs male and female controls. The KS cohort exhibited increased insulin resistance, enhanced inflammatory and procoagulatory status, higher waist circumference, dyslipidemia and a markedly shorter 12-lead electrocardiogram QTc-interval (partly located within the pathological range) vs male controls (all p<0.001). Clinical dyshomeostasis was associated with expression patterns of dysregulated genes (all p<0.01). Parental origin of the supernumerary X-chromosome was a confounder regarding insulin resistance and cardiac phenotype (p<0.05). Results are considered preliminary as gene expression was measured in blood cells. Conclusions: The supernumerary X chromosome contributes to a number of pathologies in KS. The pattern of gene expression is altered in KS and the degree of differential gene expression is associated with the clinical phenotype.
    Journal of Clinical Endocrinology &amp Metabolism 12/2014; 100(3):jc20142780. DOI:10.1210/jc.2014-2780 · 6.31 Impact Factor
  • Abdulmaged M Traish, Andre T Guay, Michael Zitzmann
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    ABSTRACT: Abstract 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.
    Hormone molecular biology and clinical investigation 12/2014; 20(3):73-80. DOI:10.1515/hmbci-2014-0025
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    ABSTRACT: Klinefelter syndrome (47, XXY) is the most frequent genetic cause of male infertility and individuals share the endocrine hallmark of hypergonadotropic hypogonadism. Single-nucleotide polymorphisms located within the FSHB/FSHR gene were recently shown to impact serum follicle-stimulating hormone (FSH) levels and other reproductive parameters in men. The objective of this study was to analyse the effect of FSHB-211G>T (c.-280G>T, rs10835638) as well as FSHR c.2039G>A (rs6166) and FSHR c.-29G>A (rs1394205) on endocrine and reproductive parameters in untreated and testosterone-treated Klinefelter patients. Patients were retrospectively selected from the clientele attending a university-based andrology centre. A total of 309 non-mosaic Klinefelter individuals between 18 and 65 years were included and genotyped for the variants by TaqMan assays. The untreated group comprised 248 men, in which the FSHB -211G>T allele was significantly associated with the reduced serum follicle-stimulating hormone levels (-6.5 U/l per T allele, P=1.3 × 10(-3)). Testosterone treatment (n=150) abolished the observed association. When analysing patients before and under testosterone treatment (n=89), gonadotropin levels were similarly suppressed independently of the FSHB genotype. The FSHR polymorphisms did not exhibit any significant influence in any group, neither on the endocrine nor reproductive parameters. In conclusion, a hypergonadotropic setting such as Klinefelter syndrome does not mask the FSHB -211G>T genotype effects on the follicle-stimulating hormone serum levels. The impact was indeed more pronounced compared with normal or infertile men, whereas gonadotropin suppression under testosterone treatment seems to be independent of the genotype. Thus, the FSHB -211G>T genotype is a key determinant in the regulation of gonadotropins in different reproductive-endocrine pathopyhsiologies.European Journal of Human Genetics advance online publication, 23 July 2014; doi:10.1038/ejhg.2014.142.
    European journal of human genetics: EJHG 07/2014; DOI:10.1038/ejhg.2014.142 · 4.23 Impact Factor
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    ABSTRACT: Although there is no evidence that testosterone (T) therapy increases risk of prostate cancer (PCa), there is a paucity of long-term data.
    The Journal of Urology 06/2014; 193(1). DOI:10.1016/j.juro.2014.06.071 · 3.75 Impact Factor
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    ABSTRACT: IntroductionDespite increasing use of testosterone therapy (TTh) for men with testosterone deficiency (TD), there remains uncertainty determining who is a candidate for treatment.AimThe aim if this study was to report the opinions of international experts on TTh, as initially presented at the meeting of the World Meeting on Sexual Medicine in Chicago, United States in August 2012.Methods Expert responses to questions regarding the diagnosis of TD based on their own clinical and research experience.ResultsAll experts emphasized the primacy of symptoms for the diagnosis of TD. Total testosterone (T) thresholds used to identify TD ranged from 350 ng/dL to 400 ng/dL (12–14 nmol/L); however, experts emphasized the diagnostic limitations of this test. Free T was obtained by all, with some valuing this test more than total T for clinical decision making. Only one expert routinely used a screening questionnaire. None used age-adjusted values. Bioavailable T and the free androgen index were not used. Luteinizing hormone (LH) and sex hormone-binding globulin levels were routinely obtained at evaluation. Additional supportive evidence for TD diagnosis included small testicular volume, high androgen receptor CAG repeats, elevated LH, and presence of diabetes or metabolic syndrome. Two T tests were generally obtained but not always required. Some experts did not require morning testing in men 50 years and older. All monitored prostate-specific antigen and hematocrit after initiation of TTh. All but one expert would consider a trial of TTh to a symptomatic man with total T within the normal range. Recent studies suggesting increased cardiovascular risk with T therapy were not found to be credible.Conclusions Determining who is a candidate for TTh requires clinical assessment based on symptoms and signs, with confirmatory laboratory evaluation. These expert opinions differed from some published guidelines by the emphasis on symptoms as paramount, recognition of the limitations of total T as a diagnostic test, and the potential utility of a therapeutic trial in symptomatic cases with normal total T concentrations. Morgentaler A, Khera M, Maggi M, and Zitzmann M. Commentary: Who is a candidate for testosterone therapy? A synthesis of international expert opinions. J Sex Med **;**:**–**.
