Gynecomastia in Children and Adolescents

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Gynecomastia in children and adolescents

Author: Sharonda A Taylor, MD, FAAP, FSAHM, Dipl. of ABOM
Section Editors: Diane Blake, MD, Mitchell E Geffner, MD
Deputy Editor: Mary M Torchia, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2020. | This topic last updated: Apr 01, 2020.
INTRODUCTION
This topic will focus on the evaluation of gynecomastia in children and adolescents. Gynecomastia in adults is
discussed separately:
● (See "Epidemiology, pathophysiology, and causes of gynecomastia".)

● (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults".)
● (See "Management of gynecomastia".)
DEFINITION AND CHARACTERISTIC FEATURES
Gynecomastia is the benign proliferation of glandular breast tissue in males. It differs from proliferation of
breast tissue in females in that there is no terminal alveolar development in response to progesterone [1].
Gynecomastia is characterized by a mass or ridge of glandular tissue that is symmetrically distributed around
the areolar-nipple complex (figure 1). It can generally be detected when the glandular tissue is >0.5 cm (0.2
inches) in diameter. Gynecomastia may be tender to palpation early in the course. It is usually bilateral, but
some patients present with unilateral enlargement or bilateral enlargement with one side larger than the other
or enlarging weeks to months before the other [2-4].
The distinct mass of glandular tissue, central location, and symmetrical shape distinguish gynecomastia from
other causes of male breast enlargement in children and adolescents [1,5,6]. (See 'Mimics of gynecomastia'
below.)
EPIDEMIOLOGY
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In children and adolescents, gynecomastia is common during the neonatal period and during puberty (figure
2). Gynecomastia is uncommon in prepubertal boys. The epidemiology of gynecomastia is discussed in detail
separately. (See "Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Epidemiology'.)
PATHOPHYSIOLOGY
Gynecomastia is presumed to be caused by a relative imbalance between androgens (testosterone and

androstenedione) and estrogens (estradiol and estrone). The hormonal imbalance may be caused by an
absolute increase in free estrogens, decrease in endogenous free androgens, a relative increase in the free
estrogen-to-free androgen ratio, androgen insensitivity, or estrogen-like drug effects (table 1). (See
"Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Pathophysiology'.)
Transient neonatal gynecomastia is thought to result from placental transformation of dehydroepiandrosterone

and dehydroepiandrosterone sulfate (derived from the fetus and mother) to estrone and estradiol, which enter
the fetal circulation and stimulate glandular proliferation in the breast. (See "Epidemiology, pathophysiology,
and causes of gynecomastia", section on 'In utero' and "Placental development and physiology", section on
'Steroid hormones'.)
The pathophysiology of pubertal gynecomastia is likely related to the transient estrogen/androgen imbalance
caused by the earlier rise of serum estradiol than serum androgen concentrations to adult levels. However,
most observational studies have not found differences in single point measurements of estradiol in boys with
and without pubertal gynecomastia [7-10]. In observational studies, boys with gynecomastia have greater
expression of aromatase in skin fibroblasts and higher concentrations of insulin-like growth factor-1 (IGF-1)
than boys without gynecomastia [10,11]. Aromatase locally converts androgen to estrogen, and IGF-1 is
necessary for breast proliferation [10,11]. Additional studies suggest that changes in sex hormone-binding
globulin levels (due to medications and illnesses such as liver disease) may impact estradiol levels [12]. (See
"Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Puberty'.)
CAUSES OF GYNECOMASTIA
Physiologic gynecomastia — The majority of cases of gynecomastia in children and adolescents are
physiologic (table 2) [2].
Neonatal breast hypertrophy — Neonatal breast hypertrophy (which occurs in both boys and girls) is
presumably related to placental transformation of androgens to estrogens, which enter the fetal circulation and
stimulate glandular proliferation (picture 1). (See "Epidemiology, pathophysiology, and causes of
gynecomastia", section on 'In utero' and "Placental development and physiology", section on 'Steroid
hormones'.)
Neonatal breast hypertrophy usually regresses spontaneously and completely within the first year of life.
Approximately 5 percent of cases may be associated with galactorrhea [13]. (See "Breast masses in children

and adolescents", section on 'Neonates and infants'.)
Pubertal gynecomastia — Pubertal gynecomastia is a physiologic enlargement of the glandular breast

tissue that occurs in some boys during puberty. In most studies, it occurs in >50 percent of male adolescents
(range 4 to 69 percent) [1,3,12,14-16]. The wide range is related to differences in study population, diagnostic
criteria, and observer technique [5].
The prevalence of pubertal gynecomastia peaks during mid-puberty, coinciding with peak height velocity at
age 12 to 14 years, pubic hair sexual maturity rating (Tanner stage) 3 to 4 (picture 2), and testicular volumes
of 8 to 10 mL bilaterally (figure 3) [3,5,10,14,15,17-19]. It is usually bilateral (64 percent of cases in the largest
cross-sectional study) [3].
Adolescents with pubertal gynecomastia usually complain of a mass or lump behind the nipple [5]. The
enlargement occurs gradually and should not exceed 4 cm (1.6 inches) in diameter. Palpable fibroglandular
enlargement ≥4 cm (1.6 inches) in diameter or rapidly progressive glandular enlargement may be associated
with an underlying disorder [5,20,21]. (See 'Pathologic gynecomastia' below.)
The breast may be tender for approximately six months after onset, but tenderness gradually resolves as the
glandular tissue undergoes fibrosis and the inflammatory reaction and stretching of tissues diminish [5].
When left untreated, pubertal gynecomastia regresses substantially or resolves in >70 percent of patients
after one year [2,14,15], although it may take up to three years for some patients [18,19]. Gynecomastia that
persists for ≥1 year or after age 17 years is less likely to spontaneously regress [14,15,22].
Pathologic gynecomastia — Pathologic gynecomastia is rare in children and adolescents but may be
associated with substantial morbidity (eg, testicular, adrenal, or pituitary tumors) (table 2). Pathologic
gynecomastia usually is associated with other abnormalities on physical examination or clinical features that
are not characteristic of physiologic gynecomastia, such as [5,6,20,23]:
● Occurrence outside the neonatal or pubertal age group

● Occurrence in prepubertal boys who have no other secondary sexual characteristics (eg, testicular
enlargement, pubic hair or axillary hair, axillary odor)
● Rapid progression
● Enlargement >4 cm (1.6 inches) in diameter [20]
● Persistence for more than one year or after age 17 years; persistent pubertal gynecomastia accounts for
a large proportion of gynecomastia in young adults [6]
Pathologic gynecomastia has a number of causes including:
Drugs — The proportion of cases of gynecomastia in children and adolescents that are related to drugs is
unknown. A variety of prescription, over-the-counter, and illicit drugs may be associated with gynecomastia
(table 3), but the association is not necessarily causal [1,15,24-26].
Children and adolescents may be exposed to the following drugs/substances that have been associated with
gynecomastia:
● Estrogens or substances that act like estrogens in medications (eg, oral contraceptive pills, digitalis) and
cosmetics (lotions, lavender oil, and tea tree oil) [27-29] (see "Endocrine-disrupting chemicals")
● Drugs that enhance endogenous estrogen production (eg, gonadotropins, clomiphene)
● Drugs that inhibit testosterone synthesis and/or action (eg, ketoconazole, metronidazole, cimetidine); the
effect is related to dose and duration of use
● Antiretroviral therapy for HIV (see "Overview of antiretroviral agents used to treat HIV", section on 'Non-
nucleoside reverse transcriptase inhibitors (NNRTIs)')
● Drugs with other mechanisms (eg, hyperprolactinemia) of gynecomastia: isoniazid, calcium channel
blockers, ACE inhibitors, amphetamines, diazepam, haloperidol, antipsychotics (especially risperidone),
and tricyclic antidepressants [26]
● Alcohol and recreational or illicit drugs, including [1,20]:
• Marijuana, particularly if used ≥4 times per week [30-32]
• Anabolic steroids (see "Use of androgens and other hormones by athletes", section on
'Gynecomastia')
Hypogonadism — Primary (hypergonadotropic) hypogonadism accounts for approximately 8 percent and

