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Biomedical subjects

H M Behre

Publications and source records attributed to H M Behre.

At least 73 records · Page 4Linked to original sources
PubMed1997

Long-term effect of testosterone therapy on bone mineral density in hypogonadal men.

In both men and women, a decrease in bone mineral density (BMD) is a major symptom of hypogonadism. Although the effects of estrogens on osteoporosis in women are well documented, comparatively little is known about the effects of long term testosterone substitution on BMD in hypogonadal men. Therefore, we studied BMD in 72 hypogonadal patients (37 men with primary and 35 men with secondary hypogonadism) under testosterone substitution therapy that continued for up to 16 yr. Thirty-two of these men were also seen before initiation of therapy. At annual intervals, trabecular BMD of the lumbar spine was measured by quantitative computed tomography, a true volumetric and reproducible method for long term serial BMD measurements. Serum levels of testosterone increased to the normal range in all androgen-treated hypogonadal men. The most significant increase in BMD was seen during the first year of testosterone treatment in previously untreated patients, when BMD increased from 95.2 +/- 5.9 to 120.0 +/- 6.1 mg/cm3 hydroxyapatite (mean +/- SE). Long term testosterone treatment maintained BMD in the age-dependent reference range in all 72 hypogonadal men, independent of the type of hypogonadism. Transdermal testosterone patches applied to the scrotum were as effective in normalizing BMD as im testosterone enanthate injections. In summary, testosterone therapy increases BMD in hypogonadal men regardless of age. The greatest increase is seen during the first year of treatment in previously untreated patients with low initial BMD. In hypogonadal men, BMD can be normalized and maintained in the normal range by continuous, long term testosterone substitution.

Administration, Cutaneous↗
PubMed1997

The cynomolgus monkey prostate under physiological and hypogonadal conditions: an ultrasonographic study.

PURPOSE: Although the prostate of the cynomolgus monkey has been shown to be a particularly suitable model for the human, in vivo data on this organ are hardly available. We therefore applied transrectal ultrasonography to the investigation of the physiology and pathophysiology of monkey prostate under normogonadotropic and hypogonadal conditions in vivo. MATERIALS AND METHODS: Five intact and 7 long-term castrated monkeys were analysed repeatedly for assessment of the feasibility and variability of the method. In addition, cross-sectional evaluation was performed on 30 intact monkeys of various ages and on 7 long-term castrated monkeys. Finally, the vehicle (n = 5) controlled effects of androgen deprivation treatment with the GnRH antagonist cetrorelix (n = 4) for 25 days followed by semicastration at day 16 and full castration on day 25 were examined and prostate size was followed thereafter. RESULTS: The monkey prostate shows an ellipsoid shape and ultrasonic appearance similar to the human prostate. Variability in 5 intact monkeys (mean +/- SE = 4.67 +/- 0.55 ml.) and 7 long-term castrated monkeys (0.88 +/- 0.08 ml.) was 8.5% and 5.6% respectively. In intact animals a linear correlation between age and prostate size/animal surface area was found (p = 0.0001). Prostate size in castrated animals was reduced (p < 0.001) compared to intact animals. In the experimental study, GnRH antagonist led to a significant reduction of prostate volume and testosterone levels compared to the vehicle group, while semicastration had no influence. Following removal of the second testis a further decrease of prostate volume was seen (p < 0.0001). When compared, castration and GnRH antagonist treatment induced a similar decrease of prostate volume over time. CONCLUSION: Transrectal ultrasonography provides a feasible and reproducible approach for determination of prostate size in cynomolgus monkeys. Castration and GnRH antagonist treatment are equally effective in reducing prostate size.

Animals↗
PubMed1996

Functional and clinical consequences of mutations in the FSH receptor.

The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In females FSH is required for ovarian development and follicle maturation whereas in males FSH determines Sertoli cell number and quantitatively and qualitatively normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor expressed solely in granulosa and Sertoli cells. The FSH-receptor (FSHR) gene is localized on chromosome 2 p21 and spans a region of 54 kb. It consists of ten exons; exon one to nine encode the large extracellular domain and the transmembrane domain is comprised of exon ten. Mutations in the FSHR gene could severely affect gametogenesis and result in infertility. Therefore screening programs have been initiated, in which patients with disturbed fertility were searched for mutations in the FSHR gene. Several Finnish families were identified displaying an inherited pattern of ovarian dysgenesis, a disease leading to streaky underdeveloped ovaries and primary amenorrhea. By genetic linkage the locus of the genetic defect was confined to chromosome 2 p21. Analysis of the FSHR gene resulted in the identification of a mutation (Ala189Val) homozygous in all affected females. Functional studies revealed that the mutation affects the proper protein folding and thereby inactivates the receptor. In a male patient hypophysectomized because of a pituitary tumor, who despite undetectable serum gonadotropins had normal semen parameters, we hypothesized an activating mutation of the FSHR. Screening of exon ten of the FSHR gene resulted in the identification of a Asp567Gly transition in the third intracytoplasmatic loop. Functional studies resulted in a 1.5-fold increase in basal cAMP production compared to wild type FSHR, indicating that the heterozygous mutation leads to a ligand-independent constitutive activation of the FSHR. This patient provides an exceptional model of nature defining the role of FSH in human spermatogenesis. Mutations of the FSHR might have differential effects in each gender. For example activating mutations have not been described in women, therefore it is not clear whether the constitutive activity of the receptor could disturb normal follicular development resulting in certain infertility.

Amino Acid Sequence↗
PubMed1996

Cryopreservation of semen from adolescent patients with malignancies.

In adult oncological patients semen cryopreservation offers the possibility of preserving fertility prior to aggressive therapy that may lead to infertility. The cryopreserved semen can later be used to induce pregnancies in the partner by techniques of assisted fertilization. In adolescent boys the question of fertility is often beyond consideration when the young patient's life is threatened acutely. However, improved survival rates increasingly prompt the question of quality of life after therapy, including fertility. Semen quality is known to be impaired in patients with malignancies and may be further impaired by the process of cryopreservation. Since normal values for semen in adolescents are not known and spermatogenesis may be impaired by the malignant disease, it was unclear whether semen samples from adolescents with malignancies warrant cryopreservation at all. In order to demonstrate the feasibility of semen cryopreservation in adolescent males, we compared the results from 12 pubertal boys aged 14-17 years with those from 17 young adults aged 18-20 years who had similar malignancies and, additionally, to 210 adults with malignancies (> 20 years). Luteinizing hormone serum values were significantly lower in adolescents than in adult patients. Follicle stimulating hormone showed a significant increase with age. Testosterone serum levels and testicular volumes showed similar distribution patterns in adolescent and adult men. Sperm concentrations, sperm motility, and normal sperm morphology in the adolescent patients did not show significant differences compared with adults. Thus cryopreservation of semen should be considered as an option to young male patients whose cancer therapy will include potentially gonadotoxic treatment.

Adolescent↗
PubMed1996

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11.

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.

Chromosome Mapping↗
PubMed1996

The role of phosphocreatine kinase in the motility of human spermatozoa supported by different metabolic substrates.

In the spermatozoa of some species creatine kinase (CK: E.C. 2.7.3.2) is involved in shuttling energy, in the form of creatine phosphate, between the mid-piece mitochondria and flagellum. In this study, the effects of the CK inhibitor dinitrofluorobenzene (DNFB) on human sperm CK activity, motility and ATP concentrations were assessed with different energy substrates. There was a dose-dependent inhibition of CK activity by DNFB but inhibition was incomplete and there was no effect on the percentage of flagellating cells, irrespective of substrate. However, when lactate alone supported the cells DNFB decreased velocities and increased amplitude of head displacement (fewer progressively motile forms were observed), whereas ATP concentrations in spermatozoa were unaltered. Demembranated sperm models could be reactivated by ADP plus creatine phosphate, but not to the extent caused by ATP, and were able to be inhibited by myokinase inhibitors. Increased velocities, linearity (LIN) and beat cross frequency (BCF) were demonstrated for spermatozoa incubated with lactate, in contrast to glucose as sole energy source, and higher velocities and BCF were generated in the presence of both substrates. This suggests that the production of ATP by glycolysis and respiration are independent and complementary. CK is not obligatory for sperm motility but supplements energy provision under certain conditions.

Adenosine Triphosphate↗
PubMed1996

Reproductive parameters of older compared to younger men of infertile couples.

In order to evaluate possible age-dependent influences on male infertility, semen parameters, sex hormone levels and pregnancy rates were compared retrospectively in three groups of men attending our fertility clinic: group A: 39 patients > 50 years. Group B (39 patients < 30 years) was established as the 'standard infertile patient' seen in our Institute. These patients were matched with patients of group A according to the year of their first visit to the clinic. Group C: 39 young patients (< 30 years) who were selected on the basis of their wives' advanced age. The frequency of sexual intercourse in group A was significantly lower compared to group C. The period of sexual abstinence was longer in group A than in group B. Ejaculate volume and sperm motility in group A were lower compared to groups B and C. The differences in other semen parameters were only minor. The differences in serum levels of testosterone and FSH were significant between group A and groups B and C. Pregnancies were reported in 6 of 26 couples from group A (duration of infertility: mean 79 months, range 16-187), in 17 of 28 couples from group B (duration of infertility; mean 54 months, range 16-104) and in nine of 30 couples from group C (duration of infertility; mean 66 months, range 25-125). Since the infertility pattern of the older patients desiring offspring was not significantly different from that of younger patients, it is concluded that the age of the female partner, rather than the age of the husband, is most important in determining the fertility chances of couples presenting with infertility.

Adult↗
PubMed1996

Long-term effects on testicular function of high-dose testosterone treatment for excessively tall stature.

High-dose testosterone treatment is applied during puberty to reduce the predicted adult height in excessively tall boys. To date it has remained unclear whether this therapy produces any long-term effects on reproductive functions of the patients. To clarify this question, we performed a follow-up study in 47 tall men, determining seminal and hormonal parameters 10.6 +/- 2.5 years (mean +/- SD) after cessation of therapy. The tall men treated were compared with 123 normal men attending the Institute of Reproductive Medicine as volunteers for various clinical studies. Clinical examination revealed a significantly higher prevalence of varicoceles and history of maldescended testes in the testosterone-treated tall men compared with the controls. Semen analysis revealed significantly lower progressive motility in the tall men compared with the normal men (49.2 +/- 13.4 vs. 54.3 +/- 12.8%). A nonsignificant tendency towards lower sperm concentration (43.8 +/- 35.4 vs. 57.8 +/- 45.6 mL/mL), lower total sperm count (184.4 +/- 158.0 vs. 225.4 +/- 277.5 mL/ejaculate), and reduced normal sperm morphology (27.6 +/- 12.5 vs. 30.9 +/- 13.1%) was evident in the testosterone-treated tall men. Although there was no difference in testicular volume and FSH between the groups, testosterone was lower in the testosterone-treated tall men (19.9 +/- 7.4 vs. 23.9 +/- 7.0 nmol/L). Statistical analysis of the subgroups of testosterone-treated tall men and control men without varicocele and cryptorchidism revealed no differences in any ejaculate parameter. The small difference in semen variables may be explained by a higher prevalence of varicocele and maldescended testes in the testosterone-treated tall men.

Adult↗
PubMed1996

Effects of gonadotropin-releasing hormone on bioactivity of follicle-stimulating hormone (FSH) and microstructure of FSH, luteinizing hormone and sex hormone-binding globulin in a testosterone-based contraceptive trial: evaluation of responders and non-responders.

Only a proportion of normal men participating in testosterone-based contraceptive trials develop azoospermia (responders). This study analyzed whether serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) are qualitatively different between responders and non-responders. Determination of in vitro bioactive FSH after stimulation with gonadotropin-releasing hormone (GnRH) and analysis of molecular heterogeneity of serum FSH, LH and SHBG was carried out by chromatofocusing and concanavalin-A affinity chromatography in eight men who had participated in a previous contraceptive study with testosterone buciclate. Blood was withdrawn at 15-min intervals on two basal occasions and 30, 45 and 60 min after i.v. administration of GnRH (100 micrograms). Pools of sera were separated by chromatofocusing in the pH range 3-6 and by lectin chromatography on concanavalin A. Immunoreactive FSH, LH and SHBG were assayed in the eluates. Bioactive FSH was analyzed by the rat Sertoli cell bioassay. Serum bioactive FSH increased after GnRH stimulation, without significant differences between responders and non-responders. The chromatofocusing profiles of serum FSH showed a significant shift towards the less acidic region after GnRH. The isoform distribution was similar in responders and non-responders. No significant differences were found in the relative proportion of FSH, LH and SHBG retained by concanavalin A. It is concluded that the extent of suppression of sperm production by androgen administration cannot be foreseen either on the basis of the response of bioactive FSH to GnRH administration or from the glycosylation pattern of serum FSH, LH and SHBG.

Adult↗
PubMed1995

Recombinant human follicle-stimulating hormone and human chorionic gonadotropin for induction of spermatogenesis in a hypogonadotropic male.

