Pincus S M, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis J D
Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14100-5. doi: 10.1073/pnas.93.24.14100.
New statistical perspectives on the secretory patterns of both luteinizing hormone (LH) and testosterone (T) may prove useful in further understanding the aging process, and possibly ultimately in improving the diagnosis and treatment of spermatogenetic failure and loss of sexual interest. We examined serum concentration time-series for LH and T in 14 young (21-34 years of age) and 11 aged (62-74 years of age) healthy men. For each subject, blood samples were obtained at 2.5-min intervals during a sleep period, with an average sampling duration of 7 hr. For each of LH and T, we used the model-independent statistic approximate entropy (ApEn) to quantify the irregularity of the serum concentration time-series; to quantify joint LH-T secretory asynchrony, we employed the recently introduced cross-ApEn. Although mean (and SD) LH and T concentrations were indistinguishable in the two age groups (P > 0.25), for LH, aged subjects had greater ApEn values (1.525 +/- 0.221) than younger individuals (1.207 +/- 0.252), P < 0.003, indicating more irregular secretion in the older cohort. For T, aged subjects also had greater ApEn values (1.622 +/- 0.120) than younger counterparts (1.384 +/- 0.228), P < 0.004. In young, but not older men, ApEn(T) significantly exceeded ApEn(LH), P < 0.02. Aged subjects had greater cross-ApEn values (1.961 +/- 0.121) than younger subjects (1.574 +/- 0.249), P < 10(-4), with nearly 100% sensitivity and specificity, indicating greater LH-T asynchrony in the older group. In conjunction with previous findings of greater irregularity of growth hormone release with increasing age, we propose that increased secretory irregularity with advancing age may be a widespread hormonal phenomenon. Finally, theoretically, we clarify the need for quantifications such as ApEn and cross-ApEn via a study of a "variable lag" pulsatile process, and empirically note the potential wide applicability of cross-ApEn to quantify asynchrony in interconnected (hormonal) networks.
对促黄体生成素（LH）和睾酮（T）分泌模式的新统计观点可能有助于进一步理解衰老过程，并最终可能改善生精功能衰竭和性兴趣丧失的诊断与治疗。我们检测了14名年轻（21 - 34岁）和11名老年（62 - 74岁）健康男性的LH和T血清浓度时间序列。对于每个受试者，在睡眠期间每隔2.5分钟采集一次血样，平均采样持续时间为7小时。对于LH和T，我们使用与模型无关的统计量近似熵（ApEn）来量化血清浓度时间序列的不规则性；为了量化LH - T联合分泌的不同步性，我们采用了最近引入的交叉近似熵（cross - ApEn）。尽管两个年龄组的LH和T平均（及标准差）浓度无显著差异（P > 0.25），但对于LH，老年受试者的ApEn值（1.525±0.221）高于年轻个体（1.207±0.252），P < 0.003，表明老年组分泌更不规则。对于T，老年受试者的ApEn值（1.622±0.120）也高于年轻受试者（1.384±0.228），P < 0.004。在年轻男性中，ApEn（T）显著超过ApEn（LH），P < 0.02，但老年男性并非如此。老年受试者的交叉近似熵值（1.961±0.121）高于年轻受试者（1.574±0.249），P < 10⁻⁴，敏感性和特异性接近100%，表明老年组LH - T不同步性更强。结合先前关于生长激素释放随年龄增长不规则性增加的研究结果，我们提出随着年龄增长分泌不规则性增加可能是一种普遍的激素现象。最后，从理论上讲，我们通过对“可变滞后”脉冲过程的研究阐明了对ApEn和交叉近似熵等量化方法的需求，并通过实证指出交叉近似熵在量化相互关联（激素）网络中的不同步性方面具有潜在的广泛适用性。
