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Biomedical subjects

E Nieschlag

Publications and source records attributed to E Nieschlag.

At least 37 records · Page 2Linked 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

CAG repeat length in the androgen receptor gene affects the risk of male infertility.

During recent years several studies have suggested that a slight increase in the number of CAG repeat sequences in exon 1 of the androgen receptor gene causes idiopathic oligozoospermia. We tested whether CAG repeats are more numerous in men with idiopathic infertility compared to those with known causes of oligozoospermia. CAG repeats were analysed in a consecutive sample of 217 infertile men covering a wide range of diagnoses and sperm counts. Data were compared with those of a control group of 131 normozoospermic men including 62 fathers. CAG repeats (x +/- SD) did not differ between idiopathically (21.4 +/- 2.9) and non-idiopathically infertile men (21.6 +/- 2.8) or normozoospermic men of unproven fertility (20.6 +/- 3.0). Only fathers had significantly fewer repeats (19.4 +/- 3.1; p < 0.001). Different from controls, no correlation between CAG repeats and any semen parameter existed in patients. Comparison of our and published studies showed that odds ratios for infertility in men with CAG repeat length in the upper quartile of the normal range increased when the controls were selected by proven fertility. We conclude that more numerous CAG repeats do not directly cause oligozoospermia and propose that men with longer CAG repeats might be more prone to develop infertility in response to any pathogen/epigenetic factors.

Adenine↗
PubMed2003

Androgens shorten the longevity of women: sopranos last longer.

Earlier we found that longevity of castrati was identical to that of intact singers. These findings were in disagreement with the prevailing concept that testosterone might shorten life and might be responsible for the shorter life expectancy of men compared to women. We have now continued our research into the life expectancy of singers, considering them as a paradigm of nature to investigate life-long effects of sex hormones, and resulting in the finding that sopranos, being more oestrogenised, live significantly longer than altos who are more androgenised, while basses, more androgenised, show a tendency towards a longer life than tenors, who are less androgenised. These findings, supported by results of epidemiological investigations indicate that women are protected from cardiovascular diseases, diabetes and osteoporosis by higher oestrogen levels, while the same effect maybe exerted in men by testosterone.

Aged↗
PubMed2003

Genetic damage in oligozoospermic patients detected by fluorescence in-situ hybridization, inverse restriction site mutation assay, sperm chromatin structure assay and the Comet assay.

BACKGROUND: The possibility that oligozoospermic men may have elevated levels of genetic damage in their sperm is of particular concern as they could transmit defects to their offspring. METHODS: Sperm samples were obtained from 12 infertile, oligozoospermic patients and 12 healthy normozoospermic volunteers. Fluorescence in-situ hybridization (FISH) was used to determine aneuploidy rates in sperm and inverse restriction site mutation (iRSM) assay to determine gene mutations; defective chromatin packaging was quantified by sperm chromatin structure assay (SCSA) and DNA strand breaks by the Comet assay. RESULTS: FISH analysis showed a significant increase in gonosomal X,Y,18 (P < 0.01) disomy and diploid sperm with X,Y,18,18 (P < 0.05) in the infertility patients compared with the controls. A significant increase (P < 0.01) in disturbed sperm chromatin was found in the infertility patients compared with the control group using the SCSA assay. In the Comet assay, a significant increase (P < 0.01) in the tail moment was found in the infertility patients compared with the control group, indicating significantly high levels of DNA strand breaks. There was no significant increase in point mutations detected by iRSM assay. CONCLUSIONS: The data indicate that infertile oligozoospermic men have an elevated level of XY aneuploidy and XY diploidy in the germ-line, as well as elevated levels of sperm chromatin disturbances and sperm DNA strand breaks. These data demonstrate that oligozoospermic infertility patients show several different types of genetic damage in their sperm. Thus, such men appear to have defects at a variety of levels of spermatogenesis and their infertility may not just be a result of the oligozoospermia.

Adult↗
PubMed2003

Gonadal protection from radiation by GnRH antagonist or recombinant human FSH: a controlled trial in a male nonhuman primate (Macaca fascicularis).

