Dutta Deep, Mohindra Ritin, Kumar Manoj, Sharma Meha
Department of Endocrinology, CEDAR Superspeciality Healthcare, Dwarka New Delhi, India.
Department of Medicine, Post-Graduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Endocrinol Metab. 2022 Nov-Dec;26(6):501-509. doi: 10.4103/ijem.ijem_3_22. Epub 2022 Dec 20.
No meta-analysis is available which has analysed the role of aromatase inhibitors (AIs) in hypogonadism in adult males related to obesity and aging. This meta-analysis intended to address this knowledge gap. Electronic databases were searched for studies involving adult males with hypogonadism. The primary outcomes were changes in total testosterone (TT). Secondary outcomes were alterations in oestradiol, luteinizing hormone (LH), and side-effect profile. From initially screened 177 articles, data from three randomised controlled trials(RCTs) (118 patients) and three uncontrolled studies(52 patients) were analysed. AIs were associated with significantly greater improvement in TT after three months [mean difference (MD) 7.08 nmol/L (95% Confidence Interval (CI): 5.92-8.24); < 0.01; I = 0%], six months [MD 6.61 nmol/L (95% CI: 5.30-7.93); < 0.01] and 12 months [MD 5.20 nmol/L (95% CI: 3.78-6.62); < 0.01] therapy. AIs were associated with greater reduction in oestradiol after three months [MD -3.07 pmol/L (95% CI: -5.27- -0.87); < 0.01; I2 = 40%], six months [MD -5.39 pmol/L (95% CI: -7.18- -3.60); < 0.01] and 12 months [MD -8.3 pmol/L (95% CI: -15.97- -0.63); = 0.03] therapy. AIs were associated with greater increase in LH after three months [MD 1.79 IU/L (95% CI: 0.77-2.81); < 0.01; I2 = 0%], six months [MD 2.20 IU/L (95% CI: 0.29 - 4.11); = 0.02] and 12 months [MD 1.70 IU/L (95% CI: 0.28-3.12); = 0.02] therapy. Occurrence of treatment-emergent adverse events[Risk ratio (RR) 1.48 (95% CI: 0.47-4.66); = 0.45; I = 0%] and severe adverse events[RR 2.48 (95% CI: 0.42-14.66); = 0.32; I = 0%] were similar among AIs and controls. Following six-month treatment, AIs were associated with significantly lower bone mineral density (BMD) at lumbar-spine [MD -0.04 gm/cm2 (95% CI: -0.08- -0.01); = 0.03], but not total hip [MD 0.01 gm/cm2 (95% CI: -0.02-0.04); = 0.55] and femoral neck [MD 0.02 gm/cm (95% CI: -0.01-0.05); = 0.12] compared to controls. This meta-analysis highlights the good efficacy of AIs in improving TT over 3-12 months of use. Adverse impact on spine bone density remains a concern in obese ageing males and warrants further evaluation.
目前尚无荟萃分析探讨芳香化酶抑制剂（AIs）在成年男性与肥胖和衰老相关的性腺功能减退中的作用。本荟萃分析旨在填补这一知识空白。通过电子数据库检索涉及成年男性性腺功能减退的研究。主要结局指标为总睾酮（TT）的变化。次要结局指标为雌二醇、促黄体生成素（LH）的改变以及副作用情况。从最初筛选的177篇文章中，分析了3项随机对照试验（RCTs）（118例患者）和3项非对照研究（52例患者）的数据。使用AIs治疗3个月后，TT有显著更大程度的改善[平均差值（MD）7.08 nmol/L（95%置信区间（CI）：5.92 - 8.24）；P < 0.01；I² = 0%]，6个月时[MD 6.61 nmol/L（95% CI：5.30 - 7.93）；P < 0.01]，12个月时[MD 5.20 nmol/L（95% CI：3.78 - 6.62）；P < 0.01]。使用AIs治疗3个月后，雌二醇有更大程度的降低[MD -3.07 pmol/L（95% CI： -5.27 - -0.87）；P < 0.01；I² = 40%]，6个月时[MD -5.39 pmol/L（95% CI： -7.18 - -3.60）；P < 0.01]，12个月时[MD -8.3 pmol/L（95% CI： -15.97 - -0.63）；P = 0.03]。使用AIs治疗3个月后，LH有更大程度的升高[MD 1.79 IU/L（95% CI：0.77 - 2.81）；P < 0.01；I² = 0%]，6个月时[MD 2.20 IU/L（95% CI：0.29 - 4.11）；P = 0.02]，12个月时[MD 1.70 IU/L（95% CI：0.28 - 3.12）；P = 0.02]。治疗中出现的不良事件[风险比（RR）1.48（95% CI：0.47 - 4.66）；P = 0.45；I² = 0%]和严重不良事件[RR 2.48（95% CI：0.42 - 14.66）；P = 0.32；I² = 0%]在AIs组和对照组中相似。治疗6个月后，与对照组相比，AIs组腰椎骨矿物质密度（BMD）显著降低[MD -0.04 g/cm²（95% CI： -0.08 - -0.01）；P = 0.03]，但全髋关节[MD 0.01 g/cm²（95% CI： -0.02 - 0.04）；P = 0.55]和股骨颈[MD 0.02 g/cm（95% CI： -0.01 - 0.05）；P = 0.12]无明显变化。本荟萃分析强调了AIs在使用3 - 12个月期间改善TT的良好疗效。对肥胖老年男性脊柱骨密度的不良影响仍是一个关注点，值得进一步评估。
