Update on pulsatile luteinizing hormone-releasing hormone therapy in males with idiopathic hypogonadotropic hypogonadism and delayed puberty.
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Gonadotropin-Releasing Hormone↗
Biomedical subjects
M Giusti
Publications and source records attributed to M Giusti.
Growth hormone secretion in aging. Effect of pyridostigmine on growth hormone responsiveness to growth hormone-releasing hormone.
Recent studies in adults have shown that cholinergic enhancement by pyridostigmine (PD) has a stimulatory effect on growth hormone (GH) response to GH-releasing hormone (GHRH). PD probably reduces somatostatin release from the hypothalamus by increasing the central cholinergic tone. The aim of this study was to evaluate the effect of PD (120 mg orally) or placebo pretreatment on GH responsiveness to GHRH (1 micrograms/kg b.w. i.v.) or placebo in 10 normal elderly males (68-92 years). PD induced a significant increase in GH secretion (GH peak 7.3 +/- 1.8 micrograms/L, mean +/- SEM) over the basal value (0.9 +/- 0.2 micrograms/L; P less than 0.01) and enhanced GH response to GHRH (peak after GHRH: 17.0 +/- 3.8 micrograms/L; after PD plus GHRH: 42.6 +/- 12.2 micrograms/L; P less than 0.05). There was a significant difference in the secretory areas of GH among tests (P less than 0.05). The secretory area was greater after PD plus GHRH (2722 +/- 801 micrograms/L/120 min) than after GHRH (1185 +/- 206 micrograms/L 120 min; P less than 0.01). The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging. During the life-span cholinergic neurons and/or the somatostatin pathways could exert a differential effect on GH control.
Aged↗
Role of pulsatile luteinizing hormone releasing-hormone therapy in males with idiopathic hypogonadotropic hypogonadism and delayed puberty.
The aim of our work was to review the literature to evaluate the importance of pulsatile LHRH administration therapy in males with idiopathic hypogonadotropic hypogonadism (IHH) and delayed pubertal development. Among the various routes of administration (iv, sc, nasal) we believe that sc administration is better in IHH males whereby a long-term therapy is needed. With regard to the differential diagnosis of pubertal delay, the diagnostic use of LHRH administration for a short-period is still being debated. Biochemical controls show that response to therapy is quick in all of the subjects treated. 30-50% of IHH subjects can obtain adequate sperm production. The appearance of antibodies to LHRH is a rare phenomenon. We can conclude that pulsatile sc therapy is more physiological and better tolerated for a longer time.
Adolescent↗
Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man.
The effect of short-term pulsatile LHRH administration was studied in 8 healthy subjects ranging from 60 to 81 yr to see if the decrease of pituitary gonadal function could be in part due to changes in the discharge of LHRH from the hypothalamus. Gonadotropin and testosterone (T) secretion was evaluated two weeks before and during LHRH (122-160 ng/kg bw every 120 min sc) infusion. In addition, a bolus dosage of LHRH (50 mu iv) was given both at the beginning and at the end of pulsatile LHRH administration in order to test gonadotrophs sensitivity. A significant increase in gonadotropin levels from day 0 to day 4 was found, and was followed by a subsequent decrease from day 7 to day 14. A slight significant increase in T levels was observed during LHRH administration (p less than 0.01). LH pulses were identified in 5 out of 8 subjects on day 0. On day 14, all the exogenous LHRH pulses were followed by significant LH bursts. There was not a significant decrease in the pituitary LH responsiveness to LHRH test from day 0 to day 14. Our study seems to indicate that pituitary - gonadal unit in normal elderly men can be modulated by pulsatile administration of LHRH. A pulse frequency of LHRH which is probably similar to the physiological one, could induce a slight increase in T levels via qualitative changes in LH activity. We can assume that clinical changes in gonadal activity might also be connected to some disturbances in endogenous LHRH pulsar.
Aged↗
The bacteriophage Mu gem gene: a positive regulator of the C operon required for normal levels of late transcription.
