Effects of Long-Term Erythropoietin Therapy on the Hypothalamo–Pituitary–Testicular Axis in Male Capd Patients

2001 ◽  
Vol 21 (5) ◽  
pp. 448-454 ◽  
Author(s):  
Bülent Tokgöz ◽  
Cengiz Utaş ◽  
Ayhan Dogukan ◽  
Muhammet Güven ◽  
Hülya Taşkapan ◽  
...  

Objective Gonadal dysfunction has been recognized for a long time in uremic male patients. The present study assesses the hypothalamo–pituitary–testicular axis and growth hormone status in male continuous ambulatory peritoneal dialysis (CAPD) patients, before and after recombinant human erythropoietin (rHuEPO) therapy. Design Single-center prospective study. Subjects Ten anemic male patients with chronic renal insufficiency, and 11 healthy volunteers with normal renal function, matched for age, were included in the study. All patients were on CAPD therapy and none had received rHuEPO treatment previously. Main Outcome Measures Blood samples were collected between 0800 and 0900 hr from all patients for the determination of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) levels. A luteinizing hormone-releasing hormone (LH-RH) stimulation test was carried out using LH-RH 100 mg intravenous as a bolus injection. Blood for FSH, LH, and GH determinations was drawn every 30 minutes during the 3-hour test period. Human chorionic gonadotropin (hCG) test was performed after 48 hours. After estimations of basal serum total and free testosterone levels, 2000 IU hCG was administered intramuscularly and repeated 48 hours later. Total and free testosterone levels were measured in blood samples collected before and 48 hours after two injections of hCG. After improvement in anemia with exogenous rHuEPO, LH-RH and hCG tests were repeated. Results Baseline FSH concentrations before and after rHuEPO treatment were slightly higher in CAPD patients than in healthy volunteers ( p = 0.85 and p = 0.70, respectively). Areas-under-the-curve (AUCs) for FSH secretion before and after rHuEPO treatment were also slightly higher in patients than in healthy volunteers ( p = 1.00 and p = 0.75, respectively). The pretreatment basal LH levels in patients were significantly higher than in controls ( p < 0.001). After the improvement in anemia with rHuEPO, serum LH levels declined significantly ( p < 0.05). The AUCs for LH secretion before and after rHuEPO treatment were significantly higher in patients than in controls ( p < 0.05). All patients had elevated basal levels of GH with paradoxical response to LH-RH. Baseline GH levels in patients were significantly higher than those in healthy subjects ( p < 0.001) before rHuEPO treatment. After treatment with rHuEPO, basal GH levels declined but did not normalize, and baseline levels of free testosterone increased significantly ( p < 0.05). Conclusion Anemic uremic male patients on CAPD have normal levels of testosterone with normal response to hCG administration, elevated basal levels of GH, and elevated basal levels of LH, with exaggerated response to LH-RH administration. Improvement in anemia with rHuEPO reduced the basal levels of LH and GH, but exaggerated the LH response; paradoxical GH response to LH-RH administration persisted. These results indicate a defect at the level of the hypothalamus and pituitary gland in uremic male patients undergoing CAPD, and that the improvement in anemia with rHuEPO partially restores some of these endocrine abnormalities.

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S102-S103
Author(s):  
Y S Kamel

Abstract Introduction/Objective The aim of this study was to investigate the effects of GH administration on basic coagulation parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before and during one year of GH replacement. Methods Twenty-one adult patients with severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital based, prospective, interventional study. All patients were treated with rhGH for 12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF-1 concentrations were determined using RIA-INEP kits. Basic coagulation tests, i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and 12 months of treatment with rhGH. Control values were obtained from fourteen “healthy” subjects matched by age, sex and body mass index (BMI). Results At baseline, we observed no significant differences in PT, aPTT and fibrinogen values between GHD and healthy subjects. IGF-1 concentrations increased significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l, p &lt;0.05) and remained stable thereafter. A significant increase in PT values, which was more pronounced in female subjects, was noted after 6 and 12 months of treatment with GH. aPTT values increased significantly after 12 months of treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p &lt;0.05). No significant changes in fibrinogen concentrations were found during the study. Conclusion Twelve months of GH replacement therapy led to a significant increase in PT and aPTT values in adult GHD patients, while fibrinogen concentrations did not change. Changes in PT were more pronounced in female GHD patients, while an increase in aPTT values was observed only in male patients with GHD. The clinical significance of these changes needs further evaluation.


2011 ◽  
Vol 55 (4) ◽  
pp. 266-271 ◽  
Author(s):  
Rogerio Silicani Ribeiro ◽  
Julio Abucham

OBJETIVE: To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS: Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS: After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS: Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.


