Testosterone Cypionate Gynecomastia Severity Grading Rubric

How is gynecomastia graded?

The severity grading used for gynecomastia in general comes from plastic surgery. Rohrich and colleagues, publishing in Plastic and Reconstructive Surgery in 2003, proposed a classification and graduated treatment plan based on two things: how much of the enlargement is glandular versus fibrous, and how much breast ptosis (skin excess) is present [2]. It is a surgical planning tool.

The Depo-Testosterone label (intramuscular testosterone cypionate) does not grade gynecomastia. Under warnings it states that gynecomastia may develop and occasionally persists in patients being treated for hypogonadism, and the adverse reactions section names gynecomastia among endocrine and urogenital reactions alongside excessive frequency and duration of penile erections [1]. Carcinoma of the breast is listed as a contraindication in men [1].

Why breast tissue grows on testosterone cypionate

Estrogens stimulate growth of breast tissue, androgens inhibit it, and most cases of gynecomastia result from deficient androgen action or excessive estrogen action in the breast [3]. Aromatase is the enzyme that converts androgens to estrogens, and it is expressed in the testes and other male tissues [5].

Gynecomastia is common outside of testosterone use: reported prevalence in males is 32 to 65%, depending on age and the criteria used [4]. The same guideline notes that proper investigation of adult gynecomastia may reveal an underlying pathology in 45 to 50% of cases [4].

How gynecomastia is evaluated

The European Academy of Andrology guideline sets out the evaluation. The purpose is to detect underlying pathological conditions and reversible causes, and to tell gynecomastia apart from other breast lumps, particularly breast cancer. Assessment includes a thorough history plus examination of the breast and genitalia, including testicular ultrasound. Laboratory tests that may be part of the evaluation include testosterone, estradiol, sex hormone-binding globulin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, prolactin, hCG, alpha-fetoprotein, and liver and renal function tests. Breast imaging may be used when the clinical examination is equivocal; in suspicious lesions, core needle biopsy should be sought directly [4].

What the grade changes about treatment

In Rohrich's graduated plan, ultrasound-assisted liposuction was effective for most grades, and excisional techniques were reserved for severe gynecomastia with significant skin excess after attempted ultrasound-assisted liposuction. The authors' series covered 61 patients treated between 1987 and 2000, with an overall success rate of 86.9% using suction-assisted lipectomy and then ultrasound-assisted liposuction [2].

The 2019 European Academy of Andrology guideline states that selective estrogen receptor modulators, aromatase inhibitors and non-aromatizable androgens are not justified in general, and that surgery is the therapy of choice for patients with long-lasting gynecomastia. It recommends watchful waiting after treating an underlying pathology or discontinuing a substance associated with gynecomastia, and it says testosterone treatment should be offered to men with proven testosterone deficiency [4].

A double-blind crossover study of 10 patients with benign gynecomastia, not specific to testosterone treatment, compared one-month courses of placebo with tamoxifen 10 mg taken twice daily. Seven of the ten had a decrease in breast size on tamoxifen; the reduction was partial and may have needed a longer course. All four patients with painful gynecomastia had symptom relief, and the investigators reported no toxicity [6].