臨床泌尿器科69巻1号

2015年01月発行

特集 LOH症候群診療—最近の進歩

テストステロンと性機能

著者： 佐藤嘉一¹

所属機関： ¹三樹会病院

ページ範囲：P.32 - P.39

文献概要

要旨　Testosterone（T）は性機能維持に関与する中枢・末梢のすべての器官・組織で促進的に関与している。それぞれの組織で，異なる機序と閾値で調節が行われている。性機能の維持はTのみならず，E2，DHT，またSHBGレベル，ARのアンドロゲン活性の遺伝的相違など多くの要因が関与している。

　LOH症候群における性機能低下は，診断や予後の観点から大きな意義を持つ。LOH症候群におけるEDに対する治療には，加齢に伴う性機能に影響を与える合併症などの多要因が関与しているため，T replacement therapy（TRT）では不十分なことも多い。PDE5阻害薬による治療がまず行われ，無効な場合にはTRTが追加される。しかしPDE5阻害薬とTRT併用の有効性はいまだ確立されていない。

参考文献

1）Wang C, Nieschlag E, Swerdloff R, et al：Investigation, treatment, and monitoring of late-onset hypogonadism in males：ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 55：121-130, 2009

2）Bhasin S, Cunningham GR, Hayes FJ, et al：Testosterone therapy in men with androgen deficiency syndromes：an Endocrine Society clinicalpractice guideline. J Clin Endocrinol Metab 95：2536-2559, 2010

3）Buvat J, Maggi M, Gooren L, et al：Endocrine aspects of male sexual dysfunctions. J Sex Med 7：1627-1656, 2010

4）日本泌尿器科学会/日本Men's Health医学会「LOH症候群診療ガイドライン」検討ワーキング委員会（編）：加齢男性性腺機能低下症候群診療の手引き．じほう，東京，pp2-28，2007

5）Araujo AB and Wittert GA：Endocrinology of the aging male. Best Pract Res Clin Endocrinol Metab 25：303-319, 2011

6）Ilpo Huhtaniemi：Late-onset hypogonadism：current concepts and controversies of pathogenesis, diagnosis and treatment Asian Journal of Andrology 16：192-202, 2014

7）Morgentaler A, Khera M, Maggi M, et al：Commentary：Who is a candidate for testosterone therapy? A synthesis of international expert opinions. J Sex Med 11：1636-1645, 2014

8）Corona G, Vignozzi L, Sforza A, et al：Risks and benefits of late onset hypogonadism treatment：an expert opinion. World J Mens Health 31：103-125, 2013

9）Lunenfeld B, Mskhalaya G, Kalinchenko S, et al：Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism in men—a suggested update Aging Male 16：143-150, 2013

10）Bhasin S, Cunningham GR, Hayes FJ, at al：Testosterone therapy in adult men with androgen deficiency syndromes：an endocrine society clinical practice guideline. J Clin Endocrinol Metab 91：1995-2010, 2006

11）Wu FC, Tajar A, Beynon JM, et al（EMAS Group）：Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 363：123-135, 2010

12）Isidori AM, Buvat J, Corona G, et al：A critical analysis of the role of testosterone in erectile function：from pathophysiology to treatment-a systematic review. Eur Urol 65：99-112, 2014

13）Yassin AA and Saad F：Testosterone and erectile dysfunction. J Androl 29：593-604, 2008

14）Dean RC and Lue TF：Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am 32：379-395, 2005

15）Andersson KE：Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev 63：811-859, 2011

16）佐藤嘉一：性機能障害 勃起障害（ED）（1）勃起のメカニズム．排尿障害プラクティス10：7-13，2002

17）Hull EM, Lorrain DS, Du J, et al：Hormone-neurotransmitter interactions in the control of sexual behavior. Behav Brain Res 105：105-116, 1999

18）Bellefontaine N, Hanchate NK, Parkash J, et al：Nitric oxide as key mediator of neuron-to-neuron and endothelia-to-glia communication involved in the neuroendocrine control of reproduction. Neuroendocrinology 93：74-89, 2011

19）Yang R, Huang YC, Lin G, et al：Lack of direct androgen regulation of PDE5 expression. Biochem Biophys Res Commun 380：758-762, 2009

20）O'Connor DB, Lee DM, Corona G, et al：European Male Ageing Study Group. The relationships between sex hormones and sexual function in middle-aged and older European men. J Clin Endocrinol Metab 96：E1577-1587, 2011

21）Bhasin S, Pencina M, Jasuja GK, et al：Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. J Clin Endocrinol Metab 96：2430-2439, 2011

22）Zitzmann M, Faber S and Nieschlag E：Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 91：4335-4343, 2006

23）Krithivas K, Yurgalevitch SM, Mohr BA, et al：Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrinol 162：137-142, 1999

24）Yeap BB, Alfonso H, Chubb SA, et al：Reference ranges and determinants of testosterone, dihydrotestosterone, and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. J Clin Endocrinol Metab 97：4030-4039, 2012

25）Wu FC, Tajar A, Pye SR, et al：Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors：the European Male Aging Study. J Clin Endocrinol Metab 93：2737-2745, 2008

26）Giannetta E, Gianfrilli D, Barbagallo F, et al：Subclinical male hypogonadism. Best Pract Res Clin Endocrinol Metab 26：539-550, 2012

27）Pye SR, Huhtaniemi IT, Finn JD（EMAS Study Group）et al：Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab 99：1357-1366, 2014

28）Bhasin S, Woodhouse L, Casaburi R, et al：Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281：E1172-1181, 2001

29）Gray PB, Singh AB, Woodhouse LJ, et al：Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab 90：3838-3346, 2005

30）Sato Y, Shibuya A, Adachi H, et al：Restoration of sexual behavior and dopaminergic neurotransmission by long term exogenous testosterone replacement in aged male rats. J Urol 160：1572-1575, 1998

31）Lakshman KM, Kaplan B, Travison TG, et al：The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab 95：3955-3964, 2010

32）Wu D and Gore AC：Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats. Horm Behav 58：306-16, 2010

33）Isidori AM, Giannetta E, Gianfrilli D, et al：Effects of testosterone on sexual function in men：results of a meta-analysis. Clin Endocrinol 63：381-394, 2005

34）Bolona ER, Uraga MV, Haddad RM, et al：Testosterone use in menwith sexual dysfunction：a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 82：20-28, 2007

35）Hackett G, Cole N, Bhartia M, et al：Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parametersvs. placebo in a population of men with type 2 diabetes. J SexMed 10：1612-1627, 2013

36）Zitzmann M, Mattern A, Hanisch J, et al：IPASS：A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadismin a worldwide sample of 1,438 men. J Sex Med 10：579-588, 2013

37）Jannini EA, Isidori AM, Gravina GL, et al：The ENDOTRIAL study：aspontaneous, open-label, randomized, multicenter, crossover studyon the efficacy of sildenafil, tadalafil, and vardenafil in the treatment of erectile dysfunction. J Sex Med 6：2547-2560, 2009

38）Spitzer M, Basaria S, Travison TG, et al：Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction：a parallel, randomized trial. Ann Intern Med 157：681-691, 2012

39）Andric SA, Janjic MM, Stojkov NJ, et al：Testosterone-inducedmodulation of nitric oxide-cGMP signaling pathway and androgenesis in the rat Leydig cells. Biol Reprod 83：434-442, 2010

40）Buvat J and Bou Jaoudé G：Significance of hypogonadism in erectile dysfunction. World J Urol 24：657-667, 2006

41）Shabsigh R, Kaufman JM, Steidle C, et al：Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 179（5 Suppl）：S97-102, 2008

42）Buvat J, Montorsi F, Maggi M, et al：Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1％ hydroalcoholic testosterone gel in the treatment of erectile dysfunction（TADTEST study）. J Sex Med 8：284-293, 2011

43）Goldfischer ER, Kim ED, Seftel AD, et al：Impact of low testosterone on response to treatment with tadalafil 5mg once daily for erectile dysfunction. Urology 83（6）：1326-1333, 2014

44）Tsertsvadze A, Fink HA, Yazdi F, et al：Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction：a systematic review and meta-analysis. Ann Intern Med 151：650-661, 2009