OBJECTIVE: To determine the efficacy of recombinant FSH administration to induce spermatogenesis. DESIGN: Case report, clinical study. SETTING: Tertiary center for reproductive medicine of the university. PATIENT: A 44-year-old hypogonadal man with postpubertal pituitary insufficiency due to surgical removal of a prolactinoma. INTERVENTIONS: Recombinant FSH (150 IU three times weekly) was administered together with hCG (1,500 IU twice weekly). Control examinations were performed every 6 weeks, including hormone determinations, safety parameters, testicular volume measurements, and semen analysis. MAIN OUTCOME MEASURE: Semen parameters. RESULTS: After 18 weeks of treatment, first sperm were seen in the ejaculate and reached normal sperm concentrations after 24 weeks of treatment. Serum hormone levels were in the normal range and testicular volume increased. No adverse side effects were observed. CONCLUSIONS: Recombinant human FSH in combination with hCG can be used successfully for stimulation of testicular function in gonadotropin-deficient men.

Adult↗
PubMed1995

Treatment of varicocele: counselling as effective as occlusion of the vena spermatica.

Occlusion of the spermatic vein by surgical or angiographic techniques is generally accepted as the treatment of choice in infertile patients with varicocele. We have recently demonstrated that surgical ligation and radiological embolization are equally effective in terms of pregnancies following treatment. Since, however, it remains unclear whether any treatment is more effective than no treatment, we initiated a controlled, randomized prospective study to address this question. Infertile patients with varicocele were investigated twice using Doppler sonography, ultrasonography of the scrotal contents, semen analysis according to World Health Organization guidelines and serum follicle stimulating hormone, luteinizing hormone and testosterone measurements. Other causes of male infertility were excluded. The patients' wives were free of obvious causes of infertility such as anovulation or tubal blockage. Subjects fulfilling the admission criteria were randomly allocated to groups receiving ligation, embolization or no treatment. Thereafter, all patients were investigated and counselled every 3 months for a period of 1 year. In all, 47 couples in the treatment group (23 ligations and 24 embolizations) and 48 in the non-treatment group concluded the study. When entering the study, there were no significant differences in semen analysis and hormonal parameters between the two groups, nor between the subgroups undergoing treatment. While no significant changes in semen parameters occurred in the non-treatment group, the sperm concentration increased significantly (P = 0.008) in the treated patients from 16.5 +/- 2.5 x 10(6)/ml (mean +/- SE) before to 25.1 +/- 4.1 x 10(6)/ml at the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders.

Suppression of serum LH and FSH, by testosterone (T) alone or in combination with other agents, has proved to be the most promising approach to male contraception. T enanthate, the only androgen preparation tested in male contraceptive efficacy trials so far, must be injected every week due to its short terminal elimination half-life of 4.5 days and leads to supraphysiological T serum levels. A new T ester synthesized under WHO and NIH auspices, testosterone buciclate (TB), showed a favorable pharmacokinetic profile, with a terminal half-life of 29.5 days when tested in hypogonadal men. Here we describe the results of the first clinical trial with TB for male contraception. After two control examinations, normal healthy male volunteers were given a single im injection of 600 mg TB (group I; n = 4) and 1200 mg TB (group II; n = 8) on day 0. Follow-up examinations were performed every 2 weeks up to week 32. In both groups mean serum T levels remained in the normal physiological range throughout the study course. Serum levels of dihydrotestosterone (DHT) showed a dose- and time-dependent increase, with serum levels slightly above the normal range in group II for several weeks and a maximal concentration of 3.8 +/- 0.5 nmol/L (mean +/- SE) in week 6. No suppression of spermatogenesis to oligozoospermia was observed in group I. However, in group II, spermatogenesis was suppressed to azoospermia in three of eight volunteers in week 10 that persisted up to weeks 14, 20, and 22, respectively. In these three men, LH and FSH were suppressed by TB injections to the respective assay detection limits, whereas in the other five subjects, mean serum levels were only decreased to values near the lower normal limit for LH and FSH, respectively. In addition, throughout the study course, a significant difference in serum sex hormone-binding globulin was detected between the responders (mean values, 21.2-26.4 nmol/L) and nonresponders (mean values, 36.2-46.3 nmol/L). Serum levels of LH as well as total and free T at baseline and after TB injection were lower in the responders than in the nonresponders. Both subgroups showed similar increases in serum LH and FSH after GnRH stimulation. In a newly introduced GnRH antagonist suppression test, serum LH and T were decreased to significantly lower levels in the responders. These results indicate a different hormonal equilibrium and probably different susceptibility to feedback regulation of the responders compared to the nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1995

Endocrine control of testicular somatic and premeiotic germ cell development in the immature testis of the primate Macaca mulatta.

