Colao A, Spiezia S, Di Somma C, Marzullo P, Cerbone G, Pivonello R, Faggiano A, Lombardi G
Department of Clinical and Molecular Endocrinology and Oncology, 'Federico II' University of Naples, Naples, Italy.
Eur J Endocrinol. 2000 Jul;143(1):61-9. doi: 10.1530/eje.0.1430061.
The role of IGF-I in prostate development is currently under thorough investigation since it has been claimed that IGF-I is a positive predictor of prostate cancer.
To investigate the effect of chronic GH and IGF-I deficiency alone or associated with testosterone deficiency on prostate pathophysiology in a series of patients with hypopituitarism.
Pituitary, androgen and prostate hormonal assessments and transrectal prostate ultrasonography (TRUS) were performed in 30 men with adulthood onset GH deficiency (GHD) and 30 age-matched healthy controls, free from previous or concomitant prostate disorders.
Plasma IGF-I levels were significantly lower in GHD patients than in controls (Pearson's coefficient P<0.0001). At study entry, 6 of the 13 hypogonadal patients and 7 of the 17 eugonadal patients had plasma IGF-I below the age-adjusted normal range. At study entry, testosterone levels were low in 13 patients (mean +/-s.e.m., 3.8+/-1.0 nmol/l) while they were normal in the remaining 17 (19.4+/-1.4 nmol/l). No difference in prostate-specific antigen (PSA), and PSA density was found between GHD patients (either hypo- or eugonadal) and controls, while free PSA levels were significantly higher in eugonadal GHD than in controls (0.4+/-0.04 vs 0.2+/-0.03 microg/l; P<0.01). No difference in antero-posterior prostate diameter and transitional zone volume (TZV) was observed among groups, while both transverse and cranio-caudal diameters were significantly lower in hypogonadal (P<0.01) and eugonadal GHD patients (P<0.05) than in controls. Prostate volume (PV) was significantly lower in hypogonadal GHD patients (18.2+/-3.0 ml) and eugonadal GHD patients (22.3+/-1.6 ml), than in controls (25.7+/-1.4, P<0.05). The prevalence of prostate hyperplasia (PV>30 ml) was significantly lower in hypogonadal and eugonadal GHD patients, without any difference between them (15.3% and 5.8%), than in controls (43.3%) (chi(2)=6.90, P=0.005). No difference was found in PV between patients with normal or deficient IGF-I levels both in the hypogonadal group (19. 9+/-4.7 vs 17.3+/-4.0 ml) and in the eugonadal group (22.6+/-2.3 vs 21.8+/-2.5 ml). When controls and patients were divided according to age (<60 years and >60 years), PV was significantly lower in hypogonadal GHD patients aged below 60 years than in age-matched controls (P<0.01) or eugonadal GHD patients (P<0.01), without any difference between controls and eugonadal GHD patients. Controls aged above 60 years had significantly higher PV than both hypogonadal and eugonadal GHD patients (P<0.01). Calcifications, cysts or nodules were found in 56.7% of patients and in 50% of controls (chi(2)=0.067, P=0.79). In controls, but not in GHD patients, PV and TZV were correlated with age (r=0.82, r=0.46, P<0. 0001 and P<0.01 respectively). PV was also correlated with GH (r=-0. 52, P=0.0026), IGF-I (r=-0.62, P=0.0002) and IGF-binding protein 3 (IGFBP-3) levels (r=-0.39, P=0.032) but neither with testosterone or dihydrotestosterone (DHT) levels. In GHD patients TZV but not PV was correlated with age (r=0.58, P=0.0007) and neither TZV nor PV were correlated with GH, IGF-I or IGFBP-3 levels.
Chronic GH deficiency in adulthood causes a decrease in prostate size, mostly in patients with concomitant androgen deficiency and age below 60 years, without significant changes in the prevalence of structural prostate abnormalities.
由于胰岛素样生长因子-I（IGF-I）被认为是前列腺癌的一个阳性预测指标，其在前列腺发育中的作用目前正在深入研究。
在一系列垂体功能减退患者中，研究单纯慢性生长激素（GH）和IGF-I缺乏或与睾酮缺乏相关联对前列腺病理生理学的影响。
对30名成年起病的生长激素缺乏（GHD）男性患者和30名年龄匹配、无既往或伴随前列腺疾病的健康对照者进行垂体、雄激素和前列腺激素评估以及经直肠前列腺超声检查（TRUS）。
GHD患者的血浆IGF-I水平显著低于对照组（Pearson系数P<0.0001）。在研究开始时，13名性腺功能减退患者中有6名以及17名性腺功能正常患者中有7名的血浆IGF-I低于年龄校正后的正常范围。在研究开始时，13名患者的睾酮水平较低（均值±标准误，3.8±1.0 nmol/L），而其余17名患者的睾酮水平正常（19.4±1.4 nmol/L）。GHD患者（性腺功能减退或正常）与对照组之间在前列腺特异性抗原（PSA）及PSA密度方面未发现差异，而性腺功能正常的GHD患者的游离PSA水平显著高于对照组（0.4±0.04 vs 0.2±0.03 μg/L；P<0.01）。各组之间在前前列腺直径和移行区体积（TZV）方面未观察到差异，而性腺功能减退（P<0.01）和性腺功能正常的GHD患者的横径和头-尾径均显著低于对照组（P<0.05）。性腺功能减退的GHD患者（18.2±3.0 ml）和性腺功能正常的GHD患者（22.3±1.6 ml）的前列腺体积（PV）显著低于对照组（25.7±1.4，P<0.05）。性腺功能减退和性腺功能正常的GHD患者中前列腺增生（PV>30 ml）的患病率显著低于对照组（分别为15.3%和5.8%），两者之间无差异，而对照组为43.3%（χ²=6.90，P=0.005）。在性腺功能减退组（19.9±4.7 vs 17.3±4.0 ml）和性腺功能正常组（22.6±2.3 vs 21.8±2.5 ml）中，IGF-I水平正常或缺乏的患者之间在PV方面未发现差异。当根据年龄（<60岁和>60岁）将对照组和患者分组时，60岁以下性腺功能减退的GHD患者的PV显著低于年龄匹配的对照组（P<0.01）或性腺功能正常的GHD患者（P<0.01），对照组和性腺功能正常的GHD患者之间无差异。60岁以上的对照组的PV显著高于性腺功能减退和性腺功能正常的GHD患者（P<0.01）。56.7%的患者和50%的对照组发现有钙化、囊肿或结节（χ²=0.067，P=0.79）。在对照组中，PV和TZV与年龄相关（r=0.82，r=0.46，P<0.0001和P<0.01），但在GHD患者中并非如此。PV还与GH（r=-0.52，P=0.0026）、IGF-I（r=-0.62，P=0.0002）和胰岛素样生长因子结合蛋白3（IGFBP-3）水平（r=-0.39，P=0.032）相关，但与睾酮或双氢睾酮（DHT）水平无关。在GHD患者中，TZV与年龄相关（r=0.58，P=0.0007），而PV与年龄无关，TZV和PV均与GH、IGF-I或IGFBP-3水平无关。
成年期慢性GH缺乏导致前列腺体积减小，主要见于伴有雄激素缺乏且年龄低于60岁的患者，前列腺结构异常的患病率无显著变化。