secondary (hypogonadotropic) hypogonadism accounts for approximately 2 percent of cases of gynecomastia
in adult patients seeking consultation for gynecomastia [1]. It is not known how frequently hypogonadism
causes gynecomastia in children and adolescents.
● Klinefelter syndrome, polysomy X, is the most common congenital cause of primary hypogonadism
and often presents during adolescence. As many as 70 percent of patients with Klinefelter syndrome
have gynecomastia, which usually is slowly progressive [5]. Rapidly progressive gynecomastia in patients
with Klinefelter syndrome may indicate an extragonadal human chorionic gonadotropin (hCG)-secreting
tumor in the mediastinum; these malignant germ cell tumors occur in approximately 1 percent of patients
with Klinefelter syndrome [33,34]. Other clinical features of Klinefelter syndrome include tall, thin body
habitus; long arms and legs; learning, language, or behavioral difficulties; and small (<3 cm [1.2 inches] in
length or 5 mL in volume), firm testes in pubertal-aged males. Patients with Klinefelter syndrome have an
increased risk of breast cancer [35]. (See "Causes of primary hypogonadism in males", section on
'Klinefelter syndrome' and 'Tumors' below and "Breast cancer in men", section on 'Alterations of the
estrogen to androgen ratio'.)
● Other congenital causes of primary hypogonadism that may be associated with gynecomastia include:
• Cryptorchidism, including anorchia (testicular regression) (see "Undescended testes (cryptorchidism)

in children: Clinical features and evaluation")
• Enzyme defects of testosterone production (see "Causes of primary hypogonadism in males",

section on 'Disorders of androgen biosynthesis')
• Other genetic conditions, syndromes, or polymorphisms (examples can be found in the Online
Mendelian Inheritance in Man [OMIM] database by searching on "gynecomastia")
● Acquired causes of primary hypogonadism in children and adolescents include infections that affect the
testes (mumps, echovirus, group B arboviruses, leprosy), trauma (eg, testicular torsion), and radiation.
● Secondary hypogonadism may be congenital (eg, congenital gonadotropin-releasing hormone

deficiency) or acquired (eg, pituitary tumor [36], hyperprolactinemia). (See "Causes of secondary
hypogonadism in males".)
Tumors — A variety of tumors may cause gynecomastia by presumably altering the balance of androgens
and estrogens. (See "Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Causes of
gynecomastia'.)
● Testicular tumors (Leydig or Sertoli cell tumors, germ cell tumors) occur predominantly in young men
(15 to 35 years). The reported incidence of testicular tumors in men with gynecomastia is 3 percent
[1,37]; gynecomastia may be the only clinical finding at the time of diagnosis [37-39].
A testicular mass may be palpable on examination. (See "Clinical manifestations, diagnosis, and staging
of testicular germ cell tumors", section on 'Clinical manifestations'.)
The risk of testicular cancer is increased in patients with a history of cryptorchidism. (See "Undescended
testes (cryptorchidism) in children: Management", section on 'Testicular cancer'.)
The risk of Sertoli cell tumors is increased in patients with Peutz-Jeghers syndrome, an autosomal
dominant condition characterized by multiple hamartomatous polyps in the gastrointestinal tract,
mucocutaneous pigmentation (picture 3A-C), and increased risk of gastrointestinal and
nongastrointestinal cancer. (See "Peutz-Jeghers syndrome: Clinical manifestations, diagnosis, and
management", section on 'Testicular tumors'.)
● Feminizing adrenal tumors typically are aggressive and malignant; males with feminizing adrenal
tumors may have testicular atrophy and decreased libido in addition to gynecomastia. (See
"Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Other rare causes' and
"Clinical presentation and evaluation of adrenocortical tumors", section on 'Androgen and estrogen-
secreting tumors'.)
● hCG-producing tumors may arise in the testes (germ-cell tumors), lungs, mediastinum, liver, kidneys, or
brain.
Other pathologic causes
● Chronic liver or kidney diseases – Chronic liver or kidney diseases may be associated with
gynecomastia [16]. Chronic liver disease affects sex hormone binding globulin levels, which alter the
circulating levels of estradiol and testosterone. Kidney disease alters testosterone production from Leydig
cells. There is also an increase in estradiol and luteinizing hormone. In addition, the effects of chronic

disease on the hypothalamic-pituitary-testicular (HPT) axis, medications used in disease management,

and declining nutrition contribute to the development of gynecomastia [40]. It is estimated that chronic
disease accounts for approximately 8 percent of cases of gynecomastia in adult patients seeking
consultation for gynecomastia [1]. It is not known how frequently chronic disease causes gynecomastia in
children and adolescents.
● Malnutrition – Malnutrition suppresses the HPT axis leading to decreased testosterone production.
However, during refeeding, the HPT axis re-engages. This increases production of testosterone and
estradiol similar to that seen during physiologic puberty. (See 'Pubertal gynecomastia' above.)
● Hyperthyroidism – Hyperthyroidism is an uncommon cause of gynecomastia, estimated to cause

approximately 1.5 percent of cases in adult patients evaluated for gynecomastia [1]; it is not known how
frequently hyperthyroidism causes gynecomastia in children.
Other features of hyperthyroidism in children and adolescents include goiter, accelerated growth,
ophthalmopathy (exophthalmos, stare, and lid lag), tachycardia, increased appetite without weight gain
(or with weight loss), and tremor. However, gynecomastia may be the first manifestation of
hyperthyroidism [41]. (See "Clinical manifestations and diagnosis of Graves disease in children and
adolescents".)
● Aromatase excess syndrome – Aromatase excess syndrome (also called familial prepubertal
gynecomastia) is a heterogeneous autosomal dominant disorder characterized by accelerated early linear
growth, prepubertal gynecomastia, and testicular failure [5,42]. It is caused by a gain-of-function mutation
in the CYP19 (aromatase) gene [43-45].
● Partial androgen insensitivity syndrome – Partial androgen insensitivity syndrome (PAIS) is an X-

linked disorder caused by mutations in the androgen receptor (AR) gene that is associated with
gynecomastia, decreased virilization, and a small phallus in males. In a retrospective case series, 14 of
14 male patients with PAIS developed gynecomastia at puberty [46]. (See "Pathogenesis and clinical
features of disorders of androgen action", section on 'Partial androgen insensitivity (PAIS)'.)
Partial androgen insensitivity occurs in X-linked spinal and bulbar muscular atrophy (also known as
Kennedy disease), which may present with gynecomastia in adolescence or before puberty [47-49].
Associated clinical features may include muscle fasciculations, weakness, muscle cramps, and calf
hypertrophy. (See "Pathogenesis and clinical features of disorders of androgen action", section on
'Spinobulbar muscular atrophy'.)
● Congenital adrenal hyperplasia – Various forms of congenital adrenal hyperplasia, including 11-beta-
hydroxylase deficiency [50,51], 3-beta hydroxysteroid dehydrogenase deficiency [52], and late-onset 21-
hydroxylase deficiency [53], on rare occasion, present with gynecomastia due to increased production of
estrogen precursors [54-56]. (See "Uncommon congenital adrenal hyperplasias" and "Genetics and
clinical presentation of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase
deficiency".)

