What is the cause of unexplained anemia and hypogonadism (testosterone deficiency)?

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From the Guidelines

Unexplained anemia and hypogonadism (testosterone deficiency) are often interrelated, and treating the testosterone deficiency may partially improve the anemia, as testosterone stimulates erythropoiesis.

Diagnosis and Evaluation

To diagnose and manage these conditions, it is essential to consult with both a hematologist and an endocrinologist. The diagnostic workup for anemia should include:

  • Complete blood count
  • Iron studies
  • Vitamin B12 and folate levels
  • Reticulocyte count
  • Possibly bone marrow examination For testosterone deficiency, the diagnosis should be made based on a total testosterone level below 300 ng/dL, measured on two separate occasions in the early morning, combined with symptoms and/or signs such as reduced energy, reduced endurance, diminished work and/or physical performance, fatigue, visual field changes, anosmia, depression, reduced motivation, poor concentration, impaired memory, irritability, infertility, reduced sex drive, and changes in erectile function 1.

Treatment

Treatment for anemia depends on the underlying cause but may include:

  • Iron supplementation (typically 325mg ferrous sulfate 1-3 times daily)
  • Vitamin B12 injections (1000mcg monthly)
  • Erythropoietin therapy in certain cases For testosterone deficiency, replacement therapy options include:
  • Testosterone gel (50-100mg applied daily)
  • Injections (typically testosterone cypionate 100-200mg every 2 weeks)
  • Patches (4-6mg daily) Before starting testosterone replacement therapy, prostate-specific antigen and hematocrit levels should be checked, as testosterone can worsen prostate conditions and increase red blood cell production 1.

Monitoring and Lifestyle Modifications

Regular monitoring of both conditions is essential, with:

  • Complete blood counts every 3-6 months
  • Testosterone levels every 6-12 months after stabilization Lifestyle modifications including:
  • Adequate sleep
  • Regular exercise
  • A balanced diet rich in iron and protein can support overall improvement. It is crucial to note that the risk of hemoconcentration is greater if the patient also has a condition that may itself be associated with an increase in the hematocrit, such as chronic obstructive pulmonary disease, and therefore, careful monitoring is necessary 1.

From the Research

Causes of Unexplained Anemia and Hypogonadism

  • Unexplained anemia and hypogonadism (testosterone deficiency) can be related to the interaction of hypothalamo-pituitary and testicular factors 2
  • Testosterone deficiency syndrome (TDS) is a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels 2
  • Testosterone treatment can stimulate erythropoiesis and increase hemoglobin levels in older men with unexplained anemia 3, 4
  • Iron deficiency can attenuate the effect of testosterone on erythropoiesis, and testosterone treatment may worsen anemia in iron-deficient individuals due to ineffective erythropoiesis 3, 5

Role of Testosterone in Erythropoiesis

  • Testosterone stimulates iron-dependent erythropoiesis and suppresses hepcidin, a hormone that regulates iron metabolism 3, 5
  • Testosterone treatment can increase red cell count and hemoglobin levels in iron-replete individuals, but may reduce red cell count in iron-deficient individuals 5
  • Testosterone deficiency may be a cause of anemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease 6

Relationship between Testosterone and Iron

  • Iron plays an important role in mediating testosterone's effects on erythropoiesis, and iron deficiency can affect the response to testosterone treatment 3, 5
  • Testosterone treatment can suppress hepcidin and increase iron mobilization, but this effect may be attenuated by iron deficiency 3
  • The relationship between testosterone and iron is complex, and further research is needed to understand the mechanisms underlying their interaction 3, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Recent trends in the treatment of testosterone deficiency syndrome.

International journal of urology : official journal of the Japanese Urological Association, 2007

Research

The role of iron in mediating testosterone's effects on erythropoiesis in mice.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020

Research

Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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