醫學新知 謝昌成 1,2 蕭雅尤 1 前言 (late-onset hypogonadism, LOH) (testosterone) (andropause) (partial androgen deficiency of the ageing male, PADAM) (testosterone deficiency syndrome) 流行病學 LOH 20% 40 79 50% 80 (European Male Aging Study, 2010, EMAS) 40 79 2.1% LOH 70-79 5.1% (Massachusetts Male Aging 1 大林慈濟醫院家庭醫學科主治醫師 2 慈濟大學醫學系 late-onset hypogonadism, andropause, testosterone deficiency Study) 70 18.4% LOH 15% 生理學 1-2% (free testosterone, FT) (sex hormone binding globulin, SHBG) 30 1-2% SHBG (luteinizing hormone, LH) (follicle stimulating hormone, FSH) (gonadotropin-releasing hormone, GnRH) 10 10 原因 272 家庭醫學與基層醫療 第八期
( ) ( ) LOH ( ) (Leydig cell) SHBG - LOH 2 (sarcopenia) / / LH LOH 症狀 LOH ( ) 診斷 (biochemical hypogonadism) <11 nmol/l( ) EMAS(2010) 3000 40-79 LOH (1) <8 nmol/ l (2) 8-11 nmol/l FT<220 pmol/l 2 3 ( ) 10 Travison (2008) 50% LOH 表一 LOH 的症狀 性相關症狀性慾減退 勃起障礙 ( 特別是晨間勃起 ) 陰莖敏感度降低 肌肉 骨骼與身體組成 肌肉質量減少 內臟脂肪增加 腹部肥胖 體重增加 骨頭疼痛 骨質流失 骨折 資料來源 : 參考資料 4, 7, 10 認知與活力 注意力 記憶力 認知功能衰退 視覺空間辨識障礙 活力與機能衰退 疲累 缺乏動力 情緒低落 焦慮 睡眠障礙 夜間盜汗 熱潮紅 其他 家庭醫學與基層醫療 第八期 273
SHBG ( ) FT LOH LOH 治療 LOH ( ) SHBG (testosterone replacement therapy, TRT) LOH TRT TRT PSA (>4 ng/ml) PSA>3 ng/ml ( ) (International Prostate Symptom Score, IPSS >19 ) >50% TRT 40 PSA >1.4 ng/ml/ TRT TRT 3 6 2 3 6 PSA TRT 的可能益處 LOH ( ) (lean body mass) ( ) ( ) TRT 的可能風險一 紅血球增生症 (polycythemia) TRT TRT 1 3 6 274 家庭醫學與基層醫療 第八期
圖一性腺低下症的診斷流程 性腺低下症狀 測量清晨 TT( 早上 10 點以前 ) TT 偏低 (<8 nmol/dl) TT 為邊緣值 (8-11 nmol/dl) TT 正常 (>11 nmol/dl) 重複檢驗清晨 TT 觀察追蹤, 評估其他原因 TT 偏低 (<8 nmol/dl) TT 為邊緣值 (8-11 nmol/dl) TT 正常 (>11 nmol/dl) 檢驗性腺激素 (gonadotropins): LH, FSH 檢驗 SHBG 計算 FT FT 偏低 FT 正常 (<220 pmol/l) (>220 pmol/l) 性腺激素偏高 性腺激素正常或偏低 (1) 原發性性腺低下症 (2) 老化相關的睪丸衰竭 次發性性腺低下症 (1) 腦垂腺疾病 : 檢驗泌乳激素及其他腦垂腺相關激素, 蝶鞍部磁振造影 (2) 浸潤性疾病, 如血鐵沉積症 : 檢驗鐵 TIBC ferritin (3) 遲發型性腺功能低下症 (4) 藥物 : 酒精 葡萄糖皮質醇 類鴉片藥物 抗憂鬱劑 胃藥 (cimetidine) 利尿劑(spironolactone) 與抗黴菌藥物 (5) 感染 (HIV) 註 TT:total testosterone, 總睪固酮 FT:free testosterone, 游離態睪固酮 LH:luteinizing hormone, 促黃體生成激素 FSH:follicle stimulating hormone, 濾泡促進激素 TIBC:total iron binding capacity, 總鐵結合能力資料來源 : 參考資料 7, 10 家庭醫學與基層醫療 第八期 275
54% 50% TRT 二 攝護腺癌 Pierorazio (2010) (>65 ) TRT TRT TRT 3 6 PSA PSA>4 ng/ml PSA 1.0 ng/ dl PSA 0.7-1.0 ng/dl 3 6 三 心血管疾病 Basaria (2010) TRT 2 LOH TRT (lipoprotein lipase) TRT TRT TRT TRT 四 睡眠中止 (obstructive sleep apnea syndrome, OSA) TRT OSA OSA TRT 五 其他可能的影響 有關 TRT (14-24 nmol/l) TRT LOH LOH TRT TRT LOH 276 家庭醫學與基層醫療 第八期
一 經皮吸收凝膠 1-2% ( ) ( ) 5 ( 50 ) 3 4 1 10 二 肌肉注射型睪固酮酯化物 (ester) (testosterone undecanoate) (testosterone enanthate) (testosterone cypionate) 1000 6 1000 12 14 1000 75 100 2 3 150 200 (first pass effect) TRT ( testosterone undecanoate) (transbuccal testosterone) 篩檢 (Saint Louis University Androgen Deficiency in the Aging Male questionnaire, ADAM questionnaire) (Aging Males Symptoms rating scalequestionnaire, ADAM questionnaire) LOH ( 88% 96%) (60% 30%) Spetz (2007) Emmelot-Vonk (2011) ADAM/AMS ADAM/AMS LOH (2010) 結論 LOH LOH 家庭醫學與基層醫療 第八期 277
TRT TRT 參考資料 1. Bhasin S, Cunningham GR, Hayes FJ et al: Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536-59. 2. Basaria S: Testosterone levels for evaluation of androgen deficiency. JAMA 2015; 313:1749-50. 3. Chen CY, Wang WS, Liu CY, Lee SH: Reliability and validation of a Chinese version of the Aging Males' Symptoms scale. Psychol Rep 2007; 101:27-38. 4. Corona G, Rastrelli G, Maggi M: Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013; 27:557-79. 5. Emmelot-Vonk MH, Verhaar HJ, Nakhai-Pour HR, Grobbee DE, van der Schouw YT: Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males Symptoms rating scale (AMS) questionnaires. Clin Endocrinol (Oxf) 2011; 74:488-94. 6. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR: Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001; 86:724-31. 7. Huhtaniemi I: Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J Androl 2014; 16:192-202. 8. Samaras N, Frangos E, Forster A, Lang PO, Samaras D: Andropause: a review of the definition and treatment. Eur Geriatr Med 2012; 3:368-73. 9. Spetz AC, Palmefors L, Skobe RS et al: Testosterone correlated to symptoms of partial androgen deficiency in aging men (PADAM) in an elderly Swedish population. Menopause 2007;14:999-1005. 10. Surampudi PN, Wang C, Swerdloff R: Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy. Int J Endocrinol 2012; 625434:1-20. 278 家庭醫學與基層醫療 第八期