● Ovotesticular disorder of sex development – Ovotesticular disorders of sex development (previously

called "true hermaphroditism") are characterized by the presence of both ovarian follicular and testicular
tubular tissue in the same individual. Associated clinical features may include hypospadias and
cryptorchidism [57]. (See "Causes of disorders of sex development", section on 'Gonadal overproduction
of androgens'.)
MIMICS OF GYNECOMASTIA
Mimics of gynecomastia in infants include:
● Mastitis – In infants younger than two months, unilateral or bilateral breast enlargement may be caused
by mastitis (cellulitis or abscess of the breast). Associated clinical features include swelling, erythema,
warmth, tenderness, and induration of the breast with or without purulent nipple discharge. Gynecomastia
is not warm, indurated, or associated with purulent nipple discharge. (See "Mastitis and breast abscess in
infants younger than two months", section on 'Introduction'.)
● Galactocele – Galactocele (a benign milk-filled cystic lesion, which may be associated with milky nipple
discharge) is a rare cause of unilateral or bilateral breast enlargement in infants [58,59].
Mimics of gynecomastia in children and adolescents include:
● Pseudogynecomastia – Pseudogynecomastia is fatty infiltration of the breast (also called lipomastia). It

is a common finding, especially in overweight (body mass index [BMI] ≥85th and <95th percentile for age)
and obese (BMI ≥95th percentile for age) adolescents. The lack of a discrete mass or ridge of glandular
tissue distinguishes pseudogynecomastia from gynecomastia (figure 1). On palpation,
pseudogynecomastia feels similar to adjacent adipose tissue in the anterior axillary fold [33].
● Breast carcinoma and other tumors – Breast carcinoma is extremely rare in male children and
adolescents [60,61]; <1 percent of breast cancer occurs in males, with a median age of 67 years [62,63].
Risk factors for breast cancer in males include Klinefelter syndrome, gonadal failure, obesity, radiation
exposure, and positive family history of BRCA2 gene mutations [64,65]. Other primary or metastatic
tumors may present with breast masses including rhabdomyosarcoma, angiosarcoma, lymphoma,
leukemia, and neuroblastoma [66].
In contrast to gynecomastia, breast carcinoma and other tumors usually are eccentrically located and
fixed to the chest wall (figure 1). Breast carcinoma may be associated with skin dimpling, nipple
retraction, and nipple bleeding, or discharge [67], none of which is typical of gynecomastia. Breast
carcinoma usually is not associated with tenderness, which may occur in the early development of
gynecomastia.
● Other breast masses – Other masses that may occur in the male breast include lipomas, hemangiomas,
hematomas, neurofibromas, lymphangiomas, and dermoid cysts [16,68]. Unlike gynecomastia, these
often are unilateral and tend to be eccentrically located.

APPROACH TO DIAGNOSIS
The history and examination of children and adolescents with gynecomastia focus on clinical features of
pathologic causes of gynecomastia (table 2). Laboratory and imaging studies usually are not necessary in
adolescents with clinical features typical of physiologic gynecomastia.
History — Important aspects of the history in children and adolescents with gynecomastia include:
● Breast enlargement – The size, timing of onset, and duration of breast enlargement: Breast size ≥4 cm
and rapid progression may indicate greater hormone imbalance and a pathologic cause [5]
● Pubertal status and age – Beyond the neonatal period, prepubertal gynecomastia is always pathologic;
pubertal gynecomastia is most common during mid-puberty (eg, age 12 to 14 years, during peak height
velocity, or at sexual maturity rating [Tanner stage] 3 to 4 (figure 3)) [5,10,17-19]
● Associated symptoms – Mild pain is normal during the early development of physiologic gynecomastia,
and may also occur with mastitis, but is unusual in breast carcinoma; galactorrhea may indicate
hyperprolactinemia
● Review of systems – Symptoms of a previously undiagnosed endocrine abnormality or chronic illness,

particularly [6]:
• Hypogonadism – Atypical genitalia, undervirilization

• Hyperthyroidism – Goiter, tachycardia, tremor, increased appetite without weight gain, accelerated
linear growth
• Aromatase excess syndrome – Early accelerated linear growth
• Liver disease – Anorexia, nausea, vomiting, acholic stools, edema, jaundice, spider angiomata
• Renal disease – Anorexia, nausea, vomiting, edema, changes in urination, hematuria
• Human chorionic gonadotropin (hCG)-producing tumor – Rapid and significant virilization with only
slightly enlarged testes, headache
• Prolactinoma – Headache, galactorrhea
● Family history – Family history of gynecomastia or hypogonadism (table 4), testicular cancer, and liver
or kidney disease (see 'Pathologic gynecomastia' above)
● Medications/drugs – Exposure to medications, including over-the-counter drugs, marijuana, dietary

supplements, and herbal products that are associated with gynecomastia (table 3) (see 'Drugs' above)
● Psychosocial effects – The degree to which gynecomastia affects school or social life (may have
bearing on management and follow-up) (see 'Management' below)
Physical examination — Important aspects of the physical examination of children and adolescents with
gynecomastia include:

● Breast – Proper examination of the breast differentiates gynecomastia from pseudogynecomastia

(lipomastia) and other causes of breast enlargement. The patient is examined in the supine position with
his hands beneath his head (figure 1) [6].
Galactorrhea may indicate hyperprolactinemia. Overlying skin changes (skin dimpling), nipple bleeding or
discharge, or axillary adenopathy may be associated with breast carcinoma (extremely rare in children
and adolescents).
● Genitalia
• Sexual maturity rating – Physiologic gynecomastia typically occurs at pubic hair sexual maturity
rating (Tanner stage) 3 to 4 (picture 2); pathologic causes of gynecomastia should be considered if
the sexual maturity rating is stage 1 or 5.
• Testes – Physiologic gynecomastia typically occurs at testicular volumes of 8 to 10 mL bilaterally

(figure 3).
Testes that are small (<2.5 cm [1 inch] in length or <5 mL in volume (picture 4)), atrophied, or absent
suggest that the patient is prepubertal or has hypogonadism, and additional evaluation is warranted.
Small, firm testes may suggest Klinefelter syndrome. A testicular mass may indicate testicular
cancer.
• Scrotum and phallus – A bifid scrotum and/or hypospadias may indicate partial androgen
insensitivity or other causes of congenital hypogonadism.
● Other aspects of the physical examination – Other aspects of the physical examination may suggest a
pathologic cause or mimic of gynecomastia:
• Body mass index – Overweight (body mass index [BMI] ≥85th and <95th percentile) and obesity
(BMI ≥95th percentile) may indicate pseudogynecomastia rather than gynecomastia, although
overweight/obesity do not exclude gynecomastia, as both may coexist [4]; weight loss (or lack of
gain) may indicate hyperthyroidism or malignancy.
• Height – Early accelerated linear growth in prepubertal boys may suggest aromatase excess
syndrome or hyperthyroidism; tall stature with long extremities may suggest Klinefelter syndrome.
• Thyroid – Palpable goiter suggests hyperthyroidism; other signs of hyperthyroidism include

ophthalmopathy (exophthalmos, stare, and lid lag), tachycardia, and tremor.
• Abdomen – An abdominal mass may indicate an adrenal tumor or extragonadal germ cell tumor.
Hepatomegaly may indicate a hCG-secreting tumor or chronic liver disease.
• Virilization – Undervirilization may indicate hypogonadism, partial androgen insensitivity, congenital

adrenal hyperplasia (3-beta hydroxysteroid dehydrogenase deficiency), or an ovotesticular disorder
of sex development. Rapid or precocious virilization may indicate an hCG-secreting tumor.

