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E Nieschlag

Publications and source records attributed to E Nieschlag.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2001

Is inhibin B a pharmacodynamic parameter for FSH in normal men?

OBJECTIVE: This study aims to investigate the pharmacodynamic effect of FSH on inhibin B serum levels in normal men in order to elucidate the physiological regulation of inhibin B secretion in more detail. DESIGN AND METHODS: Injections of 3000 IU recombinant, human FSH (rhFSH) were followed by single-blinded injections of placebo, 1000 and 2000 IU rhFSH spaced by at least 28 days between injections. RESULTS: After injection of 3000 IU rhFSH, inhibin B values were significantly elevated above baseline for 24, 96 and 120 h (maximal increase after 96 h, mean +/- s.e.m. 303+/-18 pg/ml). Injection of 2000 IU rhFSH led to a significant increase in inhibin B (maximum mean +/- s.e.m. 318+/-20 pg/ml) from 24 to 120 h. Injection of 1000 IU rhFSH led to a significant increase in inhibin B after 96 h (maximum mean +/- s.e.m. 300+/-16 pg/ml). The inhibin B areas under the curve after injection of 2000 and 3000 IU rhFSH were significantly higher than those following the placebo and 1000 IU rhFSH. In the 12 fertile men investigated, at baseline a strong diurnal rhythm of inhibin B parallel to that of testosterone was observed. CONCLUSIONS: Serum inhibin B can be considered only a partial pharmacodynamic parameter of FSH in vivo, since the integrity of the spermatogenic process appears to be a second fundamental component in the regulation of its secretion from the testis.

Adult↗
PubMed2001

Inhibin B in male reproduction: pathophysiology and clinical relevance.

The recent availability of specific inhibin assays has demonstrated that inhibin B is the relevant circulating inhibin form in the human male. Inhibin B is a dimer of an alpha and a betaB subunit. It is produced exclusively by the testis, predominantly by the Sertoli cells in the prepubertal testis, while the site of production in the adult is still controversial. Inhibin B controls FSH secretion via a negative feedback mechanism. In the adult, inhibin B production depends both on FSH and on spermatogenic status, but it is not known in which way germ cells contribute to inhibin B production. The regulation of inhibin B production changes during life. There is an inhibin B peak in serum shortly after birth only partly correlated with an increase in serum FSH, probably reflecting the proliferating activity of the Sertoli cells during this phase of life. Afterwards, inhibin B levels decrease and remain low until puberty, when they rise again, first as a consequence of FSH stimulation and then as a result of the combined regulation by FSH and the ongoing spermatogenesis. In the adult, serum inhibin B shows a clear diurnal variation closely related to that of testosterone. The administration of FSH increases the secretion of inhibin B in normal men, but is much more pronounced in males with secondary hypogonadism. The treatment of infertile men with FSH, however, does not result in an unequivocal inhibin B increase. There is a clear inverse relationship between serum inhibin B and FSH in the adult. Serum inhibin B levels are strongly positively correlated with testicular volume and sperm counts. In infertile patients, inhibin B decreases and FSH increases. In general, there is very good correlation with the degree of spermatogenetic damage, with the arrest at the earlier stages having the lowest inhibin B levels. However, for unknown reasons, there are cases of Sertoli-cell-only syndrome with normal inhibin B levels. Inhibin B and FSH together are a more sensitive and specific marker for spermatogenesis than either one alone. However, the inhibin B concentrations are not a reliable predictor of the presence of sperm in biopsy samples for testicular sperm extraction. Suppression of spermatogenesis with testosterone and gestagens leads to a partial reduction of inhibin B in serum but it is never completely suppressed. In contrast, testicular irradiation in monkeys or humans leads to a rapid and dramatic decrease of inhibin B, which becomes undetectable when germ cells are completely absent. In summary, although inhibin B is a valuable index of spermatogenesis, the measurement of serum inhibin B levels is still of limited clinical relevance for individual patients.

Aging↗
PubMed2001

Testosterone-induced inhibition of spermatogenesis is more closely related to suppression of FSH than to testicular androgen levels in the cynomolgus monkey model (Macaca fascicularis).

