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Biomedical subjects

H M Behre

Publications and source records attributed to H M Behre.

106 records · Page 6Linked to original sources
PubMed1991

Evaluation of a peripherally selective antiandrogen (Casodex) as a tool for studying the relationship between testosterone and spermatogenesis in the rat.

The endocrine profile and the effects on spermatogenesis of the new antiandrogen, Casodex [2RS)-4-cyano-3-(4-fluorophenylsulphonyl)-2-anilide, CAS) were evaluated in the adult rat. In the first experiment rats were administered CAS at daily doses of 10, 20 and 40 mg/kg for 14 days. For comparison groups receiving flutamide (FL, 10 mg/kg) and ethane dimethane sulphonate (EDS) were included. Unlike FL, administration of CAS (10 and 20 mg/kg) did not significantly raise serum concentrations of gonadotropic hormones and testosterone. With 40 mg/kg CAS gonadotropin secretion, but not testosterone levels, were elevated on day 15. Administration of CAS lowered the weight of the seminal vesicles and coagulating glands comparable to the administration of the Leydig cell toxin EDS. In contrast to FL a significant loss of germ cells in stage VII of spermatogenesis was observed with CAS. In a second experiment the ability of FL and CAS to block testicular androgen action was compared in rats with reduced testicular androgen production induced by a gonadotropin-releasing hormone antagonist. Both antiandrogens markedly enhanced spermatogenic involution as revealed by quantitative flow cytometric analysis of germ cell numbers. The study demonstrates that (a) CAS is a peripherally selective antiandrogen and (b) CAS might provide a feasible approach to study androgen dependence of spermatogenesis in the presence of normal FSH levels.

Androgen Antagonists↗
PubMed1991

Human follicle-stimulating hormone exerts a stimulatory effect on spermatogenesis, testicular size, and serum inhibin levels in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis).

The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal-Lys; [N-acetyl-D-2-naphthyl-Ala1,D-4-chloro-Phe2,D-pyridyl-Ala3, nicotinyl-Lys5,D-nicotinyl-Lys6,isopropyl-Lys8,D-Ala10 ]-GnRH) was used at a daily dose of 450 micrograms/kg to suppress endogeneous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 x 15 IU/day.animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of orchidectomized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrasts, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A-pale spermatogonia and spermatocytes 2- to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), 1C (round spermatids), and 1CC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of 1CC cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Comparative effects of chronic administration of the non-steroidal antiandrogens flutamide and Casodex on the reproductive system of the adult male rat.

The effects of chronic blockade of androgen action by the antiandrogens flutamide and Casodex on serum and pituitary concentrations of LH and FSH, serum and testicular androgen levels, reproductive organ weights, and on spermatogenesis were compared in the adult rat. Animals were treated for 3 and 8 weeks with vehicle, Casodex (20 mg.kg-1.(day)-1, flutamide (20 mg.kg-1.(day)-1) and GnRH antagonist (150 micrograms/day, Detirelix). Treatment with GnRH antagonist suppressed gonadotropin and testosterone production, reduced the weights of testes, epididymides and seminal vesicles, and inhibited germ cell development. Flutamide administration markedly elevated serum and pituitary levels of gonadotropins as well as serum and testicular androgen concentrations. Casodex-induced elevation of gonadotropin concentrations was less pronounced and serum and testicular levels of androgens did not change significantly. The reduction of seminal vesicle weights was similar after Casodex and GnRH antagonist treatment, whereas flutamide was less effective. Testicular weight and spermatogenesis (assessed by light microscopical and flow-cytometric analysis) remained unaffected by Casodex and flutamide. It is concluded, that 1. Casodex, in contrast to flutamide, is a peripherally selective antiandrogen, and 2. Casodex influences release of gonadotropins into circulation less than flutamide. Therefore this antiandrogen might be useful clinically for selectively blocking androgen actions in the accessory sex glands.

Androgen Antagonists↗
PubMed1990

Computerized semen analysis with sperm tail detection.

