射精功能障礙為年齡大於五十歲的男性常見的性功能障礙項目之一。統計資料顯示在五十歲以上的高加索男性，其射精功能障礙約百分之三至百分之三十五；而在亞洲族群中則約為百分之六十八。然而截至目前為止，射精功能障礙在台灣地區的盛行率尚未有文獻報導。臨床上，雖然有部分因素被認為可能導致射精功能障礙，但射精功能障礙的致病成因多半還是未知。本研究中，以男性性健康問卷(Male Sexual Health Questionnaire, MSHQ)中與射精功能評估相關的段落(Ejaculatory domain)作為調查工具，針對二十歲至八十歲的男性發出問卷500份。問卷回收率為百分之七十五。問卷結果顯示在五十歲以下的男性，不等程度射精功能障礙的比率佔百分之十八；但在五十歲以上的男性，不等程度射精功能障礙的比率可達百分之五十。問卷結果也顯示老年男性射精功能障礙多以無射精症、延遲射精、射精強度減弱、射精量減少、射精愉悅感降低，以及射精伴隨之疼痛或不舒服感頻率增加來表現。接著我們進一步的使用微陣列分析(microarray study) 對射精功能障礙及射精功能之正常老年男性進行其儲精囊基因表現的比對。微陣列分析的結果進一步上傳至生物反應路徑資料庫暨分析平台(Ingenuity Pathway Analysis)軟體分析，其中相關基因與臨床已知網絡比對帶入後，最為顯著的為發炎相關反應。隨機選擇此網絡中的八個基因作為個別儲精囊檢體之基因訊息核糖核酸(mRNA)轉錄量確認。定量即時聚合酉每連鎖反應(qRT-PCR)之結果與微陣列分析之結果相符。其中向上調控的基因有KLK3, MMP14, MMP3, TIMP4, UBE2B；向下調控的基因則有MMP-7。一系列發炎相關的基因表現增多或降低意涵著組織內的發炎反應活性較高，也表示發炎反應可能為老年男性射精功能障礙眾多致病因素之一。 除此之外，我們更進一步的將老化相關之射精功能障礙以動物實驗模式來加以證實。 藉由電刺激二十四週、四十週、以及八十週三組不同年紀的大鼠儲精囊並加以記錄，可以觀察到隨著老化的過程，射精強度隨之減弱、射精量隨之減少、射精時間隨之縮短。而發炎反應的最終產物膠原蛋白，在八十週的大鼠儲精囊中相較於在二十四週的大鼠儲精囊中含量顯著升高。這樣的發現也暗示著當儲精囊中膠原蛋白取代平滑肌所造成組織結構的改變，會導致儲精囊功能失常，最終表現為射精功能障礙。就我們所知，這是第一個提供台灣區二十至八十歲男性射精功能障礙的盛行率及其表現的研究。除此之外，本研究的結果也顯示發炎反應是一個潛在的射精功能障礙致病機因素。未來對於其他相關網絡的了解，會讓我們對於射精功能障礙致病機轉的分子層面有更深一層的了解。

Ejaculatory dysfunction (EjD) is a common problem among men with age more than 50 years old. Reported prevalence rates of EjD in men age 50 and older are 3% to 35% in Caucasian and 68% in Asian population, respectively. However, to date, the prevalence rate of EjD in Taiwanese men has not been reported. Clinically, although several risk factors have been linked to the development of EjD, the causes of EjD at the molecular level remain largely unknown. In this study, Male Sexual Health Questionnaire-Ejaculatory domain was delivered to 500 men with age ranged between 20 to 80 years old. The questionnaire retrieval rate was 75.6%. The results showed that the prevalence of EjD was 18% versus 50% in Taiwanese men with age less versus more than 50 years old, respectively. Men with EjD in the elderly tend to have presentations of anejaculation, delay ejaculation, decreased ejaculatory strength, volume, orgasm pleasure and increased frequency of painful ejaculation. Then cDNA microarray analysis was used to identify the seminal vesicle (SV) genes that are differentially expressed in elderly men with and without EjD. Those genes were uploaded into Ingenuity Pathway Analysis software analysis, and a number of significantly associated networks were generated. Of those associated networks, inflammation responses related network reveals the top one significant network. To validate the mRNA expressions, eight genes were randomly selected from this network for further transcript level quantification. The results of qRT-PCR were generally consistent with the results of microarray, showing the significant up-regulation of KLK3, MMP14, MMP3, TIMP4, UBE2B, and significant down-regulation of MMP-7. Increasing activity of inflammation related genes in EjD implies that inflammation is one of the predisposing factors related to EjD in the elderly. In addition, aging related EjD were further studied in an in vivo rat model. By measuring the SV response to electrostimulation in 24-, 40-, 80-wk-old rat groups, the declining