We have investigated the antigonadotropic and antispermatogenic effects of exposure to a long-acting testosterone ester in the cynomolgus monkey model. Groups of five adult animals were exposed either to vehicle or to 10 mg/kg or 20 mg/kg testosterone buciclate (TB) over a 26-week period with injections given in weeks 0, 11 and 18. In week 26, testicular biopsy tissue was collected. Serum testosterone levels were in the upper normal range with 10 mg/kg TB and were approximately twofold higher with 20 mg/kg TB. The estradiol pattern followed that of testosterone and body weights increased in a testosterone-dependent manner. TB completely abolished serum LH bioactivity. Serum concentrations of FSH and inhibin-alpha were suppressed in a TB dose-dependent manner. During weeks 4-8 after the first injection, a rebound of FSH and inhibin but not bioactive LH secretion occurred. This rebound was followed immediately by a restimulation of testis size and sperm numbers. After the next TB injections these parameters were once again suppressed. Nadir testis size was 30-40% of baseline and animals were severely oligozoospermic or transiently azoospermic. Consistent azoospermia was not achieved. Quantitation of serum inhibin B, proliferating cell-nuclear antigen staining and flow cytometric analysis of germ cell populations revealed pronounced suppression of spermatogenesis in both TB-treated groups whereas androgen receptor expression remained unchanged. Testicular androgens levels, determined in week 26, did not differ among all three groups and did not correlate with sperm numbers, histological and immunocytochemical findings. All suppressive effects were fully reversed during the recovery period. We have concluded that pronounced suppression of primate spermatogenesis seemingly requires inhibition of FSH rather than testicular androgen levels, at least in this preclinical non-human primate model. For the purpose of male contraception, FSH inhibition appears mandatory.

Analysis of Variance↗
PubMed2000

Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses.

Deletion of any of three regions of the human Y chromosome results in spermatogenic failure and infertility. We previously sequenced one of these regions, azoospermia factor a (AZFa) and found that it spanned approximately 800 kb. By sequence-tagged site (STS) content mapping, we roughly defined deletion breakpoints in two unrelated, azoospermic men with AZFa deletions. The positions of proximal and distal breakpoints were similar in the two men. Hypothesizing that the deletions might have been generated by homologous recombination, we searched electronically for DNA sequence similarities between the proximal and distal breakpoint regions. These comparisons revealed the most striking sequence similarities anywhere along or near the AZFa region. In the proximal breakpoint region, we identified a 10 kb provirus of the recently defined HERV15 class of endogenous retroviruses. In the distal breakpoint region, we found a second HERV15 provirus, 94% identical in DNA sequence to the first and in the same orientation. (A partial LINE insertion in this distal provirus proved to be the basis of the previously described DYS11/p12f polymorphism.) The AZFa deletions in the two men differed slightly, but all breakpoints fell within the HERV15 proviruses. Indeed, sequencing of deletion junctions from the two men revealed that homologous recombination had occurred within large domains of absolute sequence identity between the proximal and distal proviruses. When combined with published STS mapping data for other AZFa-deleted men, our findings suggest that recombination between these two HERV15 proviruses could account for most AZFa deletions.

Base Sequence↗
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↗
PubMed2000

Association of cyclophosphamide-induced male-mediated, foetal abnormalities with reduced paternal germ-cell apoptosis.

To investigate the mechanism by which malformed offspring can result from the exposure of males to mutagens, we treated adult male rats with 0, 1.4, 3.4 or 5.1 mg/kg cyclophosphamide, 6 days per week for 9 weeks, a treatment regimen known to induce heritable abnormalities. Testis samples from some of the animals were then collected for fixation in Carnoy's fluid and subsequent analysis of germ-cell apoptosis and proliferation. The remainder were mated, resulting in a greater than 11-fold increase in the proportion of abnormal offspring produced in the 5.1 mg/kg group. The number of apoptotic cells per stage XII/XIII tubular cross-section decreased with increasing dose, significantly so at 5.1 mg/kg (P<0.05). No statistically significant effect was found on spermatocyte numbers at this dose, indicating that a reduction in the amount of cells available to undergo apoptosis cannot explain the decrease. The inappropriate survival of damaged germ-cells caused by a lowering of the incidence of apoptosis may, therefore, account for the rise in the proportion of foetal malformations.

Analysis of Variance↗
PubMed2000

[Testosterone substitution in the aging man].

