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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient hypogonadotrophic hypogonadism commonly occurs after major medical insults. Because data on testosterone precursors are sparse and because little is known about the aetiology of these changes, we studied the interactions of traumatic brain injury with gonadal steroidogenesis and with sympathetic nervous system activation. Patients were divided into two groups based upon the severity of neurological dysfunction using the Glasgow Coma Score (GCS); Group 1 less than 8, Group 2 greater than or equal to 8. Group 1 was further divided into those patients treated (Group 1b) and those not treated with dexamethasone (Group 1a). Plasma levels of testosterone, androstenedione, 17-hydroxyprogesterone, DHEA sulphate, cortisol, LH, FSH, and the catecholamines noradrenaline (NE), adrenaline (EPI) and dopamine were measured in 31 acutely brain injured men, aged 18-95, shortly after their accident and 4 days later. In all patients, NE and EPI were elevated on admission (NE: 841 +/- 105 (SEM) pg/ml; EPI: 191 +/- 32 pg/ml and there were highly significant inverse correlations between admission NE (r = -0.52, P less than 0.003) and EPI (r = 0.44, P less than 0.02) levels and day 4 testosterone concentrations. Testosterone fell 53% (P less than 0.001) in 13 Group 1a men, but only 25% (P = NS) in the less severely injured. Similar reductions occurred in cortisol and the steroid precursors. However, only testosterone, 17-hydroxyprogesterone, and DHEA sulphate levels were significantly lower than normal on day 4. LH and FSH levels were also significantly reduced from elevated admission levels. In the eight men treated with dexamethasone (8-40 mg/ml) (Group 1b), the decrease in testosterone, LH and FSH concentrations were similar to those present in Group 1a. Thus, severe traumatic brain injury leads to hypogonadotrophic hypogonadism which affects testosterone and its precursors. The magnitude of the hormonal dysfunction is dependent upon the severity of the neurological insult. Finally, the decrease in testosterone is significantly correlated with admission catecholamine levels, which may suggest a role for the sympathetic nervous system (SNS) in mediating this response in men.
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PMID:Transient hypogonadotrophic hypogonadism after head trauma: effects on steroid precursors and correlation with sympathetic nervous system activity. 309 64

Several lines of evidence indicate that hypothalamic-pituitary-gonadal activity varies among men with idiopathic hypogonadotropic hypogonadism (IHH). To test the hypothesis that a spectrum of abnormalities of GnRH secretion underlies the syndrome of IHH, we characterized the patterns of GnRH-induced gonadotropin secretion during periods of frequent sampling in 50 consecutive men with IHH and contrasted them with those in 20 normal men. The largest group of IHH patients (n = 42) had no detectable LH or FSH pulsations and could be categorized into 2 subsets according to the presence or absence of evidence of spontaneous puberty. The most severely affected subset (n = 32), who recalled no history of puberty, had testes with a mean volume of 3.3 +/- 0.5 (+/- SEM) ml, with a prepubertal appearance on biopsy, and often were anosmic (n = 17). The second subset of apulsatile IHH men (n = 10) had histories of partial or complete spontaneous sexual development with subsequent isolated loss of sexual function, testes with a mean volume of 13.3 +/- 1.9 ml (P less than 0.01 compared to the first subset), a pubertal or adult appearance of the testes on biopsy, and an intact sense of smell. In a second group of IHH patients (n = 3), LH was secreted predominantly in a nighttime pattern similar to that of normal children during early puberty. These men were aged 18-24 yr, had a mean testicular volume of 10.5 +/- 2.3 ml, pubertal changes on testicular biopsy, and an intact sense of smell. A third group of IHH men (n = 4) had LH pulses of abnormally low amplitude. Only one patient in this group had a history of spontaneous sexual development. The mean testicular volume of these patients was 5.6 +/- 1.9 ml, and the testes appeared prepubertal (n = 3) or pubertal (n = 1) on biopsy. In addition to these groups, another patient had apparent LH pulsations and nearly normal amplitude, but the LH was bioinactive and appeared to consist chiefly of alpha-subunit. Testing of other anterior pituitary hormone functions did not distinguish IHH men from normal men. However, those IHH patients with some evidence of endogenous GnRH secretion had higher basal and stimulated serum PRL levels than IHH men without such evidence (P less than 0.05), suggesting an influence of GnRH on PRL secretion.
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PMID:The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations. 309 71

To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response.
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PMID:Differential control of luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone pulse frequency in man. 310 45

Hyperprolactinaemia was found in 15 of 135 infertile patients with regular menstrual cycles, biphasic basal body temperature record and no galactorrhoea. In those 15 women, mean serum prolactin levels during the mid-follicular and mid-luteal phases of the menstrual cycle were 29.8 (SEM 1.8) ng/ml and 29.5 (SEM 1.3) ng/ml, respectively. Although serum FSH and LH levels were similar in normal and hyperprolactinaemic women, serum oestradiol level during the mid-follicular phase was subnormal in hyperprolactinaemic women (P less than 0.05). In contrast, serum oestradiol and progesterone levels during the mid-luteal phase and luteal phase length were similar in normoprolactinaemic and hyperprolactinaemic groups. The results suggest that hyperprolactinaemia is associated with defects of follicle development as measured by oestradiol production during the mid-follicular phase, but not with corpus luteum function as measured by progesterone production during the mid-luteal phase, and luteal phase length.
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PMID:Serum gonadotrophin and sex steroid hormone levels during mid-follicular and mid-luteal phases in hyperprolactinaemic women with regular menstrual cycles. 310 71

