男性淋病感染與生殖器官惡性腫瘤之相關性

中文摘要背景：淋病為全球第二常見性傳染病，由奈瑟氏淋病雙球菌（Neisseria gonorrhoeae）引起，可能導致生殖道慢性發炎。然而，淋病感染與男性生殖器官惡性腫瘤（包括攝護腺癌、睪丸癌、陰莖癌）之間的關聯性尚未明確。本研究旨在評估男性罹患淋病後十年內發生生殖器官惡性腫瘤之風險，並探討年齡、種族、吸菸及肥胖等因素的分層效應。方法：本研究採用回顧性世代研究設計，利用TriNetX國際醫療資料庫，該資料庫涵蓋美國68家醫療機構2.5億筆去識別化電子病歷。研究運用傾向分數匹配（propensity score matching）方法，以1：1匹配校正年齡、種族、社會經濟地位、生活習慣、醫療利用等多項共變數，最終納入7,841名淋病患者與等數量之對照組，進行長達十年的追蹤分析。主要結果為男性生殖器官惡性腫瘤發生率，次要結果為全因死亡率。結果：在調整多項混雜因素後，整體而言，淋病感染史與十年內發生男性生殖器官惡性腫瘤之間未觀察到統計上顯著差異（HR：1.437, 95％ CI：0.893－2.313）。然而，年齡分層分析顯示，年齡≧46歲組之淋病患者罹患男性生殖器官惡性腫瘤風險顯著升高（HR：1.883, 95％ CI：1.134－3.129），尤其是攝護腺癌（HR：1.874, 95％ CI：1.114－3.150）。此外，研究意外發現全因死亡風險顯著較低的情形僅在年齡介於20－45歲的淋病組個案中觀察到（HR：0.582, 95％ CI：0.385－0.881），推測可能反映醫療行為差異或健康就醫效應。結論：本研究利用大規模全球電子健康紀錄系統進行長期追蹤分析，結果顯示淋病感染可能並非一般男性族群生殖器官惡性腫瘤的主要獨立危險因子，但在中高齡男性淋病感染者的攝護腺癌風險顯著增加，提示年齡可能扮演關鍵調節因子。建議臨床針對曾有淋病感染史的中高齡男性加強攝護腺癌篩檢，並鼓勵未來深入探討研究慢性發炎在攝護腺上皮細胞惡性轉化的生物學機制，以完善男性生殖健康之預防策略。

AbstractBackground：Gonorrhea, caused by Neisseria gonorrhoeae, is the second most common sexually transmitted infection globally and can lead to chronic inflammation of the urogenital tract. However, the association between gonorrhea infection and the risk of malignant neoplasms of the male reproductive organs, including prostate, testicular, and penile cancers, remains inconclusive. This study aimed to assess the ten-year risk of developing malignant neoplasms of the male reproductive organs following a gonorrhea diagnosis and to explore the stratified effects of factors such as age, race, smoking, and obesity.Methods：This retrospective cohort study utilized the TriNetX Research Network, a global federated database of de-identified electronic health records from 68 healthcare organizations in the United States. Using a 1:1 propensity score matching method, we balanced multiple covariates including age, race, socioeconomic status, lifestyle habits, and healthcare utilization. A final cohort of 7,841 male patients with gonorrhea and an equal number of non-infected controls were included for a ten-year follow-up analysis. The primary outcome was the incidence of malignant neoplasms of the male reproductive organs, and the secondary outcome was all-cause mortality.Results：After adjusting for multiple confounding factors, no statistically significant association was observed between a history of gonorrhea infection and the development of malignant neoplasms of male reproductive organs within ten years overall (HR: 1.437, 95% CI: 0.893-2.313). However, age-stratified analysis revealed that patients aged ≥46 years with prior gonorrhea infection demonstrated a significantly elevated risk of developing malignant neoplasms of male reproductive organs (HR: 1.883, 95% CI: 1.134-3.129), with prostate cancer showing a particularly pronounced association (HR: 1.874, 95% CI: 1.114-3.150). Additionally, an unexpected finding emerged showing a significantly reduced risk of all-cause mortality, which was observed exclusively among gonorrhea patients aged 20-45 years (HR: 0.582, 95% CI: 0.385-0.881). This phenomenon may reflect differences in healthcare-seeking behaviors or the healthy user effect.Conclusion：This long-term analysis, based on a large-scale global health records network, suggests that gonorrhea infection may not be a major independent risk factor for malignant neoplasms of the reproductive organs within the general male population. Nevertheless, the significantly increased risk of prostate cancer among middle-aged and older men with a history of gonorrhea highlights age as a critical modifying factor. These findings support the recommendation for enhanced prostate cancer screening for this specific demographic. Future research is encouraged to investigate the biological mechanisms through which chronic inflammation contributes to the malignant transformation of prostate epithelial cells, which could refine preventive strategies for male reproductive health.