睪固酮相關因子與老年男性症狀量表之關連研究

Abstract

前言 男性血液中的睪固酮濃度會隨著年齡而下降，因而產生一些相關症狀。生殖腺官能低下(Hypogonadism)即代表了血液中睪固酮不足的狀況。而晚發性生殖腺官能低下(late-onset hypogonadism, LOH)即表示除了血液中睪固酮濃度不足以外，還加上有相對應的症狀。老年男性症狀量表即用來評估相對應的症狀。之前有一些研究探討了它與血液中睪固酮濃度的相關性，但是結果都很不一致。因此本研究主要目的試探討睪固酮與其相關生物標記和男性老年症狀評量表之相關性。此外，本研究也探討是否有其他因子會干擾此相關性。 方法與研究對象 本研究納入了774位40歲以上，於2008年十一月至2009年十月間至台大醫院接受自費健檢的男性。他們均回答了老年男性症狀評量表，也接受抽血檢測，包含睪固酮在內的多項生化值。睪固酮的絕對值被分為三等分，此外，本研究創造了兩個生物標記，即生物可利用睪固酮比例(bioavailable testosterone ratio, BTR)與游離睪固酮比例(free testosterone ratio, FTR)。本研究的結果即老年男性症狀量表，將其依嚴重度雙切。此外，一些其他重要的變項也一起放入模式中調整。統計使用邏輯斯回歸進行資料分析。 結果 睪固酮會隨著年齡增加而降低（此趨勢的p值小於0.0001）。被三等份的睪固酮與老年男性症狀量表的相關性十分不一致也不穩定。相反的，較高的BTR與FTR產生精神性症狀的危險性較低（BTR調整後的勝算比為0.98, 95%信賴區間 0.97-0.99，FTR調整後勝算比為0.62, 95%信賴區間0.40-0.95）。同樣的，較高的BTR與FTR產生總和症狀的危險性也較低（BTR調整後的勝算比為0.94, 95%信賴區間 0.90-0.98，FTR調整後勝算比為0.25, 95%信賴區間0.08-0.72）。而當使用多項邏輯斯回歸分析時也得到相似的結果。一些重要共變項，如：高血壓、高血脂、高尿酸、婚姻狀態、年紀、與C反應蛋白(CRP)等，與睪固酮並不存在交互作用，其交互作用p值均大於0.05。 討論 由於平均年齡增加，老年已變成一個重要的議題。LOH會使得健康相關的生活品質惡化，因此在無禁忌症且有正確診斷的情況下，可以考慮給補充睪固酮。過去的研究大多以睪固酮的絕對值來分析研究而得到了不一致的結果，因此對LOH的診斷較無幫助。BTR與FTR為兩個相對穩定的生物標記，可代表一段時間內的睪固酮分布，在本研究中它顯示了與老年男性症狀評量表的精神症狀一致且穩定的保護相關性。睪固酮可以穿過腦-血管-障蔽並與腦內的睪固酮受器作用，因此會影響人類的情緒與精神狀況。至於其他的重要共變項則不存在與BTR, FTR的交互作用。 結論 本研究顯示，BTR與FTR與老年男性症狀評量表中的精神領域與總和症狀有保護性的相關性。相反的，睪固酮的絕對值則顯示出不一致且不穩定的相關性。因此，使用BTR與FTR應該可以幫助泌尿科醫師在診斷 LOH並進一步給與治療時更有實用價值。

Introduction Serum testosterone can be classified as sex hormone binding globulin (SHBG)-bound, albumin-bound and free forms. The latter two combined are termed bioavailable testosterone. Testosterone decreases with age and thus causes related symptoms. Hypogonadism indicates the condition of decreased serum testosterone. Late-onset hypogonadism (LOH) has been used to describe hypogonadism in combination with its related symptoms. The crude prevalence is about 12% in Taiwan. Aging males’ symptoms scale (AMS) has been used widely to evaluate symptoms related to hypogonadism. Its association with serum testosterone has been studied with inconsistent conclusions. Our aim is to explore the association between serum testosterone related markers and the symptoms of hypogonadism. In addition, this study also explored other factors which may interfere with the association. Materials and Methods This was a cross-sectional study. A total of 774 men aged 40 years or older were recruited from the self-paid health checkup service at National Taiwan University Hospital (NTUH) from November 2008 to October 2009. All of them completed the AMS and blood sample was collected to determine serum testosterone level along with other biomarkers. Absolute value of testosterone was tertiled and two testosterone-related markers were created, bioavailable and free testosterone ratio (BTR, FTR). The outcome of this study was AMS, and it was dichotomized by severity. Other covariates were also adjusted in the study. Logistic regression and multinomial logistic regression analyses were used for data analysis. Results Testosterone decreased with age (p for trend <0.0001). The association between tertiled testosterone and AMS was inconsistent and unstable. In contrast, higher BTR and FTR showed a decreased risk of developing psychological symptoms (AOR for BTR=0.98, 95% CI=0.97-0.99; AOR for FTR=0.62, 95% CI=0.40-0.95). Higher BTR and FTR were also associated with decreased risks of developing severe overall symptoms (AOR for BTR=0.94, 95% CI=0.90-0.98; AOR for FTR=0.25, 95% CI=0.08-0.72). Similar results were also found by multinomial logistic regression. However, effect modification by some covariates, e.g., hypertension, hyperuricemia, hyperlipidemia, CRP, marital status and age, were not significant. Discussions Lifespan has expanded nowadays so aging has become an important issue. LOH may deteriorate health-related quality of life so testosterone replacement therapy can be considered if correct diagnosis is made, and no contraindication exists. Previous studies used absolute value of testosterone to analyze its association with symptoms, but the conclusions were inconsistent. In our study, BTR and FTR were two stable biomarkers which were consistently associated with psychological AMS. Testosterone can cross the blood-brain-barrier and act on the androgen receptors in the brain. Therefore, decreased testosterone is associated with the development of psychological symptoms. Other covariates were also adjusted in this study. However, none of them significantly modified the association between testosterone related markers and AMS. Conclusions Bioavailable and free testosterone ratios (BTR and FTR) were significantly associated with psychological and total AMS with a protective effect. In contrast, the association between absolute value of testosterone and AMS was inconsistent and unstable. Therefore, BTR and FTR can help urologists in making correct diagnosis of LOH.