Is it necessary to order estradiol and Follicle-Stimulating Hormone (FSH) in men with suspected low testosterone?

Measurement of Estradiol and FSH in Men with Suspected Low Testosterone

Routine measurement of estradiol and FSH is not necessary in the initial evaluation of men with suspected low testosterone, but these tests should be ordered when specific clinical scenarios arise during the diagnostic workup.

Initial Testosterone Evaluation

When evaluating men for possible testosterone deficiency, the following approach is recommended:

1. Initial laboratory testing:

   • Measure morning total testosterone levels (between 8-10 AM) on at least two separate occasions 1
   • The threshold for low testosterone is defined as consistently <300 ng/dL 1

2. If low testosterone is confirmed:

   • Measure serum luteinizing hormone (LH) levels (Strong Recommendation; Grade A) 1
   • LH helps establish the etiology of testosterone deficiency and determines if additional tests are needed 1

When to Measure Estradiol

Estradiol measurement is indicated in specific clinical scenarios:

• Presence of breast symptoms or gynecomastia prior to starting testosterone therapy (Expert Opinion) 1
• During testosterone therapy if the patient develops gynecomastia or breast symptoms (breast pain, tenderness) 1
• When secondary hypogonadism is suspected with low/low-normal LH, as increased aromatization of testosterone to estradiol in adipose tissue can cause estradiol-mediated negative feedback suppressing LH secretion 1, 2

When to Measure FSH

FSH measurement is indicated in specific clinical scenarios:

• When fertility is a concern for the patient 1
• To distinguish primary from secondary hypogonadism when LH levels are already measured 1
• When evaluating reproductive health status in men with testosterone deficiency who are interested in preserving fertility 1
• When elevated FSH is found, it typically indicates impaired spermatogenesis (hypergonadotropic hypogonadism) 1

Diagnostic Algorithm for Low Testosterone

1. Confirm low testosterone: Morning total testosterone <300 ng/dL on at least two measurements 1

2. Measure LH: To determine if hypogonadism is primary (testicular) or secondary (pituitary/hypothalamic) 1

   • High LH = Primary hypogonadism
   • Low/normal LH = Secondary hypogonadism

3. Additional testing based on LH results:

   • If LH is low/normal:

     • Measure prolactin (Strong Recommendation; Grade A) 1
     • Consider estradiol if obesity is present or gynecomastia is observed 1
     • Consider pituitary MRI if testosterone <150 ng/dL 1

   • If fertility is a concern or preservation is desired:

     • Measure FSH 1
     • Perform testicular examination 1

Clinical Pitfalls to Avoid

• Relying on screening questionnaires instead of laboratory testing (not recommended) 1
• Single testosterone measurement instead of confirming with at least two measurements 1
• Not measuring LH when testosterone is low (prevents determining the cause) 1
• Not considering obesity as a cause of secondary hypogonadism through increased aromatization of testosterone to estradiol 1, 2
• Overlooking fertility concerns when evaluating testosterone deficiency 1
• Not measuring estradiol when gynecomastia or breast symptoms are present 1

By following this targeted approach to laboratory testing, clinicians can efficiently diagnose testosterone deficiency while avoiding unnecessary tests, ultimately improving patient outcomes related to morbidity, mortality, and quality of life.