Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in Male due to the growth of breast tissue as a result of a hormone imbalance between and .[ Updated by Brent Wisse (10 November 2018)]
Gynecomastia can be normal in newborn male babies due to exposure to estrogen from the mother, in adolescent boys going through puberty, in older men over the age of 50, and in obese men.
Gynecomastia is the most common benign disorder of the male breast tissue and affects 35% of men, being most prevalent between the ages of 50 and 69.
/ref> and even in rare cases of gynecomastia from disorders such as aromatase excess syndrome or Peutz–Jeghers syndrome,
Definition
Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between
estrogen and
androgen.
Gynecomastia is different from "pseudogynecomastia",
which is defined as an excess of
skin and/or
adipose tissue in the male
without the growth of true
Mammary gland;
this is commonly associated with
obesity and can be ruled out by physical exam.
Signs and symptoms
In gynecomastia there is always enlargement of one or both breasts, symmetrically or asymmetrically, in a man. A soft, compressible, and mobile mass of breast tissue is felt under the
nipple and
areola in contrast to softer
adipose tissue which is not associated with a mass.
It may also be accompanied by breast tenderness or nipple sensitivity, which is commonly associated with gynecomastia observed in adolescents, typically early in development.
Gynecomastia that is painful, bothersome, rapidly-growing, associated with masses in other areas of the body, or persistent should be evaluated by a clinician for potential causes.
Dimpling of the skin, nipple discharge, and nipple retraction are not typical features of gynecomastia and may be associated with other
Breast cancer.
from the nipple is not a typical finding, but may be seen in a gynecomastic individual with a
prolactinoma.
An increase in the diameter of the
areola and asymmetry of the chest are other possible signs of gynecomastia.
Much of the research on gynecomastia has focused on its causes and treatment, but little has explored its effects on mental health and overall quality of life. Gynecomastia has psychosocial implications that may be particularly challenging for adolescents who are experiencing physical maturation and self-identity formation, which includes body image disturbances, negative attitudes towards eating, self-esteem problems, social withdrawal, anxiety, and shame.
Causes
Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen action, a decrease in androgen action, or a combination of these two factors.
Estrogen and androgens have opposing actions on breast tissue: estrogens stimulate proliferation while androgens inhibit proliferation.
The cause of gynecomastia is unknown in around 25% of cases.
Known causes can be physiologic (occurring normally) or non-physiologic due to underlying pathologies such as drug use, chronic disease, tumors, or
malnutrition.
Physiologic
Physiologic or normal gynecomastia can occur at three timepoints in life: shortly after birth in both female and male infants, during puberty in adolescent males, and in older adults over the age of 60.
Newborns
60-90% of male and female newborns may show breast development at birth or in the first weeks of life.
During pregnancy, the
placenta converts the androgenic hormones dehydroepiandrosterone (DHEA) and
DHEA sulfate to the estrogenic hormones
estrone and
estradiol, respectively; after these estrogens are produced by the placenta, they are transferred into the
Fetus circulation, thereby leading to temporary gynecomastia in the baby.
In some infants, neonatal milk (also known as "witch's milk") can leak from the nipples.
The temporary gynecomastia seen in newborn babies usually resolves after two or three weeks.
Adolescents
Hormonal imbalance (elevated ratio of estrogen to androgen) during early puberty, either due to decreased androgen production from the adrenals and/or increased conversion of androgens to estrogens, leads to transient gynecomastia in adolescent males. It can occur in up to 65% of adolescents as early as age 10 and peaks at ages 13 and 14.
It is self-limited in 75–90% of adolescents and usually resolves spontaneously within 1 to 3 years as pubertal progression increases testosterone levels and cause regression of breast tissue.
By age 17, only 10% of adolescent males have persistent gynecomastia.
Older adults
Declining testosterone levels and an increase in the level of subcutaneous
Adipose tissue seen as part of the normal aging process can lead to gynecomastia in older males. Increased fatty tissue, a major site of aromatase activity, leads to increased conversion of androgenic hormones such as testosterone to estrogens.
Additionally, levels of sex hormone binding globulin (SHBG) increase with age and bind with less affinity to estrogen than androgens.
Put together, the elevated ratio of estrogen to androgen leads to gynecomastia, also known as senile gynecomastia in this group.
There is a 24–65% prevalence of senile gynecomastia in older males.
Non-physiologic
Drugs
About 10–25% of gynecomastia cases are estimated to result from the use of medications or exogenous chemicals.
Drugs can increase estrogen activity or increase the estrogen to androgen ratio through various mechanisms, such as binding to estrogen receptors, promoting estrogen synthesis, providing precursors that can be aromatized into estrogen, causing damage to the testes, inhibiting testosterone synthesis, inhibiting the action of androgens, or displacing estrogen from SHBG.