LHRH antagonists compete with endogenous LHRH for binding to receptors on pituitary gonadotrophs and thereby inhibit gonadal function by suppressing gonadotropin secretion. We studied the effects of a recently developed LHRH antagonist on the pituitary-gonadal axis in man. The antagonist Detirelix [( N-Ac-D-Nal(2)1, D-pCl-Phe2,D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH) was given as a single sc injection to nine normal men at three dose levels (5, 10, and 20 mg) at intervals of at least 7 days. Serum FSH, LH, and testosterone levels were measured before treatment, at frequent intervals for 48 h, and 72, 96, and 168 h after administration of the antagonist. Mean serum FSH levels decreased (P less than 0.001) from 6.9 +/- 0.5 (+/- SEM) mIU/mL to nadirs of 4.4 +/- 1.1, 3.6 +/- 0.9, and 4.1 +/- 0.9 after the 5-, 10-, and 20-mg doses, respectively. Serum LH levels decreased (P less than 0.001) from 6.2 +/- 0.3 mIU/mL to nadirs of 3.3 +/- 0.4, 2.8 +/- 0.3, and 2.7 +/- 0.3 after all three doses. Serum testosterone levels decreased (P less than 0.001) in a dose-dependent fashion from 5.1 +/- 0.2 ng/mL to nadirs of 1.3 +/- 0.3, 0.9 +/- 0.3, and 0.6 +/- 0.1 after the same doses. After the initial testosterone decrease, however, escape occurred 12-28 h after the lower doses. The area under the response curve, describing hormone concentrations as a function of time during the study, diminished by 23 +/- 2%, 36 +/- 4%, and 36 +/- 3% for FSH, by 14 +/- 6%, 30% +/- 6%, and 34 +/- 5% for LH, and by 41 +/- 5%, 58 +/- 6%, and 68 +/- 4% for testosterone with the same doses, respectively. The apparent plasma disappearance half-life of Detirelix by RIA was at least 41 h after all three doses. Detirelix elicited only a minor local reaction; no systemic side-effects were observed within the dose range used. These results indicate that this LHRH antagonist is a safe, highly potent inhibitor of the human pituitary-gonadal axis with an exceptionally long duration of action.
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PMID:Suppression of pituitary-gonadal function by a potent new luteinizing hormone-releasing hormone antagonist in normal men. 310 88

Testicular function declines with normal aging, while serum immunoreactive LH and FSH levels increase. Since there are reports of an age-related decrease in the ratio of bioactivity to immunoreactivity (B/I ratio) for LH, we used a newly available bioassay for FSH to assess age-associated changes in the bioactivity and B/I ratio of FSH in man. Thirty-nine healthy men (23 young and 16 elderly) had single blood samples drawn. In addition, a subset of these men (12 young and 13 elderly) underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Hourly blood samples from the 24-h sampling were pooled, and these, along with the single samples, were assayed for FSH by an in vitro bioassay system, using estrogen production by immature rat granulosa cells as the end point, and by RIA. Baseline single sample mean FSH, as measured by bioassay, was similar in young and elderly men [386 +/- 98 (+/- SEM) and 342 +/- 77 ng/mL, respectively]. Baseline mean FSH, measured by RIA, was significantly higher (P less than 0.001) in elderly men (234 +/- 31 ng/mL) than in young men (122 +/- 12 ng/mL). The baseline FSH B/I ratio based on single sampling was significantly lower (P less than 0.01) in elderly men (1.4 +/- 0.2) than in young men (2.7 +/- 0.3). In the men given CC and sampled for 24 h, mean bioactive FSH levels increased significantly in both the young (1180 +/- 282 ng/mL) and the elderly (992 +/- 227 ng/mL; P less than 0.01 for both values compared to baseline). Mean FSH by RIA also increased to similar levels in these young (217 +/- 34 ng/mL) and elderly (258 +/- 45 ng/mL) men. The FSH B/I ratio was 4.8 +/- 0.8 in young and 4.7 +/- 1.1 in elderly men after CC administration. We conclude that serum bioactive FSH levels are similar in elderly and young men, suggesting that the age-related decline in testicular function in man cannot be explained by a chronic deficiency in FSH stimulation; elderly men have a lower serum FSH B/I ratio than young men, which may reflect changes in the circulating form of FSH with aging; and administration of CC to young and elderly men increases both bioactive and immunoreactive serum FSH, implying preserved hypothalamic-pituitary responsiveness in the elderly.
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PMID:Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men. 310 93

