Genazzani A D, Forti G, Maggi M, Milloni M, Cianfanelli F, Guardabasso V, Toscano V, Serio M, Rodbard D
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
J Endocrinol Invest. 1990 Nov;13(10):777-86. doi: 10.1007/BF03349621.
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.
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.
我们重新评估了性腺功能减退男性在睾酮替代治疗前后促黄体生成素（LH）分泌的脉冲模式问题。选取5名正常男性作为参照组，对4名性腺功能减退男性在庚酸睾酮替代治疗前及治疗期间进行研究。所有受试者每5分钟采样一次，共采样12小时（08:00至20:00）。使用基于统计学且经验证的脉冲检测程序DETECT对数据进行分析。正常受试者的LH脉冲频率为10.2±1.7个峰值/12小时（平均值±标准误），平均持续时间为48.8±14分钟，而在未进行睾酮替代治疗的性腺功能减退患者中，LH峰值频率（27.5±2个峰值/12小时）显著高于正常受试者（p<0.05），且峰值的平均持续时间低于对照组（17.2±1.2分钟；p<0.01）。在接受慢性庚酸睾酮替代治疗（每两周肌肉注射200mg）后，这些患者的LH峰值持续时间增加，频率显著降低（从27.5±2降至18.2±2.1个峰值/12小时；p<0.01），但脉冲频率仍显著高于正常受试者（p<0.01）。这一发现与假阳性检测率的p值选择无关（p = 0.01或p = 0.005），但确实取决于采样频率，并受峰值检测阈值的大幅（四倍）变化影响。我们使用“离散反卷积”技术估算了两组患者的瞬时分泌率（ISR）。使用ISR得到的结果证实了通过分析观察到的血浆LH测量值所获得的发现。ISR计算还表明，无论是正常受试者还是性腺功能减退患者在睾酮给药前及给药期间，促性腺激素分泌事件的持续时间均显著短于根据血浆浓度估算的持续时间（p<0.01）。
性腺功能减退男性在基础状态下观察到的LH脉冲频率远高于原发性睾丸功能衰竭中先前报道的频率；在传统睾酮替代治疗期间，性腺功能减退男性的LH脉冲频率显著降低，但仍高于正常男性（p<0.01）。这一发现可能与性腺功能减退男性在替代治疗期间睾酮血浆水平低于正常有关；使用10分钟采样间隔对数据进行分析得到的结果与先前报道相似，证实采样间隔的选择可显著影响对频繁LH脉冲分泌的评估。