The gem product of bacteriophage Mu modulates synthesis of various host proteins and alters the host chromosome topology. To elucidate the role of the gem gene in Mu development, we analyzed the behavior of several mutants in this gene. The results, obtained with two Mu gem- phages, show that (1) phage growth is significantly delayed and inhibited, (2) early transcription is normal but late transcription is delayed and reduced, (3) DNA replication appears normal, and (4) the Mu C gene, whose product positively regulates Mu late genes, is one of the gem target sites. Transcription of a C promoter-lacZ fusion, carried by the pPH91 plasmid, is stimulated both after infection with Mu gem+ or Mu gem3 and is strains lysogenic for the same phages in the presence of viral immunity. These data suggest that the primary role of the gem product is modulation of gene expression. This control could be carried out by direct interaction with transcription factors or by changing DNA supercoiling.
Bacteriophage mu↗
[The role of pulsatile LHRH therapy in women: the treatment of delayed puberty and of hypothalamic amenorrhea].
The importance of gonadotropin pulsatility for normal hypothalamic-pituitary-gonadal axis function is well known. The most important aim of exogenous LHRH administration, given in females with delayed puberty or hypothalamic amenorrhea is to physiologically restore LH pulsatility to a more physiologic way as possible. In fact, a variable degree of LHRH endogenous defect is present in these conditions. Moreover, exogenous LHRH pulsatile administration is able to restore normal pubertal development until menarche appears and normal ovulatory cycles occur and pregnancy is induced. We reported our experience and review the literature regarding the importance and use of LHRH pulsatile therapy in delayed puberty and hypothalamic amenorrhea. We have also evaluated the data for various administration routes, the choice of patients, response to therapy and the possible diagnostic use of pulsatile LHRH with regard to the differential diagnosis of delayed puberty.
Adolescent↗
Injection sites and pharmacokinetics of luteinizing hormone releasing hormone: comparison of two different subcutaneous administration routes.
A normal pituitary-gonadal function is reinduced by iv or sc pulsatile LHRH therapy, administered by a portable pump. In order to evaluate the differences between different sites of injection on the LHRH bioavailability, we compared the LHRH plasma concentration after a single LHRH injection in the lower abdominal wall and in the upper arm, in 5 patients with idiopathic hypogonadotropic hypogonadism, during LHRH treatment. Our data showed no significant differences in using both administration routes. In fact, LHRH absorption (secretory area and peak value) is quite similar. However, patients tolerated LHRH administration in the abdominal wall more so than in the upper arm. Both ways of administration are effective with regards to the pituitary responsiveness but we can not forget that patients compliance is of great importance in order to obtain the best results in a long-term therapy.
Abdomen↗
Prolactin secretion in idiopathic hypogonadotropic hypogonadism during pulsatile luteinizing hormone-releasing hormone long-term administration.
Recent data seem to suggest that LHRH may be involved in the modulation of PRL secretion. We studied the PRL pattern in 9 males (age range 18-38 yr) with idiopathic hypogonadotropic hypogonadism (IHH) before and during long-term pulsatile LHRH therapy (120-160 ng/kg bw every 120 min sc) in order to evaluate variations in the spontaneous PRL secretion or LHRH-induced presence of PRL pulse. LH, FSH and PRL secretion was evaluated every 15 min for 3 h on day 0, day 30 and days 90-150. Before and during LHRH therapy PRL 24-h integrated concentration (IC) and gonadotropin or PRL response to LHRH test (50 micrograms iv/bolus) were evaluated. On day 0 spontaneous PRL pulses were found in 2 IHH patients. On day 30 PRL pulses were found in 4 cases. On days 30-90 PRL pulses were sporadically concomitant with LHRH-induced LH pulses. Mean PRL levels and 24-h IC of PRL were found to be significantly (p less than 0.05) increased during pulsatile LHRH administration. A significant positive (p less than 0.01) correlation was observed between testosterone and PRL levels during LHRH therapy. When compared to a significant LH response to LHRH iv bolus, no modification of PRL secretion was found. The present study did not show any relationship between LHRH administration and PRL secretion. It might be hypothesized that LHRH does not play a determinant role in PRL secretion and does not seem to modulate PRL secretory pattern in IHH males.
Adolescent↗
Effect of subacute cabergoline treatment on prolactin, thyroid stimulating hormone and growth hormone response to simultaneous administration of thyrotrophin-releasing hormone and growth hormone-releasing hormone in hyperprolactinaemic women.