Hypogonadism is the main indication for testosterone substitution in the ageing male. The choice of the testosterone preparation should be based on the principle that serum levels of testosterone remain in the normal range and fast termination of therapy is possible. To date, transdermal testosterone systems appear to be best suited for substitution therapy in the ageing male. Future promising developments are testosterone gels and intramuscular testosterone undecanoate. Any testosterone therapy in the ageing male has to be monitored closely, especially regarding erythropoiesis and the prostate.

Adult↗
PubMed2000

Seminal plasma characteristics as indicators of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in men with obstructive azoospermia.

OBJECTIVE: To determine the prognostic value of seminal plasma volume, pH, fructose, and alpha-glucosidase for the detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. DESIGN: Retrospective data analysis. SETTING: University infertility clinic (referral center). PATIENT(S): Fifty-nine men with obstructive azoospermia. INTERVENTION(S): Semen analysis including seminal plasma volume, pH, fructose, alpha-glucosidase, molecular genetic diagnosis of CFTR mutations and FSH measurement. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of seminal plasma markers for the detection of CFTR mutations. RESULT(S): A CFTR mutation was detected in 26 of 59 patients with obstructive azoospermia. Patients carrying a mutation had significantly lower seminal plasma volume (mean +/- SEM: 1.5 +/- 1.4 mL vs. 2.8 +/- 2.2 mL), lower pH levels (25th percentile, median, 75th percentile: 6.5, 6.8, 7.5 vs. 7.7, 7. 9, 7.9) and lower fructose content (1.0, 1.1, 3.7 vs. 5.8, 20.0, 83. 0 micromol/ejaculate) than those without mutations. Diagnostic efficacy for detection of mutations was best (pH 81.4%, fructose 81. 8%) at a cutoff level for pH of 7.4 and fructose of 2 micromol/ejaculate. CONCLUSION(S): Seminal plasma markers provide an effective, noninvasive method to predict CFTR mutations in men with obstructive azoospermia.

Adolescent↗
PubMed2000

Prospective evaluation of the ultrasound appearance of the endometrium in a cohort of 1,186 infertile women.

OBJECTIVE: To investigate the effect of differences in endometrial thickness and pattern as visualized with present-day high-resolution transvaginal ultrasound equipment on the outcome of assisted reproductive treatment. DESIGN: Prospective cohort study. SETTING: Two large infertility units in university hospitals. PATIENT(S): The endometrial characteristics of 981 patients during 1,600 assisted reproductive treatment cycles were compared with those of 205 untreated women. In addition, abnormal echogenic patterns of the endometrium were characterized histologically in 44 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): The endometrium was significantly thinner in untreated women and women treated with IUI than in women treated with IVF or intracytoplasmic sperm injection. The exponential proliferation of the endometrium was similar in conception and nonconception cycles. The odds for a successful pregnancy were significantly lower in the presence of a thin endometrium in women treated with IUI but not in women treated with the long stimulation protocol for IVF or intracytoplasmic sperm injection. Singleton pregnancies were more common than multiple pregnancies in patients with thin endometria. CONCLUSION(S): The pregnancy rates of assisted reproductive procedures are influenced only marginally by the degree of endometrial proliferation, and treatment should not be canceled because of inadequate endometrial thickness.

Cell Division↗
PubMed2000

Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception.

OBJECTIVE: Approaches to hormonal male contraception are based on injectable testosterone esters alone or in combination with gestagens or GnRH analogs but the short half-life of clinically used testosterone esters have long hindered further development. This study was designed to prove the efficacy of the long-acting testosterone undecanoate ester (TU) alone or in combination with oral levonorgestrel (LNG) in a phase II clinical trial. DESIGN AND SUBJECTS: Twenty-eight healthy men were randomized to receive injections of 1000 mg TU every 6 weeks in combination with daily oral LNG (250 microg) or daily oral placebo treatment over a period of 24 weeks, followed by a control period of 28 weeks. MEASUREMENTS: During the course of the study semen analysis, reproductive hormone analysis, analysis of clinical chemistry and lipid parameters, well-being and sexual function, sonography of scrotal contents and prostate were performed. RESULTS: Marked suppression of gonadotrophins in both treatment groups resulted in azoospermia in 8/14 and 7/14 volunteers and severe oligozoospermia (< 3 x 1012/l) in 4/14 and 7/14 in the placebo and gestagen treated groups, respectively. Time to induction of azoospermia (mean +/- SEM) was not significantly different between the placebo (week 19.5 +/- 2.2) and LNG groups (week 15.4 +/- 2.2). During the whole treatment period mean testosterone serum concentrations remained within normal limits. Although not significant, it was evident that volunteers who became azoospermic had a better suppression of gonadotrophins and lower SHBG levels during treatment compared to non-azoospermic volunteers. Despite better gonadotrophin suppression in the LNG group no significant differences compared to placebo could be observed in the extent and kinetics of suppression of spermatogenesis, thus not demonstrating a major beneficial effect of LNG in the combination with injectable TU. Treatment led in both groups to a decrease of HDL and Lp(a) which was more pronounced in the LNG group (P > 0.05). CONCLUSION: Treatment with 1000 mg testosterone undecanoate injected at 6 weekly intervals or in combination with levonorgestrel showed suppression of spermatogenesis comparable to weekly injections of 200 mg testosterone enanthate. Because of its long half-life and in the absence of severe side-effects, testosterone undecanoate can be considered as first choice testosterone ester in further studies of hormonal male contraception.