We evaluated a recently developed computerized semen analyser that detects spermatozoa not only by the criteria of size, contrast and movement but also by the morphological characteristics of the sperm tail. Comparison of the sperm concentration in 33 semen samples measured by conventional and by computerized semen analysis, as well as by flow cytometry, showed acceptable agreement between all three methods, although the mean differences and standard deviations were less for conventional than for computerized analysis when compared to flow cytometry as a reference method. Motility estimates were lower by the computer system for values between 1 and 40%. Higher motilities showed no systematic error. In conclusion, the improved algorithms for sperm detection yield more reliable data for sperm concentration and motility than previous systems of computerized semen analysis.

Flow Cytometry↗
PubMed1990

Bio and immuno-activity of FSH in serum after intramuscular injection of highly purified urinary human FSH in normal men.

The pharmacokinetics of a human FSH preparation widely used in clinical practice was evaluated in healthy male volunteers whose endogenous FSH was suppressed by 19-nortestosterone injections. 9.7 h following intramuscular injection of 150 IU FSH the mean immunoreactive peak concentration over baseline was 3.8 IU/1. Injection of 450 IU FSH led to a mean immunoreactive peak level of 10.4 IU/1 at 9.8 h. Mean half-life was 24.6 h (150 IU FSH) and 32.6 h (450 IU FSH). Serum bioFSH concentrations were suppressed below the detection limit after injection of the 19-nortestosterone and rose to preinjection levels after administration of FSH. Mean bioactive peak level for the 450 IU FSH was 7.3 IU/1 FSH at 7.4 h. The half-life of bioFSH was calculated to be 13.4 h and is considerably shorter than the half-life of immunoFSH. Serum inhibin levels were suppressed by 19-nortestosterone and did not change significantly after injection of the FSH preparation, suggesting that the FSH dose was insufficient to elicit this biological response. It is concluded that the currently used dose regimen for the treatment of male hypogonadism is inadequate for maintenance of serum bioFSH levels in the normal range.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates.

The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone-enanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosterone-enanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290 +/- 340 (dihydrotestosterone-enanthate) vs 2920 +/- 485 (testosterone-enanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half-life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys.

Androgens↗
PubMed1990

External quality control in the andrology laboratory: an experimental multicenter trial.

An external quality control study for semen analysis was performed involving 10 andrology laboratories in geographically separate locations. For the evaluation of sperm concentration, eight samples with different concentrations, and for the assessment of sperm morphology three slides prepared from different semen samples were distributed. Sperm motility was evaluated in five samples delivered cryopreserved to the participants. The coefficients of variation (CVs) for sperm counts varied with the sperm concentrations showing highest variability for low and lowest for high concentrations (range 23% to 73%). The CV for sperm morphology ranged from 25% for normal heads to 87% for abnormal midpieces. The CV for motility of sperm was 21%. For comparison the mean CVs for internal quality control were as follows: 10% for concentration, 8% for morphology (normal heads), and 8% for motility.

Clinical Laboratory Techniques↗
PubMed1989

Objective measurement of testicular volume by ultrasonography: evaluation of the technique and comparison with orchidometer estimates.

Ultrasonography of the scrotum is a valid and safe method for differentiating testicular and extratesticular disease. In the present study the accuracy and reproducibility of ultrasonographic estimation of testicular volume was evaluated. A high correlation (r = 0.992) between actual testicular volume (measured by weighing and water displacement) and the volume determined by ultrasonography was found on examination of 14 tests from patients at autopsy without any systematic under- or over-estimation. The ultrasound method proved to be highly reproducible with a coefficient of variation of 7.0 +/- 0.7%. Using different ultrasound scanners did not significantly influence the results obtained. The comparison of Prader orchidometer measurements, performed by four different clinical investigators, and ultrasonography in 256 patients revealed a significant correlation of 0.91, but the degree of correlation was dependent on the investigator's clinical experience. Volume estimates by comparative palpation appear to be valuable in most clinical settings. Ultrasonography provides an excellent tool for determining testicular volume when objective, accurate and reproducible measurements of testicular volume are required.

Evaluation Studies as Topic↗
PubMedDate not supplied

Lack of correlation between cadmium in seminal plasma and fertility status of nonexposed individuals and two cadmium-exposed patients.