It is known that dopaminergic neurotransmission is involved in the control of PRL, TSH and GH secretion. Cabergoline (CAB) is a new ergolinic derivative with a long-acting dopaminergic activity. We evaluated 11 women with pathological hyperprolactinaemia before and during sub-acute CAB treatment (0.8-1.2 mg/p.o.; 8 weeks). Simultaneous administration of TRH (200 micrograms i.v.) and GHRH 1-44 (50 micrograms i.v.) were carried out before and after 4, 8 and 10 week intervals from the beginning of CAB treatment. Basal PRL levels (2453.5 +/- S.E. 444.5 mU/l) were significantly reduced during CAB administration (week 4: 164.5 +/- 66.5 mU/l; week 8: 168.0 +/- 66.5 mU/l; P less than 0.01) and no variations were observed 2 weeks after drug discontinuation (week 10: 210.0 +/- 98.0 mU/l). PRL percentage change after TRH was increased by CAB (P less than 0.05). No variation in basal and TRH-stimulated TSH levels was found during CAB administration. A slight increase in GH basal levels (3.0 +/- 0.6 mU/l) was found after weeks 4 (6.4 +/- 2.0 mU/l) and 10 (5.8 +/- 1.6 mU/l) (P less than 0.05). GH response to GHRH was significantly enhanced (ANOVA: P less than 0.01) during sub-acute CAB treatment. A positive correlation was found between GH secretory area and weeks of CAB therapy (P less than 0.01). Our data show that CAB is very effective in lowering PRL secretion in hyperprolactinaemia, and is able to modify PRL and GH responses after TRH and GHRH. The increasing trend in GH basal and GHRH-stimulated GH levels seems to indicate that CAB can override the central dopaminergic tone which is operative in hyperprolactinaemia.
Adult↗
Effectiveness and tolerability of long term treatment with cabergoline, a new long-lasting ergoline derivative, in hyperprolactinemic patients.
Cabergoline (CAB) is a new oral dopaminergic compound showing a very long-lasting PRL-lowering activity and reported to be well tolerated. The efficacy and tolerability of chronic treatment with CAB in 30 female hyperprolactinemic patients, aged 18-52 yr (6 microadenomas, 3 macroadenomas, and 21 functional hyperprolactinemias), were studied. In a group of 10 patients who received CAB (0.8 mg once weekly or 0.4 mg twice weekly) for 8 weeks PRL levels normalized while on treatment and remained normal (8 patients) or greatly reduced (1 patient) for 1-2 months after discontinuation of the drug. Twenty-six patients underwent chronic treatment (6-12 months) with an initial dose of 0.5 mg once weekly, subsequently increased to 1-2 mg in 10 patients and decreased in the other 2. Due to severe side-effects CAB was discontinued in 3 patients, in 1, 8, and 12 weeks. A significant reduction of PRL levels was already observed after the first week of treatment (mean +/- SEM basal values, 90.1 +/- 13.3 vs. 29.5 +/- 6.3 micrograms/L; P less than 0.001). Twenty-two patients had normal PRL levels in 1-36 weeks (mean, 6 weeks) with 0.5-2 mg CAB. Twenty-two patients resumed regular menses; 2 patients became pregnant after 3-11 months of treatment. Thirteen patients complained of side-effects (nausea, hypotension, headache, gastric pain, dizziness, and weakness) that disappeared with time in 10 of them. The comparison with a previous bromocriptine treatment regimen in 20 patients had shown that the number of patients requiring discontinuation of the latter drug was significantly higher (7 vs. 3 patients; P less than 0.001). However, 2 patients who needed to discontinue CAB were able to tolerate bromocriptine therapy. A computed tomographic scan performed after 12 months of therapy in 7 patients showed a significant reduction (50%) of the adenoma in 5. In conclusion, our results show that CAB is a well tolerated new dopamine agonist with long-lasting activity that represents an advance in chronic medical treatment of hyperprolactinemic conditions.
Adenoma↗
The effect of long-term pulsatile GnRH administration on the 24-hour integrated concentration of GH in hypogonadotropic hypogonadic patients.
