Does Testosterone Replacement Therapy (TRT) help lower estrogen levels in males?

TRT Does Not Lower Estrogen in Males—It Can Actually Raise It

Testosterone replacement therapy (TRT) does not help lower estrogen levels in males; instead, testosterone is converted to estradiol through aromatization, which can elevate estrogen levels in some men. 1, 2

Understanding the Testosterone-Estrogen Relationship

How TRT Affects Estrogen Levels

• Testosterone is converted to estradiol by the enzyme aromatase, primarily in adipose (fat) tissue, meaning TRT can paradoxically increase estrogen levels rather than decrease them 1, 2
• In a large study of 34,016 men screened at Low T Centers, 20.2% (7,215 men) developed high estradiol levels (≥42.6 pg/mL) while on injectable testosterone therapy 2
• The conversion rate varies by individual factors, particularly body composition and age 2

Risk Factors for Elevated Estrogen on TRT

• Higher body mass index (BMI) and increased adipose tissue correlate with greater aromatization and higher estradiol levels 2, 3
• Injectable testosterone formulations appear to have higher rates of estradiol elevation compared to topical formulations (38.6% vs 18.5% usage in men requiring aromatase inhibitors) 1
• Age plays a role: men aged 45-65 years showed the highest rates of elevated estradiol (22.1%), while those under 25 had the lowest rates (3.3%) 2

Management of Elevated Estrogen on TRT

When to Treat Elevated Estradiol

• Aromatase inhibitors (specifically anastrozole) should be prescribed for symptomatic men with estradiol >60 pg/mL or >40 pg/mL with symptoms 1
• Common symptoms warranting treatment include gynecomastia, though this is rarely documented as the primary indication 2
• Interestingly, high estradiol levels were NOT associated with higher rates of low libido—men with normal or lower estradiol actually had higher documented rates of low libido 2

Aromatase Inhibitor Therapy

• Anastrozole 0.5 mg three times weekly is the most commonly used regimen, though significant variability exists in prescribing patterns (ranging from 1 mg weekly to 1 mg daily) 1, 4
• Anastrozole effectively reduces estradiol levels by approximately 50-66%: median pre-treatment estradiol of 65 pg/mL decreased to 22 pg/mL post-treatment 1, 5
• Testosterone levels remain stable during aromatase inhibitor therapy (616 ng/dL pre-treatment vs 596 ng/dL post-treatment, P=0.926) 1
• Only 68% of men treated with anastrozole had pre-treatment estradiol ≥60 pg/mL, indicating many clinicians treat based on symptoms rather than strict laboratory cutoffs 1

Important Caveats About Estrogen Suppression

• Estrogen plays critical roles in male physiology, including bone health, cardiovascular function, and regulation of the gonadotropin axis 6, 5
• Short-term aromatase inhibition (10 weeks) does not negatively impact bone calcium turnover or body composition in males 5
• Estrogen is the main regulator of gonadal-pituitary feedback for the gonadotropin axis in men, not testosterone alone 5
• Over-suppression of estrogen should be avoided, as estradiol contributes to bone density and metabolic health in males 6, 5

Alternative Strategies to Lower Estrogen

Lifestyle Modifications

• Weight loss through low-calorie diets can reduce aromatization by decreasing adipose tissue, the primary site of testosterone-to-estradiol conversion 6, 2, 3
• Regular physical activity correlates with improved testosterone levels and reduced body fat, thereby decreasing aromatase activity 6
• These lifestyle changes produce modest testosterone increases (1-2 nmol/L) but can meaningfully impact estradiol levels through fat mass reduction 6, 3

Monitoring Recommendations

• Only 54.7% of practitioners monitor estradiol levels in patients on TRT, despite 62.4% checking levels at initial evaluation 4
• Fellowship-trained and North American practitioners are more likely to monitor estrogen levels during TRT 4
• Regular monitoring allows for early detection and management of elevated estradiol before symptoms develop 1, 4

Special Population: Transgender Men

• Estradiol levels actually DECREASE significantly in transgender men on testosterone therapy, contrary to concerns in treatment guidelines 3
• With testosterone treatment achieving normal male levels, estradiol falls to and remains within the normal male range even after 6 years of follow-up 3
• There is no role for aromatase inhibitors or estrogen-reducing strategies in transgender men on appropriate testosterone therapy 3
• The mechanism likely involves decreased fat mass with testosterone therapy, reducing the substrate for aromatization 3

Clinical Pitfalls to Avoid

• Do not assume TRT will lower estrogen—counsel patients that estrogen may rise and require management 1, 2
• Do not treat elevated estradiol based solely on laboratory values without considering symptoms, as high estradiol may not correlate with sexual dysfunction 2
• Do not use excessive doses of aromatase inhibitors—start conservatively with anastrozole 0.5 mg three times weekly and titrate based on response 1
• Do not ignore the beneficial effects of estrogen in males—aim for normal male estradiol ranges (typically 10-40 pg/mL), not complete suppression 6, 5