Hogervorst E, Combrinck M, Smith A D
Oxford Project To Investigate Memory and Ageing, Department of Pharmacology, University of Oxford, Oxford, UK.
Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):203-8.
Sex steroids such as testosterone and estradiol might protect the brain against Alzheimer's disease (AD). We previously found lower levels of testosterone in men with AD compared with controls. We wanted to assess levels of pituitary gonadotropins that regulate sex steroid levels, to determine whether primary or secondary hypogonadism was responsible for low levels of testosterone in cases.
We included 45 men with AD (McKhann, 1987), 15 men with other types of dementia and 133 elderly controls from the Oxford Project to Investigate Memory and Ageing. Gonadotropins (follicle stimulating hormone or FSH and luteinizing hormone or LH), sex hormone binding globulin (SHBG, which determines the amount of free testosterone) and testosterone were measured using enzyme immunoassays.
We found no difference in average LH (8.7 +/- 9 UI/L), FSH (13 +/- 17 UI/L) or SHBG (44 +/- 18 nmol/L) levels between AD cases and controls. Similar to our earlier findings, testosterone levels were significantly lower in men with AD (13 +/- 6 nmol/L) compared with controls (17 +/- 8, O.R. = 0.92, 95% C.I. = 0.87 to 0.97, p<0.005). Results were unchanged when controlled for age, SHBG and gonadotropin levels.
Although normal, the levels of gonadotropins were inappropriately low for the levels of testosterone. Our results support a preliminary conclusion that secondary hypogonadism occurs in men with AD. This could be a consequence of brain degeneration. This is contrary to an earlier study (Bowen, 1999) that found raised levels of gonadotropins in cases with AD, suggesting primary hypogonadism. Our cohort was younger than theirs and gonadotropin levels increase with age. We are enlarging our data set to investigate whether primary hypogonadism occurs in older cases with AD or whether secondary hypogonadism precedes cognitive dysfunction in men at risk for AD. If this is true, testosterone replacement therapy for hypogonadal men at risk for dementia may be indicated.
睾酮和雌二醇等性类固醇可能对大脑起到保护作用，预防阿尔茨海默病（AD）。我们之前发现，与对照组相比，AD男性患者的睾酮水平较低。我们想要评估调节性类固醇水平的垂体促性腺激素水平，以确定原发性或继发性性腺功能减退是否导致了病例中睾酮水平低下。
我们纳入了牛津记忆与衰老研究项目中的45名AD男性患者（麦肯标准，1987年）、15名患有其他类型痴呆症的男性以及133名老年对照者。使用酶免疫分析法测定促性腺激素（促卵泡激素或FSH以及促黄体生成素或LH）、性激素结合球蛋白（SHBG，其决定游离睾酮的量）和睾酮。
我们发现AD病例与对照组之间的平均LH（8.7±9 UI/L）、FSH（13±17 UI/L）或SHBG（44±18 nmol/L）水平没有差异。与我们之前的研究结果相似，AD男性患者的睾酮水平（13±6 nmol/L）显著低于对照组（17±8，优势比=0.92，95%置信区间=0.87至0.97，p<0.005）。在对年龄、SHBG和促性腺激素水平进行校正后，结果不变。
尽管促性腺激素水平正常，但相对于睾酮水平而言却异常低下。我们的研究结果支持一个初步结论，即AD男性患者存在继发性性腺功能减退。这可能是大脑退化的结果。这与早期一项研究（鲍恩，1999年）相反，该研究发现AD病例中促性腺激素水平升高，提示原发性性腺功能减退。我们的队列比他们的队列年轻，且促性腺激素水平会随着年龄增长而升高。我们正在扩大数据集，以研究老年AD病例中是否存在原发性性腺功能减退，或者继发性性腺功能减退是否先于有AD风险男性的认知功能障碍出现。如果情况属实，对于有痴呆风险的性腺功能减退男性，可能需要进行睾酮替代治疗。
