Search PubMed⌕ Search

Biomedical subjects

H M Behre

Publications and source records attributed to H M Behre.

At least 91 records · Page 5Linked to original sources
PubMed1994

Serum FSH and testicular morphology in male infertility.

OBJECTIVE: In patients with azoospermia serum FSH helps to differentiate between obstruction or spermatogenetic dysfunction as the possible cause of this condition. The role of FSH in the diagnosis of infertile men with oligoasthenoteratozoospermia is less clearly defined. In order to evaluate the diagnostic significance of serum FSH in the management of male infertility, serum FSH levels were related to testicular morphology from bilateral biopsies of infertile men. DESIGN AND PATIENTS: Testicular biopsies were obtained from 213 infertile men and evaluated in semi-thin sections. Biopsies were performed either in order to distinguish between obstructive and non-obstructive azoospermia or because of subnormal semen variables when history, clinical investigation and hormone levels failed to explain infertility. Serum FSH was measured by fluoroimmunoassay. RESULTS: Patients were divided into five groups on the basis of morphological criteria. The mean serum FSH value of patients with obstructive azoospermia and normal histology (group 1, n = 14) was normal (3.0 (2.2-4.1) IU/l) (mean (95% confidence limits)). Serum levels of FSH in non-obstructive oligo or azoospermia were as follows: group 2: mixed atrophy of tubular tissue without focal Sertoli cell only syndrome (SCO) (n = 104) (4.5 (4.0-5.1) IU/l), group 3: mixed atrophy with unilateral focal Sertoli cell only (n = 39) (7.4 (6.1-9.0) IU/l), group 4: mixed atrophy with bilateral focal SCO (n = 36) (10.7 (8.7-13.0) IU/l). Group 5: bilateral or unilateral total Sertoli cell only (n = 20) (16.0 (12.1-20.9) IU/l). Mean serum FSH levels were significantly different between all groups (P < 0.05). CONCLUSIONS: Elevation of serum FSH correlates with the appearance of Sertoli cell only tubules. Elevated FSH serum levels make testicular biopsies superfluous for diagnostic purposes, but normal FSH does not exclude severe derangement of spermatogenesis in individual cases.

Adult↗
PubMed1994

Sustained suppression of serum LH, FSH and testosterone and increase of high-density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men.

OBJECTIVE: Recently we have shown that single dose injections of the new GnRH antagonist cetrorelix ([Ac-D-Na(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala]GnRH; SB-75) decrease serum LH and testosterone in a dose-dependent manner in normal men. These results prompted us to investigate the effectiveness and safety of multiple daily injections of cetrorelix in normal male volunteers. DESIGN AND VOLUNTEERS: Following two control examinations 16 young men were randomly assigned to four study groups (n = 4/group). Daily doses of 0 (placebo), 2, 5, and 10 mg cetrorelix were injected subcutaneously at 0800 h for 8 days and morning and evening blood samples were obtained for 3 weeks. RESULTS: One day after the first cetrorelix injection, serum LH and testosterone concentrations were significantly suppressed in all treatment groups. Whereas in the 2 and 5-mg dose groups LH and testosterone showed some fluctuations, daily injections of 10 mg cetrorelix consistently suppressed LH and testosterone in all men. In addition, in this group serum FSH concentrations were significantly suppressed to subnormal values 1 day after the first injection and remained in this range up to 5 days after the last injection. A time and dose-dependent increase of high-density lipoprotein cholesterol was observed during cetrorelix-induced testosterone deprivation with a maximal increase of 0.38 +/- 0.13 mmol/l (14.8 +/- 5.1 mg/dl; mean +/- SEM) in the 10-mg dose group. In addition, parallel to suppressed testosterone the volunteers' libido was significantly reduced under the GnRH antagonist. Apart from those symptoms caused by androgen deficiency, the only adverse side-effect observed was a mild painless local erythema at the injection site that disappeared within an hour. CONCLUSIONS: Daily injections of 10 mg cetrorelix effectively and consistently suppress serum LH, FSH and testosterone concentrations, and therefore it has potential for treatment of sex hormone-dependent diseases and for male contraception.

Adult↗
PubMed1994

Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls.

OBJECTIVE: The potential use of testosterone preparations for substitution therapy for ageing men and for male contraception, in addition to the well established substitution therapy of male hypogonadism, make increased testosterone use likely. However, little clinical information is available on the effect of testosterone therapy on the prostate in hypogonadal men. DESIGN AND MEASUREMENTS: In a controlled cross-sectional study, prostate volume measured by transrectal ultrasonography, serum levels of prostate-specific antigen (PSA) and sex hormones, and uroflow parameters were determined. PATIENTS: Three groups of age-matched men were enrolled in the study: 47 newly diagnosed hypogonadal men before testosterone treatment, 78 hypogonadal men with at least 6 months of effective testosterone therapy and 75 normal men. RESULTS: Regression analysis revealed a significant positive correlation of prostate volume with age in normal men and testosterone-treated hypogonadal men, whereas no significant correlation was detected in untreated hypogonadal men. Prostate volume was significantly lower in untreated hypogonadal men (12.2 (11.0-13.5) ml) (mean (95% confidence limits)) compared to both other groups. However, no significant difference in prostate volume was detected between testosterone-treated hypogonadal men (21.3 (19.9-22.8) ml) and normal men (22.9 (21.4-24.4) ml). Similar results were obtained for PSA with comparable values in the testosterone-treated hypogonadal men (0.98 (0.88-1.10) micrograms/l) and normal men (1.02(0.91-1.14) micrograms/l), and significantly lower concentrations in the untreated hypogonadal men (0.64 (0.55-0.73) micrograms/l). No differences in uroflow parameters were detected between the three study groups. CONCLUSIONS: Effective testosterone treatment of hypogonadal men results in prostate volume and prostate-specific antigen levels comparable to age-matched normal men. Therefore, testosterone-induced prostate growth should not preclude hypogonadal men from testosterone substitution therapy.

Adult↗
PubMed1994

Peroxidase-positive round cells and microorganisms in human semen together with antibiotic treatment adversely influence the outcome of in-vitro fertilization and embryo transfer.

Human semen contains not only spermatozoa but also other cells routinely differentiated as being peroxidase-positive (e.g. leucocytes) and peroxidase-negative (e.g. immature germ cells and lymphocytes) cells. Considerable uncertainty exists about their role in male fertility. To assess the clinical value of both parameters, and of microorganisms in semen, 391 treatments with in-vitro fertilization and embryo transfer were analysed retrospectively, and the concentrations of both peroxidase-positive and -negative cells, together with the presence of microorganisms in semen, were compared with both the fertilization and pregnancy rates. The data indicate that the results of treatment were affected only by excessively elevated concentrations of peroxidase-positive cells (> 6 x 10(6)/ml) and only marginally by the presence of microorganisms in the semen. The pregnancy rate after in-vitro fertilization and embryo transfer was not improved by antibiotic treatments preceding gamete recovery by several weeks. The increased presence of peroxidase-negative cells (e.g. germ cells) in semen was not associated with a significant change in the pregnancy rate. However, the concentration of peroxidase-negative cells in semen correlated significantly with sperm numbers (p < 0.01), sperm concentration (p < 0.01), and normal morphology rates (p < 0.01). It is concluded that short-term antibiotic treatment of asymptomatic patients before assisted reproduction should be handled with caution. The widespread view that peroxidase-negative cells in semen are harmful is rejected.

Anti-Bacterial Agents↗
PubMed1994

Seminal sperm antibodies exhibit an unstable spontaneous course and an increased incidence of leucocytospermia.

The prognostic significance of seminal sperm antibodies for male fertility is difficult to define. Among other factors, spontaneous remissions and transient induction through genito-urinary infections may change their significance for male fertility considerably. We therefore investigated their spontaneous course over time and their association with leucocytospermia. For the investigation of possible relationships between the mixed antiglobulin reaction (MAR) test results for IgA and IgG sperm antibodies and leucocytospermia, 138 patients with > or = 1 million leucocytes/ml ejaculate were compared with 1051 patients with < 1 million leucocytes/ml ejaculate (WHO normal range). In a second part of the study the spontaneous course of MAR IgG and IgA test results was investigated in 58 of the 1189 patients who had three or more MAR tests and a leucocyte concentration of < 1 million/ml ejaculate. The mean interval between the first and second MAR test was 4.1 (SD +/- 4.2) and between the second and third MAR test 6.0 (SD +/- 6.7) months. In total, 64% of patients with an MAR IgG test result > 40% showed a stable spontaneous course. Patients with lower MAR IgG test results and the majority of all MAR IgA-positive patients were found to have an undulating course of MAR test results. There was a higher incidence of leucocytes > or = 1 million/ml ejaculate in patients with higher MAR results (p < 0.05 for IgG, p < 0.001 for IgA).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1994

High efficacy of gonadotropin or pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadal men.

In order to determine the efficacy of gonadotropin and gonadotropin-releasing hormone (GnRH) therapy in hypogonadotropic hypogonadal men, we performed a retrospective clinical analysis in the outpatient clinic of a University Center for Reproductive Medicine, Twenty-six men with either hypothalamic (idiopathic hypogonadotropic hypogonadism, N = 6; Kallmann syndrome, N = 8) or pituitary disorders (N = 12) were treated with gonadotropins or GnRH for induction of spermatogenesis in 33 treatment cycles and, additionally, for induction of pregnancy in the female partner in 18 out of 33 cases (12 of 26 patients). Patients were treated with a combination of 1000-2500 IE of human chorionic gonadotropin twice per week and 75-150 IE human menopausal gonadotropin three times per week intramuscularly or subcutaneously. Alternatively, GnRH was administered at doses of 5-20 micrograms every 120 min subcutaneously to men with hypothalamic disorders. Treatment lasted until sperm appeared in the ejaculate or pregnancy was induced. During therapy, testosterone levels increased into the normal range. Total testicular volumes increased significantly during therapy despite low initial testicular volumes and histories of maldescended testes. Sperm appeared in the ejaculate in 30 of 33 treated patients. Pregnancies occurred in 15 out of 18 cases even with sperm counts far below the normal range. We could not detect differences in the efficacy of gonadotropin or GnRH treatment in hypogonadotropic hypogonadism. Thus, we conclude that both gonadotropin and pulsatile GnRH therapy are most effective in the induction of spermatogenesis and pregnancies in hypogonadotropic hypogonadal men, despite maldescended testes, low initial testicular volumes or sperm concentrations below the normal limit.

Adult↗
PubMed1994

Duration of the cycle of the seminiferous epithelium, estimated by the 5-bromodeoxyuridine technique, in laboratory and feral rats.

The stability of the duration of the cycle of the seminiferous epithelium was determined by investigating incorporation of 5-bromodeoxyuridine into S-phase germ cells of normal and hemicastrated standard laboratory rats (Sprague-Dawley) and feral Brown/Norway rats (Rattus norvegicus). Feral rats were trapped on farms in the surroundings of Münster. The duration of the cycle of the seminiferous epithelium, determined at intervals of 12 days (3 h versus 12 days 3 h after 5-bromodeoxyuridine injection), was remarkably constant and similar in intact laboratory rats (12.49 +/- 0.05 days, n = 13, mean +/- SEM) and feral rats (12.44 +/- 0.06 days, n = 8). In hemicastrated laboratory and feral rats the duration of the cycle was similar to that in intact animals, indicating that hemicastration did not influence the kinetics of the seminiferous epithelium cycle. However, the coefficients of variation of the estimated duration of the cycle of the seminiferous epithelium were at least three times lower in hemicastrated rats (one testis from the same animal serving as reference point) compared with that of intact rats (the reference point based on the average staining frequency at 3 h). Overall, no significant differences between laboratory and feral rats could be observed with regard to testis weight and serum concentrations of FSH and testosterone. The number of cells per testis, determined by flow cytometry, was similar in laboratory and feral rats, except for a slight but significant difference in the haploid:tetraploid cell ratio (6.3 +/- 0.2 versus 7.5 +/- 0.3, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Can testosterone alone maintain the gonadotrophin-releasing hormone antagonist-induced suppression of spermatogenesis in the non-human primate?

The combination of gonadotrophin-releasing hormone (GnRH) antagonist and delayed testosterone substitution provides a promising approach towards male contraception. However, the GnRH antagonists used clinically so far cause side-effects and have to be administered continuously. We therefore used the non-human primate model to see whether the GnRH antagonist cetrorelix (which exhibits a favourable benefit-to-risk ratio in terms of anti-gonadotrophic action in normal men) induces complete and reversible suppression of spermatogenesis and whether GnRH antagonist-induced suppression of spermatogenesis can be maintained by testosterone alone. Four groups of adult cynomolgus monkeys (Macaca fascicularis; five per group) were injected daily with 450 micrograms cetrorelix/kg ([N-acetyl-D-2-naphthyl-Ala1, D-4-chloro-Phe2, D-pyridyl-Ala3, D-Cit6, D-Ala10]-GnRH). Group 1 received the GnRH antagonist for 7 weeks followed by vehicle administration for another 11 weeks; group 2 was treated with GnRH antagonist for the entire 18 weeks with each animal receiving a single testosterone implant during weeks 11-18 to restore the ejaculatory response to electrostimulation; group 3 received the GnRH antagonist for 18 weeks and testosterone buciclate (TB) was injected during week 6 of GnRH antagonist treatment; group 4 was subjected to GnRH antagonist administration for 7 weeks and received TB (200 mg/animal) during week 6. Under GnRH antagonist treatment alone serum concentrations of testosterone were suppressed. TB maintained testosterone levels two- to fourfold above baseline levels in groups 3 and 4 and prevented the recovery of LH secretion for about 20 weeks after GnRH antagonist withdrawal, whereas inhibin levels increased significantly from week 8 onwards. Group 2 animals were azoospermic during weeks 12-18 of GnRH antagonist administration. The TB-replaced groups developed azoospermia or became severely oligozoospermic. Quantitation of cell numbers by flow cytometry during weeks 6 and 18 revealed that TB (groups 3 and 4) had prevented a further decline of germ cell production compared with group 2 but had maintained the spermatogenic status present at week 6 (onset of TB substitution). All inhibitory effects of cetrorelix and/or TB were reversible after cessation of treatment. These findings demonstrate that cetrorelix reversibly inhibits spermatogenesis in a non-human primate model. Although TB maintained the GnRH antagonist-induced suppression of spermatogenesis, azoospermia was not achieved. This latter effect may reflect either a direct spermatogenesis-supporting effect of the high dose of TB or the partial recovery of inhibin secretion (indirectly reflecting FSH secretion) or a combination of both.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Restoration of spermatogenesis by follicle-stimulating hormone despite low intratesticular testosterone in photoinhibited hypogonadotropic Djungarian hamsters (Phodopus sungorus).

By exposing male Djungarian hamsters to short-day photoperiods, a hypogonadotropic condition resembling that of hypophysectomized animals can be achieved without resorting to surgery. By use of this animal model, differential effects of gonadotropins on spermatogenesis have been studied revealing that FSH selectively restimulates spermatogenesis up to the level of spermatids. In the present study, we investigated whether FSH (6 IU/day) also restores fertility in hamsters exposed to short-day photoperiods (8L:16D). Animals kept under long-day photoperiod (16L:8D) served as controls. After 8 wk under 8L:16D, gonads were involuted and the animals (n = 9-10 per group) were treated with FSH, or testosterone implants, or both for the following 33 days. An additional group received FSH for 33 days and, for the last 12 days only, FSH plus testosterone to induce copulatory and ejaculatory behavior. The implants caused no increase in intratesticular testosterone as compared to that in short-day controls. All males were paired with adult females for the last 5 days of treatment, and killed thereafter. Litter sizes were determined 22 days later. The examination of the testes by flow-cytometrical techniques revealed qualitatively normal spermatogenesis in animals receiving FSH, whereas testosterone caused an insignificant increase to a few round spermatids. In most FSH-treated animals, sperm were present in the epididymides. In hamsters receiving FSH along with testosterone, treatment resulted in restoration of full fertility as compared to long-day controls. Fertility was also restored in animals receiving testosterone only for the last 12 days of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate.

Gonadotropin-releasing hormone (GnRH) agonists induce a clinically undesirable, transitory but very pronounced initial rise of gonadotropin and gonadal steroid secretion. We investigated, in a non-human primate model, whether the initial stimulatory effects of GnRH agonists can be avoided by a short period of pretreatment and simultaneous treatment with a GnRH antagonist. Three groups of five adult male cynomolgus monkeys (Macaca fascicularis) received a single s.c. biodegradable implant loaded with the GnRH agonist, buserelin ([D-Ser(TBu)6-desGly-NH2]-GnRH), releasing approximately 50 micrograms buserelin daily. From 1 week before to 1 week after inception of administration of GnRH agonist, group 1 received the GnRH antagonist vehicle, and groups 2 and 3 were given s.c. injections of the GnRH antagonist Nal-Glu ([Ac-D-Nal(2)1,D-4-Cl-Phe2,D-Pal3,D-Arg5,D-Glu6(AA),D- Ala10]-GnRH) at a dose of 450 or 2250 micrograms/kg daily. In the absence of GnRH antagonist, the GnRH agonist induced a marked elevation of serum luteinizing hormone (LH) and testosterone lasting for 2 and 5 days, respectively. In group 2, Nal-Glu reduced basal hormone secretion and delayed the peak of GnRH-agonist-induced hormone secretion by 1 day. In group 3, the GnRH-agonist-induced rise of LH and testosterone was prevented in three animals and did not exceed baseline hormone levels in the other two animals. Areas under the LH and testosterone curves were significantly reduced in group 3 compared to group 1. After withdrawal of the GnRH antagonist, a second transient rise of hormone secretion was observed. Except for testosterone in group 2, this rise did not exceed the baseline range of hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Depot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception.

Thus far, when tested as male contraceptives, GnRH agonists in combination with androgens were not very effective in producing azoospermia. Since in previous studies androgens were always given simultaneously with the GnRH agonist or later, we tested whether GnRH agonist administration after an initial androgen suppression phase might yield better results. After a control period, 3 groups of young healthy men (n = 8/group) received an initial loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), followed by 200 mg of the ester every 3 weeks for 24 weeks. One week after the first 19NT-HPP injection, 2 groups were given a single sc implant injection of 3.3 or 6.6 mg of the GnRH agonist buserelin, respectively, whereas a placebo implant was given to the third group. In the group receiving only 19NT-HPP, serum LH and FSH were markedly suppressed and remained low during the treatment phase. In the 16 volunteers receiving the buserelin implant LH and FSH were also suppressed on day 7, followed by a marked increase in the gonadotropins up to 2 weeks after buserelin implant injection. While LH was consistently suppressed for the remaining treatment phase, FSH returned to almost normal values in weeks 9-15. In contrast to the group treated with 19NT-HPP alone, in which sperm concentrations were reduced to oligozoospermia after only 3 weeks of treatment, the first suppressive effect in the 19NT-HPP/buserelin-treated groups was not seen before week 9. After 30 weeks, when the maximal suppression of spermatogenesis was seen, 4 of 8 volunteers in the group treated with 19NT-HPP alone were azoospermic, and the remaining 4 volunteers were oligozoospermic. In the groups treated with 19NT-HPP/buserelin, no more than 4 of 16 volunteers were azoospermic, and no more than 8 of 16 volunteers were oligozoospermic at any time point. It is concluded that GnRH agonist depot preparations have a blunting effect on the suppression of pituitary and testicular function caused by androgens in men participating in contraceptive trials.

Adult↗
PubMed1992

Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men.

In rats and nonhuman primates the new GnRH antagonist cetrorelix (SB-75; [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10]GnR H) has been shown to suppress testosterone secretion effectively and persistently. A clinical phase I study was performed to assess the hormonal effects of this highly potent antagonist in normal men. After 2 control examinations 30 young male volunteers were randomly assigned to 6 treatment groups (n = 5/group), and single doses of 0 (placebo), 0.25, 0.5, 1.0, 2.0, and 5.0 mg cetrorelix were administered sc. Blood samples were obtained over the course of 7 days postinjection. After maximal cetrorelix serum levels were achieved 1 h postinjection, the GnRH antagonist serum levels decreased with a terminal t1/2 of 29.8 +/- 4.2 h (mean +/- SE). LH secretion was suppressed dose- and time-dependently; maximal suppression occurred 4-6 h postinjection. Suppression of FSH did not reach statistical significance. Doses of 1.0, 2.0, and 5.0 mg cetrorelix significantly suppressed testosterone secretion compared to that in the placebo group. After the administration of 1.0 mg cetrorelix, maximal suppression was seen 8 h after injection, with testosterone levels of 7.5 +/- 1.1 nmol/L compared to 15.8 +/- 2.2 nmol/L in the placebo group. Maximal testosterone suppression by 2.0 and 5.0 mg cetrorelix occurred 12 h after injection, with testosterone concentrations of 4.9 +/- 0.5 and 2.2 +/- 0.4 nmol/L, respectively, compared to 16.5 +/- 1.7 nmol/L in the placebo group. Twenty-four hours after the injection of 1.0 and 2.0 mg cetrorelix, testosterone values were no longer significantly different from those in the placebo group, whereas in the 5.0-mg dose group testosterone concentrations increased slightly and reached serum concentrations in the lower normal range after 48 h. The only side-effect observed after the administration of cetrorelix was a transient local erythema at the injection site that disappeared within 30 min. No local induration or pruritus, or any adverse systemic side-effect occurred in any volunteer. In conclusion, the new GnRH antagonist cetrorelix effectively decreases serum LH and testosterone concentrations in a dose- and time-dependent manner and, therefore, has potential for treatment of sex hormone-dependent diseases and male contraception.

Follicle Stimulating Hormone↗
PubMed1992

Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester.

Due to unfavorable pharmacokinetics of the available androgen esters for substitution therapy of male hypogonadism, there is a demand for new testosterone (T) preparations producing constant serum levels in the physiological range. To assess the pharmacokinetics and pharmacodynamics of the new ester testosterone buciclate (TB) [20 Aet-1] in hypogonadal men a clinical phase I-study was performed. After two control examinations 8 male patients with primary hypogonadism were randomly assigned to 2 treatment groups (n = 2 x 4) given single doses of either 200 (group I) or 600 mg (group II) TB im. Blood samples were obtained 1, 2, 3, 5, and 7 days post injection and then weekly in the course of 4 months. In group I serum androgen levels did not rise to normal values. However, in group II androgens increased significantly and were maintained in the normal range up to 12 weeks with maximal serum levels of 13.1 +/- 0.9 nmol/L (mean +/- SE) in study week 6. No initial peak release of T was observed in either study group. Pharmacokinetic analysis revealed a terminal elimination t1/2 beta of 29.5 +/- 3.9 days and a mean residence time of 65.0 +/- 9.9 days in group II. In one patient in group II dihydrotestosterone levels slightly exceeded the upper normal limit during the study course. Sex hormone-binding globulin remained unchanged and estradiol serum levels never exceeded the normal range in any patient. In group II gonadotropins were significantly suppressed, whereas no change was seen in group I. A significant increase in body weight, hematological parameters, and libido/potency was observed after TB injection which was more pronounced in the higher dose group. Regardless of the dose administered, no significant change was seen in uroflow, prostate volume measured by transrectal ultrasonography, or prostate specific antigen. No adverse side-effects including changes in clinical chemistry were observed. In conclusion, single injections of 600 mg TB in hypogonadal patients show favorable pharmacokinetics and pharmacodynamics. This new long-acting T ester is a promising new agent for substitution therapy of male hypogonadism and for male contraception.

Adult↗
PubMed1992

Pharmacokinetics of the gonadotropin-releasing hormone agonist buserelin after injection of a slow-release preparation in normal men.

The pharmacokinetics of the gonadotropin-releasing hormone (GnRH) agonist buserelin (D-Ser(BUt)6-GnRH-(1-9) nonapeptide-ethylamide, Hoe 766, CAS 57982-77-1) after injection of a slow-release preparation was investigated in 16 healthy young male volunteers. Eight volunteers received a buserelin implant of 3.3 mg and 8 volunteers one of 6.6 mg by subcutaneous injection. In order to prevent androgen deficiency symptoms caused by the GnRH agonist all volunteers were injected with an initial loading dose of 400 mg of the androgen 19-nortestosterone hexyloxyphenylpropionate one week prior to the buserelin administration, followed by injections of 200 mg once every three weeks up to week 23. Maximal buserelin serum levels were measured two days after injection of the implant. Following a slow decrease in serum concentrations up to week 8, serum buserelin had disappeared by week 14 in the 3.3 mg group and by week 17 in the 6.6 mg group. The areas-under-the-serum-concentration-versus-time-curves (AUCs) for the 3.3 and 6.6 mg implants were 691 +/- 60 ng x h/ml and 1050 +/- 102 ng x h/ml, respectively (p less than 0.01). The mean residence times (MRTs) of buserelin after administration of 3.3 mg and 6.6 mg buserelin implant were 4.7 +/- 0.4 and 4.1 +/- 0.3 weeks, respectively (p greater than 0.05). Urinary excretion of buserelin showed a similar pharmacokinetic profile. However, urinary buserelin was still detectable at very low concentrations by the end of the study, i.e. 29 weeks after implant injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