Biomedical subjects

F C Wu

Publications and source records attributed to F C Wu.

At least 37 records · Page 2Linked to original sources

PubMed1999

Kallmann's syndrome: is it always for life?

OBJECTIVE: Kallmann's syndrome (KS) is defined by the association of olfactory deficit with irreversible, congenital gonadotrophin deficiency (IHH). We present evidence for the existence of a variant form of KS, in which endogenous gonadotrophin secretion recovers spontaneously in later life. DESIGN: Longitudinal clinical study. PATIENTS: Five men with anosmia or severe hyposmia, who originally presented in their late teens or early twenties as a result of severe pubertal delay and were thus presumed to have KS. RESULTS: Spontaneous onset of endogenous gonadotrophin secretion, evidenced by progressive normalization of testicular volume and of serum testosterone concentration, occurred in these men over a period of years following the initial diagnosis. CONCLUSIONS: This variant form of Kallman's syndrome is not well recognized and may well be under-diagnosed. Once full virilization has been induced, males with congenital gonadotrophin deficiency whose testes have significantly increased in size should be reassessed, off androgen replacement therapy, to identify those who no longer require treatment.

Adolescent↗

PubMed1999

Adrenal and gonadal contributions to urinary excretion and plasma concentration of epitestosterone in men--effect of adrenal stimulation and implications for detection of testosterone abuse.

OBJECTIVE: The ratio of urinary testosterone (T) to epitestosterone (EpiT) is used to detect T abuse in sport. Also, plasma or urinary concentrations of EpiT have been measured to assess testicular steroidogenesis during hormonal male contraception. Further investigations are required to evaluate the relative contributions of the testis and adrenal to EpiT production. To this purpose, we have compared basal urinary EpiT glucuronide and plasma EpiT and the response to synthetic adrenocorticotrophic hormone (ACTH) stimulation between eugonadal and hypogonadal men. DESIGN AND SUBJECTS: The basal urinary excretion rate of EpiT glucuronide was determined in 34 eugonadal men. Six men, clinically diagnosed as hypogonadal, and 6 out of the 34 eugonadal men previously described, received an intramuscular injection of synthetic ACTH depot (1 mg) at 0800 h on two consecutive days. Blood samples were collected prior to and then at 1.5, 8, 24, 25.5, 32 and 48 h with respect to the first administration (0 h). 24-h urine specimens were collected from 0800 h on days 1 and 2 (baseline) and 3 and 4 (stimulation). MEASUREMENTS: Plasma EpiT, T and cortisol were measured by RIA and urinary EpiT and T, following glucuronide hydrolysis, by gas chromatography-mass spectrometry (extract combines aglycones with a minor amount of urinary free steroids). RESULTS: Basal excretion rates of EpiT glucuronide in eugonadal men (range: 62-751 nmol/24 h) were considerably greater than in hypogonadal men (range: 3-34 nmol/24 h). Mean basal plasma EpiT in eugonadal men (1.32 +/- 0.08 nmol/l) were greater than in hypogonadal men (0.68 +/- 0.04 nmol/l). In each group, synthetic ACTH stimulation increased plasma cortisol 4-fold. In eugonadal men, plasma and urinary EpiT were unchanged whereas plasma and urinary T glucuronide decreased in response to ACTH. In hypogonadal patients, ACTH increased plasma and urinary EpiT while plasma T remained unchanged. CONCLUSION: The testes are the major source of epitestosterone, the adrenal contribution being relatively modest. Following adrenal stimulation, urinary epitestosterone glucuronide increases considerably in hypogonadal men but this increase is masked in eugonadal men because testicular production is probably suppressed by the ACTH-induced rise in cortisol. Activation of the adrenal cortex results in no change or only a small decrease in the urinary T/EpiT ratio in eugonadal men.

Adrenal Glands↗

PubMed1999

Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men.