Drugs with good evidence for association with gynecomastia include
cimetidine,
ketoconazole, gonadotropin-releasing hormone analogues,
growth hormone, human chorionic gonadotropin, 5α-reductase inhibitors such as
finasteride and
dutasteride, certain estrogens used for
prostate cancer, and
such as
bicalutamide,
flutamide, and
spironolactone.
Drugs with fair evidence for association with gynecomastia include calcium channel blockers such as verapamil, amlodipine, and nifedipine; risperidone, olanzapine, ,
Refeeding gynecomastia
Malnutrition and significant loss of body fat suppress
gonadotropin secretion, leading to
hypogonadism. This is reversible when adequate nutrition resumes, where the return of gonadotropin secretion and
function cause a transient imbalance of estrogen and androgen that mimics puberty, resulting in transient gynecomastia.
This phenomenon, also known as refeeding gynecomastia, was first observed when men returning home from prison camps during World War II developed gynecomastia after resuming a normal diet. Similar to pubertal gynecomastia, refeeding gynecomastia resolves on its own in 1–2 years.
Chronic disease
Many kidney failure patients experience a hormonal imbalance due to the suppression of testosterone production and testicular damage from
Uremia also known as uremia-associated hypogonadism.
Additionally, gynecomastia has been observed in 50% of patients with chronic kidney disease undergoing dialysis. Similar to the mechanism behind refeeding gynecomastia, dialysis allows patients with renal failure who were previously malnourished to expand their diets and regain weight. Dialysis-associated gynecomastia resolves spontaneously within 1–2 years.
In individuals with liver failure or cirrhosis, the liver's ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcoholic drinks may also contribute to a higher estrogen to testosterone ratio.
A small proportion of male gynecomastia cases may be seen with rare inherited disorders such as spinal and bulbar muscular atrophy and the very rare aromatase excess syndrome.
Hypogonadism
Gynecomastia can be caused by absolute deficiency in androgen production due to primary or secondary hypogonadism. Primary hypogonadism results when there is damage to the testes (due to radiation, chemotherapy, infections, trauma, etc.), leading to impaired androgen production.
It can also be caused by chromosomal abnormality seen in Klinefelter syndrome, which is associated with gynecomastia in about 80% of cases.
Secondary hypogonadism results when there is damage to the hypothalamus or pituitary (due to radiation, chemotherapy, infection, trauma, etc.), and similarly lead to impaired androgen production. The net effect is reduced androgen production while serum estrogen levels (from peripheral aromatization of androgens) remain unaffected.
The lack of androgen-mediated inhibition of breast tissue proliferation combined with relative estrogen excess result in gynecomastia.
Tumors
Testicular tumors such as Leydig cell tumors, Sertoli cell tumors
(such as in Peutz–Jeghers syndrome)
and hCG-secreting
choriocarcinoma may result in rapid-onset gynecomastia by causing excess production of estrogen.
Other tumors such as
, pituitary gland tumors (such as a
prolactinoma), or
lung cancer, can produce hormones that alter the male–female hormone balance and cause gynecomastia.
Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia.
Pathophysiology
The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen, which stimulates breast tissue growth, and androgens, which inhibit breast tissue growth.
Breast prominence can result from
Hypertrophy of glandular breast tissue, chest
adipose tissue (fat) and skin, and is typically a combination.
As in females, estrogen stimulates the growth of breast tissue in males.
In addition to directly stimulating breast tissue growth, estrogens indirectly decrease secretion of testosterone by suppressing luteinizing hormone secretion, resulting in decreased testicular secretion of testosterone.
Estrogen excess
One of the main mechanisms for imbalance between estrogens and androgens is the overproduction of estrogens. A possible cause may be a
neoplasm that originates from estrogen-secreting cells.
Tumors that produce hCG stimulate production of estradiol while reducing other testicular hormone production.
is another common cause of excess serum estrogens due to the presence of
aromatase in peripheral tissue, which is a protein that converts androgens into estrogens.
Peutz-Jeghers syndrome is a rare cause of testicular tumors that affect aromatase expression, which results in elevated serum estrogen levels.
Aromatase excess syndrome is a rare genetic disorder that leads to increased conversion of androgens to estrogens in the body.
Androgen deficiency
Primary
hypogonadism (indicating an intrinsic problem with the
testes in males) leads to decreased testosterone synthesis and increased
Aromatase potentially leading to a gynecomastic appearance.
Klinefelter syndrome is a notable example of a disorder that causes hypogonadism and gynecomastia, and has a higher risk of breast cancer in males (20–50 times higher than males without the disorder).
Secondary hypogonadism (indicating a problem with the brain) leads to decreased production and release of luteinizing hormone (LH, a stimulatory signal for endogenous steroid hormone synthesis) which leads to decreased production of testosterone and estradiol in the testes.
Increased levels of sex hormone-binding globulin
Estrogens can increase blood levels of the protein sex hormone-binding globulin (SHBG), which binds free testosterone (the active form) more strongly than estrogen, leading to decreased action of testosterone in male breast tissue.
Conditions such as
hyperthyroidism and chronic liver disease affect levels of SHBG, leading to symptomatic gynecomastia.
Androgen resistance
Dysfunction in the androgen receptor prevents the effects of testosterone from acting on its target tissues. Androgen insensitivity syndromes result from the different degrees of resistance to the effects of androgens, and can cause external
genitalia that may not be aligned with the
genotype of the individual's
.
Complete androgen insensitivity syndrome results in the failure to develop external genitalia such as the penis and scrotum along with development of breasts in an individual with testes. Partial androgen insensitivity syndrome may result in a variety of presentations. Minimal androgen insensitivity syndrome may present as gynecomastia in adolescence and may additionally be associated with
infertility.
Medications
Medications are known to cause gynecomastia through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means.
Potential causative agents include oral contraceptive pills,
spironolactone, and
.
High levels of prolactin in the blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia.
Chronic disease
Individuals who have
cirrhosis or chronic liver disease may develop gynecomastia for several reasons. Those diagnosed with cirrhosis tend to have increased secretion of the androgenic hormone
androstenedione from the adrenal glands, increased conversion of this hormone into various types of estrogen,
and increased levels of SHBG, which leads to decreased blood levels of free testosterone.
Around 10–40% of males with Graves' disease (a common form of
hyperthyroidism) experience gynecomastia.
Increased conversion of testosterone to estrogen by increased aromatase activity,
increased levels of SHBG and increased production of testosterone and estradiol by the testes due to elevated levels of LH cause the gynecomastia. Proper treatment of the hyperthyroidism can lead to the resolution of the gynecomastia.
| +
!Estrogen excess
!Androgen deficiency
!Increased levels of sex hormone-binding globulin
!Androgen resistance
!Medications |
-
Tumors (Testicular, Choriocarcinoma, Adrenal, Pituitary gland, Lung)
-
Peutz-Jeghers syndrome
-
Aromatase excess syndrome
-
Obesity
-
Aging
|
-
Primary hypogonadism (Klinefelter's syndrome)
-
Secondary hypogonadism
| |
-
Androgen insensitivity syndromes
| |
Diagnosis
To diagnose gynecomastia, a thorough history and physical examination are obtained by a
physician. Important aspects of the physical examination include evaluation of the male breast tissue with palpation to evaluate for breast cancer and pseudogynecomastia (male breast tissue enlargement solely due to excess
adipose), evaluation of
Penis size and development, evaluation of
Testes development and an assessment for masses that raise suspicion for testicular cancer, and proper development of secondary sex characteristics such as the amount and distribution of
pubic hair and
underarm hair.
Gynecomastia usually presents with bilateral involvement of the breast tissue but may occur unilaterally as well.
Diagnosis of men with breast enlargement can be evaluated using an algorithm. A review of the medications or substances an individual takes may reveal the cause of gynecomastia.
High levels of prolactin are uncommon in people with gynecomastia.
Differential diagnosis
While there can be many potential causes of male patients that present with increased breast tissue, differential diagnoses are most concerning for gynecomastia, pseudogynecomastia, and
breast cancer (which is rare in men). Other potential causes of male breast enlargement such as
mastitis,
,
sebaceous cyst,
dermoid cyst,
Breast hematoma,
metastasis, ductal ectasia,
fat necrosis, or a
hamartoma are typically excluded before making the diagnosis.
Imaging
Mammography is the method of choice for
Radiology examination of male breast tissue in the diagnosis of gynecomastia when breast cancer is suspected on physical examination.
If a mass/lump is felt during a physical exam some features of the lump that would point to
malignancy would be painless, non moveable (fixed), irregularly shaped, and skin changes. Mammography is rarely indicated for men since breast cancer is an unlikely diagnosis.
If mammography is performed and does not reveal findings suggestive of breast cancer, further imaging is not typically necessary.
If a tumor of the
or the
testes is thought to be responsible for the gynecomastia,
Ultrasonography examination of these structures may be performed.
Histology
Early histological features expected to be seen on examination of gynecomastic tissue attained by fine-needle aspiration biopsy include the following: proliferation and lengthening of the ducts, an increase in connective tissue, an increase in inflammation, and
Edema surrounding the ducts, and an increase in
in the connective tissue.
Chronic gynecomastia may show different histological features such as increased connective tissue
fibrosis, an increase in the number of ducts, less inflammation than in the acute stage of gynecomastia, increased subareolar fat, and hyalinization of the stroma.
When surgery is performed, the gland is routinely sent to the lab to confirm the presence of gynecomastia and to check for tumors under a microscope. The utility of pathologic examination of breast tissue removed from male adolescent gynecomastia patients has recently been questioned due to the rarity of breast cancer in this population.
Classification
The spectrum of gynecomastia severity has been categorized into a grading system:
-
Grade I: Minor enlargement, no skin excess
-
Grade II: Moderate enlargement, no skin excess
-
Grade III: Moderate enlargement, skin excess
-
Grade IV: Marked enlargement, skin excess
Treatment
If the gynecomastia doesn't resolve on its own in two years, then medical treatment is necessary. The options are medication or surgical intervention.
Medication
Gynecomastia can respond well to medical treatment although it is usually only effective when done within the first two years after the start of male breast enlargement.
Selective estrogen receptor modulators (SERMs) such as
tamoxifen,
raloxifene, and
clomifene may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia.
Clomifene seems to be less effective than tamoxifen or raloxifene.
Tamoxifen may be used to treat gynecomastia in adults and of the medical treatments used,
tamoxifen is the most effective.
Recent studies have shown that treatment with tamoxifen may represent a safe and effective mode of treatment in cases of cosmetically disturbing or painful gynecomastia.
Aromatase inhibitors (AIs) such as
anastrozole have been used off-label for cases of gynecomastia occurring during puberty but are less effective than SERMs.
A few cases of gynecomastia caused by the rare disorders aromatase excess syndrome and Peutz–Jeghers syndrome have responded to treatment with AIs such as anastrozole.
Surgery
If chronic gynecomastia does not respond to medical treatment, surgical removal of glandular breast tissue is usually required.
The American Board of Cosmetic Surgery reports surgery is the "most effective known treatment for gynecomastia."
Surgical treatment should be considered if the gynecomastia persists for more than 12 months, causes distress (i.e. physical discomfort or psychological distress), and is in the fibrotic stage.
In adolescent males, it is recommended that surgery is postponed until puberty is completed (penile and testicular development should reach
Tanner scale Stage V).
Surgical approaches to the treatment of gynecomastia include Nipple delay, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities.
Others
Radiation therapy and
Nolvadex have been shown to help prevent gynecomastia and breast pain from developing in prostate cancer patients who will be receiving androgen deprivation therapy. The efficacy of these treatments is limited once gynecomastia has occurred and are therefore most effective when used prophylactically.
In the United States, many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on the basis that it is a cosmetic procedure.[are]
Prognosis
Gynecomastia itself is a benign finding. It does not confer a poor prognosis, for some patients with underlying pathologies such as testicular cancer the prognosis may be worse.
The
glandular tissue typically grows under the influence of hormonal stimulation and is often tender or painful. Furthermore, gynecomastia frequently presents social and psychological difficulties such as low self-esteem, depression or shame.
Epidemiology
Gynecomastia is the most common
Benign tumor disorder of the male breast tissue and affects 35 percent of men, being most prevalent between the ages of 50 and 69.
New cases of gynecomastia are common in three age populations: newborns, adolescents, and men older than 50 years.
The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of the disorder is not fully understood.
History
The term gynaecomastia was coined by
Galen. He also recognised glandular enlargement of the male breast; however, this wasn't a condition of gynaecomastia according to him.
A surgical procedure for treatment of gynaecomastia was described by
Albucasis in his second book of
Kitab al-Tasrif.
Society and culture
Gynecomastia can result in psychological distress for those with the condition. Support groups exist to help improve the self-esteem of affected people.
Moob, a portmanteau of man and boob, is a popular term to refer to male breasts. Use of anabolic steroids can result in gynecomastia, and male breasts are sometimes referred to using the pejorative bitch tits in bodybuilding communities.
In Murray v. Janssen Pharmaceuticals, Murray was a Risperidone user who was prescribed the medication at age nine and developed male breasts. A jury decided in Murray's favor in November 2015 and awarded him $1.75 million. The $1.75 million jury verdict represented damages for "disfigurement and mental anguish," though it was later reduced to $680,000.
In 2019, a 12-person Philadelphia jury awarded $8 billion in punitive damages to plaintiffs tied to the use of risperidone. Risperidone is an atypical antipsychotic that was originally approved to treat psychosis, but its use in children, including those with autism, ADHD, and schizophrenia diagnoses, has grown over the last two decades.
Etymology
The term comes from
Greek language γυνή
gyné (stem
gynaik-) 'female' and μαστός
mastós 'breast'.
See also
- Explanatory notes
- Citations
External links