tendency in ejaculation strength, ejaculation duration, and ejaculation volume were noted in aging rats. Collagen fiber content, the end product of inflammation reaction, was further evaluated in the SV tissues in rats of different age. Significant higher percentages of collagen fiber content was noted in 80-wk-old rats compared to those in 24-wk-old rats, suggesting that alternation of SV histological components may lead to SV dysfunction. To the best of our knowledge, this is the first study provides an overview of the prevalence and presentations of EjD in men age between 20 to 80 years old in Taiwan. In addition, our data provide the potential causative roles of inflammatory processes in EjD. A better understanding of these networks will bring us closer to an understanding of the molecular mechanisms underlying the causes of EjD.

Aizenberg D, Zemishlany Z, Weizman A et al. Cyproheptadine treatment of sexual dysfunction induced by serotonin reuptake inhibitors. Clin Neuropharmacol. 18: p320-24, 1995.
Andersson KE. Mode of action of alpha-1 adrenoceptor antagonists in the treatment of lower urinary tract symptoms. BJU Int. 85(suppl. 2): p12-18, 2000.
Basson R and Schultz W. Sexual sequelae of general medical disorders. The Lancet 369: p409–24, 2007.
Bechman N, Waern M, Gustafson D et al. Secular trends in self reported sexual activity and satisfaction in Swedish 70 year olds: cross sectional survey of four populations, 1971–2001. BMJ 337:a279, 2008.
Beshay E, Rehman K, Carrier S et al. Impact of Aging on Reproduction and Sexual Function. Interdiscipl Top Gerontol. 33: p94-106, 2004.
Bini A, Wu D, Schnuer J, Kudryk BJ et al. Characterization of stromelysin 1 (MMP-3), matrilysin (MMP-7), and membrane type 1 matrix metalloproteinase (MT1-MMP) derived fibrin(ogen) fragments D- dimer and D-like monomer: NH2-terminal sequences of late-stage digest fragments. Biochemistry 38(42): p13928-36, 1999.
Blanker MH, Bosch JR, Groeneveld FP et al. Erectile and ejaculatory dysfunction in a community based samples of men 50 to 78 years old: Prevalence, concern, and relation to sexual activity. Urology 57: p763–68, 2001.
Delmonte MM. Meditation as a clinical intervention strategy: a brief review. Int J Psychosom. 33: p9-12, 1986.
Feldman HA, Goldstein I, Hatzichristou DG et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151: p54-61, 1994.
Gan M, Smit M, Dohle GR et al. Determinants of ejaculatory dysfunction in a community-base longitudinal study. BJU Int. 99: p1443-48, 2007.
Giuliano F, Bernabe J, Droupy S et al. A comparison of the effects of tamsulosin and alfuzosin on neurally evoked increases in bladder neck and seminal vesicle pressure in rats. BJU Int 93(4): p605-8, 2004.
Gott M and Hinchliff S. How important is sex in later life? The views of older people. Social Science & Medicine 56: p1617-28, 2003.
Helgason AR, Adolfsson J, Dickman P et al. Sexual desire, erection, orgasm and ejaculatory functions and their importance to elderly Swedish men: a population-based study. Age Ageing. 25:p285-91, 1996.
Hellstrom WJ and Sikka SC. Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers. J Urol 176: p1529-33, 2006.
Hernandez-Barrantes S, Shimura Y, Soloway PD et al. Differential roles of TIMP-4 and TIMP-2 in pro-MMP-2 activation by MT1-MMP. Biochemical Biophysical Research Communications 281(1): p126-30, 2001.
Hiller O, Lichte A, Oberpichler A et al. Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII. Journal of Biological Chemistry 275(42): p33008-13, 2000.
Jeffrey PW and Wayne JG. Current Concepts in Ejaculatory Dysfunction. Reviews in Urology 8(Sippl.4): S18-25, 2006.
Jung JH, Kam SC, Choi SM et al. Sexual dysfunction in male stroke patients: correlation between brain lesions and sexual function. Urology 71(1): p99–103, 2008.
Kaplan SA, Gonzalez RR, Alexis ET et al. Combination of Alfuzosin and Sildenafil is Superior to Monotherapy in Treating Lower Urinary Tract Symptoms and Erectile Dysfunction. European Urology 51(6): p1717–23, 2007.
Kennedy S and Rizvi S. Sexual dysfunction, depression and the impact of antidepressants. Journal Clinical Psychopharmacology 29: p157–64, 2009.
Kraft PJ, Haynes-Johnson DE, Patel L et al. Fluorescence polarization assay and SDS-PAGE confirms matrilysin degrades fibronectin and collagen IV whereas gelatinase A degrades collagen IV but not fibronectin. Connective Tissue Research 42(2): p149-63, 2001.
Laumann EO, Das A, Waite LJ et al. Sexual dysfunction among older adults: prevalence and risk factors from a nationally representative U.S. probability sample of men and women 57–85 years of age. J Sex Med 5(10): p2300–11, 2008.
Li MK, Garcia LA, Rosen R et al. Lower urinary tract symptoms and male sexual dysfunction in Asia: a survey of ageing men from five Asian countries. BJU Int. 96: p1339-54, 2005.
Lindau ST, Schumm LP, Laumann EO et al. A study of sexuality and health among older adults in the United States. N Eng J Med 357: p762-74, 2007.
Liu YE, Wang M, Greene J et al. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4). Journal of Biological Chemistry 272(33): p20479-83, 1997.
Masumori N, Tsukamoto T, Kumamoto Y et al. Decline of sexual function with age in Japanese men compared with American men–results of two community-based studies. Urology 54: p335–44, 1999.
McMahon CG, Abdo C, Incrocci L et al. Disorders of orgasm and ejaculation in men. J Sex Med 1: p58-65, 2004.
Nickel JC, Narayan P, McKay J et al. Treatment of chronic prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomized double blind trial. J Urol 171: p1594–7, 2004.
Nikel JC, Downey J, Hunter D et al. Prevalence of prostatitis-like symptoms in a population based study using the National institute of Health Chronic Prostatitis symptom Index. J Urol 165: p842-5, 2001.
Pulito VL, Li X, Varga SS et al. An investigation of the uroselective properties of four novel alpha(1a)-adrenergic receptor subtype-selective antagonists. J Pharmacol Exp Ther 294: p224-29, 2000.
Raffetto JD and Khalil RA. Matrix Metalloproteinases and their Inhibitors in Vascular Remodeling and Vascular Disease. Biochem Pharmacol. 15; 75(2): p346–59, 2008.
Rees P, Fowler C, Maas C et al. Sexual function in men and women with neurological disorders. The Lancet 369: p512–25, 2007.
Rosen R, Altwein J, Boyle P et al. Lower urinary tract symptoms and male suxual dysfunction: The multinational survey of the aging male (MSAM-7). European Urology 44: p637-49, 2003.
Rosen RC, Catatania J , Pollack L et al. Male Sexual Questionnaire (MSHQ): Scale development and psychometric validation. Urology 64(4): p777-82, 2004.
Shrivastava RK, Shrivastava S, Overweg N et al. Amantadine in the treatment of sexual dysfunction associated with selective serotonin reuptake inhibitors. J Clin Psychopharmacol. 15: p83-84, 1995.
Wylie K and Kenney G. Sexual dysfunction and the ageing male. Maturitas 65: p23–27, 2010.
Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 117(3): p524-29, 2007.