• Skin – Perioral pigmentation (ie, dark blue to dark brown macules around the mouth or on the buccal
mucosa (picture 3A-B)) may indicate Peutz-Jeghers syndrome, which is associated with an
increased risk of Sertoli cell tumors. (See "Peutz-Jeghers syndrome: Clinical manifestations,
diagnosis, and management", section on 'Extra-intestinal cancers' and "Peutz-Jeghers syndrome:
Clinical manifestations, diagnosis, and management", section on 'Genital tract cancers'.)
Jaundice and spider angiomata may indicate liver disease.
Edema may indicate renal disease. (See "Clinical presentation and evaluation of chronic kidney
disease in children", section on 'Clinical presentation'.)
• Musculoskeletal – Muscle fasciculations, weakness, and calf hypertrophy may indicate X-linked
spinal and bulbar muscular atrophy, which is associated with partial androgen insensitivity.
Initial laboratory evaluation and management
Drug or medication exposure — If the patient has been exposed to a drug (eg, marijuana), medication,
or herbal therapy that is known to be associated with gynecomastia (table 3), the agent should be
discontinued. Improvement (decreased tenderness and softening of the glandular tissue) within one month of
discontinuation supports the agent as the cause [6]. However, drug-induced gynecomastia of >12 months'
duration is unlikely to regress because of fibrosis.
Other cause suggested by history or examination — Targeted laboratory and imaging studies should
be performed if the initial evaluation suggests an underlying cause other than drug/medication exposure (table
5) [5].
Prepubertal gynecomastia — Gynecomastia in prepubertal boys without any other secondary sexual
characteristics (eg, increased testicular volume, pubic hair) is usually pathologic and should prompt a search
for an underlying etiology [69]. If the initial evaluation and/or the targeted evaluation do not suggest a cause,
we suggest obtaining an early morning blood sample to measure serum hCG, estradiol, testosterone,
luteinizing hormone (LH), and dehydroepiandrosterone (DHEA) [5]. An early morning sample is recommended
because serum testosterone concentration varies during the day and is highest in the morning. Referral to a
pediatric endocrinologist is recommended [5,16]. Although a specific cause is rarely identified [70], evaluation
is necessary because of the potential morbidity associated with the various causes. (See 'Indications for
referral' below and 'Pathologic gynecomastia' above.)
The interpretation of initial laboratory studies is discussed below. (See 'Laboratory interpretation and
additional evaluation' below.)
Pubertal gynecomastia
● Typical pubertal gynecomastia – Laboratory studies generally are not necessary for adolescents with
clinical features typical of pubertal gynecomastia [1,16,19,33,71]:
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• Tender gynecomastia with onset at mid-puberty (ie, age 12 to 14 years, pubic hair sexual maturity
rating [Tanner stage] 3 or 4, testicular volume 8 to 10 mL)
• History and physical examination not suggestive of a pathologic cause
Management of physiologic pubertal gynecomastia typically entails reassurance and observation. The
majority of cases resolve spontaneously within one to three years of onset [14,15,18,19]. (See
'Physiologic gynecomastia' below.)
● Pubertal gynecomastia with atypical features – Clinical features that are not typical of physiologic
pubertal gynecomastia include rapid progression, diameter ≥4 cm (1.6 inches), rapid and/or precocious
virilization, and persistence for ≥24 months or after age 17 years [18,72]. Consensus regarding the
laboratory evaluation of adolescents with asymptomatic, atypical pubertal gynecomastia is lacking
[18,73]. Our evaluation typically includes early morning measurement of serum hCG, estradiol,
testosterone, LH, and DHEA [1,5].
The interpretation of initial laboratory studies is discussed below. (See 'Laboratory interpretation and
additional evaluation' below.)
Laboratory interpretation and additional evaluation — The results of the laboratory tests direct additional
laboratory or imaging studies (table 6). Laboratory results must be interpreted in the context of age and
pubertal status (eg, low testosterone is normal for a prepubertal boy but abnormal for a pubertal-aged
adolescent).
Increased hCG — Elevated hCG (regardless of the other results) suggests an hCG-secreting tumor
(testicular germ cell, extragonadal germ cell tumor, or hCG-secreting nontrophoblastic tumor).
Additional evaluation typically includes testicular ultrasonography for testicular mass.
● A testicular mass in a patient with elevated hCG suggests a testicular germ cell tumor. Referral to a
pediatric urologist or oncologist is warranted.
● In the absence of a testicular mass, imaging of the chest and abdomen (and possibly other sites [eg,
brain]) is warranted to look for an extragonadal germ cell tumor or hCG-secreting nontrophoblastic tumor.
If found in the anterior mediastinum, a karyotype is mandatory to assess for Klinefelter syndrome. (See
"Extragonadal germ cell tumors involving the mediastinum and retroperitoneum" and "Intracranial germ
cell tumors".)
Increased estradiol — Elevated estradiol in a child or adolescent with gynecomastia may indicate a
Leydig or Sertoli cell testicular tumor, feminizing adrenal tumor, increased extraglandular aromatase activity,
congenital adrenal hyperplasia, or ovotesticular disorder of sex development (table 6 and algorithm 1).
Increased testosterone — Increased testosterone and increased LH may indicate androgen resistance or
hyperthyroidism (table 6 and algorithm 2).

Additional evaluation includes thyroid function tests (free thyroxine, total tri-iodothyronine, and thyroid-
stimulating hormone [TSH]):
● Increased free thyroxine and/or tri-iodothyronine and decreased TSH indicate hyperthyroidism. (See
"Clinical manifestations and diagnosis of Graves disease in children and adolescents".)
● Androgen resistance (eg, partial androgen insensitivity) should be considered if free thyroxine, total tri-
iodothyronine, and TSH are normal. (See "Diagnosis and treatment of disorders of the androgen
receptor".)
Decreased testosterone — Decreased testosterone in a pubertal-aged male may indicate primary or

secondary hypogonadism or hyperprolactinemia (table 6 and algorithm 2).
● Decreased testosterone with increased LH indicates primary hypogonadism. (See "Causes of primary
hypogonadism in males" and "Clinical features and diagnosis of male hypogonadism".)
● Decreased testosterone with normal or decreased LH may indicate secondary hypogonadism or

hyperprolactinemia, possibly due to a prolactin-secreting pituitary tumor (even in the absence of
galactorrhea).
Additional evaluation includes measurement of serum prolactin.
• Elevated prolactin (hyperprolactinemia) may indicate the presence of a prolactin-secreting pituitary

tumor; additional evaluation may include magnetic resonance imaging of the head. (See "Clinical
manifestations and evaluation of hyperprolactinemia", section on 'Laboratory/imaging tests'.)
• Normal prolactin suggests other causes of secondary hypogonadism. (See "Causes of secondary
hypogonadism in males".)
MANAGEMENT
The management of gynecomastia is discussed in detail separately. (See "Management of gynecomastia".)
Physiologic gynecomastia — Although the majority of cases of physiologic pubertal gynecomastia resolve
spontaneously within a year of onset, management decisions are individualized according to the degree of
psychosocial distress.
Given the usual natural history, many patients can be managed with reassurance and observation. Adjunctive
psychotherapy may be beneficial for adolescents with psychosocial consequences of gynecomastia (eg,
bullying and decreased self-esteem) [72].
The frequency of follow-up varies with the degree of psychosocial distress and the clinical setting. Primary
care providers may monitor pubertal gynecomastia every three to six months (often in conjunction with follow-
up of other adolescent health issues), particularly if gynecomastia affects the patient's school or social life
[1,6,16,23]. Less frequent follow-up, or no follow-up, may be appropriate for patients who are not bothered by

