Pulsatile secretion of luteinizing hormone in agonadal men before and during testosterone replacement therapy.
We have reevaluated the question regarding the pulsatile pattern of LH secretion in agonadal men before and following testosterone replacement therapy. Five normal males were used as a reference group and four agonadal men were studied before and during replacement therapy with testosterone enanthate. All the subjects were sampled every 5 min for 12 h (08:00 to 20:00). Data were analyzed using the statistically based and validated pulse detection program DETECT. The normal subjects showed an LH pulse frequency of 10.2 +/- 1.7 peaks/12 h (mean +/- SEM) and a mean duration of 48.8 +/- 14 min, while in agonadal patients without testosterone replacement the frequency of LH peaks (27.5 +/- 2 peaks/12h) was significantly higher than for normal subjects (p less than 0.05), and the mean duration of peaks was lower than in controls (17.2 +/- 1.2 min; p less than 0.01). Following chronic testosterone enanthate replacement therapy (200 mg im every two weeks) these patients showed an increase in the duration and a significant reduction in the frequency of LH peaks (from 27.5 +/- 2 to 18.2 +/- 2.1 peaks/12 h; p less than 0.01) but pulse frequency remained significantly higher than for normal subjects (p less than 0.01). This finding is independent of the choice of p values for false positive detection rate (p = 0.01 or p = 0.005), but it does depend on sampling frequency and is influenced by large (four-fold) changes in the thresholds for peak detection. Using a "discrete deconvolution" technique we estimated the instantaneous secretory rate (ISR) for the two groups of patients. The results using ISR corroborated the findings obtained using analysis of observed plasma LH measurements. ISR computation also showed that the duration of the secretory events of the gonadotropes is significantly shorter (p less than 0.01) than the one estimated on plasma concentration, both in normal subjects and in agonadal patients before and during testosterone administration.


CONCLUSIONS
LH pulse frequency observed in basal conditions in agonadal men was much higher than previously reported in primary testicular failure; during conventional testosterone replacement therapy LH pulse frequency of agonadal men was significantly reduced but still higher (p less than 0.01) than in normal men. This finding is probably related to the subnormal plasma levels of testosterone found in agonadal men during the replacement therapy; the analysis of data using a sampling interval of 10 min gave results similar to previous reports, confirming that the choice of sampling interval can markedly affect the evaluation of frequent LH pulsatile secretion.
Genazzani
A D
AD
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Forti
G
G
Maggi
M
M
Milloni
M
M
Cianfanelli
F
F
Guardabasso
V
V
Toscano
V
V
Serio
M
M
Rodbard
D
D
D000328:Adult; D001800:Blood Specimen Collection; D013196:Dihydrotestosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D006059:Gonadal Dysgenesis / Q000503:physiopathology*; D006207:Half-Life; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009919:Orchiectomy; D010507:Periodicity; D012984:Software; D013737:Testis / Q000002:abnormalities*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors
D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate; D007986:Luteinizing Hormone