History and exam
Key diagnostic factors
common
presence of risk factors
Anabolic steroid usage, medications that reduce testosterone synthesis or impair testosterone action, medications that increase oestrogen levels, gender dysphoria, and prostate cancer treatment are strong risk factors for development of gynaecomastia.
palpable breast tissue
The patient should be examined in the supine position.[11][27]
Thumb and forefinger are placed on the outer and inner breast margins and are brought together in a pincer movement along the chest wall until they reach a mound of firm breast tissue located concentrically under the nipple/areola.
The diameter is measured with a ruler or measuring tape.
A diameter of 2 cm or less is considered normal in an adult.
newborn age
Newborns have high oestrogen levels derived from the mother and placenta.
pubertal age
In puberty there is a physiological response to the increase in testosterone fuelled by marked increases in growth hormone, insulin-like growth factor-1, follicle-stimulating hormone, and luteinising hormone. Testosterone increases 30-fold, and oestrogen increases 3-fold but peaks earlier than testosterone.
older adult age
Decrease in free testosterone and increase in adipose tissue with ageing.
accidental medication exposure in children
Opportunities for children to obtain adult medications (including contraceptives) should be reviewed.
substance use disorder
acne in adult males
The triad of marked muscle development, small testicles, and adult acne suggests exogenous androgen usage.
obesity
Testosterone is converted to oestrogen by aromatase in fat tissue.
uncommon
breast pain
Symptomatic men are more likely to note irritation than pain, with chafing of the breast.
small or soft testicles
Sign of low testosterone.
Decreased body hair, female fat distribution, decreased strength, or small or soft testicles suggest hypogonadism.
The triad of marked muscle development, small testicles, and adult acne suggests exogenous androgen usage.
Other diagnostic factors
common
erectile dysfunction or decreased libido
May be due to low testosterone, although there are many other causes.
uncommon
nutritional supplements
Exposure to oestrogenising substances may result from supplement ingestion, some of which may be adulterated with anabolic steroids.
differences in sex development (DSD)
Gynaecomastia can result from genetic factors (e.g., testicular feminisation, Klinefelter syndrome [47, XXY]).
delayed secondary sex characteristics
Low testosterone leading to gynaecomastia can result from orchitis, haemochromatosis, chemotherapy or radiotherapy, spinal cord injury, or trauma.
precocious puberty
Any history of abnormal sexual development may be related to imbalance of the testosterone-to-oestrogen ratio.
weight loss and malnutrition
In severe physiological stress testosterone decreases more than oestrogen and takes longer to re-bound.
Weight loss may also be an indicator of hyperthyroidism.
signs or symptoms of hypothalamic or pituitary disease
May include headache or visual loss.
Gynaecomastia can result from low follicle-stimulating hormone and luteinising hormone (LH), leading to low Leydig cell stimulation and testosterone production.
High prolactin suppresses the gonadotropin-releasing hormone pulse generator needed for normal LH production.
signs or symptoms of liver failure (e.g., jaundice, ascites, spiders)
There may be a history of alcohol use or hepatitis. Other signs and symptoms include Dupuytren's contracture or hepatosplenomegaly. Because of decreased testosterone catabolism in the face of hepatic insufficiency, more testosterone is available for conversion to oestrogen.
signs or symptoms of hyperthyroidism (e.g., heat intolerance, weight loss, goitre)
Other signs and symptoms include sweating, stare or lid lag, exophthalmos, pre-tibial myxoedema, palpitations, and tremor.
Hyperthyroidism results in high sex hormone binding globulin and increased oestrogen production.
decreased body hair
Sign of low testosterone. Decreased body hair, female fat distribution, decreased strength, or small or soft testicles suggest hypogonadism.
painless or enlarging testicular mass
Gynaecomastia can result from human chorionic gonadotropin-producing testicular tumours and oestrogen-producing Leydig cell tumours.
diminished strength or muscle atrophy
Sign of low testosterone.
Risk factors
strong
anabolic steroid usage
prostate cancer
Oestrogen and anti-androgen therapy in the treatment of prostate cancer may contribute to breast enlargement.[34]
hormone therapy for gender dysphoria
Oestrogen and anti-androgen therapy for gender dysphoria (e.g., in male-to-female transgender individuals) may contribute to breast enlargement.[35]
drugs that reduce testosterone synthesis
Include the following: gonadotrophin-releasing hormone (GnRH) agonists (which down-regulate pituitary luteinising hormone production); cancer chemotherapeutic agents; ketoconazole; metronidazole; spironolactone (reduces synthesis more than eplerenone; also impairs testosterone action); some antipsychotics (increase prolactin, which suppresses GnRH pulses).[22][36][37]
drugs that impair testosterone action
Include the following: androgen receptor blockers (bicalutamide, flutamide); spironolactone (which also reduces testosterone synthesis); 5-alpha reductase inhibitors (e.g., finasteride); H2 antagonists (e.g., cimetidine); proton-pump inhibitors (impair less than H2 antagonists).[28][29][30][31][38]
weak
occupational exposure to embalming fluid or oral contraceptives
contact with environmental phyto-oestrogens or phthalates
Environmental phyto-oestrogens (plant oestrogens) and other compounds activating oestrogen receptors include shampoos, creams and cosmetics, tea tree oil, or lavender oil.[45][46][47] Phthalates are industrial compounds found in many cosmetic products and plastics.[48] Children are particularly vulnerable.
hyperthyroidism
renal failure
Multi-factorial mechanisms may lead to gynaecomastia.
cirrhosis
Androgen catabolism is reduced, so there is greater availability of androgens for conversion to oestrogen.[51]
drugs with complex or unknown mechanisms
ACE inhibitors, alcohol, amiloride, amiodarone, amfetamines, calcium-channel blockers, ciclosporin (cyclosporine), diazepam, growth hormone, haloperidol, heroin, anti-retroviral therapy, human chorionic gonadotrophin, isoniazid, marijuana, methadone, methyldopa, reserpine, risperidone, theophylline.[22][23][24]
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