Testosterone Cypionate and Gynecomastia: When to Call Your Doctor

Why testosterone cypionate can cause gynecomastia

Testosterone is converted to estradiol by the enzyme aromatase [4]. In breast tissue, estrogens stimulate growth and androgens inhibit it, and most gynecomastia comes from either too little androgen action or too much estrogen action [2]. The Depo-Testosterone label states that gynecomastia may develop and occasionally persists in patients treated for hypogonadism, and gynecomastia appears in the label's list of adverse reactions reported with androgens [1].

How a new breast lump is sorted out

Gynecomastia is benign enlargement of the glandular tissue of the male breast, and the clinical job is to tell it apart from other breast lumps, particularly breast cancer [3]. Breast cancer in men is much less common than benign gynecomastia, and the two are usually distinguishable by a careful physical examination [2].

The guideline uses breast imaging whenever the clinical examination is equivocal and says core needle biopsy should be sought directly in suspicious lesions [3].

Breast carcinoma in men is a contraindication to the drug on the Depo-Testosterone label [1], and the Endocrine Society guideline recommends against starting testosterone therapy in men with breast cancer [6].

What the evaluation involves

The guideline calls for a thorough history and an examination of the breasts and genitalia, including testicular ultrasound, and says laboratory tests may be part of the evaluation: testosterone, estradiol, sex hormone-binding globulin, LH, FSH, TSH, prolactin, hCG, alpha-fetoprotein, and liver and renal function [3]. In adults, proper investigation may reveal an underlying condition in 45 to 50% of cases [3].

Does gynecomastia on testosterone cypionate go away?

The label's wording is that gynecomastia may develop and occasionally persists in patients treated for hypogonadism [1].

The guideline recommends watchful waiting after the underlying condition is treated or the substance linked to gynecomastia is discontinued [3]. It also states that surgery is the treatment of choice for patients with long-lasting gynecomastia [3]. A review of gynecomastia makes the same point: surgery may be needed when the enlargement does not resolve spontaneously or with medical therapy [2].

Treatments that have been studied

Tamoxifen. A preliminary report gave 40 mg of tamoxifen daily for 1 to 4 months (median 2 months) to 61 men with idiopathic gynecomastia; 80% had complete regression of breast swelling, with no comparison group, and no long-term side effects were observed over a median follow-up of 36 months [5]. Idiopathic gynecomastia means no cause was identified, so this was not a group selected for testosterone use.

Aromatase inhibitors. A randomized, double-blind, placebo-controlled trial gave anastrozole 1 mg daily or placebo for 6 months to 80 boys aged 11 to 18 with pubertal gynecomastia. A response of 50% or greater reduction in combined breast volume occurred in 38.5% on anastrozole versus 31.4% on placebo, a difference that was not statistically significant (P = 0.47) [7]. That is an adolescent population with pubertal gynecomastia, not adults on testosterone replacement.

The guideline states that selective estrogen receptor modulators, aromatase inhibitors and non-aromatizable androgens are not justified in general for gynecomastia [3].