1978 ◽  
Vol 76 (3) ◽  
pp. 417-425 ◽  
Author(s):  
C. A. BLAKE ◽  
PATRICIA K. BLAKE ◽  
NANCY K. THORNEYCROFT ◽  
I. H. THORNEYCROFT

The effects of coitus and injection of luteinizing hormone releasing hormone (LH-RH) on serum concentrations of LH, testosterone and dihydrotestosterone (17β-hydroxy-5α-androstan-3-one; DHT) were tested in male rabbits. Before experimentation, male and female rabbits were housed in individual cages in the same room. Male rabbits were then bled by cardiac puncture before and after placement with female rabbits or intravenous injection of LH-RH. Serum LH, testosterone and DHT were measured by radioimmunoassay. Sexual excitement (sniffing, chasing and mounting), with or without intromission, caused a marked rise in serum testosterone and DHT concentrations in only some of the bucks. These increases were accompanied or preceded by a small, transient increase in serum LH. In the rest of the bucks, sexual excitement with or without intromission had either no effect on serum levels of all three hormones, or only serum testosterone and DHT decreased during the collection period. Similar responses were measured in bucks which were housed in a room without does for 2–4 weeks before experimentation. Injection of 10, 30 or 100 ng or 50 μg LH-RH caused serum LH, testosterone and DHT to rise in all bucks tested, but the magnitude of the rises in serum testosterone and DHT were not related to the magnitude of the LH rise. In both mated and LH-RH-injected bucks, the rises in serum testosterone and DHT were greatest in animals with low initial testosterone and DHT values. Under the conditions of this study, the data suggest that: (1) serum testosterone and DHT rise in only some male rabbits after sexual excitement (with or without intromission), (2) the rises in serum testosterone and DHT are dependent on a small transient increase in serum LH and (3) sexual excitement is less likely to cause release of LH-RH in bucks with raised serum testosterone and DHT concentrations.


2002 ◽  
pp. 143-148 ◽  
Author(s):  
AN Moulas ◽  
JD Veldhuis ◽  
JC Chan ◽  

OBJECTIVE: To determine the effect of repeated treatments with the growth hormone secretagogue (GHS) L-163,255 on the pulsatile release of GH when administered in meal-fed rats before and after feeding. DESIGN: The first group of rats (AL, n=6) had food available ad libitum. The second (restricted, R, n=6), third (GHSB, n=6), and fourth (GHSA, n=6) groups were fed from 1100 to 1400 h. Groups GHSB and GHSA were given GHS by gavage, 3.0 mg/kg L-163,255, at 1000 h (before feeding, B) and at 1500 h (after feeding, A) respectively. Three weeks after the initiation of the treatment, blood samples were collected at 10-min intervals over 6 h, and GH levels were determined. RESULTS: In group R, the concentrations of GH were higher before feeding (17.6+/-2.4 ng/ml) than during feeding (11.2+/-1.2 ng/ml), P<0.05. The average concentrations of the peak in response to GHS were higher when GHS was administered before (121.70+/-33.68 ng/ml) than after (49.67+/-17.87 ng/ml) feeding. The mass of GH, as calculated by deconvolution analysis was also higher in the GHSB group than in the GHSA group (251.6+/-64.1 ng/ml per min vs 85.3+/-22.9 ng/ml per min respectively, P<0.05). CONCLUSION: L-163,255 is effective in inducing GH release after repeated oral administration in rats. The effectiveness is greater when GHS is administered before rather than after feeding in meal-fed animals.


1976 ◽  
Vol 68 (3) ◽  
pp. 409-417 ◽  
Author(s):  
J. P. FOSTER ◽  
S. L. JEFFCOATE ◽  
D. B. CRIGHTON ◽  
D. T. HOLLAND

SUMMARY Luteinizing hormone and LH-RH-like immunoreactivity were measured in the jugular venous plasma of Clun Forest ewes at various stages of the oestrous cycle. Blood samples were collected through jugular venous cannulae every 2 h for at least 20 days from three ewes during the breeding season. The ewes were checked twice daily for oestrus using a vasectomized ram. Plasma LH peaks of apparent height 112–192 ng NIH-LH-S17 equivalents/ml were detected at oestrus with basal levels of 2–15 ng/ml during most of the remainder of the 17-day oestrous cycle. Peaks of LH-RH-like immunoreactivity occurred at various times of the cycle. The apparent maximal level of these peaks was 220 pg/ml compared with basal levels of < 10 pg/ml. Further ewes (two for each group) were sampled at 4 min intervals for 12 h, (1) from onset of oestrus, (2) 36–48 h after onset of oestrus or (3) on day 10 of the oestrous cycle. In the ewes sampled at oestrus, peaks of LH-RH-like immunoreactivity were detected before, during and after the preovulatory LH peak. Those detected after the LH peak were unassociated with any further increases in the plasma LH level. In the ewes sampled 36–48 h after onset of oestrus and on day 10 of the cycle, several peaks of LH-RH-like immunoreactivity unassociated with any increases in the LH level were detected. These peaks, and those detected at oestrus, had durations of only one or two samples, and in some cases reached levels of several ng/ml compared with basal levels of < 10 pg/ml. The significance of these results is discussed.


1974 ◽  
Vol 77 (3) ◽  
pp. 422-434 ◽  
Author(s):  
Philippe E. Gamier ◽  
Jean-Louis Chaussain ◽  
Elisabeth Binet ◽  
Ariane Schlumberger ◽  
Jean-Claude Job

ABSTRACT Plasma gonadotrophins (LH and FSH) were radio-immunoassayed before and after injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone (LH-RH) in infants 1 to 12 months old, prepubertal children aged more than 12 months, and pubertal subjects of both sexes. The pubertal changes of gonadotrophins include a highly significant increase of LH pituitary mobilizable reserve in both sexes, while the FSH reserve shows a significant decrease in females and no significant variation in males. From the first year of life up to childhood, the basal blood levels of FSH and LH decrease significantly in girls but do not vary in boys, while the FSH reserve decreases significantly in girls and increases significantly in boys, the LH reserve showing a non-significant decrease in both sexes. In the first year of life, girls show a very significantly higher FSH secretion and reserve than boys, while boys have a significantly higher LH reserve than girls. After the end of the first year up to the onset of puberty, the FSH reserve remains significantly higher in girls than in boys. The interpretation of these facts is discussed.


1978 ◽  
Vol 79 (3) ◽  
pp. 319-326 ◽  
Author(s):  
C. A. BLAKE

There are many drugs which act on the central nervous system to block the spontaneous, preovulatory surge of LH in the plasma of the rat when administered just before the start of the LH surge at pro-oestrus. Several of these drugs have been tested for their ability to inhibit LH release after the start of the LH surge. Four day cyclic rats were each fitted with an indwelling right atrial cannula during the morning of pro-oestrus. Serial blood samples were collected through the cannula during the afternoon of pro-oestrus, starting at a time when the level of LH in the plasma was expected to be raised. Drugs were then administered at doses known to block the surge of LH. Additional blood samples were collected and subsequently the plasma concentration of LH was measured by radioimmunoassay. In rats with a raised level of LH, i.p. injection of phenobarbitone or pentobarbitone, s.c. injection of atropine or i.v. injection of ethanol caused the concentration of LH to fall rapidly starting within 15 min after the injection. The mean half-lives for the disappearance of LH from plasma ranged from 23·5 to 28·6 min over a 30 min period. In contrast, s.c. injection of nicotine, i.p. injection of urethane or continuous exposure to ether fumes resulted in a biphasic effect on the concentration of LH in the plasma. The value rose rapidly, reached a peak within 5–20 min and declined rapidly (range of mean half-lives 25·3– 28·6 min). Nicotine, urethane and ether caused a small, transient increase in the plasma level of LH when administered before the start of the spontaneous surge of LH. These results and the fact that luteinizing hormone releasing hormone (LH-RH) is far more effective at raising the concentration of LH in the plasma when given after the start of the LH surge than just before it, suggest that LH-RH must prime the pituitary gland before nicotine, urethane or ether can cause a substantial increase in the plasma level of LH in pro-oestrous rats.


1974 ◽  
Vol 60 (1) ◽  
pp. 101-106 ◽  
Author(s):  
C. B. KATONGOLE ◽  
F. NAFTOLIN ◽  
R. V. SHORT

SUMMARY Three adult Suffolk rams were bled at weekly intervals for 14 months, and at hourly intervals for 24 h during the summer (one ram) and autumn (two rams). Luteinizing hormone (LH) was measured by radioimmunoassay, and testosterone by a competitive protein binding assay. There were episodic bursts of LH secretion during the 24 h period in both the summer and the autumn; the frequency of discharge was lower in the summer, but the amplitude (0·1–8·0 ng/ml) did not appear to change. It was not always possible to detect seasonal changes in LH concentration in single blood samples taken once a week throughout the year. The blood testosterone levels also showed marked fluctuations throughout the 24 h, and the frequency of the peaks was lower in the summer. But in contrast to LH, the magnitude of the testosterone peaks also changed throughout the year; from January to September the testosterone concentration ranged from 0·5 to 10 ng/ml plasma, whereas from October to December it ranged from 3 to 28 ng/ml. Thus in temperate regions the ram, like the ewe, shows seasonal changes in gonadal endocrine activity, although some degree of spermatogenesis continues throughout the whole year.


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