What is the best course of treatment for a 28-year-old male with elevated estrogen levels, a body fat percentage of 18.8%, and low total testosterone (hypogonadism)?

Critical Clarification Required: This Patient Does NOT Have Hypogonadism

This 28-year-old male has a total testosterone of 965 ng/dL, which is well above the diagnostic threshold for hypogonadism (<300 ng/dL), and therefore should NOT receive testosterone therapy or any treatment for "low testosterone." 1, 2 The question appears to contain a fundamental error—the patient has high-normal testosterone, not hypogonadism.

Understanding the Clinical Picture

Testosterone Status

• Total testosterone of 965 ng/dL is in the upper-normal range (normal: 300-1000 ng/dL), confirming this patient is eugonadal, not hypogonadal 1, 2
• The European Association of Urology explicitly and strongly recommends against testosterone therapy in eugonadal men, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1, 2
• Body fat of 18.8% is within normal range for males (healthy range: 10-20%), and does not indicate a pathological condition requiring hormonal intervention 1

The "High Estrogen" Concern

If estrogen levels are truly elevated in this eugonadal patient, the approach is fundamentally different from treating hypogonadism:

• Serum estradiol should be measured in patients who present with breast symptoms or gynecomastia, but elevated estradiol in the absence of symptoms does not automatically require treatment 1
• Men with elevated baseline estradiol measurements should be referred to an endocrinologist for evaluation of underlying causes 1
• Adding testosterone to a eugonadal man will worsen the situation, as exogenous testosterone undergoes aromatization to estradiol in adipose tissue, potentially increasing estrogen levels further 2, 3

Diagnostic Algorithm for This Patient

Step 1: Confirm Estradiol Elevation

• Measure serum estradiol on two separate occasions to confirm persistent elevation, as single measurements can be spurious 1
• Normal male estradiol range: 10-40 pg/mL 4
• Assess for symptoms: gynecomastia, breast tenderness, nipple sensitivity, erectile dysfunction, or decreased libido 1, 5

Step 2: Identify Underlying Causes

• Increased aromatization in adipose tissue is the most common cause—even at 18.8% body fat, visceral adiposity may drive aromatase activity 2, 3
• Evaluate for medications that increase estrogen: anabolic steroids, marijuana, alcohol, certain antipsychotics, or antiretrovirals 1
• Screen for liver disease (cirrhosis increases SHBG and reduces estrogen clearance) 2
• Rule out testicular tumors (rare but important, especially Leydig or Sertoli cell tumors) 1
• Assess thyroid function, as hyperthyroidism increases SHBG and can alter sex hormone metabolism 2

Step 3: Determine If Treatment Is Needed

Treatment is indicated ONLY if:

• Symptomatic gynecomastia with breast pain or tenderness that persists beyond 3-6 months of observation 1
• Documented estradiol >50-60 pg/mL with symptoms 5
• Reversible causes have been addressed without symptom resolution 1, 2

Treatment Options (If Truly Indicated)

First-Line: Lifestyle Modification

• Weight loss through hypocaloric diet and regular exercise reduces adipose tissue aromatase activity and can normalize estradiol levels without medication 1, 2
• Target 5-10% body weight reduction over 3-6 months 2
• This approach is preferred because it addresses the root cause rather than adding medications 1

Second-Line: Aromatase Inhibitors (Use With Extreme Caution)

• Anastrozole 0.25-0.5 mg twice weekly is the most commonly used regimen for symptomatic hyperestrogenemia in eugonadal men 5
• Starting doses vary significantly in practice (from 1 mg weekly to 1 mg daily), but lower doses (0.25-0.5 mg twice weekly) minimize risk of over-suppression 5
• Critical warning: Excessive estrogen suppression can worsen bone density, lipid profiles, and sexual function—estradiol is essential for male bone health and cardiovascular protection 2
• Monitor estradiol levels every 4-6 weeks during dose titration, targeting estradiol in the 20-30 pg/mL range 5

Third-Line: Selective Estrogen Receptor Modulators (SERMs)

• Clomiphene citrate 25 mg three times weekly can be used off-label to improve the testosterone/estradiol ratio by stimulating endogenous testosterone production while blocking estrogen receptors 4, 6, 7
• In one study, clomiphene improved the T/E ratio from 8.7 to 14.2 (P<0.001) without side effects 4
• This approach is particularly useful if the patient has borderline-low testosterone with elevated estrogen, but this patient has high-normal testosterone and does not need stimulation 4, 6

Critical Pitfalls to Avoid

• Never prescribe testosterone to eugonadal men—this violates evidence-based guidelines and will worsen estrogen levels through increased aromatization 1, 2
• Never prescribe aromatase inhibitors prophylactically or for asymptomatic elevated estrogen—only 14.4% of practitioners do this, and it risks over-suppression with adverse effects on bone and cardiovascular health 5
• Never treat based on a single estradiol measurement—confirm persistent elevation before intervening 1
• Never assume "high estrogen" requires treatment without symptoms—many men have mildly elevated estradiol without clinical consequences 1, 5

Monitoring Requirements If Treatment Is Initiated

• Measure estradiol every 4-6 weeks during dose titration of aromatase inhibitors 5
• Assess for symptom resolution (gynecomastia, breast tenderness) at each visit 1
• Monitor bone mineral density annually if long-term aromatase inhibitor use is required, as estrogen is critical for male bone health 2
• Evaluate lipid profile every 6-12 months, as estrogen suppression can worsen cholesterol 2
• If no symptom improvement after 3-6 months, discontinue treatment—the risks outweigh benefits in asymptomatic patients 1, 5

Most Likely Scenario: No Treatment Needed

In the absence of symptomatic gynecomastia or documented estradiol >50-60 pg/mL, the best course of action is:

• Reassure the patient that testosterone of 965 ng/dL is excellent and does not require intervention 1, 2
• Encourage weight optimization through diet and exercise to reduce any excess aromatase activity 1, 2
• Monitor symptoms clinically without routine estradiol testing unless breast symptoms develop 1
• Avoid unnecessary medicalization of normal physiology 1, 2