Four groups(N = 3 per group) of juvenile rhesus monkeys (Macaca mulatta, 14-20 months old) received either vehicle or highly purified human follicle-stimulating hormone (FSH; 10 IU kg-1 day-1), human chorionic gonadotropin (hCG; 250 IU every alternate day) or both hormones for a period of 4 weeks. Testicular volume and weight increased more than twofold after single and more than sixfold after combined hormone treatment. Serum and intratesticular testosterone were at supraphysiological levels in hCG-treated animals and rose even more after combined treatment; a minor elevation of intratesticular testosterone was also observed after FSH treatment. Serum inhibin was elevated after hCG or FSH treatment and increased more than twofold during the first 3 weeks of combined treatment. Semiquantitative analysis of cell numbers showed a statistically non-significant increase in Sertoli cells and Ad- and Ap-spermatogonia after single hormone treatment. Combined treatment induced a further increase in the number of spermatogonia. Leydig cells were only encountered after hCG treatment; their number was more than threefold higher after combined treatment compared with hCG alone. Follicle-stimulating hormone stimulated Sertoli cell and Ap spermatogonia proliferation but did not induce morphological differentiation of Sertoli cells, peritubular cells or Leydig cells. Human CG treatment, however, induced Sertoli cell proliferation and morphological differentiation. It had effects on spermatogonial proliferation but induced differentiation of peritubular cells. Combined treatment initiated the greatest morphological and functional differentiation of Sertoli cells, peritubular cells, Leydig cells and spermatogonia. Flow cytometric analysis confirms an increase of mitotically active cells. The observations show that FSH and testosterone can induce Sertoli cell proliferation. Morphological differentiation of Sertoli cells may be mediated indirectly by environmental and paracrine stimuli released from peritubular cells, whose differentiation is androgen dependent. Leydig cells are stimulated mainly by hCG. Our present and previous data lead us to propose that FSH contributes to the final number and activity of Leydig cells, which secrete immunoreactive inhibin in response to hCG.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1995

Clinical relevance of scrotal and transrectal ultrasonography in andrological patients.

Sonography of the scrotal contents, the prostate and the seminal vesicles has become an important diagnostic tool in andrology. In a prospective study of 1048 consecutive patients attending the Institute of Reproductive Medicine only 520 patients (49.6%) did not show sonographic abnormalities of the scrotal contents. The leading abnormality in the other 528 patients (50.4%) was a varicocele (194 patients, 18.5%), increased size of the epididymis (147 patients, 14.0%), epididymal cyst or spermatocele (55 patients, 5.2%), hydrocele (104 patients, 9.9%), testicular non-homogeneity (92 patients, 8.8%), testicular hypoechogenicity (132 patients, 12.6%), testicular cyst (12 patients, 1.1%) and testicular tumour (5 patients, 0.5%) (sum of percentages exceeds 50.4% because of multiple abnormalities in individual patients). In addition to the high incidence of pathological findings, the significantly higher incidence of testicular tumours compared to the general population and the early detection by ultrasonography render scrotal sonography a diagnostic procedure with high clinical relevance. Transrectal sonography of the prostate and seminal vesicles is valuable for detection of chronic urogenital infections or functional abnormalities of the seminal vesicles in infertile patients. In hypogonadal patients, transrectal examination of the prostate should be performed longitudinally to monitor the biological efficacy of testosterone treatment by measuring prostate growth and, in combination with palpation and PSA measurements, to screen for prostate cancer.

Humans↗
PubMed1994

Ineffectiveness of kallikrein in treatment of idiopathic male infertility: a double-blind, randomized, placebo-controlled trial.

In order to clarify the potential of kallikrein for treatment of idiopathic male infertility, a double-blind, randomized, placebo-controlled study was performed. A total of 44 patients were treated with 600 IU/day kallikrein and 47 patients with placebo for 12 weeks. Following two basal investigations, control examinations were performed at 6 and 12 weeks and included conventional and computer-aided semen analysis, hormone measurements and evaluation of drug safety. No significant changes in sperm concentration, normal sperm morphology and sperm motility evaluated by conventional analysis were detected. Computer-aided semen analysis revealed a significant increase in average path velocity and lateral head displacement of spermatozoa only in the placebo group. Within the observation period of 6 months four pregnancies occurred in each group. In conclusion, kallikrein treatment at a dose of 600 IU/day leads neither to an improvement of semen variables nor does it increase the pregnancy rate of the female partners, and is therefore not suited for therapy of idiopathic male infertility.

Adolescent↗