昨天我说到女性长寿的秘密在于雌激素的“神奇”作用——抗炎。不过,行家和明眼人一看,就知道其中还有很多矛盾之处和未解之谜。 比如,女性在绝经期后雌性激素分泌大减,它又如何能让女性长寿?其次,有很多数据都表明,老年女性比老年男性更易患上老年痴呆症,这岂不是与雌激素抗炎并导致女性长寿的推论相矛盾? 还是让事实说话吧!有关女性更易患老年痴呆症的结论来自流行病学研究,一是女性老年痴呆患者占2/3;二是女性老年痴呆症患者脑部的噬斑沉积更严重;三是女性老年痴呆症的病理变化与临床特征更吻合。于是,女性绝经期后雌激素分泌下降被理所当然地归结为女性更易患老年痴呆症的主要原因。 的确,女性绝经期后血清雌二醇水平急剧下降,甚至低于正常男性的血清浓度。然而,令人惊讶的是,无论衰老还是痴呆,大脑中类固醇激素的水平始终不变,也就是说血清雌二醇水平的降低不会导致大脑雌二醇水平的降低! 一项雌二醇定量测定发现,女性老年痴呆症患者大脑中雌二醇含量,在60-79岁之间与正常值比较无显著差异,只有80岁以上才会出现下降。倒是正常男性大脑组织的睾酮含量随年龄增长而不断下降。 这些研究结果似乎都不支持女性更易患老年痴呆症的结论,更不支持患病原因就是更年期后雌二醇分泌减少。退一步说,假如女性老年痴呆症确实与雌二醇减少有关,那么给患者补充雌二醇应能改善病情吧? 可是,事与愿违,在一项“妇女健康引领记忆研究”(WHIMS)的临床试验中,共有4532位年龄在68岁以上女性参与研究,经过4年半的激素治疗,老年痴呆症患者却增加两倍,而且增加乳腺癌、肺动脉栓塞和中风的风险。 由此可见,女性老年痴呆患者较多的原因并非雌二醇下降,而有可能是另外的原因,比如女性寿命较长,可能带病生存,而男性寿命较短,难以跟同龄女性比较。另外,女性易患妇科疾病,尤其常被白色念珠菌(病原真菌)感染,体内炎症水平很高也是一个可能的原因。 参考文献 Barnes LL, Wilson RS, Bienias JL, Schneider JA, Evans DA,Bennett DA (2005) Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry 62(6):685–691 Corder EH, Ghebremedhin E, Taylor MG, Thal DR, Ohm TG, Braak H (2004) The biphasic relationshipbetween regional brain senile plaque and neurofibrillary tangle distributions: modification by age, sex, and APOE polymorphism. Ann N Y Acad Sci 1019:24–28 Grimm A,Lim YA,Mensah Nyagan AG, Götz J, Eckert A(2012) Alzheimer's Disease, Oestrogen and Mitochondria:an Ambiguous RelationshipMol Neurobiol 46:151–160 Hy LX, Keller DM (2000) Prevalence of AD among whites: a summary by levels of severity. Neurology 55(2):198–204 Rosario ER, Chang L, Head EH, Stanczyk FZ, Pike CJ (2011) Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease. Neurobiol Aging 32:604–613.
NEJM:男性衰老,雌激素分泌不足也是关键 本·艾弗森参与了一项针对20岁至50岁男性的研究。受试者志愿让睾酮停止分泌16周。科学家们正在跟年长的男性身上重复此项研究,以衡量他们的生命力。 这是许多中年男人的痛苦:他们开始有了大肚腩,开始减少健身器械的配重,而且不知为何,没有了年轻时候的性欲。 一个已经明确的元凶是睾酮,因为随着时间的流逝,男人产生的雄性激素渐渐变少。但现在还出现了一个令人惊讶的新答案。医生称这个答案会为有关男性身体如何变老的研究注入新的活力。结果证明,雌激素,也就是女性荷尔蒙,在男性身体中发挥的作用远大于之前的想像,而且,与女性一样,雌激素水平降低会导致男性腰围增大。 http://www.bio360.net/news/show/7055.html 原文 http://www.nejm.org/doi/full/10.1056/NEJMoa1206168 Start A-Literature C-Literature B-list Filter Literature A-query: estrogen deficiency and men C-query: aging The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 150 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 8922 and can be accessed from the start page after you leave this session. There are 148 terms on the current B-list ( 27 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi job id # 8922 started Thu Sep 12 22:03:33 2013 Max_citations: 50000 Stoplist: /var/www/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 A_query_raw: estrogen deficiency and men Thu Sep 12 22:03:38 2013 A query = estrogen deficiency and men started Thu Sep 12 22:03:38 2013 A query resulted in 548 titles C_query_raw: estrogen deficiency and men Thu Sep 12 22:03:40 2013 C: estrogen deficiency and men 548 A: pubmed_query_A 548 AC: ( estrogen deficiency and men ) AND ( estrogen deficiency and men ) 548 C_query_raw: aging Thu Sep 12 22:03:52 2013 C: aging 288515 A: pubmed_query_A 548 AC: ( estrogen deficiency and men ) AND ( aging ) 150 C_query_raw: aging Thu Sep 12 22:03:55 2013 C: aging 288515 A: pubmed_query_A 548 AC: ( estrogen deficiency and men ) AND ( aging ) 150 C query = aging started Thu Sep 12 22:03:56 2013 C query resulted in 50000 titles A AND C query resulted in 150 titles 2225 B-terms ready on Thu Sep 12 22:04:49 2013 Sem_filter: Genes Molecular Sequences, and Gene Protein Names 148 B-terms left after filter executed Thu Sep 12 22:07:15 2013 Sem_filter: Activities Behaviors Anatomy Chemicals Drugs Concepts Ideas Devices Disorders Genes Molecular Sequences, and Gene Protein Names Geographic Areas Living Beings Objects Occupations Organizations Phenomena Physiology Procedures 148 B-terms left after filter executed Thu Sep 12 22:08:24 2013 B-list on Thu Sep 12 22:20:14 2013 1 wnt 2 akt 3 beta catenin 4 metabolic syndrome 5 aromatase 6 bone mineral density 7 abeta 8 rankl 9 adiposity 10 body mass index 11 igf 12 estrogen receptor alpha 13 estrogen receptor 14 fat mass 15 sclerostin 16 femur 17 hip 18 receptor gene 19 eralpha 20 estrogen receptor beta 21 androgen receptor gene 22 bace1 23 insulin growth factor 24 body mass 25 aromatase gene 26 protein kinase 27 diabetes mellitus http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/view_b_txt.cgi?ID=8922 知识发现实例:男人雌激素缺乏与骨矿物质密度,衰老与 骨矿物质密度的关系研究文献。 Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature estrogen deficiency and men bone mineral density aging 1: Bone Mineral Density and Testicular Failure: Evidence for a Role of Vitamin D 25-Hydroxylase in Human Testis. 2011 Add to clipboard 2: Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma. 2011 Add to clipboard 3: A novel mutation in the human aromatase gene: insights on the relationship among serum estradiol, longitudinal growth and bone mineral density in an adult man under estrogen replacement treatment. 2008 Add to clipboard 4: Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density . 2008 Add to clipboard 5: Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency. 2007 Add to clipboard 6: Circulating sex steroids, sex hormone-binding globulin, and longitudinal changes in forearm bone mineral density in postmenopausal women and men: the Tromso study. 2007 Add to clipboard 7: Self-reported number of remaining teeth is associated with bone mineral density of the femoral neck, but not of the spine, in Japanese men and women. 2004 Add to clipboard 8: Relationship of estrogen receptor genotypes to bone mineral density and to rates of bone loss in men. 2004 Add to clipboard 9: Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age. 2003 Add to clipboard 10: Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys. 2003 Add to clipboard 11: Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study. 2002 Add to clipboard 12: Relation of ascorbic acid to bone mineral density and self-reported fractures among US adults. 2001 Add to clipboard 13: Estrogen replacement therapy in a man with congenital aromatase deficiency: effects of different doses of transdermal estradiol on bone mineral density and hormonal parameters. 2000 Add to clipboard 14: Correlation between bone mineral density and sexual hormones in healthy Chinese women. 2000 Add to clipboard 15: Serum oestradiol and oestrogen-receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males. 1998 Add to clipboard 16: Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral density and bone turnover. 1997 Add to clipboard 17: Determination of bone mineral density by quantitative computed tomography and single photon absorptiometry in subclinical hyperthyroidism: a risk of early osteopaenia in post-menopausal women. 1992 Add to clipboard 1: Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study. 2013 Add to clipboard 2: Effect of dietary taurine and arginine supplementation on bone mineral density in growing female rats. 2013 Add to clipboard 3: The Influence of Aging on the Association Between Adiposity and Bone Mineral Density in Jordanian Postmenopausal Women. 2013 Add to clipboard 4: Effects of low-dose testosterone undecanoate treatment on bone mineral density and bone turnover markers in elderly male osteoporosis with low serum testosterone. 2013 Add to clipboard 5: Longitudinal changes in bone mineral density of healthy elderly women in southern Taiwan. 2013 Add to clipboard http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/show_sentences.cgi