Labeled methyltrienelone was used to determine androgen receptor (AR) levels in cultured pubic skin fibroblasts in 40 infertile men with primary seminiferous tubule disorders and 18 normal men. LH pulse patterns and mean serum LH levels were also determined by blood sampling at 10-min intervals for 6 h. The infertile men and the normal men had similar mean receptor levels [mean, 28.1 +/- 2.0 (+/- SEM) and 24.8 +/- 1.8 fmol/mg protein, respectively]. However, 5 men with chromosomal disorders had a higher mean AR level (41.3 +/- 6.2 fmol/mg protein) than the normal men, and 5 of the remaining infertile men (14.2%) had receptor levels that were less than the minimum value in normal men. In men with idiopathic oligospermia, 19.0% had low receptor levels. Although mean serum FSH and testosterone levels were similar in the infertile men with low AR levels and in the normal men, mean LH levels were significantly elevated in this group (7.1 vs. 3.6 IU/L), the higher values being a result of increased LH pulse amplitude (mean, 5.6 vs. 2.8 IU/L). The LH-testosterone product (an index of androgen resistance) was also elevated in these men. When infertile men with low AR levels were matched with infertile men with normal receptor levels, the mean LH values were significantly elevated in the former, as was the LH-testosterone product. Testosterone values were similar in the two groups of men. After excluding subjects with chromosomal disorders, there were no significant correlations between AR levels and other indices of androgen action, such as semen volume, seminal fructose, or sex hormone-binding globulin levels. We conclude that AR levels are higher in patients with severe testicular failure associated with X-chromosome disorders. Also, AR defects were found in 19.0% of infertile men with idiopathic oligospermia. Finally, elevation of mean LH levels in men with seminiferous tubule disorders may reflect resistance to androgen action.
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PMID:Variable androgen receptor levels in infertile men. 310 95

To evaluate the suitability of the sc route for the pulsatile delivery of GnRH, plasma GnRH, LH, and FSH levels were measured by RIA in five women with hypothalamic amenorrhea after sc injection of single doses of 2.5, 5, and 10 micrograms GnRH. The results were compared with those obtained after bolus iv injection of 10 micrograms GnRH. After sc injection, plasma GnRH levels rose to a dose-related maximum after 5-10 min and fell to less than 10% of the peak value by 90 min. The mean plasma disappearance half-time was 24 min (range, 18-30 min). After bolus iv injection, an initial rapid phase of disappearance (t1/2, 2.8 min) was followed by a slower phase (t1/2, 33 min), falling within the 95% confidence intervals for the disappearance half-time after sc administration (12-36 min). The patterns of LH response to sc and iv GnRH were similar, with maximum levels reached between 20 and 30 min after injection, then declining to 50-69% of the peak value by 90 min after sc injection and 61% of the peak value 90 min after iv injection. There was no significant difference between peak LH responses to 10 micrograms iv and sc doses of GnRH [15.2 +/- 2.5 (+/- SEM) vs. 13.2 +/- 2.2 IU/L]. Subcutaneous administration of three consecutive GnRH pulses at 90-min intervals to four women resulted in gonadotropin responses to each GnRH pulse. We conclude that sc GnRH administration results in pulsatile plasma GnRH and gonadotropin responses, the latter resembling those seen after iv GnRH. These results confirm the suitability of the sc route for pulsatile GnRH delivery.
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PMID:Subcutaneous administration of gonadotropin-releasing hormone: absorption kinetics and gonadotropin responses. 310 5

The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin, HOE 766) was studied in plasma and urine after intranasal (300 micrograms) or sc (10 micrograms/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (+/- SEM) was 0.46 +/- 0.08, 0.50 +/- 0.10, 0.28 +/- 0.04, 0.24 +/- 0.04, 0.13 +/- 0.03, and 0.08 +/- 0.02 micrograms/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 +/- 1.96 micrograms/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 +/- 3.0, 25.9 +/- 0.8, 21.2 +/- 0.9, 17.1 +/- 0.7, 12.8 +/- 1.1, 8.9 +/- 0.4, and 5.9 +/- 0.8 micrograms/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 +/- 61 micrograms/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17 beta-E2 and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.
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PMID:Pharmacodynamics of [D-Ser (t-Bu)6,Des-Gly10]GnRH ethylamide (Buserelin) in 6 normal volunteers. Its usefulness to monitor treatment of central precocious puberty. 311 Nov 38

Plasma LH and FSH were measured every 20 min in a group of patients with Klinefelter's syndrome before and after placebo or naloxone administration (8 mg iv as a bolus followed by an infusion of 4 mg/h for 4 h) both in baseline conditions (N = 6) and during treatment with testosterone enanthate (200 mg im every two weeks; N = 4). The mean LH areas measured during saline infusion in baseline conditions (7888 +/- 758 IU/l per min mean +/- SEM) and during testosterone treatment (5042 +/- 2039 IU/l per min) were not significantly different from those measured during naloxone infusion (baseline 8317 +/- 818 IU/l per min; during testosterone treatment 5395 +/- 2007 IU/l per min). Similar results were obtained for FSH. These data suggest that in patients with Klinefelter's syndrome, the opioidergic inhibition of gonadotropin release is lacking and is not restored by testosterone replacement therapy.
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PMID:Naloxone administration does not affect gonadotropin secretion in patients with Klinefelter's syndrome. 311 47


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