Hypogonadism and Anemia: The Relationship and Clinical Implications
Yes, hypogonadism can cause anemia, particularly in men, as testosterone plays a critical role in stimulating erythropoiesis. 1 This relationship is well-established in medical literature and has important clinical implications for patient management.
Pathophysiological Mechanism
Testosterone stimulates erythropoiesis through multiple mechanisms:
- Production of hematopoietic growth factors
- Improvement of iron bioavailability
- Direct stimulation of bone marrow activity 2
The New England Journal of Medicine recognizes anemia as a symptom of hypogonadism, listing it among the clinical manifestations that may improve with testosterone replacement therapy 1
Evidence Supporting the Relationship
Men with hypogonadism have significantly lower hematocrit levels compared to eugonadal men 3
- In one study of men with type 2 diabetes, those with hypogonadotropic hypogonadism had a mean hematocrit of 40.6% versus 43.3% in eugonadal patients (p = 0.011) 3
The prevalence of normocytic normochromic anemia (hemoglobin <13 g/dL) was 37.8% in men with hypogonadotropic hypogonadism compared to only 3% in eugonadal men (p < 0.01) 3
A large study of older adults found that men and women in the lowest quartile of total and bioavailable testosterone were significantly more likely to have anemia than those in the highest quartile 4
- Men: OR 5.4 (95% CI 1.4-21.8) for total testosterone
- Women: OR 2.1 (95% CI 0.9-5.0) for total testosterone 4
Testosterone Replacement and Anemia Correction
A 2023 randomized clinical trial demonstrated that testosterone replacement therapy (TRT) was more efficacious than placebo in correcting anemia in men with hypogonadism 5
- At 6 months: 41.0% of testosterone-treated men had anemia correction versus 27.5% in the placebo group
- This benefit persisted throughout the 48-month study period (p = 0.002)
Among men without anemia at baseline, a significantly smaller proportion of testosterone-treated men developed anemia compared to placebo-treated men 5
Changes in hemoglobin levels were associated with improvements in energy levels, suggesting clinical significance beyond laboratory values 5
Clinical Considerations
When evaluating anemia in men, particularly older men or those with risk factors for hypogonadism, testosterone levels should be measured 1
Morning total testosterone levels using an accurate and reliable assay are recommended for diagnosis 1
In men with borderline total testosterone levels, free testosterone concentrations should be determined either directly from equilibrium dialysis assays or by calculations using total testosterone, sex hormone binding globulin, and albumin concentrations 1
Erythrocytosis is a potential side effect of testosterone replacement therapy, requiring monitoring:
- Occurs in 3-18% with transdermal administration
- Up to 44% with injectable testosterone 1
- Hematocrit or hemoglobin should be monitored during treatment
Special Populations
Athletes with unexplained anemia should be evaluated for hypogonadism, as extreme training and unbalanced nutrition can lead to secondary hypogonadotropic hypogonadism 6
In patients with chronic kidney disease, testosterone deficiency may contribute to anemia and reduced responsiveness to erythropoiesis-stimulating agents 2
Men with type 2 diabetes have a higher prevalence of hypogonadotropic hypogonadism, which may contribute to their increased risk of anemia 3
In conclusion, hypogonadism is a well-established cause of anemia, and testosterone replacement therapy has been shown to effectively correct anemia in hypogonadal men. Clinicians should consider measuring testosterone levels in men with unexplained anemia, particularly in older men or those with risk factors for hypogonadism.