Adolescent↗
PubMed2000

Potential of norethisterone enanthate for male contraception: pharmacokinetics and suppression of pituitary and gonadal function.

OBJECTIVE: Gestagens are known to suppress gonadotrophins in women and are currently also under investigation for the development of hormonal male contraceptives. The aim of the study was to assess the potential of norethisterone enanthate (NETE) for male contraception. DESIGN AND MEASUREMENTS: The suppressive effect of a single injection of 200 mg NETE on serum gonadotrophins, serum testosterone, lipids, spermatogenesis, well-being and sexual function was evaluated in seven healthy men. RESULTS: In this single dose study treatment was well tolerated by all volunteers. NETE led to a rapid, profound and significant suppression of serum LH (day 6 - day 10), FSH (day 2 - day 29), testosterone (day 1 - day 29 and day 35) and SHBG (day 6 - day 35). At study end sperm counts were significantly suppressed. Numbers of spontaneous erections (day 17, 23 and 26), number of sexual fantasies (day 20 and 23) as well as libido (day 20 and 26) were significantly decreased compared to baseline. All other parameters including lipids, augmented glucose, testicular volume and well-being showed no significant alterations. CONCLUSION: Because of its strong, rapid and sustained suppression of serum FSH and testosterone norethisterone enanthate offers great potential for hormonal male contraception if combined with testosterone esters.

Adult↗
PubMed2000

Dazl protein expression in adult rat testis is up-regulated at meiosis and not hormonally regulated.

The Y-chromosomal DAZ (deleted in azoospermia) gene and the autosomal Dazl (deleted in azoospermia-like) gene are two crucial factors for the achievement and maintenance of spermatogenesis. Whereas Y-chromosomal DAZ is present in certain primates, it is lacking in rodents and other species. We have investigated the expression of Dazl protein during spermatogenesis in the adult rat testis using immunohistochemistry. Dazl immunoreactivity was found predominantly in the cytosol of primary pachytene spermatocytes. A weaker but clearly detectable signal was present in intermediate and B spermatogonia and in early spermatocytes from preleptotene to zygotene. The highest expression patterns were observed between stages IV and VIII during the spermatogenic cycle when spermatocytes prepare for the first meiotic division. Specific staining could also be observed in step 11-19 elongating spermatids in the acrosome region. Treatment for 42 days with a potent GnRH-antagonist abolished gonadotrophin secretion and led to a regressed testis, lacking most of the advanced germ cell types such as spermatids but still bearing spermatogonia and spermatocytes. No difference in staining pattern for Dazl protein was observed in GnRH antagonist-treated rats despite the lack of gonadotrophins and substantial impairment of the spermatogenic process, indicating that Dazl expression is clearly hormone-independent. The localization and level of Dazl expression suggests an important role in the regulation of the first meiotic stages of spermatogenesis. The hormone independent onset of expression points to an autonomous cell-cycle event in which Dazl seems to be essential for the entry into meiosis. The presence of Dazl in the acrosome region of elongating spermatids might reflect an unknown role of Dazl as a morphogenetic factor during spermiogenesis.

Animals↗
PubMed2000

Sperm number and condition affect the number of basal cells and their expression of macrophage antigen in the murine epididymis.

