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Biomedical subjects

H M Behre

Publications and source records attributed to H M Behre.

At least 19 recordsLinked to original sources
PubMed1999

Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men.

In a phase I single-center, open, randomized pilot study with a three-way cross-over design the pharmacokinetics of three testosterone-containing transdermal therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1, high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To eliminate the influence of endogenous serum testosterone, the endogenous testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all subjects under GnRH antagonist treatment a marked suppression of LH, FSH, testosterone, DHT and estradiol was observed. Physiologic testosterone levels were achieved during the 24-hour-application period. Maximal serum levels were reached after 4 hours with both TTS systems. Both systems appear suited for further testing because both enable a physiological circadian profile to be achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect of exogenous testosterone in clinical studies, when, due to fluctuations in endogenous hormone levels, an estimation of the proportion of exogenous steroid is not possible.

Administration, Cutaneous↗
PubMed1999

Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception.

Approaches to hormonal male contraception are predominantly based on injectable testosterone (T) application. As most users would prefer an injection-independent modality, this study was designed to develop a self-applicable hormonal male contraceptive regimen by combining transdermal T with an oral gestagen. Eleven healthy men (23-40 yr old) were treated with oral levonorgestrel and transdermal T for 24 weeks. T was applied daily as a transdermal patch to be worn on the trunk. Levonorgestrel was taken orally at a dose of 250 microg daily up to week 12, followed by 500 microg to week 24 in those volunteers who had not become azoospermic by that time. Within 24 weeks, 2 of 11 volunteers had become azoospermic, and 3 of 11 showed sperm concentrations below 3 million/mL. The sperm concentrations of the remaining volunteers declined, but failed to reach the limit considered compatible with contraception by WHO. Treatment resulted in suppression of LH, FSH, and sex hormone-binding globulin, whereby the volunteers with lower sperm concentrations showed more pronounced suppression than the others. Mean T concentrations remained within the lower limit of normal and on occasions were below this level. There were no complaints of hypoandrogenism. Although mean levels of low density lipoprotein cholesterol, apolipoprotein B, as well as basal and postprandial insulin increased, high density lipoprotein cholesterol and apolipoprotein A-I decreased during the treatment phase. Changes in lipid parameters were normalized within 3 weeks after cessation of medication. Although only 5 of 11 volunteers reached the target sperm counts (<3 million/mL), the study shows that a self-applicable hormonal male contraceptive could be developed.

Administration, Cutaneous↗
PubMed1999

Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies.

OBJECTIVE: In the search for long-acting testosterone preparations suited for substitution therapy of hypogonadal men, testosterone undecanoate (TU) dissolved in either tea seed oil or castor oil was investigated. DESIGN: In study I, 1000 mg TU in tea seed oil (125 mg/ml) were injected in equal parts into the gluteal muscles of seven hypogonadal men. In study II, 1000 mg TU in castor oil (250 mg/ml) were injected into one gluteal muscle of 14 patients. RESULTS: In comparison with published data on testosterone enanthate, most widely used for i.m. injections, the kinetic profiles of both TU preparations showed extended half-lives and serum levels not exceeding the upper limit of normal. The castor oil preparation had a longer half-life than TU in tea seed oil (33.9+/-4.9 vs 20.9+/-6.0 days (mean pm S.E.M.)). CONCLUSION: The longer half-life and the smaller injection volume make TU in castor oil a strong candidate for further applications in substitution therapy and in trials for male contraception.

Adult↗
PubMed1998

[Treatment of varicocele in the age of "evidence-based medicine". Medical counseling is as successful as interventional treatment (ligation or embolization)].

In the age of "evidence-based medicine" the results of controlled clinical trials form the basis of therapeutic decisions. Until recently, interventional treatment has been the routine therapy for an infertile man with varicocele. However, recent controlled studies have shown that intensive counselling of the infertile couples results in as many pregnancies as ligation of embolization of the spermatic vein. Therefore, the traditional treatment regimen for varicocele should be reconsidered and the pathophysiology of the varicocele should be elucidated to provide a basis for rational treatment.

Adolescent↗
PubMed1998

Creatine kinase activity in human spermatozoa and seminal plasma lacks predictive value for male fertility in in vitro fertilization.

OBJECTIVE: To examine the predictive value of creatine kinase in human spermatozoa and seminal plasma from patients treated in an IVF program. DESIGN: Prospective, blind clinical study. SETTING: Male infertility clinic. PATIENT(S): Seventy-three patients and 32 fathers (age, <45 years). INTERVENTION(S): Determination of creatine kinase activity in seminal plasma, washed spermatozoa, and swim-up purified spermatozoa from patients treated in an IVF program. MAIN OUTCOME MEASURE(S): Creatine kinase activity in seminal plasma, washed spermatozoa, and swim-up purified spermatozoa. RESULT(S): Creatine kinase activity in washed spermatozoa correlated significantly with normal sperm morphology. No significant correlations were found between creatine kinase activity or creatine kinase isoenzyme ratio in seminal plasma, washed spermatozoa, or swim-up purified spermatozoa and success in the IVF program. The percentage of spermatozoa with normal morphology was significantly lower in patients whose sperm did not fertilize than in patients whose sperm did fertilize oocytes and in the control group of proven fathers. CONCLUSION(S): Total creatine kinase activity and creatine kinase isoenzyme distribution are not sperm function markers for prediction of male fertility in IVF treatment.

Adult↗
PubMed1998

Influence of sperm surface antibodies on spontaneous pregnancy rates.

OBJECTIVE: To determine the rates of spontaneous pregnancies among women whose infertile male partners had sperm surface antibodies. DESIGN: Retrospective analysis. SETTING: Infertility clinic of a university referral center. PATIENT(S): One hundred fifty-seven infertile couples; the male partner had IgA and/or IgG sperm surface antibody concentrations of >10%. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Spontaneous pregnancy rates (PRs) over 6 years. RESULT(S): Spontaneous PRs correlated negatively with antibody concentrations. CONCLUSION(S): Although the chance of spontaneous pregnancy among women whose partners had sperm antibody concentrations of <50% was good, intracytoplasmic sperm injection should be recommended to patients with concentrations of >90%.

Female↗
PubMed1998

Prognostic value of male diagnostic profiles in intracytoplasmic sperm injection (ICSI).

Possible correlations between male hormone and semen parameters with pregnancy and oocyte fertilization rates following intracytoplasmic sperm injection (ICSI) were investigated. The study is based on 290 couples who underwent ICSI therapy for the first time. The parameters evaluated were male age, serum levels of follicle stimulating hormone (FSH) and testosterone, sperm concentration, sperm motility, normal sperm morphology, index of teratozoospermia (TZI) and sperm vitality. A marginal, barely significant association was found between the fertilization rate and serum FSH levels in the male partner (p = 0.046). There was no relevant association between male parameters and pregnancy rates. The study confirms that male hormonal and semen parameters are of low prognostic value for the outcome of ICSI.

Adult↗
PubMed1998

Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection--prevalence, types, sex distribution and reproductive relevance.

Chromosomal abnormalities are thought to be a major contributor to the genetic risks of infertility treatment by intracytoplasmic sperm injection (ICSI). Apart from abnormalities arising de novo, abnormal karyotypes in pregnancies conceived through assisted reproductive technology may be directly derived from predisposing parental aberrations. In a prospective study we have analysed the chromosomes of 868 male and female patients prior to planned ICSI treatment. A total of 33 aberrant karyotypes was diagnosed, corresponding to an abnormality rate of 7.6% per couple or 3.8% per individual studied. Even though male factor infertility was twice as common as female factor infertility in this cohort, 24 of the chromosomal abnormalities were found among the women. Low-level mosaicism for numerical sex chromosome anomalies was diagnosed in 20 individuals, and one patient had the triple X karyotype. With respect to structural chromosomal anomalies, we found six reciprocal and three Robertsonian translocations, two paracentric inversions and one marker chromosome. Many of the aberrations that we diagnosed could be classified as carrying only a small to moderate reproductive risk. Given the high rate of abnormal karyotypes among the female subjects, we suggest that not only the males, but both partners should be routinely karyotyped prior to ICSI.

Adult↗
PubMed1998

Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial.

To examine the role of recombinant human follicle stimulating hormone (rhFSH) in male idiopathic infertility a randomized, double-blind, placebo-controlled study was performed. Of 211 patients screened, 67 were finally included. After two pre-examinations, patients were randomized and treated for 12 weeks, either with 150 IU rhFSH or with placebo. Examinations (physical examination, scrotal ultrasonography, semen analysis, hormone measurements, and in 31 patients electron microscopy (EM) of spermatozoa were performed 6 and 12 weeks after treatment initiation and 6 and 12 weeks after completion of treatment. Pregnancies were recorded for a further 3 months after the last examination. Of the 67 patients included in the study, 34 treated and 31 placebo patients could be analysed. In the treated group, FSH was elevated compared to baseline values (P < 0.001). At the end of treatment testicular volume in the treated group was increased compared to placebo (P < 0.05) and baseline (P < 0.001). Apart from an increase in sperm motility (P < 0.05) in the placebo group and in sperm DNA condensation (P < 0.001) in the treated group no significant changes were observed in semen parameters. Two spontaneous pregnancies in partners of men in the treated group and none in the placebo group occurred. However, two pregnancies occurred in partners of men in the placebo group induced by intrauterine insemination or intracytoplasmic sperm injection. In conclusion, at the chosen dose and duration, rhFSH did not lead to an improvement of conventional or EM sperm parameters nor to an increase in pregnancy rates. However, the increased testicular volume and sperm DNA condensation give reason for further investigations.

DNA↗
PubMed1998

Update on treatment of varicocele: counselling as effective as occlusion of the vena spermatica.