gynecomastia provided that the gynecomastia regresses as expected over the next 12 months. Although
referral to a pediatric endocrinologist for patients with typical pubertal gynecomastia is not necessary, patients
whose diagnosis of pubertal gynecomastia has been confirmed by a pediatric endocrinologist should follow up
as recommended by the specialist.
We do not routinely suggest pharmacologic therapy for pubertal gynecomastia in adolescents. Evidence
supporting the efficacy of pharmacologic therapy for pubertal gynecomastia in adolescents is limited to case
reports and uncontrolled studies [5,74], and the US Food and Drug Administration (FDA) has not approved
any drug for this indication. Nonetheless, pharmacologic therapy may be warranted for select patients (eg,
those with physiologic gynecomastia that is >4 cm [1.6 inches] in diameter [which is unlikely to spontaneously
regress], rapidly progressive, or associated with embarrassment that interferes with normal daily activities).
Pharmacologic therapy is most effective during the proliferative phase of breast development, which lasts
approximately 12 months. Pharmacologic therapy for gynecomastia is discussed separately. (See
"Management of gynecomastia", section on 'Pharmacologic therapy'.)
Surgical therapy may be warranted for adolescents with physiologic gynecomastia that is >3 cm (1.2 inches)
in diameter, unresponsive to medical therapy, persists for more than two years or after age 16 years, or is
associated with embarrassment that interferes with normal daily activities [18,71,75,76]. Before surgery is
performed, biochemical evaluation (early morning human chorionic gonadotropin [hCG], estradiol,
testosterone, luteinizing hormone [LH], dehydroepiandrosterone [DHEA]) may be warranted (if not already
performed) to avoid delaying diagnosis of a pathologic condition that has clinical implications (eg, requires
specific directed treatment, affects fertility) [16]. When surgery is performed in adolescents, we suggest that
tissue be sent for histology, given rare reports of incidental breast carcinoma [5,77]. Surgical management of
gynecomastia is discussed separately. (See "Management of gynecomastia", section on 'Surgery'.)
Pathologic gynecomastia — Management of pathologic gynecomastia depends upon the underlying cause.
In general, gynecomastia resolves with discontinuation of the offending medication/environmental exposure or
treatment of the underlying condition. These measures should be undertaken before pharmacologic or
surgical therapy, which are discussed separately. (See "Management of gynecomastia".)
INDICATIONS FOR REFERRAL
Indications for referral in children or adolescents with gynecomastia include:
● Prepubertal gynecomastia – Refer to a pediatric endocrinologist to evaluate for an endogenous or

exogenous source of estrogen and other endocrine abnormalities [5,16,18].
● Breast enlargement that is not gynecomastia – Referral to a pediatric surgeon may be warranted for
children and adolescents with breast enlargement that is not characteristic of gynecomastia (eg, eccentric
enlargement, fixed mass, etc) [18].
● Endocrine abnormality (primary or secondary hypogonadism, hyperthyroidism, androgen resistance,

increased extraglandular aromatase activity) – Refer to a pediatric endocrinologist.
● Testicular mass on testicular ultrasonography – Refer to a pediatric urologist/oncologist.
● Other tumor (adrenal, extragonadal germ cell, pituitary) suspected on imaging – Refer to a pediatric
oncologist.
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics
patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer
the four or five key questions a patient might have about a given condition. These articles are best for patients
who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are comfortable with
some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient education" and the keyword[s] of interest.)
● Basics topics (see "Patient education: When men develop breasts (gynecomastia) (The Basics)")
● Beyond the Basics topics (see "Patient education: Gynecomastia (breast enlargement in men) (Beyond
the Basics)")
SUMMARY AND RECOMMENDATIONS
● Gynecomastia is the benign proliferation of glandular breast tissue in males and is characterized by a
mass or ridge of glandular tissue that is symmetrically distributed around the areolar-nipple complex
(figure 1). These features distinguish gynecomastia from other causes of male breast enlargement in
children and adolescents. (See 'Definition and characteristic features' above and 'Mimics of
gynecomastia' above.)
● In the pediatric age range, gynecomastia is common in the neonatal period and during puberty. (See
"Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Epidemiology'.)
● Gynecomastia is thought to be caused by a relative imbalance between androgens (testosterone and

androstenedione) and estrogens (estradiol and estrone) (table 1). (See 'Pathophysiology' above.)
● Physiologic pubertal gynecomastia typically occurs during mid-puberty. Adolescents complain of a mass
or lump behind the nipple. The breast may be tender for approximately six months after onset. Pubertal
gynecomastia regresses spontaneously in the majority of adolescents but is unlikely to regress if it
persists for ≥1 year or after age 17 years. (See 'Pubertal gynecomastia' above.)

● Clinical features suggestive of pathologic gynecomastia include:
• Occurrence outside the neonatal or pubertal age range

• Occurrence in prepubertal boys
• Rapid progression
• Enlargement >4 cm (1.6 inches) in diameter
• Rapid and/or precocious virilization
Pathologic causes of gynecomastia include drugs/medications (table 3), hypogonadism, tumors, and
endocrinologic abnormalities (table 2). (See 'Causes of gynecomastia' above and 'Pathologic
● The history and examination of children and adolescents with gynecomastia focuses on the clinical
features of pathologic causes of gynecomastia, including drugs/medications; age and pubertal status;
family history; associated symptoms; growth parameters; palpation of the breasts; and evaluation of the
testicles for size, masses, and consistency (table 2). (See 'History' above and 'Physical examination'
above.)
● The initial laboratory evaluation and management depend on whether or not a cause is suggested by the
history and examination:
• If the patient has been exposed to a medication or herbal therapy associated with gynecomastia
(table 3), the agent should be discontinued. Clinical improvement within one month of discontinuation
supports the agent as the cause. (See 'Drug or medication exposure' above.)
• If the history and examination suggest a cause other than drug/medication exposure, targeted
laboratory and imaging studies should be performed (table 5). (See 'Other cause suggested by
history or examination' above.)
• In prepubertal boys, if the history and examination do not suggest a cause, we suggest obtaining an
early morning blood sample to measure serum human chorionic gonadotropin (hCG), estradiol,
testosterone, luteinizing hormone (LH), and dehydroepiandrosterone (DHEA). (See 'Prepubertal
• In adolescents with clinical features of typical pubertal gynecomastia, laboratory studies generally are
not necessary. Initial management usually consists of reassurance and observation. (See 'Pubertal
• Clinical features that are not typical of physiologic pubertal gynecomastia include rapid progression,
diameter ≥4 cm (1.6 inches), and persistence for ≥12 months or after age 17 years. Our evaluation
for such patients consists of early morning measurement of serum hCG, estradiol, testosterone, LH,
and DHEA. (See 'Pubertal gynecomastia' above.)
● The results of the initial laboratory tests direct additional laboratory and imaging studies (table 6 and
algorithm 1 and algorithm 2). (See 'Laboratory interpretation and additional evaluation' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 14310 Version 15.0

GRAPHICS
Examination for gynecomastia
Physical examination method to distinguish gynecomastia, due to enlargement of the glandular

tissue, from pseudogynecomastia, due to excessive adipose tissue. The thumb and forefinger
are placed on opposite sides of the breast and slowly brought together towards the areolar-
nipple complex. Gynecomastia is appreciated as a concentric, rubbery-to-firm disk of tissue,
often mobile, located directly beneath the areolar area. Pseudogynecomastia presents no
discrete mass, and other masses due to disorders such as cancer tend to be eccentrically
positioned (insert).
Adapted from: Braunstein GD. Gynecomastia. N Engl J Med 2007; 357:1229.
Graphic 72334 Version 3.0

Bimodal prevalence of gynecomastia after infancy
Prevalence of gynecomastia at various chronologic ages showing peaks at

puberty and in older men. The data are derived from multiple population
studies.
Data from Braunstein GD. Gynecomastia. In: Diseases of the Breast, Harris JR,
Lippman ME, Morrow M, Hellman S (Eds), Lippincott-Raven, Philadelphia 1996. p.54.

Pathophysiologic mechanisms for gynecomastia
Absolute increase in free estrogens

Direct secretion from:
Maternal-placental-fetal unit
Testes
Adrenal glands
Extraglandular aromatization of precursors
Displacement from sex hormone-binding globulin
Decreased metabolism
Exogenous estrogen administration
Decreased endogenous free androgens

Decreased secretion
Increased metabolism
Relative increase in free estrogen/free androgen ratio
Androgen insensitivity
Congenital defects in androgen receptor structure and function
Displacement of androgens from breast androgen receptors by certain drugs
Other
Estrogen-like effect of drugs
Possible enhanced sensitivity of breast tissue
Adapted from: Braunstein GD. Gynecomastia. N Engl J Med 1993; 328:490.

Selected causes of unilateral or bilateral gynecomastia in children and adolescents
Associated clinical features
Physiologic causes
Neonatal May be associated with galactorrhea; usually resolves spontaneously within the first
year of life
Pubertal Occurs at mid-puberty: during peak height velocity at age 12 to 14 years; pubic hair
SMR stage 3 to 4; testicular volume 8 to 10 mL
Pathologic causes
Drugs
Exogenous estrogen Source of exogenous estrogen (eg, combined oral contraceptive pills, topical estrogen
cream)
Other drugs History of exposure to drug or other substances associated with gynecomastia (refer to
UpToDate content on drugs that cause gynecomastia)
Hypogonadism
Primary (hypergonadotropic)
Klinefelter syndrome Tall, thin body habitus; small firm testes in pubertal-aged males
Cryptorchidism One or both testes not within the scrotum (or history of testis that is not within the
scrotum)
Defect in testosterone Atypical genitalia; undervirilization

synthesis (eg, 17-
ketosteroid reductase
deficiency)
Acquired primary History of testicular insult or injury (eg, surgery, radiation, systemic illness, etc)
hypogonadism
Secondary (hypogonadotropic)
Acquired secondary Insult to hypothalamic-pituitary axis (eg, surgery, radiation, trauma, etc)
hypogonadism
Hyperprolactinemia Galactorrhea
Tumors
Testicular cancer (Leydig or Testicular mass; increased risk with history of cryptorchidism (any testicular cancer);
Sertoli cell) increased risk in Peutz-Jeghers syndrome (Sertoli cell tumors)
Feminizing adrenal tumor Abdominal mass
Lactotroph adenoma Galactorrhea, hypogonadism, vision problems, headaches

(prolactinoma)
hCG-producing tumors
Testicular (germ cell) Testicular mass; increased risk with history of cryptorchidism
Extragonadal germ cell May be detected with chest or abdominal imaging

tumor (eg, mediastinal,
retroperitoneal,
intracranial)
Nontrophoblastic hCG- May be detected with imaging (chest, abdomen, brain)

producing tumor
Other causes
Chronic liver or kidney Underweight; findings associated with chronic liver or kidney disease (eg,
disease/malnutrition hepatomegaly, edema, etc)
Hyperthyroidism Goiter, accelerated growth, weight loss, ophthalmopathy, tachycardia, increased

appetite, tremor

Aromatase excess syndrome Accelerated early linear growth, prepubertal gynecomastia, testicular failure
Androgen resistance (eg, partial Atypical genitalia; undervirilization; muscle fasciculations, weakness, and calf
androgen insensitivity) hypertrophy (X-linked spinal and bulbar muscular atrophy)
Congenital adrenal hyperplasia
11-beta-hydroxylase Premature adrenarche, early puberty, accelerated linear growth, hypertension

deficiency
3-beta-hydroxysteroid Atypical genitalia, undervirilization

dehydrogenase deficiency
Late-onset 21- Premature adrenarche with advanced bone age, accelerated linear growth during
hydroxylase deficiency childhood, acne
Ovotesticular disorder of sex Atypical genitalia (presence of both ovarian follicular and testicular tubular tissue in a
development (previously "true single individual); undervirilization
hermaphroditism")
SMR: sexual maturity rating (Tanner stage); hCG: human chorionic gonadotropin.
References:

Physiologic breast hypertrophy in a neonate
Symmetric enlargement of the breasts in a neonate without erythema, tenderness, or warmth.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights reserved.

Sexual maturity rating (Tanner staging) of pubic hair and

external genitalia development in boys
Stages of pubic hair development in boys:

Stage 1: Prepubertal, with no pubic hair.
Stage 2: Sparse, straight pubic hair along the base of the penis.
Stage 3: Hair is darker, coarser, and curlier, extending over the mid-pubis.
Stage 4: Hair is adult-like in appearance, but does not extend to thighs.
Stage 5: Hair is adult in appearance, extending from thigh to thigh.
Stages of external genitalia development in boys:
Stage 1: Prepubertal.
Stage 2: Enlargement of testes and scrotum; scrotal skin reddens and changes
in texture.
Stage 3: Enlargement of penis (length at first); further growth of testes.
Stage 4: Increased size of penis with growth in breadth and development of
glans; testes and scrotum larger, scrotal skin darker.
Stage 5: Adult genitalia.
Figure from: Roede MJ, van Wieringen JC. Growth diagrams 1980: Netherlands third
nation-wide survey. Tijdschr Soc Gezondheids 1985; 63:1. Reproduced with permission
from the author.

Testicular volume in each pubertal stage
Testicular volume in adolescents as a function of pubertal stage. These data are

from serial evaluations of 539 boys, ages 10 to 15 years; the subjects were
evaluated every 6 months over 3 years. Pubertal stage represents the sexual
maturity rating (Tanner stage of pubertal development).
Reproduced with permission from: Biro FM. Physical growth and development. In:
Principles of Adolescent Medicine, Friedman SB, Fisher M, Schonberg SK. Mosby-Year
Book, Inc, 1997. Figure 6-3, p.31. Copyright ©1997 Elsevier.

Drugs associated with gynecomastia
Antiandrogens/inhibitors of androgen Drugs of abuse

synthesis Alcohol
Cyproterone acetate Amphetamines
Flutamide, bicalutamide, nilutamide Heroin
Finasteride, dutasteride Marijuana
Spironolactone Methadone
Ketoconazole
Hormones
Lavender oil
Androgens
Tea tree oil
Anabolic steroids
Antibiotics Chorionic gonadotropin
Ethionamide Estrogens
Isoniazid Growth hormone
Ketoconazole
Psychoactive drugs
Metronidazole
Diazepam
Antiulcer drugs Haloperidol
Cimetidine Phenothiazines
Omeprazole Tricyclic antidepressants
Cancer chemotherapeutic drugs Atypical antipsychotics
Alkylating agents Other

Methotrexate Auranofin
Vinca alkaloids Diethylpropion
Combination chemotherapy Domperidone
Imatinib Etretinate
Cardiovascular drugs HAART
ACE inhibitors (captopril, enalapril) Metoclopramide
Amiodarone Phenytoin
Calcium channel blockers (diltiazem, nifedipine) Penicillamine
Digitoxin Sulindac
Methyldopa Theophylline
Reserpine
Most of the drugs that are listed are based on anecdotal reports and do not have high-quality evidence supporting a cause-and-
effect relationship. Using evidence-based criteria, there is good evidence of a true association with estrogens, spironolactone,
cimetidine, ketoconazole, growth hormone, gonadotropins, antiandrogen therapies, and 5-alpha-reductase inhibitors. Drugs with
fair evidence include first-generation and atypical antipsychotics in adults, calcium channel blockers, omeprazole, HIV drugs,
alkylating agents, anabolic steroids, alcohol, and opioids. [1]
HAART: highly active antiretroviral therapy; ACE: angiotensin-converting enzyme.
Reference:
1. Deepinder F, Braunstein GD. Drug-induced gynecomastia: An evidence-based review. Expert Opin Drug Saf 2012; 11:779.

Oral lesions in Peutz-Jeghers syndrome
Photograph shows the characteristic circumoral pigmentation in a patient with

the Peutz-Jeghers syndrome. The pigmentation may not be obvious as in this
patient, and it should always be sought carefully in young patients presenting
with unexplained gastrointestinal bleeding, particularly if there is a family
history of such bleeding.
Reprinted with permission from Pounder RE, Allison MC, Dhillon AP. A Colour Atlas of
the Digestive System, Wolfe, London 1989 p. 118.

Peutz-Jeghers syndrome
Prominent dark brown macular pigmentation confined to the lips in an adolescent with Peutz-Jeghers syndrome.
Courtesy of Edward W. Cowen, MD, MHSc.

Cutaneous hyperpigmentation in Peutz-Jeghers syndrome
Multiple hyperpigmented macules on the volar aspect of the thumb in a patient with Peutz-Jeghers
syndrome.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights reserved.

Selected hereditary causes of gynecomastia
Disease (gene) Associated clinical features
Primary hypogonadism (hypergonadotropic)
Congenital adrenal hyperplasia Autosomal recessive inheritance
3-beta hydroxysteroid dehydrogenase Hypogonadism (atypical genitalia, undervirilization)

defect (HSD3B2) Cortisol deficiency (fatigue, nausea, vomiting)
Aldosterone deficiency (hypotension, volume depletion, hyperkalemia,
metabolic acidosis)
17-alpha hydroxylase deficiency Hypogonadism (atypical genitalia, absence of secondary sexual

(CYP17A1) characteristics)
Cortisol deficiency (fatigue, nausea, vomiting)
Hypertension
Cytochrome P450 oxidoreductase Severe undervirilization

deficiency (POR) Cortisol deficiency (fatigue, nausea, vomiting)
Secondary hypogonadism (hypogonadotropic)
Isolated gonadotropin-releasing hormone Autosomal dominant or recessive inheritance

deficiency, also known as idiopathic Hypogonadotropic hypogonadism
hypogonadotropic hypogonadism (FGFR1,
KISS1, KISS1R, and others)
Kallmann syndrome 1 (KAL1) X-linked inheritance

Hypogonadotropic hypogonadism
Anosmia/hyposmia
Increased aromatase
Aromatase excess syndrome (CYP19A1) Autosomal dominant inheritance

Prepubertal/peripubertal gynecomastia
Accelerated early linear growth
Testicular failure
Carney complex (PRKAR1A) Autosomal dominant inheritance

Prepubertal/peripubertal gynecomastia
Multiple lentigines
Atrial and mucocutaneous myxomas
Blue nevi
Peutz-Jeghers syndrome (STK11) Autosomal dominant inheritance

Prepubertal gynecomastia
Mucocutaneous pigmentation
Multiple hamartomatous polyps in GI tract
Androgen receptor defect
Androgen insensitivity syndrome (AR) X-linked inheritance

Atypical genitalia
Undervirilization
Spinal and bulbar muscular atrophy (AR X-linked inheritance

[expanded CAG repeats]) Atypical genitalia
Undervirilization
Muscle fasciculations
Weakness
Calf hypertrophy
Adapted from: Narula HS, Carlson HE. Gynaecomastia—pathophysiology, diagnosis and treatment. Nat Rev Endocrinol 2014; 10:684.

Prader orchidometer
Photo of a Prader orchidometer for measuring testicular size. On physical examination, the patient's testicular volume is estimated
by palpation and comparison with the models on the orchidometer. Each of the beads is labeled with its volume, ranging from 1 to
25 mL. Prepubertal sizes are 1 to 3 mL, pubertal sizes are 4 to 12 mL, and adult sizes are 12 to 25 mL.

Evaluation for pathologic causes of gynecomastia suggested by the history or examination

in children and adolescents
Clinical findings Possible cause(s) Initial targeted evaluation
Testicular pain Testicular cancer Testicular ultrasonography

Testicular enlargement/mass
Perioral pigmentation Peutz-Jeghers syndrome (increased Testicular ultrasonography

Family history of Peutz-Jeghers risk of Sertoli cell tumor)
syndrome
Weight loss Adrenal tumor Adrenal imaging

Abdominal mass Extragonadal germ cell tumor Chest imaging
hCG-secreting nontrophoblastic
neoplasm
Increased appetite Hyperthyroidism Free thyroxine (T4), tri-iodothyronine

Goiter (T3), TSH
Ophthalmopathy
Tachycardia
Tremor
Tall, thin body habitus Klinefelter syndrome* Karyotype

Long arms and legs
Small (<3 cm [1.2 inches] or <5 mL in
volume), firm testes (in adolescent or
adult)
Learning, language, or behavioral
difficulties
Galactorrhea Hyperprolactinemia Serum prolactin
Undervirilization Primary or secondary hypogonadism Referral to a pediatric endocrinologist

Atypical genitalia Partial androgen insensitivity is suggested; specialized testing may
Hypospadias 3 beta-hydroxysteroid dehydrogenase be necessary
Cryptorchidism deficiency
Muscle fasciculations, weakness, calf Ovotesticular disorder of sex
hypertrophy ¶ development
Anorexia, nausea, vomiting, acholic Liver disease Liver function tests

stools
Jaundice, edema, spider angiomata
Anorexia, nausea, vomiting, edema Kidney disease BUN/creatinine

Changes in urination, hematuria
Accelerated early linear growth Aromatase excess syndrome Molecular genetic testing*
Family history of gynecomastia
Accelerated early linear growth 11-beta hydroxylase deficiency Referral to pediatric endocrinologist is
Premature adrenarche or puberty Nonclassic (late-onset) 21-hydroxylase suggested; specialized testing may be
Hypertension (11-beta hydroxylase deficiency necessary
deficiency)
hCG: human chorionic gonadotropin; TSH: thyroid stimulating hormone; BUN: blood urea nitrogen.
* Consultation with a pediatric endocrinologist or geneticist is suggested.
¶ Muscle fasciculations, weakness, and calf hypertrophy may indicate X-linked spinal and bulbar muscular atrophy, which is associated
with partial androgen insensitivity. Referral to a neurologist is also suggested.
References:
4. Narula HS, Carlson HE. Gynaecomastia--pathophysiology, diagnosis and treatment. Nat Rev Endocrinol 2014; 10:684.


Interpretation of laboratory tests in the evaluation of unilateral or bilateral gynecomastia

in phenotypically male children and adolescents*
Initial tests Additional

Potential
evaluation/supportive
cause(s)
hCG Estradiol Testosterone LH DHEA findings
Increased Normal Normal Normal Normal Testicular US: Normal Extragonadal germ-
cell tumor or hCG-
secreting
nontrophoblastic
neoplasm*
Testicular US: Mass Testicular germ cell

tumor
Normal Increased Normal Increased Normal Karyotype Possible

ovotesticular DSD ¶
Normal Increased Normal Normal or Increased Adrenal imaging: Adrenal Adrenal neoplasm
decreased mass
Adrenal imaging: Normal Possible CAH ¶
Normal Increased Normal Normal or Normal Testicular US: Normal Increased

decreased Adrenal imaging: Normal extraglandular
aromatase activity
(eg, aromatase
excess syndrome)
Testicular US: Mass Sertoli-cell tumor
Normal Increased Increased Normal or Normal Testicular US: Mass Leydig-cell tumor or
decreased Leydig-cell and
Sertoli-cell tumor
Normal Normal Increased Increased Normal TSH: Decreased Hyperthyroidism

Thyroxine: Increased
TSH: Normal Androgen resistance

Thyroxine: Normal (eg, partial
androgen
insensitivity)
Normal Normal Decreased Δ Increased Normal Refer to UpToDate content on Primary

primary hypogonadism in hypogonadism
males
Normal Normal Decreased Δ Normal or Normal Serum prolactin: Normal Secondary

decreased Δ hypogonadism
Serum prolactin: Elevated Prolactin-secreting

pituitary tumor ◊
Normal Normal Normal Normal Normal NA Pubertal or

idiopathic
gynecomastia
Our suggested initial laboratory evaluation for phenotypically male children and adolescents with unilateral or bilateral
gynecomastia in whom a potential cause is not identified on history and physical examination includes measurement of early
morning hCG, estradiol, LH, testosterone, and DHEA. The reference range for hormones may vary by age, sexual maturity
rating, and clinical laboratory. All patients may not fit into the categories in the table above.
hCG: human chorionic gonadotropin; LH: luteinizing hormone; DHEA: dehydroepiandrosterone; US: ultrasonography; CT: computed
tomography; MRI: magnetic resonance imaging; TSH: thyroid-stimulating hormone; NA: not applicable; DSD: disorder of sex
development; CAH: congenital adrenal hyperplasia.
* Further evaluation may include chest radiography and abdominal computed tomography.
¶ Referral to a pediatric endocrinologist is recommended. Refer to UpToDate content on atypical genitalia and congenital adrenal
hyperplasia for more information.
Δ Decreased testosterone and decreased LH are normal findings in prepubertal-age boys and not helpful in the evaluation of

gynecomastia.
◊ Further evaluation may include magnetic resonance imaging of the head.
References:
3. Misra M, Sagar P, Friedmann AM, et al. Case records of the Massachusetts General Hospital. Case 12-2016. An 8-Year-Old Boy
with an Enlarging Mass in the Right Breast. N Engl J Med 2016; 374:1565.

