TESTOSTERONE REPLACEMENT THERAPY IN HYPOGONADAL AND ANEMIC ELDERLY MEN: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Purpose

While the effect of testosterone on hemoglobin is well-established, its impact on anemic, hypogonadal elderly men is less clear. This study aimed to investigate whether testosterone replacement therapy (TRT) for hypogonadism in older men could also effectively treat concurrent anemia.

Materials and methods

We systematically searched PubMed, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing TRT to placebo in hypogonadal (testosterone < 300 ng/dL), anemic (Hemoglobin < 13 g/dL), and elderly men (mean age > 60 years old). We pooled mean differences (MD) for continuous outcomes and odds ratio (OR) for binary outcomes, with 95% confidence intervals (CI). Review manager was used to perform all statistical analyses.

Results

Three RCTs were included, comprising 883 patients, of whom 49.1% were treated with TRT. The mean age of the participants was 66.63 years. TRT demonstrated a significant improvement in hemoglobin (Hb) levels within six months compared to placebo (MD 0.62 g/dL; 95% CI 0.28 to 0.96; p < 0.01). Additionally, TRT significantly corrected anemia at 12 months compared to control (OR 1.81; 95% CI 1.36 to 2.41; p < 0.01) and was associated with a greater proportion of patients whose Hb concentration improved by 1.0 g/dL or more from baseline (OR 3.22; 95% CI 1.28 to 8.09; p = 0.01).

Discussion

Anemia, a common condition among older adults, is associated with significant morbidities such as fatigue, falls, increased hospitalization, and higher mortality rates. Approximately 10% of individuals aged 65 years or older have anemia; this prevalence increases to 15% among elderly men with hypogonadism. Although mild normocytic anemia is the most common type within this patient group, about one-third of these cases are classified as unexplained anemia, a multifactorial condition in which androgen deficiency may play a role. Different studies have demonstrated the correction of anemia with TRT across various types, including normocytic, unexplained, and macrocytic anemia. This supports the belief that TRT increases Hb levels through several mechanisms: it stimulates erythropoietin transcription, enhances iron availability by suppressing hepcidin, and improves red blood cell survival. Our results demonstrated that TRT significantly increased Hb levels and corrected anemia in hypogonadal men. It markedly improved the likelihood of achieving a clinically relevant Hb increase of 1.0 g/dL or more, an effect comparable to that of other erythropoiesis-stimulating agents and inhibitors of hypoxia-inducible factors. This finding underscores the potential of TRT as an effective treatment for anemia in elderly men with hypogonadism.

Conclusion

In elderly men with hypogonadism and anemia, testosterone replacement was more effective than placebo in correcting anemia. Therefore, it could be considered a viable treatment option for these patients.