This prospective randomized study was performed in order to investigate the effects of interventive treatment or counselling on pregnancy rates in infertile couples in whose male partners a varicocele was diagnosed. The present report extends a previous study using the same design. A total of 125 couples were included in the current study while the previous report comprised 95 couples. Couples fulfilling the inclusion criteria were allocated randomly either to interventive treatment (surgical ligation or angiographic embolization of the spermatic vein) (n = 62) or to counselling as the sole treatment (n = 63). Couples were followed over the subsequent 12 months and seen at 3-monthly intervals. At the end of the 12 month period pregnancy rates, as the main outcome measure, were 29% in the group given interventive treatment and 25.4% in the counselled group and were not significantly different. The only significant difference found, regardless of treatment modality, was the wives' age at admittance: the 34 wives achieving a pregnancy were 28.8 +/- 0.6 years (mean +/- SE) old while the 91 non-pregnant wives were 31.2 +/- 0.3 years old (P < 0.05). The study suggests that regular counselling of the infertile couples is as effective as interventive treatment of varicoceles in achieving pregnancies.

Adult↗
PubMed1998

Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy.

Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.

Administration, Oral↗
PubMed1998

A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: monitoring of testosterone replacement therapy with testosterone buciclate.

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I-study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2 x 4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunoassay of r = 0.89. The sample volume required by this method is only 180 microliters for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean +/- SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean +/- SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception.

Adult↗
PubMed1998

Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men.

Loss of bone and muscle mass are major findings of male hypogonadism. In order to determine the long-term effect of testosterone replacement therapy on spinal bone and muscles, the trabecular and cortical bone mineral density, vertebral body area and paraspinal muscle area were assessed by quantitative computed tomography in 32 testosterone-substituted patients, aged 18-74 years, with idiopathic hypogonadotropic hypogonadism (n=6), pituitary insufficiency (n=5), Klinefelter syndrome (n=12) or other forms of primary hypogonadism (n=9). They were followed for a mean period of 3.2+/-1.7 years (mean+/-S.D.), ranging from 1 to 7 years. A significant correlation between initial serum testosterone levels and bone mineral density was found in patients with congenital forms (r=0.58; P<0.05) but not in those with acquired forms. A significant increase in trabecular and cortical bone mineral density (P<0.001) was documented in the course of replacement therapy in all patients regardless of the type of hypogonadism and age of patients. A slight but significant increase in paraspinal muscle area was observed if all patients were taken together (P<0.01). The area of paraspinal muscle correlated with body weight (r=0.58; P<0.001) and moderately with trabecular bone mineral density (r=0.4; P<0.01). Its increase did not correspond to the change observed for trabecular and cortical bone mineral density. Vertebral body area did not change over time. It correlated only with height and weight but not with bone mineral density. In conclusion, testosterone therapy of hypogonadal men improves both trabecular and cortical bone mineral density of the spine independently of age and type of hypogonadism while vertebral area remains unchanged. The effects seen on paraspinal muscles emphasize the clinical benefit of adequate replacement therapy for the physical fitness of hypogonadal men.

Adolescent↗
PubMed1998

Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases.

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

Adult↗
PubMed1998

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes.

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.

Adolescent↗
PubMed1997

Growth retardation, testicular stimulation, and increased melatonin synthesis by weak magnetic fields (50 Hz) in Djungarian hamsters, Phodopus sungorus.

Male Djungarian hamsters (Phodopus sungorus; 45 animals per group) were either sham-exposed or exposed to a sinusoidal magnetic field for 56 days (Experiment 1: 50 Hz, 450 microTesla peak; max. dB/dt = 140 mTesla s(-1); 24 hrs day(-1)). Except for day 7, no effects were observed with respect to body weights during exposure. However, testicular cell numbers were significantly increased by exposure (tetraploid (4C): p=0.022; diploid (2C): p=0.039). Rectangular magnetic fields (Experiment 2: 360 microTesla; max. dB/dt = 2.5 Tesla s(-1)) caused a significant (p<0.001) but transient suppressing effect on body weights. Significant increases were also observed in testicular cell numbers (4C: p=0.034; haploid (1C): p=0.014) and in serum melatonin (p=0.001). It is concluded that weak magnetic fields may affect reproductive and physiological functions in the mammalian species tested and that the degree of these effects depends upon the fields' gradients.

Animals↗
PubMed1997

Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia.

OBJECTIVE: To evaluate the occurrence and prevalence of microdeletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in patients with azoospermia or severe oligozoospermia. DESIGN: Controlled clinical study. SETTING: University infertility clinic. PATIENT(S): Infertile men (n = 168) with nonobstructive, idiopathic azoospermia or severe oligozoospermia and normal LH. The control group consisted of proven fathers (n = 86). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the loci sY84, sY143, sY254, and sY255; serum FSH, LH, and T; testicular volume. RESULT(S): Deletions involving the sY254 and sY255 DAZ loci were found in three azoospermic patients and two men with sperm concentration < 1 x 10(6)/mL. Serum FSH was elevated in four patients and was normal in one. All five patients had decreased testicular volumes compared with controls. No deletions involving the sY84 and sY143 loci were found. The four loci were amplified normally in the control group. CONCLUSION(S): The estimated frequency of deletions involving the DAZ locus is 3% in azoospermic-severely oligozoospermic men consulting an infertility clinic. Polymerase chain reaction amplification of the DAZ locus is useful for the diagnosis of microdeletions of the Y chromosome. Deletions involving more proximal regions of the Y chromosome seem to be rare.

Adult↗