    Journal of Sexual Medicine 06/2014; 11(7). DOI:10.1111/jsm.12546 · 3.15 Impact Factor
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    ABSTRACT: The Klinefelter syndrome (KS), with an incidence of 1 to 2 per 1000 male neonates, is one of the most frequent congenital chromosome disorders. The 47,XXY karyotype causes infertility, testosterone deficiency and a spectrum of further symptoms and comorbidities. In recent years, significant progress has been made in the elucidation of the pathophysiology and the treatment of the KS. It became clear that, to a large extent, the clinical picture is determined by gene dosage effects of the supernumerary X-chromosome. The origin of the extra X-chromosome from either the father or the mother influences behavioural features of patients with KS. The CAGn polymorphism of the androgen receptor, located on the X-chromosome, has a distinct impact on the KS phenotype. KS predisposes to the metabolic syndrome and its cardiovascular sequelae, contributing to the increased mortality of patients with KS. Neuroimaging studies have correlated anomalies in brain structures with psychosocial problems. The unexpected possibility to produce pregnancies and live birth with either ejaculated sperm - about 8% of KS men have a few sperm in semen - or with sperm extracted from individual tubules obtained by testicular biopsy can be considered a breakthrough. Testosterone substitution requires further optimisation in terms of when to initiate therapy and which preparations and dosages to use. Recently developed animal models help to further elucidation the genetic and pathopysiological basis and may lead to new therapeutic approaches to KS.
    Annales d Endocrinologie 04/2014; 75(2). DOI:10.1016/j.ando.2014.03.007 · 0.66 Impact Factor
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    ABSTRACT: Highly compacted sperm DNA in protamine toroids and a minor fraction of nucleohistones are prerequisites for the efficient transmission of the paternal genome into the oocyte at fertilization. The objective of this study was to evaluate whether protamines might serve as a prognostic factor for stallion fertility. In situ hybridization detected specific expression of P1 mRNA in the cytoplasm of stage I to VII spermatids, whereas comparable immunohistochemical stainings showed that protein expression was delayed till elongating spermatids in differentiation stages III to VIII. No staining was detectable in cryptorchid testis because of the lack of spermatids in the seminiferous tubules. Using quantitative real-time polymerase chain reaction, we identified mRNA transcripts of P1 and 2 variants of protamine- 2 (P2, P3) in ejaculated spermatozoa from 45 thoroughbred stallions. According to the mare fertility descriptor (i.e. the ‘none-return-rate 28 percentage’ or NRR28%), stallions were divided into three groups (i.e. high, reduced and low fertility). The P2/P1 mRNA ratio was found to be significantly reduced in the group with lower fertility (p = 0.016) and was slightly correlated with sperm concentration (correlation coefficient r = 0.263). Furthermore, morphologically abnormal sperm count negatively correlated with P2/P1 mRNA ratio, indicating that spermatozoa carrying head defects display a diminished protamine ratio (r = −0.348). Conversely, the P2/P1 ratio was positively correlated with mare fertility or NRR28% (r = 0.274). Interestingly, P3/P1 mRNA ratio remained unaltered in the investigated groups indicating that this variant plays a minor role in equine sperm chromatin compaction. Aberrant protamine transcripts content in equine spermatozoa was not associated with DNA defragmentation rate as measured by flow cytometric acridine orange test. On the basis of these results, we suggest that, similar to human, equine protamine expression constitutes a checkpoint of spermatogenesis and as a corollary the level of protamine mRNA may reflect the quality of spermatogenesis and spermatozoa's fertilizing capacity.
