Role of Aromatase Inhibitors in Managing Hypogonadism in Adult Males Related to Obesity and Aging: A Systematic Review and Meta-Analysis.

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.