Muscle wasting in older men may be related to androgen deficiency. We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older (age > 60 years) men with blood testosterone levels < 14 nmol/L. Subjects (n = 7 per group) received testosterone enanthate 200 mg i.m. or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks. A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group. Total body mass, haemoglobin and packed cell volume also increased significantly (p < 0.05). No improvements in handgrip strength, isometric strength of knee flexors and extensors or leg extensor power were seen in either group. Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function.

Aged↗

PubMed1999

Apoptosis in the rat spermatogenic epithelium following androgen withdrawal: changes in apoptosis-related genes.

Programmed cell death is an important regulatory event in spermatogenesis. However, the molecular events governing apoptosis have not been characterized. Using the Leydig cell-specific toxin ethane dimethanesulfonate (EDS) to withdraw androgen support, we have investigated the relationship between apoptosis and apoptosis-related genes. Adult male Sprague-Dawley rats were injected (i.p.) with 100 mg/kg EDS and killed at times of androgen depletion 2, 5, and 8 days postinjection. A 24-fold increase in the apoptotic index 8 days after EDS administration was demonstrated in tissue sections by in situ end-labeling of fragmented DNA. Leydig cell death and androgen withdrawal were confirmed by the absence of 3beta-hydroxysteroid dehydrogenase in testes from animals treated with EDS for 2 days. After androgen withdrawal, there were no significant changes in the levels of clusterin, Bcl-xl, Bak, and Bad. However, the expression of Bcl-2 and Bax was up-regulated at 8 days after EDS administration. The induction of Bax at this time suggests that it may play a role in germ cell apoptosis following androgen withdrawal. The concomitant elevation in Bcl-2 expression may represent a survival mechanism for the remaining germ cells. There was also a decline in the expression of Fas-L and Fas-R in the pachytene spermatocytes and spermatids. Fas-R was also present in Sertoli cells, although Fas-L staining was minimal. As the colocalization of Fas-L and Fas-R correlates with the germ cell types that die in response to androgen withdrawal, the potential exists for apoptosis in the rat spermatogenic epithelium to be regulated by the Fas pathway.

Androgens↗

PubMed1999

Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference between 300 and 150 microg. Addition of T enanthate (both 50 and 100 mg weekly) induced a further fall only in high density lipoprotein cholesterol to 22.6 +/- 3.7% from the baseline. In summary, the combined actions of oral DSG with low doses of T enanthate were highly effective in suppressing pituitary-testicular functions in adult men. The optimal regimen for inducing azoospermia was 300 microg DSG daily with 50 mg T enanthate weekly. Oral DSG exerted discernible effects on lipid metabolism. We conclude that the combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception.

Administration, Oral↗

PubMed1998

DNA short tandem repeat profiling of Chinese population in Taiwan determined by using an automated sequencer.

We performed a population study on a Taiwan population using a set of nine short tandem repeat (STR) loci and the amelogenin locus. Allele and genotype frequencies of the STR systems D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820 were determined by polymerase chain reaction followed by automated sequencer analysis. A total of 80 alleles could be observed, using all systems, in a population of 500 individuals. No new intermediate fragments were found in these systems. Allele frequencies showed no deviation from the Hardy-Weinberg equilibrium. The mean exclusion power (MEP) ranged from 0.294 for TPOX to 0.711 for FGA (the combined MEP was > 0.999), the discriminating power (DP) ranged from 0.782 for TPOX to 0.964 for FGA, (the combined DP was > 0.99999999949).

Alleles↗

PubMed1998

Apoptosis and related genes in the rat ventral prostate following androgen ablation in response to ethane dimethanesulfonate.

BACKGROUND: Following androgen withdrawal, regression of the prostate is characterized by apoptotic cell death. The molecular events governing this process have not been fully characterized. METHODS: Using ethane-1,2-dimethanesulfonate (EDS) to induce androgen ablation, we investigated the role of the Bcl-2 family members and Fas pathway in this phenomenon. Prostates were examined from adult male rats injected with 100 mg/kg EDS and killed 2, 5, and 8 days later. RESULTS: Regression of the prostate was evident as a time-dependent decrease in weight. The number of apoptotic cells identified by in situ end labeling was maximal after 5 days of treatment. There was no statistically significant change in the expression of Bax, Bcl-xl, Bcl-2, or p53 following androgen withdrawal. In contrast, 5 days post-EDS treatment, testosterone-repressed prostate message (TRPM-2) and Fas-R expression were induced. There was a decline in Fas-L levels 8 days after EDS administration. CONCLUSIONS: This study extends previous work which has shown that androgen withdrawal induces apoptosis in the prostate. We have shown that although p53 and the Bcl-2 family members examined in this study do not seem to be important in this process, the Fas pathway may play a role in apoptosis of the ventral prostate in response to androgen ablation.

Androgens↗

PubMed1998

The effects of low-dose testosterone treatment on lipid metabolism, clotting factors and ultrasonographic ovarian morphology in women.

INTRODUCTION: Low doses of androgen are used in women for the symptomatic treatment of sexual dysfunction and premenstrual syndrome (PMS). However, little is known about the long-term safety of androgen use in women. This study investigated the effects of low dose exogenous testosterone (T) on lipid metabolism, markers of activation of the coagulation system and ultrasonographic ovarian morphology in women. PATIENTS: Twenty-two patients with severe PMS (age 39.6 +/- 3.1 years, mean +/- SD) treated with subcutaneous T implants (100 mg six monthly) for at least two years (mean duration 3.3 (+/- 0.9 years) were compared with 22 age-matched (age 37.7 +/- 2.9 years) control patients with severe PMS who had not previously received T treatment. All women continued to have regular menses. MEASUREMENTS: Fasting blood samples were obtained for measurement of lipids and clotting factors and ovarian ultrasound examination carried out between days 1-4 of the menstrual cycle (2.3 +/- 1.2 months after the T implant in T-treated group). RESULTS: Mean plasma T was 4.5 +/- 2.2 nmol/l, and 1.9 +/- 0.6 nmol/l in the treated and control groups, respectively. In the T-treated group apolipoprotein-A1 (Apo-A1) (treated 99.2 +/- 12 vs controls 116.2 +/- 27.7 g/l, P < 0.01) and high density lipoprotein cholesterol (HDL-C) (treated 1.3 +/- 0.3 vs controls 1.5 +/- 0.4 nmol/l, P < 0.01) were significantly decreased. In addition very low density lipoprotein cholesterol (VLDL-C) (treated 0.4 +/- 0.3 vs controls 0.2 +/- 0.1 nmol/l, P < 0.05) was increased in T-treated patients. There were no differences in total serum cholesterol and triglyceride or low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), lipoprotein(a), lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein activity. There was no difference in clotting factors between the two groups which included prothrombin time, fibrinogen, antithrombin-III, protein-C, protein-S (total and free), tissue plasminogen activator, plasminogen activator inhibitor, beta-thromboglobulin and prothrombin fragments 1.2. Ultrasound showed normal ovarian architecture with no evidence of polycystic ovarian changes in any patients in the T-treated group. No patient experienced adverse symptoms while on T treatment, in particular, there were no complaints of hirsutism or acne and no one requested termination of treatment. CONCLUSION: Low-dose testosterome administration to women for over two years did not induce changes in ovarian architecture but had small, potentially atherogenic effects on some parameters of lipid and lipoprotein metabolism. However, no differences were detected in markers of activation of the clotting system to indicate an actual increase in the risk of thrombosis. Overall, this study provides largely reassuring data about the safety of low-dose androgen treatment in women. However, caution should be exercised in women with existing or a familial predisposition to lipid abnormalities, because of the small but significant changes found in HDL-C, apo-A1 and VLDL-C.

Adult↗

PubMed1998

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment.

Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pathways in the human testes. Human testes were obtained from patients with prostate cancer, undergoing orchidectomy for permanent androgen ablative treatment. The patients were either untreated or had previously received short- or long-term anti-androgen therapy by cyproterone acetate or GnRH agonist (goserelin). In comparison with untreated patients, testicular testosterone concentrations were reduced by 83% in patients treated with cyproterone acetate and by 99% in patients treated with goserelin. Apoptotic cells were identified in tissue sections by in-situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients who received short-term anti-androgen treatment. There were few or no apoptotic cells in the seminiferous tubules following long-term anti-androgen treatment. Following short-term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in the long-term treated testes, Bcl-xl and PARP expression declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the human testis and may contribute to the regulation of germ cell populations. The apoptosis-related gene products which have been described in other tissues are present in the human testis and are modulated by androgenic stimuli.

Adult↗

PubMed1998

Which androgen replacement therapy for women?

Although the postmenopausal ovary remains an important source of testosterone (T) production, there is nevertheless a decline in total circulating androgen levels with age. A role for androgen replacement in addition to estrogens in some postmenopausal, particularly ovariectomized, women is increasingly gaining acceptance. We have compared the pharmacokinetics of two existing testosterone preparations, oral testosterone undecanoate (TU) and sc testosterone implants, with a new matrix transdermal delivery system for T. In study 1, three different doses of TU (40 mg, two 20-mg doses 6 h apart and two 10-mg doses 6 h apart, orally) were investigated in 10 postmenopausal women. Median peak levels of 18 nmol/L (range, 5.8-64.0 nmol/L; 40 mg), 12.3 nmol/L (range, 5.7-29.2 nmol/L; 20 mg), and 9.7 nmol/L (range, 7.8-28.7 nmol/L; 10 mg) were observed, but T levels varied considerably within and between subjects regardless of the dose used. In study 2, 30 women receiving s.c. estradiol therapy were randomized to receive either a 100-mg T implant or placebo. In the T-treated group, levels peaked at 8.9 +/- 1.7 nmol/L 1 month after insertion and then declined gradually to 2.9 +/- 0.4 nmol/L at 6 months. In study 3, a novel matrix transdermal delivery system for T was investigated in 6 females. Estimated daily delivery rates of 840 (TD 1), 1100 (TD2), and 3000 microg (TD3) T/24 h were investigated. T rose rapidly after a single application of TD 1 and TD2 and were relatively constant for the next 18 h, at which time peaks of 2.3 +/- 1.0 and 4.1 +/- 1.6 nmol/L, respectively, at 24 h were seen. T concentrations fell to baseline levels within 6 h after patch removal. When TD2 was applied for 7 days, a T level of 4.3 +/- 0.7 nmol was seen 24 h after application, falling gradually to 2.8 +/- 0.7 nmol/L by day 7. During twice weekly application of TD2, stable T concentrations were maintained, and all peak levels were similar (peak level, 4.2 +/- 0.3 nmol/L 24 h post-TD application) as were predose troughs (3.2 +/- 0.3 nmol). Twice weekly application of TD3 produced a similar pattern of T, and the mean peak and trough levels were 7.5 +/- 0.9 and 4.0 +/- 0.4 nmol/L, respectively. In conclusion, TU produced inappropriate high T levels at all doses, with wide variations between subjects, confirming that TU is unpredictably absorbed and unlikely to be satisfactory for use in women. Subcutaneous testosterone implants produce unphysiological T levels for at least 1-2 months. The transdermal matrix delivery system maintained relatively stable T levels within narrow ranges with little within- and between-subject variation. We conclude that such transdermal systems may be of value for androgen therapy in postmenopausal women because they provide a highly controllable way of delivering T noninvasively and reliably, and achieve mean physiological levels not possible with existing methods.

Administration, Cutaneous↗

PubMed1997

Correlation of clinical, endocrine and molecular abnormalities with in vivo responses to high-dose testosterone in patients with partial androgen insensitivity syndrome.

OBJECTIVE: To investigate the responses of two patients previously diagnosed as Reifenstein's syndrome to graded high-dose testosterone in terms of hormone levels, nitrogen balance and sebum secretion and to attempt to correlate these parameters with the properties of their androgen receptors and mutations in the androgen receptor gene. DESIGN: Nitrogen balance was determined by comparing controlled nitrogen intake to the amount excreted. Sebum excretion was measured on the forehead. Patients were studied during control periods (no treatment) and during administration of testosterone propionate. Blood samples were used as a source of genomic DNA and to measure peripheral hormone levels; androgen receptor binding was determined using genital skin fibroblasts. PATIENTS: Two patients of XY karyotype, with ambiguous external genitalia and problems of testicular descent who had required mastectomy as teenagers. Normal male controls of proven fertility. MEASUREMENTS: Nitrogen balance, sebum excretion rate and peripheral hormone levels (testosterone, dihydrotestosterone, LH and FSH) were studied before and after testosterone therapy (1 or 5 mg/kg/day). Genomic DNA was extracted from peripheral blood leucocytes and regions of the androgen receptor gene amplified by polymerase chain reaction using pairs of specific primers. Mobility of amplified DNA from patients was analysed on denaturing gradient acrylamide gels and fragments differing in mobility from those of normal controls were sequenced. Fibroblasts were cultured from scrotal skin biopsies and androgen receptor binding parameters, subcellular localization and up-regulation were determined. RESULTS: Testosterone therapy resulted in raised plasma testosterone, dihydrotestosterone and oestradiol in both patients. In patient 1 (lesser genital abnormality), LH was suppressed by 5 mg/kg/day testosterone to the upper limit of the normal range but FSH remained low normal. Both LH and FSH were suppressed by testosterone treatment in patient 2 (greater genital abnormality). Nitrogen retention was increased in both patients (4.2 and 3.0 g/24 h respectively); sebum excretion rate increased to normal in patient 1 but showed no change in patient 2. Mutations in the androgen receptor gene were identified in both patients. In patient 1 a single nucleotide change from adenosine to guanosine resulted in the substitution of glycine for glutamic acid at position 772 within the hormone binding domain of the receptor. In patient 2 a single nucleotide mutation from guanosine to adenosine resulted in the substitution of lysine for arginine at position 608 (exon 3) situated in the second zinc finger of the DNA binding domain. Both patients had a normal number of androgen binding sites in genital skin fibroblasts but those in patient 1 showed reduced binding affinity and rapid dissociation of receptor/ligand complexes while those in patient 2 showed defective nuclear localization. CONCLUSION: In patients with partial androgen insensitivity syndrome the type of androgen receptor mutation and responses to short-term androgen treatment can be correlated with the individual's potential to virilize. If there is a mutation in the androgen receptor DNA binding domain the patient may show little ability to virilize either spontaneously at puberty or after androgen treatment. Sebum excretion appears to be more discriminating than nitrogen balance or gonadotrophin suppression as an index of tissue response to androgens.

Adult↗

PubMed1997

Changes in dimeric inhibin A and B during normal early puberty in boys and girls.

OBJECTIVE: Although recently developed specific and sensitive assays of bioactive dimeric inhibin A and B have given new insights into the pituitary-gonadal axis in adult men and during the adult female menstrual cycle, there have been no reports on circulating inhibin A and B during normal human puberty. The aim of this study was to assess the relationship of dimeric inhibin A and B to pubertal stage, FSH and testosterone or oestradiol in late prepuberty and in early puberty. STUDY DESIGN AND SUBJECTS: Serial samples were collected during a prospective longitudinal trial of GH treatment in short normal children. Seven boys were studied from late prepuberty to genital stage 3, and six pre-menarche girls from late prepuberty to breast stage 4. MEASUREMENTS: Dimeric inhibin A (girls only) and inhibin B (boys and girls) were measured by highly specific and sensitive two-site ELISAs, FSH by IRMA, testosterone and oestradiol by RIA. RESULTS: In boys, inhibin B increased progressively from pubertal stages 1 to 3 (ANOVA P < 0.0001) and correlated strongly with mean testicular volume (r = 0.72, P = 0.0005). Prepubertal boys showed a positive correlation between inhibin B and FSH (r = 0.65, P = 0.056), whereas pubertal boys gave a strong negative correlation (r = 0.75, P = 0.012). In both prepubertal and pubertal boys positive correlations were observed between inhibin B (y) and testosterone (x) (r = 0.81, P = 0.008 and r = 0.62, P = 0.054 respectively), but the slope of the regression line between the two was much steeper before than after the onset of clinical puberty. In girls, both inhibin A and B increased through pubertal stages 1-4 (ANOVA P = 0.01 and P = 0.047 respectively). Both showed strong positive correlations with oestradiol (r = 0.80 and 0.79, P = 0.001) and with FSH (r = 0.83, P = 0.0004 and r = 0.80, P = 0.001). Inhibin A and B were also strongly correlated with each other (r = 0.92, P = 0.0001). CONCLUSIONS: In boys, testicular production of inhibin B increases as puberty progresses. Our results show for the first time that the initiation of puberty is accompanied by a dramatic switch from a positive to a negative relation between inhibin B and FSH as inhibin B begins to exert the expected negative feedback on FSH. The results in girls suggest that, prior to menarche, the ovarian follicles produce inhibin A and B in strict proportion, and in progressively greater amounts as puberty proceeds. Measurement of dimeric inhibin A and B may provide a sensitive new tool for determining gonadal maturity in late prepuberty and early puberty.

Adolescent↗

PubMed1997

Venous microanastomosis with the Unilink system, sleeve, and suture techniques: a comparative study in the rat.

Multiple microvascular anastomotic techniques have been described with varying rates of success. This experimental study presents the results of a comparison of three types of venous microanastomotic techniques: the Unilink system, the sleeve technique, and the suture technique. Twenty male Sprague-Dawley rats, 40 femoral veins, were used for this study. In vivo observation and microvasculography demonstrated that patency rates between the Unilink system and suture techniques were comparable (p > 0.05) and were significantly superior to the sleeve anastomosis (p < 0.05). The anastomotic time for the sleeve technique was significantly shorter than for the suture technique (p < 0.001). Compared with suture and sleeve anastomoses, the anastomotic time employing the Unilink system was significantly the shortest (p < 0.001). The Unilink system proved to be the fastest method with the highest patency rate. These results suggest that the use of the Unilink system is superior with regard to anastomotic time and patency rate, when compared to suture and sleeve techniques for venous microanastomosis.

Anastomosis, Surgical↗

PubMed1997

Physiological relationships between inhibin B, follicle stimulating hormone secretion and spermatogenesis in normal men and response to gonadotrophin suppression by exogenous testosterone.

Inhibin has been postulated to be secreted by Sertoli cells in response to follicle stimulating hormone (FSH) and in turn to exert an inhibitory effect on FSH production. We have investigated this relationship using an assay specific for dimeric inhibin B. A total of 56 normal men received 200 mg testosterone enanthate (TE) i.m. weekly, for 65 +/- 1 weeks in a trial of hormonal male contraception. Before treatment a significant negative correlation between inhibin B and FSH concentration (r = 0.49, P < 0.001) was observed. During TE treatment, luteinizing hormone (LH) and FSH were rapidly suppressed. This was followed by a parallel decline in inhibin B and sperm concentration. During the early recovery phase, inhibin B concentrations remained suppressed in men who showed a delay in resumption of spermatogenesis, despite higher FSH concentrations. Inhibin B returned to pretreatment concentrations after 24 weeks recovery, when the inverse relationship with FSH was restored. Our results showed the expected inverse physiological relationship between inhibin B and FSH in normal men, with a decline during TE treatment and alpha subsequent resumption of the inverse relationship during recovery. These data clearly support the hypothesis that inhibin B plays a physiological role in the feedback control of FSH secretion, and reflects FSH-stimulated Sertoli cell function.

Adult↗

PubMed1997

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens.

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.

Adrenal Cortex Hormones↗

PubMed1997

Effects of chemotherapy-induced testicular damage on inhibin, gonadotropin, and testosterone secretion: a prospective longitudinal study.

To investigate the role of inhibin in the control of follicle-stimulating hormone (FSH) secretion, we have measured levels of immunoreactive inhibin (ir-inhibin), inhibin B, Pro-alpha C containing inhibins, FSH, luteinizing hormone (LH), and testosterone in twelve men with hematological malignancies before, during, and after chemotherapy. Inhibin B levels fell significantly by 1 month from a mean +/- SE baseline level of 273.2 +/- 32.8 pg/mL, reaching a nadir of 52.6 +/- 15.3 pg/mL at 4 months (P < 0.0001). FSH levels increased within the first month from a baseline level of 3.9 +/- 0.6 IU/L, reaching a peak level of 22.4 +/- 3.3 IU/L at 4 months (P < 0.0001). FSH and inhibin B were significantly and inversely correlated (r = 0.69, P < 0.0001). Pro-alpha C containing inhibin levels increased significantly (P < 0.05) at 3 months and were significantly and positively correlated with FSH (r = 0.38, P = 0.002). LH levels increased significantly but to a much lesser extent than FSH, the increase becoming evident only 4 months after treatment commenced (P < 0.03). Levels of ir-inhibin and testosterone remained unchanged throughout the study. These data provide strong support to the hypothesis that inhibin B is the physiologically important form of inhibin in men, negatively regulating FSH secretion at the pituitary. Furthermore, they suggest that FSH stimulates inhibin alpha-subunit secretion by the testis.

Adult↗

PubMed1997

Endocrine aspects of anabolic steroids.

Understanding of the mechanism of androgen action has been enhanced by advances in knowledge on the molecular basis of activation of the androgen receptor and the importance of tissue conversion of circulating testosterone to dihydrotestosterone and estradiol. New evidence supports the view that supraphysiological doses of anabolic steroids do have a definite, positive effect on muscle size and muscle strength. However, the nature of the anabolic action of androgens on muscle is currently unclear and may involve mechanisms independent of the androgen receptor. The dose-response relationships of anabolic actions vs the potentially serious risk to health of androgenic-anabolic steroids (AAS) use are still unresolved. Most of the adverse effects of AAS are reversible but some are permanent, particularly in women and children. The reported incidence of acute life-threatening events associated with AAS abuse is low, but the actual risk may be underrecognized or underreported; the exact incidence is unknown. The long-term consequences and disease risks of AAS to the sports competitor remain to be properly evaluated.

Anabolic Agents↗

PubMed1997

Zinc, copper, and superoxide dismutase in hepatocellular carcinoma.

Superoxide dismutase (Cu/Zn), a metalloenzyme, activity was found to be significantly lower in the human hepatocellular carcinoma (hepatoma tissue) (0.78 +/- 0.33 U/microg protein) compared with that seen in the surrounding "normal" or cirrhotic tissue (1.40 +/- 0.48 U/microg; 1.27 +/- 0.64 U/microg). The SOD activity of "normal" appearing liver cells adjacent to the tumor or cirrhotic tissue is still lower than that level observed in the normal liver from the subjects without known liver disease (1.40 +/- 0.48 U/microg vs 2.94 +/- 1.53 U/microg). We have also observed that the trace elements of zinc and copper, which are essential in expressing the enzyme activity are also significantly lower in the hepatoma (22.54 +/- 6.73 microg and 2.83 +/- 1.16 microg per gram of tissue) compared with those in the surrounding "normal" hepatic tissue (Zn2+, 64.36 +/- 9.17 microg/g; Cu2+, 11.43 +/- 4.74 microg/g). The difference in the zinc content between the "normal" and the cirrhotic tissue is also significant (64.36 +/- 9.17 microg/g vs 42.37 +/- 10.97 microg/g). However, the copper content in the cirrhotic tissue is higher but not statistically different from that level in the "normal" tissue (15.53 +/- 5.90 microg/g vs 11.43 +/- 4.74 microg/g). Furthermore, the plasma zinc level is significantly lower among the patients who have suffered from hepatoma compared with those subjects without known liver disease (631.73 +/- 52.43 microg/L vs 845.53 +/- 68.13 microg/L). Our data suggest that the superoxide dismutase activity is impaired in the hepatoma tissue. The lower concentration of trace elements (Zn2+ and Cu2+) found in the hepatoma tissue may contribute to cause the difference in the observed enzymic activities.

Adult↗