Unilateral ligation of the mid-corpus epididymis, the proximal vas deferens and imposition of an abdominal temperature for 6 days as well as bilateral castration for 3, 6 or 14 days, resulted in a change in epithelial composition of the adult murine epididymis with regard to the number and antigen expression of basal cells. There were fewer basal cells per tubule cross-section with fewer expressing F4/80 antigen when spermatozoa were absent from the proximal lumen following short-term castration. Conversely, more basal cells with more of them demonstrating macrophage antigen expression were evident when more or damaged spermatozoa were in the proximal lumen after corpus ligation and exposure to abdominal temperature or in the cauda after long-term withdrawal of androgen support. By contrast, ligation of the vas deferens did not lead to tubule distension, and hence sperm accumulation, and did not alter the basal cell population in the cauda epididymis. The data suggest that epididymal basal cells respond in number and macrophage antigen expression to the presence of sperm autoantigens in the lumen with little dependence on circulating androgens. These changes may represent responses to minimise the interaction of sperm autoantigens with the immune system and the risk of immunological infertility.

Animals↗
PubMed2000

Prediction of ovulation by urinary hormone measurements with the home use ClearPlan Fertility Monitor: comparison with transvaginal ultrasound scans and serum hormone measurements.

The timing of sexual intercourse in relation to ovulation strongly influences the chance of conception. Daily serum LH measurements or transvaginal ultrasonography are not practical to determine ovulation in consecutive cycles for an individual. A prospective study was initiated to test the home use performance of the ClearPlan Fertility Monitor (CPFM) in ovulation prediction compared with transvaginal ultrasonography and serum hormone measurements. A total of 53 women aged 18-39 years with a normal uterus and at least one ovary, cycle length between 21-42 days and not using medication which interferes with ovarian function contributed 150 cycles for analysis. One cycle was anovulatory and no LH surge, indicating peak fertility, was detected by the monitor. Of the remaining 149 cycles, 135 (90.6%) had a monitor LH surge and ultrasonographically confirmed ovulation. Ovulation was detected in 91.1% of cycles during the 2 days of CPFM peak fertility. Ovulation was observed in 51.1% of cycles 1 day and in 43.2% of cycles 2 days after the surge in serum LH. Ovulation never occurred before CPFM peak fertility or the serum LH surge day. CPFM can help women who desire pregnancy to time intercourse. It may also have potential as a diagnostic aid and for monitoring the treatment of infertility.

Adolescent↗
PubMed2000

Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is an effective treatment modality for male factor infertility, but it could promote the transgenerational transmission of genetic defects causing gametogenic failure. Cytogenetic and molecular techniques permit the diagnosis of some infertility-causing genetic aberrations, but many more probably evade detection with currently available technology. The analysis of the recurrence pattern of infertility in infertile couples' families could define the importance of heritable factors in the pathogenesis of human infertility. We have subjected 621 consecutive infertile couples treated with ICSI in a single institution to a comprehensive genetic workup including documentation of the family history, karyotyping and various DNA tests. In all, 1302 fertile couples served as controls. Of the infertile couples 6.4% were shown to have a fertility problem with a definite genetic basis. Male, but not female fertility problems displayed a distinct pattern of familial aggregation. In addition, the infertile couples had fewer siblings than the fertile controls, a finding compatible with suboptimal fertility already among the infertile couples' parents. In summary, our data indicate that male factor infertility should be considered a potentially heritable condition. The recurrence risk for infertility in the offspring of couples treated with ICSI might be substantial.

Adult↗
PubMed2000

Non-reproductive heritable disorders in infertile couples and their first degree relatives.

The genetic safety of intracytoplasmic sperm injection (ICSI) remains a matter of continuing debate. One source of concern is the limited knowledge about the general genetic constitution and background of patients who need sophisticated reproductive technology to procreate. It has been postulated that such individuals could be carriers of genetic lesions that might result in an increased prevalence of heritable disorders among their offspring. To investigate this issue, we determined the frequency of potentially heritable non-reproductive diseases in 621 infertile couples and their first degree relatives. A total of 1302 fertile couples who underwent genetic counselling prior to prenatal diagnosis served as controls. The infertile patients had a slightly higher prevalence of potentially heritable non-reproductive disorders ('significant genetic risk factors') than the controls (1. 9 versus 0.9%; P = 0.015). In contrast, such diseases were less prevalent in their families than in the fertile couples' families. Our data do not support the hypothesis that their familial genetic background predisposes children born after ICSI to malformations or other non-reproductive genetic diseases.

Adult↗