Gynecomastia – Symptoms, Causes, Complications and Prevention

Gynecomastia (GM) is a condition where there will be an enlargement of the male breast due to non-cancerous expansion of the glandular tissue and fat deposition under the nipple area. It occurs on one or both sides.

What are its signs and symptoms? And how can we manage it? Before we address the questions about gynaecomastia, let’s try to understand the anatomy of gynaecomastia, its occurrence and its types.

Anatomy

Gynecomastia is caused by enlargement of glandular breast tissue in men. The oestrogen hormone is responsible for glandular tissue growth in men

In normal male breast tissue, it consists of muscle and fat layer under the nipple area. In gynaecomastia patients, due to increased oestrogen and decreased testosterone concentrations, there will be formation of fibrous glandular tissue and an increase in adipose tissue under the nipple area, giving the appearance of a female breast.

Gynaecomastia is very common condition among males. In India, nearly 40% to 60% of male patients were affected. Most adult men with gynecomastia report no symptoms and the prevalence of asymptomatic gynecomastia is higher in neonates (a baby who is 4 weeks old or younger).

About 50% of mid-pubertal boy’s experience gynaecomastia of puberty, which is a common condition. Among those, more than 90% of cases resolve spontaneously within 24 months.

Adults are more likely to have gynecomastia as they get older. In about 45–50% of cases, a thorough evaluation can find a cause.

Gynaecomastia in newborns is caused by oestrogen from their mother. Breast buds are quite common in newborn boys. Breast buds usually disappear by 6 months of age, but they can last longer in some babies.

• Breast buds are common in pre-teen boys during puberty. The buds can last up to two years, but they usually fade after the first year. An oestrogen-producing tumour can also cause gynecomastia.
• Gynecomastia in adolescent boys is caused by puberty's hormonal changes. Gynaecomastia is common in boys from early puberty to middle puberty. It usually resolves itself within 6 months to 2 years.

What is pseudogynecomastia?

It is defined as the enlargement of the breasts due to excess deposition of body fat tissue under the nipples, which appears as if there is a presence of breasts. It is also called lipomastia or adipomastia.

Gynecomastia vs Pseudogynecomastia | Difference between Gynecomastia and Pseudogynecomastia

Types and Stages of Gynaecomastia

• Florid gynaecomastia: In the early phases of the condition, it is typically noticed (4 months or less). An increase in ductal tissue and vascularity is seen. 
• Fibrous gynecomastia: It is observed after 12 months of duration, which is characterized by more stromal fibrosis and few ducts.
• Intermediate gynecomastia: It is also observed after 12 months of duration, which is a thought to be a progression from florid to fibrous.

Based on amount of breast enlargement, there are classified into 3 grades:

• Grade I: Minor enlargement with no excess skin
• Grade IIa: Moderate enlargement with no excess skin
• Grade IIb: Moderate enlargement with extra skin
• Grade III: Marked enlargement with extra skin

As per Rohrich et al based on the grades on severity, gynecomastia is categorised into four grades:

• Grade I: Minimal hypertrophy (< 250 g) without ptosis
• Grade II: Moderate hypertrophy (250–500 g) without ptosis
• Grade III: Severe hypertrophy (> 500 g) with grade I ptosis
• Grade IV: Severe hypertrophy with grade II or grade III ptosis

Based on the presence of symptoms, there are classified into 2 types:

• Asymptomatic
• Symptomatic

Etiology

Most cases of gynaecomastia in males have an idiopathic (unknown reason) origin. It is, however, clear that it is caused by an imbalance between the sex hormones oestrogen and testosterone in men. It is due to primary and secondary T deficiency:

Primary T deficiency: It causes low testosterone production which increases luteinizing hormone concentration, thereby increasing imbalance between oestrogen to androgen.

Secondary T deficiency: It causes low testosterone production due to the following reasons.

• Isolated hypogonadotropic hypogonadism, such as Kallmann’s syndrome.
• Other genetic defects like PROP1 gene mutations.
• Pituitary adenomas, including hyperprolactinaemia.
• Cranial irradiation.
• Treatment with opioid or its abuse can also lead to testosterone deficiency.

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Causes of Gynecomastia

1. Early puberty

During the early stages of puberty, a boy's level of oestrogen will be higher than the level of testosterone. This causes the imbalance of oestrogen to testosterone levels causes gynecomastia.

2. Diseases and conditions

Cirrhosis, or liver disease: Due to the increased production of androstenedione (steroid hormone responsible for the production of oestrogen and testosterone) from the adrenal glands, an increase in the conversion of androstenedione to oestrone and oestrone oestradiol and decreased clearance of adrenal androgens from the liver leads to a decrease in free testosterone. This causes an imbalance between the amount of oestrogen and testosterone in the body, which leads to gynecomastia.

Starvation: Malnourishment can result in gynecomastia due to decreased gonadotropin (hormone responsible for production of testosterone in males) levels followed by normal production of oestrogens by the adrenal gland, which leads to an imbalance between testosterone and oestrogen.

Male hypogonadism: Primary hypogonadism (production of low amount of sex hormones) can lead to a decrease in testosterone production.

Hyperthyroidism: In hyperthyroidism, there will be an increase in sex hormone binding globulin (protein), which leads to an increase in oestradiol levels.