    Andrology 04/2014; DOI:10.1111/j.2047-2927.2014.00211.x · 3.37 Impact Factor
  • M. Zitzmann
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    ABSTRACT: Hintergrund Eine Elternschaft im späteren Lebensalter wird von vielen Menschen als vorteilhaft wahrgenommen, da oft in vielerlei Hinsicht stabilere Lebensbedingungen gegeben sind. Auch gibt es Männer, für die eine zweite Familie eine Lebensoption darstellt. Daher rücken auch biologische Aspekte der älteren Vaterschaft in den wissenschaftlichen und klinischen Fokus. Altersabhängige Faktoren mit Einfluss auf die männliche Fertilität Das Alter beeinflusst die männliche Fertilität durch eine Reihe von Faktoren, die in ihrer Gänze nicht komplett verstanden sind. Die Spermienproduktion und -motilität nimmt aufgrund der verfallenden testikulären Feinarchitektur mit zunehmendem Alter ab. Auch nimmt mit dem Alter des Mannes die Fekundität durch weitere Faktoren ab: Ein gestörter Schwangerschaftsverlauf wird oft beobachtet. Einige sehr seltene autosomal-dominante Erkrankungen sind deutlich mit dem väterlichen Alter assoziiert. Epigenetische Effekte Hinzu kommen epigenetische Effekte, die mit neurokognitiven Störungen und möglicherweise sogar metabolischen Dysbalancen vergesellschaftet sind. Solche Effekte können sich, einmal ausgelöst, offensichtlich über mehrere Generationen erstrecken. Dabei wird ein Alter des Mannes über 40 Jahre bereits als biologischer Einflussfaktor angesehen, der möglicherweise jedoch durch ein jüngeres Alter der Partnerin ausgeglichen werden kann – zumindest in Teilaspekten. Eine entsprechende Beratung sollte auf jeden Fall patientenorientiert sein. Statistische Wahrscheinlichkeiten sind gegen individuelle Wünsche abzuwägen.
    Gynäkologische Endokrinologie 02/2014; DOI:10.1007/s10304-013-0581-3
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    ABSTRACT: Klinefelter syndrome (KS, 47,XXY) is associated with low serum testosterone (T), long thought to arise from disturbed steroidogenesis in Leydig cells. However, intratesticular testosterone (ITT) concentrations were recently found to be normal in a KS mouse model (41,XXY*). So far, nothing was known about ITT concentrations in human patients with KS. Therefore, ITT, sex hormone-binding globulin (SHBG) and histological parameters were measured in human testicular biopsies of 11 KS patients, 30 azoospermic patients with Sertoli-cell-only syndrome and nine men with normal spermatogenesis as controls. ITT concentrations showed an overall pronounced excess over intratesticular SHBG in molar terms and were significantly increased in men with KS despite of reduced serum T levels. While the ratio of ITT/serum T was markedly increased in KS, the ITT/LH-ratio was comparable between all groups. After finding significantly increased ITT levels in men with KS, a finding even more striking than in the 41,XXY* KS mouse model, we set out to find a possible ‘vascular’ explanation for the lack of T release into the testicular blood stream. In testis biopsies from patients, reliable analysis of the vessels is, however, not possible because of the bias resulting from the dissection technique requiring avoidance of larger blood vessels to prevent bleeding. Consequently, the blood vessel constitution was evaluated in whole testis sections from adult male 41,XXY* and 40,XY* mice (n = 5, each). Indeed, the blood vessel/testes surface ratio correcting for the smaller testes of XXY* mice was significantly lower in these mice compared with XY* controls. In conclusion, testicular T production does not seem to be impaired in men with KS. On the contrary, ITT concentrations are increased, but not because of increased SHBG activity. The data from the mouse model let us speculate that a reduced vascular bed might be involved in lower release of T into the bloodstream.