Cadmium concentrations were determined in semen samples of 12 men with proven fertility (group I) and 44 normozoospermic patients (group II) as well as 118 unselected patients of an infertility clinic (group III) and 2 industrial workers with occupational exposure to cadmium. Mean cadmium concentrations in seminal plasma for groups I, II, and III did not show significant differences: 0.38 +/- 0.64; 0.43 +/- 0.69; 0.44 +/- 0.73 (mean +/- SD, micrograms/L), but the two cadmium-exposed patients revealed exceptionally high cadmium levels: 3.46 micrograms/L and 2.99 micrograms/L, respectively. There was no significant correlation between seminal cadmium concentrations and conventional semen parameters or between cadmium concentration and the fertility status of the patients. However, mean cadmium concentrations in seminal plasma of normozoospermic patients were higher in the group of smokers (0.55 +/- 0.81 micrograms/L), compared with the group of nonsmokers (0.42 +/- 0.67 micrograms/L), and there was a weak correlation between cadmium concentration and number of cigarettes consumed per day.

Adult↗
PubMedDate not supplied

Diagnostic value of scrotal sonography in infertile men: report on 658 cases.

Scrotal sonography with a 7.5 MHz sector scanner was performed on 658 consecutive patients of our infertility clinic. The incidence of pathological findings was unexpectedly high. Forty per cent of the patients revealed pathological structures such as varicoceles (21%), hydroceles (7%), epididymal abnormalities (6%), spermatoceles (6%), intratesticular hyper- and hypoechoic changes (4.5%), intratesticular cysts (1%) and tumours or carcinoma in situ (CIS) (0.6%). Sonographic evaluation and measurement of the caput epididymidis was compared with palpation. Sonography distinguished size ranges of "normal" and "thickened" epididymides as diagnosed by palpation. Cystic structures were proven in 56% of cases with "thickened" epididymides. The sonographically determined diameters of doppler-negative blood vessels were significantly smaller than those of doppler-positive vessels. Sonography revealed a higher occurrence of varicoceles than diagnosed by palpation (76% by palpation). Only 58% of sonographically identified hydroceles and only 67% of sonographically detected spermatoceles were detected by palpation. One testicular tumour and one case with CIS were only seen by sonography and not suspected on palpation. The results demonstrate that sonography represents a valuable tool in the routine diagnosis of andrological patients.

Adult↗
PubMedDate not supplied

Surgical ligation vs. angiographic embolization of the vena spermatica: a prospective randomized study for the treatment of varicocele-related infertility.

Varicoceles as a common cause of male infertility are treated either by surgical ligation or, more recently, by angiographic occlusion of the spermatic vein. In the present prospective randomized study 38 patients were treated by surgical ligation and 33 by angiographic embolization. During the 12-month follow-up period a significant increase in sperm number (at 3 and 12 months) and sperm motility (at 12 months) occurred in both groups while sperm morphology remained unaffected. Altogether, 22 pregnancies (31%) were reported within the year following treatment, of which 11/38 (29%) occurred in the ligation group and 11/33 (33%) in the embolization group. Thus both treatment modalities appear equivalent, whereby embolization has the advantage that it can be performed on an outpatient basis.

Adult↗
PubMedDate not supplied

Endocrine and spermatological characteristics of 135 patients with bilateral megalotestis.

Little is known about the biological and clinical significance of bilaterally enlarged testes (bilateral megalotestes or macroorchidism). We have investigated clinical, endocrine and spermatological characteristics of 135 andrological patients with a testicular volume of more than 25 ml bilaterally. 135 patients with normal testicular volumes served as controls. Subjects with bilateral megalotestis had higher sperm counts and better sperm morphology and motility than the controls. Levels of LH, FSH, prolactin, testosterone and estradiol were lower in the megalotestis group. This was statistically significant for LH and FSH. No testicular tumours were diagnosed in either group. We conclude that in most andrological patients with bilateral megalotestes fertility parameters are excellent despite the unusually low hormone levels found in a significant minority. No specific pathology underlying the large gonadal volume could be identified.

Adult↗