Renal / kidney failure and dialysis: In haemodialysis patients, there will be abnormalities in the function of the Leydig cell (source of testosterone or androgens in males). In case of kidney failure, it leads to hormonal abnormalities, where the testosterone level goes down and oestradiol and luteinizing hormone levels go up.

Abnormal human chorionic gonadotrophin (hCG) production: Human chorionic gonadotrophin is a hormone produced by the placenta during pregnancy in females. There are undetectable concentrations of hCG in a healthy male, but when a male patient is diagnosed with either large cell lung carcinoma or gastric carcinoma or renal cell carcinoma or rarely hepatoma, human chorionic gonadotrophin production will be increased which leads to gynaecomastia.

True hermaphroditism: True hermaphroditism is characterised by the presence of both ovarian and testicular tissues. Too much ovarian oestrogen secretion can cause gynecomastia by stopping intratesticular cytochrome P450 C17 activity. This makes the testicles produce less testosterone.

Stressful life events: Oestrogen precursors in excess are secreted by the adrenal glands in a stressed condition.

Type 1 diabetes mellitus: Males with long-term type 1 diabetes mellitus can develop diabetic mastopathy (non-cancerous lesions in the breast formed due to long-term type 1 diabetes).

Kennedy’s syndrome: Gynecomastia is a feature of male patients with this syndrome.

Overweight/Obese: Overweight/Obese can raise oestrogen levels, causing breast tissue to grow. Overweight people are more likely to have excess fat, which can cause breast tissue to enlarge.

3. Maternal transfer

Gynaecomastia in newborn boy is caused by oestrogen from their mother, which passes through the placenta. Breast buds are quite common in newborn boys. Breast buds usually disappear by 6 months of age, but they can last longer in some babies.

4. Medications

• Drugs which are used to increase serum oestrogen levels.
• Drugs which decrease serum testosterone or dihydrotestosterone (Ex: ketoconazole, metronidazole, spironolactone, cancer chemotherapy, finasteride or dutasteride.
• Drugs which promote oestrogen like activity (Ex: digitoxin and herbal products)
• Drugs which block the androgen receptors (Ex: flutamide, bicalutamide, spironolactone cimetidine and marijuana).
• Drugs like antipsychotic agents, metoclopramide and verapamil which increase serum prolactin (hormone that stimulates milk production after childbirth) in men.
• Other drugs like isoniazid, amiodarone, antidepressants, human chorionic gonadotrophin, proton pump inhibitors, highly active retroviral therapy can also cause gynaecomastia.
  

Symptoms of Gynecomastia

The majority of the adult men with gynaecomastia have no symptoms. The following are some signs and symptoms of the condition:

• Enlargement of either one or both breasts
• Painful nipple or tender formation
• Nipple sensitivity with rubbing against clothes

Risk factors for Gynecomastia

The following are some of the factors that can lead to an increased risk of male gynecomastia:

Genetic:

• Klinefelter’s syndrome 

Drugs:

• Recombinant human growth hormone
• Oestrogens
• Anti-androgens
• Gonadotropin releasing hormone (GNRH) agonists
• 5-alpha reductase inhibitors

Disease:

• Testicular neoplasms
• Liver and renal damage 
• Hyperthyroidism
• Hypogonadism

Age:

• Adolescent and Older age or above 60 years

Complications of Gynecomastia

Gynecomastia has few physical complications, but it can cause psychological or emotional problems caused by appearance. It can cause anxiety, depression, low self-esteem, and even eating disorders and body dysmorphia.

Diagnosis of Gynecomastia

By palpating (squeezing the breast between the examiner's thumb and forefinger) the area starting from the outer regions of the breast to the centre, the doctor will check for firmness (the presence of glandular mass 2 cm in diameter or bigger) and make a diagnosis of gynecomastia based on physical examination (symptoms) of the patient.

The physical examination also includes :

• Presence of feminisation signs, stigmata of liver disease, regional lymph node, breast and overlying skin and thyroid.
• Height and weight
• Scrotum.

Your doctor might suggest the following blood test and radiology imaging test to better understand the condition.

• Kidney function test
• Liver function test
• Thyroid function tests
• Serum levels of testosterone (total and bioavailable), LH, FSH, prolactin.
• Serum levels of oestrogens (oestradiol)
• Tumour markers for germ cell neoplasms (β-hCG)
• Levels of adrenal androgens (serum DHEA-sulphate or urinary 17-ketosteroids)
• Biopsy is a procedure where a small amount of breast tissue is taken and examined for cancer cells.
• A low-dose X-ray of your breast (mammogram) may be performed in order to evaluate any breast abnormalities.
• Breast ultrasonography

Prevention of Gynecomastia

With a healthy lifestyle, one can prevent the underlying diseases that can cause gynecomastia. It includes:

• Avoid alcohol consumption, which can cause damage to the liver.
• Maintain normal blood pressure and sugar levels in order to protect the kidneys from failing.
• Self-medication should not be encouraged because some drugs can cause oestrogen levels to rise.

Treatment of Gynaecomastia

Frequently asked questions

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Department of Plastic and Reconstructive Surgery, Cosmetic Surgery