    Andrology 02/2014; 2(2). DOI:10.1111/j.2047-2927.2014.00190.x · 3.37 Impact Factor
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    ABSTRACT: Classic congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated. A 30 year old male presented for endocrine and fertility assessment after undergoing unilateral orchiectomy for a suspected testicular tumour. Histopathological evaluation of the removed testis revealed atrophy, testicular adrenal rest tumours (TART) and raised the suspicion of underlying CAH. The remaining testis was also atrophic (5ml) with minor TART. 17-hydoxy-progesterone serum levels were elevated, cortisol at the lower limit of normal, gonadotropins at prepubertal levels but serum testosterone was within the normal adult range. Semen analysis showed azoospermia. CAH was confirmed by a homozygous mutation g.655A/C>G (IVS2-13A/C>G) in CYP21A2. HYDROCORTISONE (24MG/M2) ADMINISTERED TO SUPPRESS ACTH AND ADRENAL ANDROGEN OVERPRODUCTION, UNMASKED DEFICIENT TESTICULAR TESTOSTERONE PRODUCTION. AS AZOOSPERMIA PERSISTED DUE TO SUSTAINED HYPOGONADOTROPIC HYPOGONADISM, A COMBINED SUBCUTANEOUS GONADOTROPIN REPLACEMENT WITH HCG (1500IU TWICE WEEKLY) AND FSH (HMG 150IU THREE TIMES WEEKLY) WAS ADDED.RESULTS: Normalisation of testosterone levels and a stable low sperm concentration (0,5 mill/ml) with good sperm motility (85% A+B progressive) was achieved within 21 months of treatment. Despite persisting TART, whilst receiving treatment, the patient successfully impregnated his wife twice, the latter leading to the birth of a healthy girl. TART in unrecognized (SV) CAH may give rise to unnecessary orchiectomy. In hypogonadotropic, azoospermic CAH, a combined treatment with oral corticosteroids and subcutaneously administered hCG and FSH can successfully restore testicular testosterone production and fertility, even if only one hypoplastic and atrophic testis with adrenal rest tumours is present.
    European Journal of Endocrinology 01/2014; DOI:10.1530/EJE-13-0449 · 3.69 Impact Factor
  • Michael Zitzmann
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    ABSTRACT: Later parenting is considered by many to have advantages, parents-to-be may feel themselves more stable to rear children. In addition, many men start a second family later in life. Thus, paternal age becomes an emerging issue. Aging affects male fertility by a scope of factors, which are not fully understood to date. Generally, the amount of produced sperm cells as well as their motility decreases with age, as testicular histological architecture deteriorates. Decreased fecundity and an increased risk for disturbed pregnancies occur with advancing paternal age. Some rare autosomal dominant pathologies are clearly related to paternal age. Altered patterns of epigenetics/gene expression in aging sperm seem to affect a range of neurocognitive disorders and also metabolic dyshomeostasis across generations. Such effects refer to men older than 40 years and may have impact on socio-economic issues. Nevertheless, councelling of older men seeking paternity should be patient-oriented and weigh statistical probabilities against the right for individual life-planning.
    08/2013; 27(4):617-28. DOI:10.1016/j.beem.2013.07.004
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    ABSTRACT: BACKGROUND: Sex hormones levels and the androgen receptor CAGn polymorphism have been shown to be involved in depressed mood in aging men. But the few prior studies found inconsistent results on the role of both factors. METHODS: 186 male participants aged ≥65 years from the community based Memory and Morbidity in Augsburg Elderly (MEMO) Study underwent a physical examination, and a medical interview including two scales (Center for Epidemiologic Studies Depression Scale (CES-D); Activities of Daily Living Scale (ADL). Testosterone, SHBG and LH levels were measured and the androgen receptor CAGn polymorphism was genotyped. χ(2), Mann-Whitney U-test, Pearson's correlations and multivariable linear and logistic regression were used in the analysis. RESULTS: Higher depressive scores were significantly associated with higher SHBG-levels (beta coefficient 0.25, p<0.001). SHBG alone explained 8% of variance of the CES-D depression score. Mortality at 10 years follow-up was predicted by higher SHBG levels, higher ADL-scores, older age, current smoking and the depression score at baseline. This model explained 35% of the variance of mortality. The number of CAG repeats was neither related to depression scores nor to mortality. CONCLUSIONS: We found positive associations between SHBG levels and old age male depression as well as mortality. Whether SHBG has a testosterone independent effect in this context should be investigated further.
    Psychoneuroendocrinology 04/2013; DOI:10.1016/j.psyneuen.2013.03.016 · 5.59 Impact Factor
  • J Rohayem, M Zitzmann, S Kliesch
    Experimental and Clinical Endocrinology & Diabetes 03/2013; 121(03). DOI:10.1055/s-0033-1336609 · 1.76 Impact Factor

Publication Stats

3k Citations
357.83 Total Impact Points

Institutions

  • 2002–2015
    • Universitätsklinikum Münster
      • Centrum für Reproduktionsmedizin und Andrologie
      Muenster, North Rhine-Westphalia, Germany
  • 2001–2015
    • University of Münster
      • Center for Reproductive Medicine and Andrology
      Muenster, North Rhine-Westphalia, Germany
  • 2011
    • Brown University
      • Alpert Medical School
      Providence, Rhode Island, United States
  • 2001–2008
    • Reproductive Medicine Institute
      Chicago, Illinois, United States
  • 2003
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany