Michael Zitzmann

Universitätsklinikum Münster, Muenster, North Rhine-Westphalia, Germany

Are you Michael Zitzmann?

Claim your profile

Publications (101)331.91 Total impact

  • [Show abstract] [Hide abstract]
    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; · 6.31 Impact Factor
  • Abdulmaged M Traish, Andre T Guay, Michael Zitzmann
    [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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; · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 3.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; · 0.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; · 3.37 Impact Factor
  • M. Zitzmann
    [Show abstract] [Hide abstract]
    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;
  • [Show abstract] [Hide abstract]
    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; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 3.69 Impact Factor
  • Michael Zitzmann
    [Show abstract] [Hide abstract]
    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.
    Best practice & research. Clinical endocrinology & metabolism. 08/2013; 27(4):617-28.
  • [Show abstract] [Hide abstract]
    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; · 5.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: For most azoospermic men testicular sperm extraction (TESE) is the only treatment, however it presents challenges for the ART laboratory, as the retrieval of motile spermatozoa is difficult. In the absence of sperm movement no unequivocal distinction can be made between either dead or immotile, but vital spermatozoa. However, a single laser shot directed to the tip of the tail allows recognition of viability because the flagellum coils at the area of impact. To rank the quality and the maturity of oocytes, polarization microscopy can be used. The zona score and the visualization of the meiotic spindle correlate with implantation and pregnancy rates. We compared 65 TESE-ICSI cycles of the years 2007 and 2008 (Group 1, G1) with 58 TESE-ICSI cycles of the years 2009 and 2010 (Group 2, G2). Testicular spermatozoa were injected according to motility and morphology into selected oocytes. In G1 both, oocyte and spermatozoa were rated using light microscopy only, whereas in G2 the laser was used for sperm selection and the oocytes were rated by light and polarization microscopy. In G2 we enhanced our fertilization rate (FR) significantly in comparison to G1 (G1 42.1% vs. G2 52.7%, p < 0.001). The fertilization rate with immotile, but vital spermatozoa improved significantly when applying laser-based selection (p = 0.006). The laser selection of immotile spermatozoa and the use of polarization microscopy can enhance the FR of TESE-ICSI. No negative effect of the laser was seen on birth rates. The FR with immotile, but vital spermatozoa clearly benefits from laser selection and is a non-hazardous and safe method for the selection of viable but immotile sperm. To our knowledge this is the first report using new technology creating novel endpoints for the analysis of spermatozoa and oocytes in TESE-ICSI.
    Andrology 01/2013; 1(1):67-74. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction.  Morbidity/mortality is higher in men with below-normal serum testosterone. Restoring testosterone to normal is beneficial. Aim.  Assessment of safety and effectiveness of injectable long-acting testosterone undecanoate (TU) in hypogonadal men in daily clinical practice. Methods.  An international, multicenter, one-arm, prospective observational study in 23 countries. Main Outcome Measures.  Parameters of erectile function, libido, vigor/vitality, mood, and ability to concentrate assessed by physician interview using items and five-point Likert scales. Physical and circulatory parameters as well as hematocrit, prostate-specific antigen (PSA) levels, glucose control, and lipid profiles. IPASS.  An International, multicenter, Post-Authorisation (after authorized use in respective country) Surveillance Study on long-acting-intramuscular TU conducted at 155 centers in 23 countries in Europe, Asia, Latin America, and Australia. Patients received up to five TU injections during 9-12 months. Results.  Of the 1,493 hypogonadal men enrolled, 1,438 (aged 49.2 ± 13.9 years) having received 6,333 injections were analyzed. Scores of mental and psychosexual functions (libido, vigor, overall mood, and ability to concentrate) improved markedly, while mean waist circumference decreased from 100 to 96 cm. Blood pressure and lipid parameters were altered in a favorable and significant manner. After four TU injection intervals, the percentage of patients with "low" or "very low" levels of sexual desire/libido decreased from 64% at baseline to 10%; moderate, severe, or extremely severe erectile dysfunction decreased from 67% to 19%. At the last observation, 89% of patients were "satisfied" or "very satisfied" with TU therapy. Adverse events and adverse drug reactions (ADRs) occurred in 12% and 6% of patients, respectively, mostly mild to moderate. The most common ADRs were increase in hematocrit, increase in PSA, and injection site pain (all <1%). No case of prostate cancer was observed. Conclusion.  In this largest worldwide sample of hypogonadal men, injectable long-acting TU was effective and well tolerated. Zitzmann M, Mattern A, Hanisch J, Gooren L, Jones H, and Maggi M. IPASS: A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. J Sex Med **;**:**-**.
    Journal of Sexual Medicine 07/2012; · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate size and function are regulated by testosterone. However, the progesterone receptor is expressed in the primate prostate. Progestins affect the prostate by endocrine suppression, but can also act directly. Examining the role of progestins, we studied the effects of norethisterone (NET) on testosterone undecanoate (TU)-induced prostate growth in castrated macaques. Two groups (n = 6 for each group) received TU every 9 weeks. Using a crossover setting, group I received norethisterone enanthate (NETE) 3 times at 3-week intervals, while group II received placebo. After 9 weeks, placebo was administered to group I, and group II received NETE. In group II, the prostate grew under TU and placebo over the first period. In group I, coadministered with NETE, the increase was lower. After the crossover, prostates of animals previously treated with NETE did not increase to normal values under placebo. Prostates of animals treated with TU and placebo in the first period shrank following NETE administration after the crossover. The long half-life of NET can explain the lack of a TU effect on animals coadministered with NETE after the crossover. Pre- and coadministration of NET reduces testosterone-induced prostate growth with possible implications for the treatment of benign prostate hyperplasia and hormonal male contraception.
    Urologia Internationalis 03/2012; 88(3):358-64. · 1.15 Impact Factor
  • Article: The reply.
    The American journal of medicine 03/2012; 125(3):e7. · 5.30 Impact Factor
  • Maturitas 03/2012; 71:S18. · 2.84 Impact Factor
  • European Urology Supplements 02/2012; 11(1):e52, e52a. · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS. In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay. Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002). The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.
    Experimental and Clinical Endocrinology & Diabetes 11/2011; 120(2):73-9. · 1.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: While associations between somatic changes and sex hormone levels in aging men have been explored in many studies, the association of testosterone and estradiol with psychic symptoms other than depression and the role of the genetically determined CAG repeat (CAGn) polymorphism of the androgen receptor (AR) have received much less attention. The purpose of this article is to investigate the associations between general anxiety, phobic anxiety and panic with sex hormone levels and the genetic androgen receptor polymorphism in aging males. This cross-sectional study of males aged ≥50 years included 120 consecutive patients of the Department of Psychosomatics and Psychotherapy, 76 consecutive patients of the Andrology Clinic, and 100 participants from the general population; all of them completed the Brief Symptom Inventory (BSI), the Aging Males' Symptoms (AMS) Scale, and the Patient Health Questionnaire (PHQ-9). Morning blood samples were analyzed for total and free testosterone, estradiol, sex hormone-binding globulin (SHBG), and the CAGn AR polymorphism. Psychosomatic patients also underwent psychiatric assessment. Scores on the Anxiety subscales of the BSI and PHQ, Anxiety disorders according to International Classification of Diseases, 10th revision (ICD-10). The two clinical samples had significantly longer CAGn of the AR and higher anxiety levels compared to the population sample. Anxiety scores were positively correlated with CAGn in psychosomatic patients and in andrological patients, in the latter also with estradiol levels, while the population sample showed no significant correlations between anxiety scores, CAGn and sex hormones. Anxiety cases according to BSI, PHQ, and ICD-10 had significantly longer CAGn of the AR when compared to the other participants, but there were no significant differences in testosterone or free testosterone levels. Our results indicate that genetically determined long CAGn of the AR is an independent risk factor for higher anxiety, panic and phobic anxiety levels.
    Journal of Sexual Medicine 08/2011; 8(12):3452-64. · 3.15 Impact Factor

Publication Stats

3k Citations
331.91 Total Impact Points


  • 2001–2014
    • Universitätsklinikum Münster
      • Centrum für Reproduktionsmedizin und Andrologie
      Muenster, North Rhine-Westphalia, Germany
    • University of Münster
      • • Center for Reproductive Medicine and Andrology
      • • Department of Psychosomatics and Psychotherapy
      • • Center of Reproductive Medicine and Andrology
      Muenster, North Rhine-Westphalia, Germany
  • 2011
    • Brown University
      Providence, Rhode Island, United States
  • 2008
    • Columbia University
      • Department of Urology
      New York City, NY, United States
  • 2007
    • Bayer HealthCare
      Leverkusen, North Rhine-Westphalia, Germany
    • Reproductive Medicine Institute
      Chicago, Illinois, United States
  • 2003
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany