EVALUATION OF THE SUBFERTILE MALE: PART 2 - BLOOD TESTING

Male fertility evaluation is an essential process for identifying and treating underlying causes of subfertility, allowing healthcare providers to offer more accurate and personalized care. This is the second of several blogs on the evaluation of the subfertile male. In this blog we will explore the primary and supplementary blood tests recommended for male fertility evaluation, their clinical significance, special testing considerations, and the diagnostic and therapeutic implications each test offers.

Primary Blood Tests

1. Follicle-Stimulating Hormone (FSH)

   • Purpose: FSH plays a critical role in spermatogenesis by stimulating Sertoli cells in the testes, essential for sperm production. Elevated FSH levels often indicate testicular failure or a reduced sperm production capability.
   • Clinical Implications: Abnormally high FSH may suggest primary testicular failure, such as in cases of Klinefelter syndrome or post-chemotherapy effects, while low levels could point toward hypothalamic or pituitary dysfunction.
   • Testing Considerations: No special time-of-day requirements, but FSH is commonly measured alongside LH and testosterone for a comprehensive hormonal profile.
   • Key Reference: Handelsman DJ, et al. "Primary hypogonadism: spectrum of clinical presentations and diagnostic approaches."

2. Luteinizing Hormone (LH)

   • Purpose: LH regulates testosterone production by stimulating Leydig cells in the testes. It’s an indirect measure of testosterone regulation.
   • Clinical Implications: High LH levels with low testosterone suggest primary testicular failure, while low LH may indicate central (pituitary or hypothalamic) causes. LH results also guide treatment, such as testosterone replacement therapy.
   • Testing Considerations: Taken with testosterone and FSH for hormonal balance assessment.
   • Key Reference: Lehtihet M, et al. "Diagnosis and treatment of male hypogonadism."

3. Testosterone (Total and Free)

   • Purpose: Testosterone is the primary male sex hormone essential for libido, secondary sexual characteristics, and spermatogenesis. Both total and free testosterone measurements are important in assessing hormonal health.
   • Clinical Implications: Low testosterone may indicate hypogonadism, impacting fertility. Understanding whether the hypogonadism is primary or secondary helps in selecting treatment, like hormone therapy or lifestyle interventions.
   • Testing Considerations: Ideally tested in the morning, when levels peak. Mass spectrometry or liquid chromatography offers more accurate results, particularly in cases of borderline testosterone.
   • Key Reference: Rosner W, et al. "Utility of free testosterone measurement in male hypogonadism."

Supplementary Blood Tests

1. Estradiol

   • Purpose: Estradiol, a metabolite of testosterone, is monitored to understand the testosterone-to-estrogen ratio, particularly in obese patients or those with gynecomastia.
   • Clinical Implications: Elevated estradiol levels could suggest aromatization of testosterone, often seen in men with obesity or liver disease, impacting fertility. Correcting estradiol imbalance may improve outcomes.
   • Testing Considerations: Morning testing, as with testosterone.
   • Key Reference: Winters SJ, "Role of estradiol in male reproductive health."

2. Prolactin

   • Purpose: High prolactin levels can interfere with LH and FSH secretion, impairing testosterone and sperm production.
   • Clinical Implications: Hyperprolactinemia could indicate a pituitary adenoma or other hypothalamic-pituitary axis dysfunction, impacting fertility. Reducing prolactin levels (e.g., with dopamine agonists) can restore normal fertility.
   • Testing Considerations: Blood draw typically occurs in the morning; levels may be affected by stress or medications.
   • Key Reference: Mancini T, et al. "Hyperprolactinemia and male infertility: clinical relevance and therapeutic approach."

3. Thyroid-Stimulating Hormone (TSH)

   • Purpose: Thyroid function influences overall metabolism and reproductive health.
   • Clinical Implications: Both hypothyroidism and hyperthyroidism can impair testosterone production and affect libido, mood, and energy. Managing thyroid disorders can improve fertility outcomes.
   • Testing Considerations: Morning draw preferred, but TSH generally stable throughout the day.
   • Key Reference: Meeker JD, et al. "Hypothyroidism and reproductive function in men."

4. Vitamin D (25-hydroxy)

   • Purpose: Vitamin D affects testicular function and semen quality.
   • Clinical Implications: Low vitamin D is associated with reduced semen quality and hypogonadism. Addressing deficiency may improve sperm quality and hormonal levels.
   • Testing Considerations: Any time of day is suitable, with serum 25-hydroxy vitamin D being the preferred test.
   • Key Reference: Hammoud AO, et al. "Vitamin D deficiency and male reproductive function.", de Angelis C et al. Rev Endocr Metab Disord (2017) 18:285–305.

5. Inhibin B

   • Purpose: Inhibin B is secreted by Sertoli cells and is an indicator of spermatogenesis.
   • Clinical Implications: Low inhibin B levels correlate with reduced spermatogenic activity and may indicate primary testicular failure. It helps in assessing the cause of azoospermia or oligospermia.
   • Testing Considerations: Requires specialized assay and may not be available at all labs.
   • Key Reference: Jensen TK, et al. "Inhibin B as a marker of spermatogenesis and male fertility."

6. Complete Blood Count (CBC)

   • Purpose: A CBC can help identify anemia or infection, which may affect fertility.
   • Clinical Implications: Anemia can signal nutritional deficiencies or chronic disease impacting fertility. Treating underlying conditions may improve reproductive health.
   • Testing Considerations: No specific timing; morning may reduce variability.
   • Key Reference: Plante BJ, et al. "The role of hematologic parameters in male fertility."

7. Comprehensive Metabolic Profile (CMP)

   • Purpose: Assesses liver and kidney function, crucial for overall health and medication management.
   • Clinical Implications: Liver disease may influence estradiol levels, while kidney function impacts medication tolerance, relevant when prescribing fertility-related therapies.
   • Testing Considerations: Morning draw, fasting preferred.
   • Key Reference: Farahani L, et al. "The importance of liver and kidney function in male fertility assessment."

8. Lipid Profile

   • Purpose: Assesses cardiovascular health, which can indirectly impact fertility.
   • Clinical Implications: Dyslipidemia is linked to lower testosterone levels and metabolic syndrome, which affects sperm quality. Managing lipid levels supports overall and reproductive health.
   • Testing Considerations: Morning, fasting recommended.
   • Key Reference: Laaksonen DE, et al. "Cardiovascular and metabolic risks in male infertility."

Urinalysis

• Purpose: Identifies underlying metabolic and infectious disorders, including diabetes and urinary tract infections, that can impair fertility.
• Clinical Implications: Glycosuria or ketonuria may suggest diabetes, while a positive leukocyte or nitrite test could indicate infection, both of which may require treatment before fertility interventions.
• Testing Considerations: Routine urinalysis with dipstick analysis; no specific timing required.
• Key Reference: Paick JS, et al. "Diabetes and male fertility: effects and interventions."

Conclusion

Blood tests provide a foundational understanding of the hormonal and systemic health affecting male fertility. Evaluating these parameters helps clinicians diagnose specific causes of infertility, offering tailored treatment options. Subsequent entries in this series will focus on Semen Analysis and Imaging Studies, expanding on the essential tools for a thorough male fertility evaluation.

References:

1. Handelsman DJ, et al. "Primary hypogonadism: spectrum of clinical presentations and diagnostic approaches."
2. Lehtihet M, et al. "Diagnosis and treatment of male hypogonadism."
3. Rosner W, et al. "Utility of free testosterone measurement in male hypogonadism."
4. de Angelis C et al. Rev Endocr Metab Disord (2017) 18:285–305