Chemotherapy and radiation often damage spermatogenesis irreversibly in oncological patients and various approaches to gonadal protection have been tested with equivocal results. In rats, hormonal protection of spermatogenesis can be achieved by blocking gonadotropin secretion. However, whether the same mechanisms can effect gonadal protection in primates remains questionable. To clarify this Issue we conducted a placebo-controlled trial in a preclinical animal model using macaques (Macaca fascicularis). Twenty adult male monkeys (five in each group) were randomized to receive either recombinant human FSH, GnRH antagonist or saline injections (two groups) for 36 days. On day 29 all groups except one saline-treated control group were exposed to a single testicular irradiation of 4 Gy. Every 2 weeks before, during and after the treatment, ejaculates, body weight, testicular Volume and hormones were analyzed until day 539. In addition, repeated testicular biopsies were performed. Testicular Volume and inhibin B decreased significantly in all irradiated groups compared with baseline and with the non-irradiated control group, followed by a gradual recovery of these parameters, which was, especially at the earlier time points, significantly better in the FSH-treated group compared with both other irradiated groups. Irradiation caused a drastic decrease of sperm parameters in all groups, followed by a partial recovery of sperm parameters, which was significantly slower in the early phases of recovery in the GnRH antagonist group compared with the vehicle group. Testicular histology showed a significant depletion on study day 261 in all irradiated animals. In conclusion, in clear contrast to rodent studies, GnRH antagonist treatment did not provide gonadal protection in this primate model. FSH treatment resulted in slightly better recovery of spermatogenesis, which appears to be of no or only little clinical relevance.

Analysis of Variance↗
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

Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation.

OBJECTIVE: Transdermal testosterone gel treatment is an effective androgen substitution therapy with several advantages over conventional substitution therapies. Whereas side-effects due to overdosing of hypogonadal patients are unlikely, testosterone gel application without protection may cause severe side-effects in other subjects (partners, family members) by contamination. Therefore, the risk of testosterone transfer of a newly developed 2.5% testosterone gel preparation was evaluated. DESIGN: In two clinical randomized open single-centre studies on healthy male volunteers the percentage of testosterone remaining on the skin after gel application over time (n = 12) and the possibility of a transfer of testosterone to another person (n = 28) was evaluated. In the second study the endogenous testosterone production in the receiving subjects was suppressed by injecting 400 mg norethisterone enanthate (NETE). RESULTS: After 8 h approximately 60% of testosterone applied to the skin could be recovered. When the skin had been previously washed with water, only about 14% of applied testosterone could be recovered. After intense skin contact with a volunteer who had applied testosterone before on his forearm, no increase in testosterone serum levels could be found in NETE-suppressed men. CONCLUSION: Although considerable amounts of testosterone remain on the intact skin for several hours after evaporation of the alcohol vehicle, contamination of a second, especially female or prepubertal, subject causing side-effects seems very unlikely.

Administration, Cutaneous↗
PubMed2002

TestisBank: an internet-based gene sequence database of the testis.

The testis is a highly transcriptionally active organ with hundreds of genes expressed during different stages of spermatogenesis. Scientists working on the testis are restricted to using two sources for further information on testicular genes, GenBank and MEDLINE. However, these two databases are not completely linked and give only very little information on the cellular type of expression or whether a gene is cloned in other tissues but is also expressed in the testis. We have generated an organ-specific database named TestisBank, which is capable of retrieving a more complete set of genes expressed in the different cell types of the testis. Furthermore, it extends to the epididymis which plays an important role in germ cell maturation. TestisBank is automatically updated to match the current status of sequence entries in the genome databases and it provides the user with an interface convenient to handle and provides useful links related to male reproduction. The TestisBank is publicly available at http://medweb.uni-muenster.de/TestisBank/. The design of the TestisBank may provide a simple model for the development of databases in which molecular and literature data are merged, thereby allowing detailed insight into the contribution of different cells/genes to the complex process of spermatogenesis.

Databases, Bibliographic↗
PubMed2002

Semen analysis and external quality control schemes for semen analysis need global standardization.

One semen analysis laboratory [the Institute of Reproductive Medicine (IRM), Münster, Germany] was enrolled in three external quality assurance programmes in Europe (United Kingdom External Quality Assurance Scheme, European Academy of Andrology, European Society of Human Reproduction) that control for the assessment of sperm concentration, sperm motility and sperm morphology. Agreement between the participating laboratory and the sperm concentrations designated by all three programmes was good. Disagreement between two quality control (QC) programmes providing motility assessment was particularly noticeable in the distinction between motility grades a and b. For the identification of normal sperm morphology, marked differences between the standards set by different QC programmes were apparent. One programme was stricter in its categorization of normal forms, such that an overestimation of normal forms was diagnosed at IRM, whereas agreement with the other programmes was achieved. Variation of results from technicians in the IRM internal QC programme was <13%. The discrepancies between external quality control (EQC) centres demonstrated here are challenging problems to be overcome partly by the andrology laboratories and partly by the providers of EQC services. The introduction of objective, computer-aided sperm assessment in providing designated values may help to rectify this situation. Until this is achieved, EQC programmes should develop an internal programme to monitor their materials and methods for assessment.