Measurement of integrated concentration of GH by means of continuous withdrawal sampling is a method of evaluating physiological hormonal secretion. Integrated concentration of GH was evaluated in 5 subjects with idiopathic hypogonadal hypogonadism (range 19-27 years) and in a 17-year-old male with idiopathic delay of puberty (5 males, 1 female) before and 30-240 days after the start of pulsatile GnRH administration. Gonadotropins and testosterone or 17 beta-estradiol were restored, whereas 24-h integrated concentration of GH (before therapy 5.4 +/- 1.3 IU/1; during GnRH 8.1 +/- 2.0 IU/1; P less than 0.05) was increased by GnRH therapy. However, no correlation was found between GH levels and sex steroid concentrations during GnRH pulsatile administration. These data further confirm that a physiological increase in gonadotropins and sex steroids can modulate GH synthesis and/or release.
Adult↗
Growth hormone and prolactin response to growth hormone-releasing in anorexia nervosa.
Anorexia nervosa (AN) is associated with several endocrine disorders. In order to investigate the role of these alterations, growth hormone-releasing hormone (GHRH) was administered in a group of 9 AN patients and in 9 healthy normal-weight women as control. Growth hormone (GH) and prolactin (PRL) levels were evaluated in both groups after GHRH and saline solution administration. In the AN group, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH) and cortisol serum levels were evaluated during GHRH administration; somatomedin-C (Sm-C) basal levels were also determined. In both groups, GHRH induced a prompt GH increase, which was significantly higher in AN patients (55.3 +/- 2.9 ng/ml, mean +/- SE) than in normal subjects (9.8 +/- 2.6 ng/ml: p less than 0.01). A significant positive correlation between mean GH basal values and GH peak after GHRH was observed only in the control group (R = 0.82, p less than 0.01). No significant relationship between GH mean peak and body mass index (BMI) or Sm-C, estradiol (E2) and glucose serum levels was found in AN patients. However, a positive significant correlation with triiodothyronine (T3) basal values was observed in this group (R = 0.80, p less than 0.01). Both groups showed no variation in PRL serum levels after GHRH infusion. Our data suggest the presence of a central derangement in hypothalamic control of pituitary function in patients with AN, which is not necessarily due to weight loss alone.
Adolescent↗
Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation.
Serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, 17 beta-estradiol, testosterone, androstenedione, dehydrotestosterone, dehydroepiandrosterone sulfate, and cortisol were examined in 14 men with rheumatoid arthritis (RA) and in age-matched osteoarthritis controls. Hypophyseal, adrenal, and testicular responses to stimulation with luteinizing hormone-releasing hormone, adrenocorticotropin, and human chorionic gonadotropin, respectively, were evaluated in 8 RA patients and in 8 age-matched healthy volunteers. Basal serum testosterone concentrations were significantly lower in male RA patients than in the osteoarthritis control subjects (P less than 0.01). After human chorionic gonadotropin stimulation, serum concentrations of testosterone were also lower in the RA patients than in normal healthy controls (P less than 0.05). These findings suggest that diminished testicular steroid biosynthesis might contribute to the serum testosterone deficiency observed in male RA patients.
Adult↗
Endogenous opioid blockade and gonadotropin secretion: role of pulsatile luteinizing hormone-releasing hormone administration in anorexia nervosa and weight loss amenorrhea.
In anorexia nervosa alterations in the hypothalamic-pituitary-gonadal unit were previously thought to have been connected to an increase of endogenous opiate tone. The authors tried to prove that the replacement of normal endogenous steroid levels could restore the functional coupling between opiatergic and luteinizing hormone-releasing hormone (LH-RH) neurons in patients with anorexia nervosa. Pulsatile LH-RH therapy has been used to achieve normal ovarian activity. The authors studied gonadotropin levels before and during intravenously (IV) pulsatile LH-RH therapy (50 to 100 ng/kg body weight/90 to 120 minutes) in three anorexia nervosa and two weight loss amenorrhea patients, during both placebo and naloxone administration (2 mg IV bolus plus 4 mg infusion lasting 120 minutes). Before therapy, naloxone administration did not significantly change gonadotropin levels in three out of five patients, while a decrease in gonadotropin levels was observed in the other two subjects. During LH-RH therapy, normal pituitary-gonadal activity was demonstrated and ovulatory cycles were found in all patients. Naloxone administration did not change gonadotropin release during LH-RH therapy. Data could support the hypothesis of either a primitive impairment of LH-RH neurons, or an alteration in central regulation of LH-RH pulsar in anorexia nervosa.
Adolescent↗
Famotidine has no significant effect on gonadal function in man.
The effect of a single bedtime dose of famotidine 40 mg on gonadal function was studied in 8 male duodenal ulcer patients. The drug was orally administered for 4 weeks. Our results show that this new H2 blocker influences basal and stimulated serum levels of neither testosterone nor gonadotrophins (LH, FSH). Besides, no significant variations were observed before and after famotidine treatment in seminal fluid characteristics evaluated in 5 out of 8 cases. It can be concluded that famotidine appears to leave gonadal function unaffected in man.
Administration, Oral↗
[Evaluation of working conditions at the work place with video terminals: a survey conducted in 6 business offices].
The Authors have taken under study 6 office buildings and a total of 165 work stations with VDTs. Lighting conditions, postures, indoor climate and air-quality have been evaluated, besides worker's subjective approach sounded by individual questionnaire. Concerning visual comfort, it has been noticed that the most simple and well-known rules are often disregarded, such as avoiding to place a screen in front of a light source because of its glare. Also, operators postures are often incorrect, making problems related to their own fixity worse. Air conditioning systems assure almost excellent conditions for thermal comfort, but air changes are often poor and microbiologic quality suffers from plant's inadequate servicing. Finally, the survey of questionnaires shows a complaint percentage which only partly corresponds with the objective data collected, reflecting instead an uneasiness to the kind of work and its organisation.
Air Microbiology↗
The GH-releasing hormone (GHRH) test in acromegaly before and after adenomectomy.
The GHRH test may represent a new tool in the study of GH dynamics in acromegaly. GH responsiveness to GHRH 1-40 (50 micrograms iv) has been studied in 21 acromegalic patients. Nineteen out of 21 had active disease. Five patients were also studied 1-12 months after neurosurgery. Two apparently cured acromegalics were studied 1-2 yr after surgery. GH secretion has been evaluated in all patients by means of TRH, bromocriptine and insulin hypoglycemia tests, too. GH response to GHRH has also been performed in 14 normal subjects. In acromegaly, GH responses after GHRH (p less than 0.01 vs placebo) were variable. The GH peak ranged from 8 to 445 ng/ml in patients with active disease. Maximum GH increase after GHRH (calculated as peak/basal value ratio) was significantly reduced in acromegaly (2.9 +/- 0.5 ng/ml; mean +/- SE) in comparison to controls (34.1 +/- 10.9 ng/ml; p less than 0.01). No significant differences in GH pattern after GHRH were found between untreated and previously treated patients with active disease. A significant correlation was found between GH basal levels and GH incremental area (p less than 0.05) and between GH basal and peak levels (p less than 0.01) after GHRH. A significant increase in PRL secretion was observed in acromegalic patients after GHRH (p less than 0.01 vs placebo). No discernable variation was found in the other pituitary hormones pattern after the peptide administration. A positive correlation was observed between GH increase after GHRH and insulin hypoglycemia (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗
Role of aging on growth hormone and prolactin release after growth hormone-releasing hormone and domperidone in man.
Growth hormone (GH) and prolactin (PRL) secretion after GH-releasing hormone (GHRH) and domperidone (DOM), an antidopaminergic drug which does not cross the blood-brain barrier (BBB), was evaluated in 8 healthy elderly men (65-91 years) and in 7 young adults (23-40 years). All received in random order at 2-day intervals: GHRH(1-40) (50 micrograms i.v.) bolus, DOM (5 mg/h) infusion, GHRH(1-40) (50 micrograms i.v.) plus DOM (5 mg/h i.v.), saline solution. In elderly men GH increase after GHRH was significantly lower than in young men. DOM alone did not change GH secretion in either of these groups, whereas it increased the GH response to GHRH only in young adults. PRL levels increased in both young and elderly men during both DOM and GHRH plus DOM, but the PRL release was more marked in young than in elderly men. Both integrated secretion of GH after GHRH and of PRL after DOM were inversely correlated to chronological age. Our data show an impairment of GH rise after GHRH and of PRL after DOM in elderly adults. It is also stressed that peripheral blockade of dopamine receptors by DOM is unable to amplify the GH response to GHRH only in elderly men. A reduction in GH release after GHRH might be related to aging, perhaps through a reduction of dopaminergic tonus.
Adult↗