Can Testosterone Replacement Therapy (TRT) be used to treat gynecomastia?

Testosterone Replacement Therapy Does Not Treat Gynecomastia and May Actually Cause or Worsen It

TRT is contraindicated as a treatment for gynecomastia and can paradoxically induce or exacerbate breast tissue enlargement through aromatization of testosterone to estradiol. 1, 2

Why TRT Causes Rather Than Treats Gynecomastia

Mechanism of TRT-Induced Gynecomastia

• Testosterone administered exogenously undergoes peripheral aromatization to estradiol, which stimulates breast glandular tissue proliferation 1, 2
• The FDA drug labels for testosterone enanthate and cypionate explicitly state that "gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism" 1, 2
• Gynecomastia results from an imbalance in the testosterone-to-estradiol ratio, and TRT can paradoxically worsen this ratio despite raising testosterone levels 3

Clinical Evidence

• Case reports document successful treatment of TRT-induced gynecomastia only after addressing the elevated estradiol caused by testosterone therapy 4
• The aromatization of exogenous testosterone to estradiol is the primary mechanism by which TRT causes breast tissue enlargement 3, 5

When TRT May Be Appropriate in Men With Gynecomastia

The Only Indication: Proven Hypogonadism

• TRT should be offered only to men with proven testosterone deficiency, not for the treatment of gynecomastia itself 3
• The 2025 European Association of Urology guidelines provide a strong recommendation against using testosterone therapy in eugonadal men 6
• If a hypogonadal man develops gynecomastia, the underlying testosterone deficiency may be treated with TRT, but this does not treat the gynecomastia 6, 3

Pre-Treatment Evaluation Required

• Measure serum estradiol in patients who present with breast symptoms or gynecomastia prior to commencing testosterone therapy 6
• Men with elevated baseline estradiol should be referred to an endocrinology specialist before initiating TRT 6
• Baseline assessment should include breast examination to document any pre-existing gynecomastia 6

Management of TRT-Induced Gynecomastia

Initial Approach: Monitoring

• For men who develop gynecomastia or breast symptoms on TRT (breast pain, tenderness, nipple sensitivity), a period of clinical monitoring should be considered as symptoms sometimes resolve spontaneously 6
• Watchful waiting is recommended after discontinuation of substances associated with gynecomastia 3

Medical Management Options

• Selective estrogen receptor modulators (SERMs) may be used to block estrogen effects at the receptor level 7
• Aromatase inhibitors have been used successfully in case reports to treat TRT-induced gynecomastia by reducing estradiol conversion 4
• After initiating aromatase inhibitor therapy, follow-up within 1-2 months is needed to assess efficacy and measure both estradiol and testosterone levels 7
• The 2019 European Academy of Andrology guidelines do not recommend routine use of SERMs or aromatase inhibitors for general gynecomastia management, though they may have a role in specific cases 3

Alternative Strategies

• Human chorionic gonadotropin (hCG) can be considered, particularly in men wishing to maintain fertility, as it stimulates endogenous testosterone production without direct aromatization 7
• For secondary hypogonadism patients seeking fertility, gonadotropin therapy is standard and avoids the aromatization issues of exogenous testosterone 6

Surgical Management

• Surgery is the treatment of choice for patients with long-lasting gynecomastia that does not regress spontaneously or following medical therapy 3
• The extent and type of surgery depend on the size of breast enlargement and amount of adipose tissue present 3

Critical Monitoring During TRT

Ongoing Surveillance

• Continue routine monitoring of hematocrit/hemoglobin, as elevated testosterone can lead to erythrocytosis 7
• Monitor PSA levels to screen for prostate abnormalities in men over 40 7
• Follow-up visits should occur at 1-2 months initially, then at 3-6 month intervals for the first year, and yearly thereafter 6

Common Pitfalls to Avoid

• Never prescribe TRT to eugonadal men for gynecomastia treatment—this represents inappropriate use and will likely worsen the condition 6
• Do not assume that raising testosterone levels will resolve gynecomastia; the opposite effect is more likely due to aromatization 1, 2
• Avoid compounded testosterone products when commercially manufactured products are available, as they may have inconsistent potency and quality 7
• Male breast cancer, though rare, remains an absolute contraindication to TRT due to the influence of testosterone and its conversion to estradiol on breast cancer growth 6