eMedicine Specialties > Endocrinology > Gonads

Gynecomastia

Author: Mark R Allee, MD, Associate Professor, Department of Medicine, University of Oklahoma Health Sciences Center
Coauthor(s): Mary Zoe Baker, MD, Professor, Department of Medicine, Section of Endocrinology, Metabolism and Hypertension, University of Oklahoma; Medical Director, University of Oklahoma Physicians, Medicine Specialty Clinic, General Medicine Clinic and Medicine Residents' Clinic
Contributor Information and Disclosures

Updated: Sep 23, 2009

Introduction

Background

Gynecomastia is a benign enlargement of the male breast resulting from a proliferation of the glandular component of the breast. Gynecomastia is defined clinically by the presence of a rubbery or firm mass extending concentrically from the nipples. The condition known as pseudogynecomastia, or lipomastia, is characterized by fat deposition without glandular proliferation. Although gynecomastia is usually bilateral, it can be unilateral.

Pathophysiology

Gynecomastia results from an altered estrogen-androgen balance, in favor of estrogen, or from increased breast sensitivity to a normal circulating estrogen level.¹ The imbalance is between the stimulatory effect of estrogen and the inhibitory effect of androgen. Estrogens induce ductal epithelial hyperplasia, ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity. The histologic picture is similar in male and female breast tissue after exposure to estrogen.²

Estrogen production in males results mainly from the peripheral conversion of androgens (testosterone and androstenedione) — through the action of the enzyme aromatase, mainly in muscle, skin, and adipose tissue — to estradiol and estrone.

The normal production ratio of testosterone to estrogen is approximately 100:1. The normal ratio of testosterone to estrogen in the circulation is approximately 300:1.

Frequency

United States

Gynecomastia is the most common reason for male breast evaluation. The condition is common in infancy and adolescence, as well as in middle-aged to older adult males. One estimate is that 60-90% of infants have transient gynecomastia due to the high estrogen state of pregnancy. 

The next peak of occurrence is during puberty,^3,4 with a prevalence ranging from 4-69%. Some reports have shown a transient increase in estradiol concentration at the onset of puberty in boys who develop gynecomastia. Pubertal gynecomastia usually has an onset in boys aged 10-12 years. It generally regresses within 18 months, and persistence is uncommon in men older than 17 years. 

The third peak occurs in older men, with a prevalence of 24-65%. Gynecomastia in adults is often multifactorial. Increased aromatization of testosterone to estradiol and the gradual decrease of testosterone production in the aging testes most often account for gynecomastia in adult males. Older men are also more likely to take medications associated with gynecomastia than are younger men.

Estimates suggest the following etiologies in males seeking medical attention for gynecomastia:

• Persistent pubertal gynecomastia – 25%
• Drugs – 10-25%
• No detectable abnormality – 25%
• Cirrhosis or malnutrition – 8%
• Primary hypogonadism – 8%
• Testicular tumors – 3%
• Secondary hypogonadism – 2%
• Hyperthyroidism - 1.5%
• Chronic renal insufficiency – 1%

Clinical

History

A thorough history is essential to evaluate the causes of gynecomastia.

• Note the age of onset and the duration.
• Ask about recent changes in the size of the nipples and the presence of pain or discharge from the nipples.
• Inquire if the patient has any history of mumps, trauma to the testicles, alcohol use, or drug use (eg, prescription medications, over-the-counter medications, recreational drugs).
• Note any family history of gynecomastia.
• Evaluate the patient's history for sexual dysfunction, infertility, or hypogonadism (impotence, decreased libido and strength).

Physical

• Perform a thorough examination of the breasts, noting their size and consistency. Also determine the presence of any nipple discharge or axillary lymphadenopathy.
• Differentiate between true gynecomastia and pseudogynecomastia. These 2 entities may be distinguished by having the patient lie on his back with his hands behind his head. The examiner then places a thumb on each side of the breast, and slowly brings the thumbs together. In true gynecomastia, a ridge of glandular tissue will be felt that is symmetrical to the nipple-areolar complex. With pseudogynecomastia, the fingers won't meet until they reach the nipple.
• Gynecomastia can be detected when the size of the glandular tissue exceeds 0.5 cm in diameter.
• Examine the testicles, noting their size and consistency. Carefully look for the presence of nodules or asymmetry.
• Note signs of feminization, including typical body hair distribution and eunuchoid habitus.
• Check for any stigmata of chronic liver disease, thyroid disease, or renal disease.

Causes

Gynecomastia can be physiologic or pathologic; the characteristics of these forms are as follows:

• Physiologic gynecomastia is seen in newborn infants, pubescent adolescents,^3,4 and elderly individuals.
• Pathologic gynecomastia can be caused by a decrease in the production and/or action of testosterone, by an increase in the production and/or action of estrogen, or by drug use; however, gynecomastia can also be idiopathic¹ :
  • Conditions that result in primary or secondary hypogonadism and cause decreased testosterone production and/or action include the following:
    • Klinefelter syndrome
    • Congenital anorchia
    • Testicular trauma
    • Testicular torsion
    • Viral orchitis
    • Kallmann syndrome - A form of hypogonadotropic hypogonadism, Kallmann syndrome is usually associated with varying degrees of abnormality in olfactory perception. This results from the defective migration of gonadotropin-releasing hormone–secreting cells (which comigrate with the cells of the olfactory epithelium) during embryogenesis.
    • Pituitary tumors
    • Malignancies that increase the serum human chorionic gonadotropin (hCG) (eg, large cell lung cancer, gastric carcinoma, renal cell carcinoma, hepatoma)¹
    • Renal failure¹
    • Hyperthyroidism
    • Malnutrition
    • Androgen insensitivity syndrome
    • Five-alpha-reductase deficiency syndrome
  • Increased estrogen production and/or action can occur at the testicular level or at the periphery.
    • From the testes, which can be due to testicular tumors or to ectopic production of hCG as is reported with carcinoma of lung, kidney, GI tract, and extragonadal germ cell tumors
    • From peripheral conversion, which can be due to increased substrate or increased activity of aromatase as in chronic liver disease, malnutrition, hyperthyroidism, adrenal tumors, and familial gynecomastia
  • Various drugs are implicated in gynecomastia and can be classified into the following categories (although drugs in the same class do not all cause gynecomastia to the same extent)^5,6 :
    • Estrogens or drugs with estrogenlike activity, such as diethylstilbestrol, digitalis, and phytoestrogens, as well as estrogen-contaminated food and estrogen-containing cosmetics
    • Drugs that enhance estrogen synthesis, such as gonadotropins, clomiphene, phenytoin, and exogenous testosterone
    • Drugs that inhibit testosterone synthesis or action, such as ketoconazole, metronidazole, alkylating agents, cisplatin, spironolactone, cimetidine, flutamide, finasteride, and etomidate
    • Drugs that act by unknown mechanisms, such as isonicotinic acid hydrazide, methyldopa, busulfan, tricyclic antidepressants, diazepam, penicillamine, omeprazole, phenothiazines, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, alcohol, marijuana, and heroin
• In pseudogynecomastia, a condition that occurs in obese men, there is only fat deposition, found in the subareolar area. This is not pathologic or physiologic. Patients with pseudogynecomastia will typically have bilateral deposition of fat, and over time, these deposits will not change in shape or size. A careful history may reveal that the lesions have remained unchanged over a span of several years. If mammography demonstrates no evidence of malignancy, a treatment option would be observation alone.

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