Additional evaluation of increased estradiol in phenotypically male

children and adolescents with gynecomastia
Our suggested initial laboratory evaluation for phenotypically male children and adolescents with
unilateral or bilateral gynecomastia in whom a potential cause is not identified on history and
physical examination includes measurement of early morning hCG, estradiol, LH, testosterone,
and DHEA. The reference range for hormones may vary by age, sexual maturity rating, and
clinical laboratory. All patients may not fit into the categories in the algorithm above. Refer to
UpToDate content on gynecomastia in children and adolescents for information about
interpretation of other laboratory results and combinations.
hCG: human chorionic gonadotropin; DHEA: dehydroepiandrosterone; LH: luteinizing hormone; CAH:
congenital adrenal hyperplasia; US: ultrasound; DSD: disorder of sex development.
* Referral to a pediatric oncologist and/or pediatric urologist (for testicular tumors) is recommended.
Refer to UpToDate content on gynecomastia in children and adolescents for additional information.
¶ Referral to a pediatric endocrinologist is recommended. Refer to UpToDate content on gynecomastia in
children and adolescents for additional information.
Δ Measured with initial laboratory studies.
Data from:
2. Ma NS, Geffner ME. Gynecomastia in prepubertal and pubertal men. Curr Opin Pediatr 2008;
20:465.
3. Misra M, Sagar P, Friedmann AM, et al. Case records of the Massachusetts General Hospital. Case
12-2016. An 8-year-old boy with an enlarging mass in the right breast. N Engl J Med 2016;
374:1565.

Additional evaluation of increased or decreased testosterone in children and

adolescents with gynecomastia and normal hCG, DHEA, and estradiol
Our suggested initial laboratory evaluation for phenotypically male children and adolescents with unilateral or
bilateral gynecomastia in whom a potential cause is not identified during the initial history and physical
examination includes measurement of early morning hCG, estradiol, LH, testosterone, and DHEA. The reference
range for hormones may vary by age, sexual maturity rating, and clinical laboratory. All patients may not fit into
the categories in the algorithm above. Refer to UpToDate content on gynecomastia in children and adolescents for
information about interpretation of other laboratory results and combinations.
hCG: human chorionic gonadotropin; DHEA: dehydroepiandrosterone; LH: luteinizing hormone; TSH: thyroid stimulating
hormone.
* Decreased testosterone and LH are normal findings in prepubertal males and are not helpful in the evaluation of
gynecomastia.
¶ Referral to a pediatric endocrinologist is recommended. Refer to UpToDate content on gynecomastia in children and
adolescents for additional information.
Δ Referral to a pediatric oncologist is recommended. Refer to UpToDate content on gynecomastia in children and
adolescents for additional information.
Data from:
3. Misra M, Sagar P, Friedmann AM, et al. Case records of the Massachusetts General Hospital. Case 12-2016. An 8-
year-old boy with an enlarging mass in the right breast. N Engl J Med 2016; 374:1565.

Contributor Disclosures
Sharonda A Taylor, MD, FAAP, FSAHM, Dipl. of ABOM Nothing to disclose Diane Blake, MD Nothing to
disclose Mitchell E Geffner, MD Grant/Research/Clinical Trial Support: Novo Nordisk [Growth]. Consultant/Advisory
Boards: Adrenas and Neurocrine Biosciences [CAH]; Daiichi-Sankyo [Type 2 diabetes]; Ferring, Novo Nordisk, Nutritional
Growth Solutions, Nutritional Growth Solutions, Pfizer, and QED [Growth]; Gilead [Growth/HIV]. Other Financial Interest:
McGraw-Hill [Pediatric endocrinology textbook royalties]; Ascendis data safety monitoring board [Growth]; Tolmar data
safety monitoring board [Precocious puberty]; Millendo data safety monitoring board [Prader-Willi syndrome]. Mary M
Torchia, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the
content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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8/9/2020 Gynecomastia in children and adolescents - UpToDate

Official reprint from UpToDate®

● (See "Epidemiology, pathophysiology, and causes of gynecomastia".)

DEFINITION AND CHARACTERISTIC FEATURES

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Gynecomastia is presumed to be caused by a relative imbalance between androgens (testosterone and

Transient neonatal gynecomastia is thought to result from placental transformation of dehydroepiandrosterone

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and adolescents", section on 'Neonates and infants'.)

Pubertal gynecomastia — Pubertal gynecomastia is a physiologic enlargement of the glandular breast

● Occurrence outside the neonatal or pubertal age group

Pathologic gynecomastia has a number of causes including:

● Drugs that enhance endogenous estrogen production (eg, gonadotropins, clomiphene)

● Alcohol and recreational or illicit drugs, including [1,20]:

• Marijuana, particularly if used ≥4 times per week [30-32]

Hypogonadism — Primary (hypergonadotropic) hypogonadism accounts for approximately 8 percent and

• Cryptorchidism, including anorchia (testicular regression) (see "Undescended testes (cryptorchidism)

• Enzyme defects of testosterone production (see "Causes of primary hypogonadism in males",

● Secondary hypogonadism may be congenital (eg, congenital gonadotropin-releasing hormone

Other pathologic causes

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disease on the hypothalamic-pituitary-testicular (HPT) axis, medications used in disease management,

● Hyperthyroidism – Hyperthyroidism is an uncommon cause of gynecomastia, estimated to cause

● Partial androgen insensitivity syndrome – Partial androgen insensitivity syndrome (PAIS) is an X-

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● Ovotesticular disorder of sex development – Ovotesticular disorders of sex development (previously

Mimics of gynecomastia in infants include:

Mimics of gynecomastia in children and adolescents include:

● Pseudogynecomastia – Pseudogynecomastia is fatty infiltration of the breast (also called lipomastia). It

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● Review of systems – Symptoms of a previously undiagnosed endocrine abnormality or chronic illness,

• Hypogonadism – Atypical genitalia, undervirilization

● Medications/drugs – Exposure to medications, including over-the-counter drugs, marijuana, dietary

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● Breast – Proper examination of the breast differentiates gynecomastia from pseudogynecomastia

• Testes – Physiologic gynecomastia typically occurs at testicular volumes of 8 to 10 mL bilaterally

• Thyroid – Palpable goiter suggests hyperthyroidism; other signs of hyperthyroidism include

• Virilization – Undervirilization may indicate hypogonadism, partial androgen insensitivity, congenital

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Jaundice and spider angiomata may indicate liver disease.

Initial laboratory evaluation and management

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• History and physical examination not suggestive of a pathologic cause

Additional evaluation typically includes testicular ultrasonography for testicular mass.

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Decreased testosterone — Decreased testosterone in a pubertal-aged male may indicate primary or

● Decreased testosterone with normal or decreased LH may indicate secondary hypogonadism or

Additional evaluation includes measurement of serum prolactin.

• Elevated prolactin (hyperprolactinemia) may indicate the presence of a prolactin-secreting pituitary

The management of gynecomastia is discussed in detail separately. (See "Management of gynecomastia".)

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INDICATIONS FOR REFERRAL

Indications for referral in children or adolescents with gynecomastia include:

● Prepubertal gynecomastia – Refer to a pediatric endocrinologist to evaluate for an endogenous or

● Endocrine abnormality (primary or secondary hypogonadism, hyperthyroidism, androgen resistance,

● Testicular mass on testicular ultrasonography – Refer to a pediatric urologist/oncologist.

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS