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Biomedical subjects

M Zitzmann

Publications and source records attributed to M Zitzmann.

13 recordsLinked to original sources
PubMed2003

Effects of androgen replacement on metabolism and physical performances in male hypogonadism.

Hypogonadism in men is associated with decreased physical performance. This phenomenon depends on significantly measurable adverse traits in body composition, namely increased body fat content and reduced muscle mass. Physical abilities in hypogonadal men are further hampered by lower oxygen supply due to decreased hemoglobin concentrations and by poor glucose utilization. In addition, dysthymia and lack of necessary aggressiveness contribute to further deterioration of physical features. T substitution can improve lipid and insulin metabolism, resuiting in changes of body composition, such as decreasing fat depots. Growth of muscle fibers can also be observed. Stabilization of the musculo-skeletal system by increased bone density will further contribute to increased physical fitness, reflected by increased strength and endurance. Treatment outcome is strongly influenced by age and training. The issues reviewed strongly support T treatment of hypogonadal men accompanied by regular monitoring.

Body Composition↗
PubMed2003

[Hypogonadism in the elderly man. Reliable diagnosis and therapy].

The definition of late-onset-hypogonadism as a hybrid form of primary and secondary hypogonadism corresponds to pathophysiological facts of the age-related decline in gonadal as well as hypothalamic-pituitary functions, eventually manifesting in clinically relevant hypogonadism. To what extent advancing age modulates incidence and nature of hypogonadal symptoms has not been completely investigated. The benefits of testosterone substitution therapy in older men await demonstration in long-term studies and to date, it should be restricted to specialized centers. Currently, serum testosterone levels <12 nmol/l, accompanied by symptoms of androgen deficiency, are regarded as an indication for substitution, provided a prostate carcinoma has been excluded. While late-onset hypogonadism decreases libido, it does not play a direct role in the increasing incidence of erectile dysfunction with advancing age; this symptom is rather associated with vessel-endothelial impairment and may serve as a sentinel symptom for cardiovascular disease. Treatment with phosphodiesterase-5-inhibitors can be regarded as standard; in case of concomitant late-onset hypogonadism, testosterone will have a positive synergistic effect on erectile function.

Aged↗
PubMed2003

Human sperm volume regulation. Response to physiological changes in osmolality, channel blockers and potential sperm osmolytes.

BACKGROUND: Volume regulation is an important sperm function because defective sperm cannot negotiate the female tract in an infertile mouse model and swollen human sperm cannot penetrate and migrate through mucus. METHODS AND RESULTS: The size of sperm from 52 donor ejaculates incubated in medium of female tract fluid osmolality (BWW290) was measured by flow cytometry to be identical to that in homologous semen osmolality (289-351 mosmol/kg), indicating effective volume regulation. Inhibition of anticipated regulatory volume decrease in BWW290 by the channel blocker quinine induced size increases and associated kinematic changes measured by computer-aided sperm analysis. Incubation in L-carnitine, myo-inositol and taurine did not change sperm volume or kinematics, but the presence of glutamate and K(+) decreased the efficiency of forward progression indicative of volume increase, suggesting them as potential osmolytes for human sperm. Linear regression suggested correlations of changes in cell volume and in kinematic parameters, and the association of faster forward progressive sperm with smaller cell size. CONCLUSIONS: Sperm volume and its regulation may be crucial to natural fertility. The identification of sperm osmolytes, ion channels and mechanisms involved would contribute to the understanding of male infertility and offer a lead for male contraception.

Adult↗
PubMed2002

The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men.

AIMS/HYPOTHESIS: The relationship of androgens to the metabolic syndrome has not been resolved. The polymorphic number of CAG repeats within the androgen receptor gene is inversely associated with the transcriptional activity of target genes. This polymorphism might thus influence testosterone effects on body fat content and serum concentrations of leptin and insulin. The direct and indirect role of androgens within the metabolic syndrome should become clearer if this genetically determined effector is taken into account. METHODS: The hypothesis was investigated in a cross-sectional study involving 106 healthy 20-50 year old males. RESULTS: Multiple regression models showed a positive independent correlation of the CAG repeat number with body fat content, leptin and insulin (partial r=0.39, 0.36 and 0.28, p<0.001, p<0.001 and p=0.006, respectively). Factor analysis yielded a five-dimensional model: two dimensions were influenced by the androgen receptor polymorphism, namely "body composition" which consisted of leptin, body fat mass, insulin, the number of CAG repeats (positive loadings) and physical activity (negative loading), and "lipid profile" which comprised low density lipoprotein cholesterol, cigarette smoking, triglycerides (positive loadings) as well as high density lipoprotein cholesterol and number of CAG repeats (negative loadings). CONCLUSIONS/INTERPRETATION: A low number of CAG repeats were independently associated with protective parameters (low body fat mass and plasma insulin) as well as with adverse parameters (low high density lipoprotein cholesterol concentrations). This suggests that the pivotal role of this polymorphism in modulating androgen effects on cardiovascular risk factors is of a complex nature and implies that its clinical impact, similar to that of androgens, is dependent on exogenous cofactors.

Adipose Tissue↗
PubMed2002

Monitoring bone density in hypogonadal men by quantitative phalangeal ultrasound.

Monitoring bone density (BMD) in hypogonadal and testosterone (T) substituted men is a major component of andrological therapy and is performed by methods that are cost-intensive and use radiation, such as quantitative computer tomography (QCT). Therefore, we assessed the feasibility of a more practical and inexpensive approach through application of phalangeal quantitative ultrasound (pQUS; IGEA DBM BP Sonic 1200, Sensweiler, Germany) in a cross-sectional study of 521 men, aged 18-91 years (224 healthy controls, 156 newly diagnosed hypogonadal, and 141 T substituted men). The method was compared with QCT of the lumbar spine in the first 80 patients. We evaluated longitudinal changes of amplitude-dependent speed-of-sound (AdSoS) in 54 hypogonadal men from the beginning of T substitution. AdSoS decreased with age (p < 0.0001) and with declining total T concentration, with a four to fivefold larger reduction in AdSoS for each nanomole-per-liter decrement in total T in the hypogonadal range (<12 nmol/L) compared with the eugonadal range (p < 0.0001). AdSoS was higher in eugonadal and substituted men than in hypogonadal patients (p < 0.0001, by analysis of covariance [ANCOVA]). Substituted men <50 years of age showed lower AdSoS than eugonadal men (p = 0.004) and untreated men with secondary hypogonadism had lower values than men with primary hypogonadism (p = 0.005). Therapeutic effects were seen regardless of age, diagnosis, or T substitution modality. In the longitudinal approach, AdSoS increased from 1986 +/- 93 to 2035 +/- 77 m/sec over 237 +/- 57 days with the highest gain in those men with initially the lowest values (p < 0.0001, by ANCOVA for repeated measurements). In comparison to QCT, patients with a lumbar content of hydroxylapatite of <100 mg/cm(3) were reliably identified by pQUS (cutoff level 1965 m/sec, T score -3.5 based on eugonadal subjects; receiver operating characteristics: area under the curve [AUC] 0.94, sensitivity 94.1, specificity 92%, p < 0.0001), but specific values of lumbar BMD could not be predicted by pQUS. pQUS represents a feasible, sensitive, and inexpensive method for assessing bone tissue in hypogonadal men over the full age range and also for monitoring the effects of T substitution.

Adolescent↗
PubMed2002

Distribution and function of FSH receptor genetic variants in normal men.

Follicle stimulating hormone (FSH) plays a key role in the maintenance of qualitatively and quantitatively normal spermatogenesis. It controls gamete development through Sertoli cells, via binding to its receptor. The influence and importance of FSH receptor (FSHR) variants on Sertoli cell function is not completely understood and remains to be investigated. In this retrospective study, we explored the impact and action of two distinct FSHR isoforms, Thr307/Asn680 and Ala307/Ser680, in a large group of men. This investigation includes 288 normal healthy men, 86 of whom were proven fathers previously studied, and 202 were newly recruited subjects. The FSHR polymorphism at position 680 was analyzed in the whole group, while position 307 was investigated in 150 subjects, both of them by single-stranded conformation polymorphism (SSCP) gel electrophoresis. The distribution frequency for position 680 was 29% for the Asn/Asn, 52% for the Asn-Ser, 19% for the Ser-Ser variant, and for position 307, 27% for the Thr-Thr, 55% for the Ala-Thr, 18% for the Ala-Ala, respectively. Polymorphism combinations that were different from Thr307/Asn680 - Ala307/Ser680 were found in four subjects. When subjects were grouped according to genotype at position 680, no significant differences between basal FSH, testosterone, inhibin B levels and semen parameters were found. This clinical finding demonstrates that, differently from females, in whom a significant correlation between FSHR polymorphism and basal FSH levels was found, the FSHR genotype has no influence on clinical parameters in males.

Base Sequence↗
PubMed2001

The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males.

OBJECTIVE: Bone metabolism and bone density (BD) are influenced by sex hormones. Testosterone (T) action is exerted through the androgen receptor (AR). We investigated the potential impact of the CAG repeat (CAGR) polymorphism within the AR gene on BD and bone metabolism in healthy younger males. PATIENTS AND MEASUREMENTS: The number of CAGRs in 110 healthy men aged 20-50 years was determined by sequence analysis. We assessed BD by the radiation-free method of quantitative ultrasound (QUS) of the phalanges. Serum levels of bone-specific alkaline phosphatase (BAP) and urine secretion of free deoxypyridinoline (DPD, corrected for creatinine), serum levels of sex hormones, body fat content and lifestyle factors were determined. RESULTS: In stepwise multiple regression models controlling for age, body fat content and lifestyle factors, the number of CAGRs was an independent negative predictor of BD (partial r = - 0.286, P = 0.001), whereas it was positively associated with markers of bone turnover (for BAP: partial r = 0.32, P= 0.001; for DPD: partial r = 0-241, P = 0.013). Levels of free T and oestradiol showed an independent and positive association with BD; age contributed significantly to lower BD. Age and free T were negatively associated with markers of bone turnover, whereas oestradiol showed a positive correlation with BAP and DPD. ANOVA in groups according to age and the CAGR length suggested an increased age-dependent bone loss in subjects with a CAGR length of 22-31 compared with 14-21 CAGRs (overall P < 0.01). CONCLUSIONS: A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age-dependent bone loss.

Adult↗
PubMed2001

Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal males under testosterone substitution therapy.

Genders differ concerning abilities of spatial cognition; positive associations of testosterone levels with corresponding scores have been reported, as well. We addressed the question whether there is a testosterone-susceptible area within cerebral structures previously described to be involved in mental rotation. Using F-18-deoxyglucose (FDG)-positron emission tomography (PET), we studied cerebral glucose metabolism during a standardized 3-dimensional mental rotation task in 6 right-handed men with hypogonadotropic hypogonadism before and under testosterone substitution therapy. Under elevated testosterone levels, enhanced cerebral glucose metabolism during mental rotation was observed in the 4 subjects with improved visuospatial capability. Areas involved were previously demonstrated to be activated by such tasks in eugonadal men.

Adult↗
PubMed2001

The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity.

Genomic effects of T are exerted via the AR. The length of the polymorphic CAG repeat sequence in the AR gene is inversely correlated with the transcriptional regulation of target genes by T. In 110 healthy men (20-50 yr), we investigated the interactions among this polymorphism, serum levels of sex hormones, cardiovascular risk factors, and flow-mediated and nitrate-induced vasodilatation of the brachial artery. The number of CAG repeat had no significant correlations with serum concentrations of total or free T. Stepwise multiple regression analysis revealed positive correlations of the number of CAG repeat with serum levels of high density lipoprotein cholesterol (partial r = 0.44; P < 0.001) and flow-mediated vasodilatation (partial r = 0.37; P < 0.001). The association of CAG repeat with high density lipoprotein (HDL) cholesterol was independent of body fat content and serum levels of free T, which both had significant negative correlations with HDL cholesterol. The association of CAG repeat with flow-mediated vasodilatation was independent of cigarette smoking and serum levels of free T and low density lipoprotein cholesterol, which also were correlated with flow-mediated vasodilatation. We conclude that a low number of CAG repeat in the AR gene implies a greater chance for low levels of HDL cholesterol and reduced endothelial response to ischemia, which are both important risk factors for coronary heart disease.

Adult↗
PubMed2001

Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs.

This review summarises the correlations between testosterone levels and male physical appearance and behaviour. Methodological shortcomings concerning the measurement of testosterone could limit the value of these findings. In addition, testosterone measured in body fluids represents only one step in the cascade of action from production to biological effect, and could therefore provide only a limited view of the complexity of physiological events. Testosterone levels are influenced by conditions that are partly controlled or initiated by the hormone itself, but also by circumstances beyond hormonal or individual control. Different kinds of behaviour are not only subject to influence by environment, but also androgens can reinforce the particular kind of conduct and the behavioural impact can wield negative or positive feedback on testosterone secretion. Therefore, both generalisation and individualisation of study results will lead to doubtful conclusions and prejudices. Results of such studies must be viewed with caution, and over-simplification as well as over-interpretation should be avoided.

Aggression↗
PubMed2000

Hormone substitution in male hypogonadism.

Male hypogonadism is characterised by androgen deficiency and infertility. Hypogonadism can be caused by disorders at the hypothalamic or pituitary level (hypogonadotropic forms) or by testicular dysfunction (hypergonadotropic forms). Testosterone substitution is necessary in all hypogonadal patients, because androgen deficiency causes slight anemia, changes in coagulation parameters, decreased bone density, muscle atrophy, regression of sexual function and alterations in mood and cognitive abilities. Androgen replacement comprises injectable forms of testosterone as well as implants, transdermal systems, sublingual, buccal and oral preparations. Transdermal systems provide the pharmacokinetic modality closest to natural diurnal variations in testosterone levels. New injectable forms of testosterone are currently under clinical evaluation (testosterone undecanoate, testosterone buciclate), allowing extended injection intervals. If patients with hypogonadotropic hypogonadism wish to father a child, spermatogenesis can be initiated and maintained by gonadotropin therapy (conventionally in the form of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or, more recently, purified or recombinant follicle stimulating hormone (FSH)). Apart from this option, patients with disorders at the hypothalamic level can be stimulated with pulsatile gonadotropin-releasing hormone (GnRH). Both treatment modalities have to be administered on average for 7-10 months until pregnancy is achieved. In individual cases, treatment may be necessary for up to 46 months. Testosterone treatment is interrupted for the time of GnRH of gonadotropin therapy, but resumed after cessation of this therapy.

Animals↗