How should a man being evaluated for infertility who has developed gynecomastia be managed to treat the underlying hormonal cause while preserving his fertility?

Management of Infertility-Associated Gynecomastia in Men

Men with infertility and gynecomastia require comprehensive hormonal evaluation to identify potentially correctable endocrine causes, with treatment focused on addressing the underlying hormonal imbalance while preserving fertility through selective use of SERMs or aromatase inhibitors for documented testosterone deficiency, but never testosterone monotherapy. 1, 2, 3

Initial Diagnostic Workup

The presence of gynecomastia in an infertile man signals a potential underlying hormonal disorder that requires systematic investigation 3:

Essential Laboratory Testing

• Measure testosterone (T), estradiol (E2), SHBG, LH, FSH, prolactin, hCG, AFP, TSH, and liver/renal function tests to identify the hormonal imbalance driving both conditions 3
• Obtain at least two semen analyses separated by 2-3 months after 2-3 days of abstinence to document the severity of male factor infertility 1, 4
• Check hCG and AFP specifically to rule out testicular germ cell tumors, which can present with both gynecomastia and infertility 3

Physical Examination Priorities

• Perform testicular examination with ultrasound to detect testicular tumors (palpation alone has low sensitivity) and assess for testicular atrophy 3
• Measure testicular volume (normal >15 mL) and consistency to evaluate spermatogenic potential 5
• Examine breast tissue to confirm true glandular gynecomastia versus lipomastia and rule out breast cancer 3

Critical Pitfall to Avoid

Never prescribe testosterone monotherapy to men interested in fertility, as it suppresses spermatogenesis through negative feedback on the hypothalamic-pituitary axis and will worsen infertility 2

Identifying the Underlying Cause

Proper investigation reveals an underlying pathology in 45-50% of adult gynecomastia cases 3:

Common Hormonal Patterns

• Low testosterone with elevated LH/FSH suggests primary testicular failure (Klinefelter syndrome, testicular damage) 3, 6
• Low testosterone with low/normal LH/FSH indicates hypogonadotropic hypogonadism (pituitary/hypothalamic dysfunction) 3, 6
• Elevated estradiol with abnormal T/E2 ratio suggests increased aromatase activity or estrogen-secreting tumor 2, 6
• Elevated hCG mandates immediate testicular ultrasound and tumor markers to rule out germ cell tumor 3

Medication and Substance Review

• Document all medications and substances associated with gynecomastia (spironolactone, cimetidine, finasteride, anabolic steroids, marijuana, alcohol) 3, 6
• Discontinue offending agents when possible, as this may resolve both gynecomastia and improve fertility parameters 3

Treatment Algorithm Based on Hormonal Profile

For Men with Low Testosterone and Abnormal T/E2 Ratio

Consider aromatase inhibitor (anastrozole 1 mg daily or letrozole 2.5 mg daily) or SERM therapy (clomiphene 25 mg daily for 25 days followed by 5 days rest) for men with documented low testosterone 2:

• These agents are indicated specifically for infertile men with low serum testosterone, representing a conditional recommendation with Grade C evidence 2
• Monitor response by repeating semen analysis after at least 2.5 months (74 days) to assess spermatogenic response 2
• Counsel patients that benefits are limited compared to ART, and treatment should not delay more effective options 2

For Men with Hypogonadotropic Hypogonadism

Use hCG alone or in combination with recombinant FSH to stimulate both testosterone production and spermatogenesis 7:

• hCG is FDA-approved for hypogonadotropic hypogonadism in males and preserves fertility unlike testosterone replacement 7
• This approach directly addresses the underlying pituitary deficiency while maintaining testicular function 1, 7

For Men with Normal Testosterone or Idiopathic Gynecomastia

Do not use SERMs, aromatase inhibitors, or non-aromatizable androgens for gynecomastia treatment in general 3:

• Watchful waiting is recommended after treating underlying pathology or discontinuing offending substances 3
• For persistent, bothersome gynecomastia lasting >12 months, surgical treatment (liposuction with mammary adenectomy) is the therapy of choice 3, 8

Fertility-Specific Considerations

When to Transition to ART

If inadequate semen parameter improvement after 3 months of medical therapy or time-sensitive fertility concerns exist, transition directly to IVF/ICSI 2:

• Female partner age is the most critical factor determining conception success, and delaying ART for empiric medical trials may reduce overall pregnancy chances 2
• IVF/ICSI provides superior pregnancy outcomes compared to prolonged medical management 2

For Non-Obstructive Azoospermia with Gynecomastia

Inform patients of the limited data supporting pharmacologic manipulation with SERMs, AIs, and gonadotropins prior to surgical intervention 2:

• Micro-TESE should not be delayed for empiric hormonal trials in men with NOA 2
• Hormonal therapy has extremely limited evidence in this population and may only delay definitive treatment 2

Important Health Implications

Men with abnormal semen parameters have higher rates of testicular cancer and overall mortality 1, 4:

• The combination of infertility and gynecomastia warrants thorough evaluation to exclude serious underlying conditions including testicular tumors 3
• This evaluation is important for overall health screening, not just fertility 4

Practical Management Summary

1. Obtain comprehensive hormonal panel and testicular ultrasound to identify correctable causes 3
2. If low testosterone with fertility desire, use SERMs/AIs or hCG—never testosterone monotherapy 2, 7
3. Monitor semen parameters after 2.5-3 months of treatment 2
4. Transition to ART if inadequate response or time constraints 2
5. For persistent gynecomastia after hormonal correction, offer surgical treatment 3, 8