Humans↗
PubMed2002

Update on medical treatment of ejaculatory disorders.

Among the treatment modalities for ejaculatory disorders pharmacological treatment is the least invasive option. In this review, medical treatments for retrograde ejaculation (RE) and anejaculation (AE) are discussed systematically. Thirty-six studies dealing with patients with RE and 40 with AE evaluated the use of medical treatment and were included in this review. In addition four articles dealing with prostatic massage in anejaculatory patients were considered. Sperm quality in patients with retrograde and AE is often impaired. In patients with RE no differences in response to medical treatment could be detected between the different underlying diagnoses. Compared with ephedrine, imipramine and chlorpheniramine + phenylpropanalamine showed significantly higher reversal rates, while differences between the other treatments were not significant. Regarding the reversal of AE, the alpha agonistic drugs were significantly inferior to treatment with parasympathetic drugs. Of the different alpha agonistic medical treatments for the reversal of AE, milodrin showed significantly better rates than imipramine (p = 0.008), pseudoephidrine (p = 0.02) and ephedrine (p = 0.044), while all other treatments were not significantly different (p = 0.4). In conclusion, medical treatment for reversal of RE offers a realistic chance of conceiving offspring naturally and should be the treatment modality of first choice. In contrast, in AE, medical treatment cannot be recommended generally as treatment of first choice as it shows low overall success rates compared with electrovibration stimulation and electroejaculation. Under consideration of the mostly uncontrolled design of the majority of studies published, controlled clinical trials comparing different treatment options appear urgently warranted.

Brompheniramine↗
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↗
PubMed2002

Age-related disease pattern in infertile men: increasing incidence of infections in older patients.

In a cross-sectional retrospective study, the age-dependency of semen parameters of men with specific andrological diseases was investigated in 3,698 men (mean age 33 years; range 19-63 years) attending a tertiary referral clinic for couple infertility. In all, 1,853 patients suffered from idiopathic infertility (mean age 33.2 years; range 19-60 years), 388 from infections of the accessory glands (34.2; 20-61), 363 had a history of maldescended testes (32.0; 20-51) and 833 a varicocele (33.6; 20-63). In 172 patients, a varicocele and an infection (34.3; 24-54) and in 94 a varicocele and a history of maldecended testes (32.5; 21-53) were found. Semen analysis was performed according to WHO criteria. An age-related decrease in testicular volume was not observed in any group. Total sperm count decreased significantly with advancing age only in patients with an infection of the accessory glands. We found no evidence for age-dependent progressive deterioration of semen variables in the other groups. It may be concluded that the causes for the spermatogenetic defects in men with idiopathic infertility, a history of maldescended testes or varicocele are acquired before adolescence and do not progress during adulthood. In contrast, infections of the accessory glands may lead to decreased sperm counts by functional impairment or partial occlusion of the seminal ducts. Thus, if in the general population declining sperm counts are observed, genital tract infections may be suspected as a contributing factor.

Adult↗
PubMed2002

Germ cell transplantation into X-irradiated monkey testes.

BACKGROUND: An intense debate is ongoing regarding options for fertility protection in oncological patients. Germ cell transplantation has been applied to restore mouse spermatogenesis. Here, an attempt to apply autologous germ cell transplantation to a primate animal model is described. METHODS: Five adult male cynomolgus monkeys were biopsied to retrieve and cryopreserve germ cells before both testes were irradiated (dose 2 Gy). Six weeks later, each monkey received an infusion of its own cell suspension into the right testis, while the left testes were infused with saline. Testis size, sperm counts and serum concentrations of inhibin, FSH and testosterone were analysed weekly for 9 months. Spermatogenic recovery was determined histologically at the end of the study. RESULTS: In four monkeys, the germ cell-infused right testes showed a slight to moderate increase in the rate of regrowth in comparison with the left testes. In two monkeys the right testis proceeded to recover more prominently, resulting in larger right testis volumes and better or full spermatogenic recovery at the study end. Restoration of spermatogenesis occurred as an all-or-nothing event. Inhibin B concentrations increased, while FSH and testosterone concentrations decreased with testicular regrowth. Sperm counts did not recover. CONCLUSIONS: The present study demonstrates the immaturity and complexity of germ cell transplantation as a clinical approach.

Animals↗