Han Thang S, Antonio Leen, Bartfai György, O'Neill Terence W, Punab Margus, Rastrelli Giulia, Maggi Mario, Słowikowska-Hilczer Jolanta, Tournoy Jos, Vanderschueren Dirk, Lean Michael E J, Huhtaniemi Ilpo T, Wu Frederick C W, Castro Ana I, Carreira Marcos C, Casanueva Felipe F
Institute of Cardiovascular Research, Royal Holloway University of London, Egham, TW20 0EX, UK.
Department of Endocrinology, Ashford and St Peter's NHS Foundation Trust, Chertsey, GU9 0PZ, UK.
Rev Endocr Metab Disord. 2024 Dec;25(6):1097-1107. doi: 10.1007/s11154-024-09890-0. Epub 2024 Jun 3.
Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.
目前缺乏关于男性血清催乳素（PRL）低正常或参考区间的实证证据，而极低PRL水平对人类健康的影响从未得到研究。除了与泌乳相关外，“PRL缺乏”的临床状态尚未明确界定。利用欧洲男性衰老研究（EMAS）的数据，我们分析了3369名社区居住的欧洲男性的PRL分布情况，这些男性在第一阶段年龄为40 - 80岁，且无急性疾病。在第一阶段和第二阶段（3至5.7年后）共收集了2948份和2644份PRL样本。所有样本均在同一中心使用相同的检测方法进行分析。在排除已知垂体疾病、PRL≥35 ng/ml以及使用包括抗精神病药物、选择性5-羟色胺再摄取抑制剂或多巴胺激动剂等会改变PRL水平的药物的个体后，有5086个数据点（第一阶段2845个，第二阶段2241个）可用于分析。结果显示，PRL随年龄的下降幅度极小（斜率 = -0.02），且与体重指数（BMI）无关。对呈正偏态分布的PRL进行对数转换，使其变为对称分布（偏度从13.3降至0.015）。使用双标准差经验法则（均值左右2[]SD），分布下端2.5%处的阈值对应PRL值为2.98 ng/ml。以PRL水平为5 - 34.9 ng/ml的个体（事件发生率 = 6.3%）为参照，PRL水平为3 - 4.9 ng/ml的个体发生2型糖尿病的校正风险逐渐增加：事件发生率 = 9.3%，比值比（95%置信区间）为1.59（0.93 - 2.71），而PRL水平为0.3 - 2.9 ng/ml的个体风险增加更为明显：事件发生率 = 22.7%，比值比为5.45（1.78 - 16.62）。基于空腹血糖水平的糖尿病前期和糖尿病也随着PRL水平降低呈现出增加趋势。然而，PRL水平与癌症、心血管疾病、抑郁症状或死亡率无关。我们的研究结果表明，PRL水平低于3 ng/ml（64 mIU/l）能显著识别出有临床重要结局（2型糖尿病）的欧洲男性，为研究和临床实践提供了一个更低的参考值。
