Gynecomastia: Causes

Pathogenesis (development of disease)

Growth and differentiation of the male mammary gland is stimulated by estradiol via estrogen receptors. Inhibitory effects are exerted by testosterone via androgen receptors. True gynecomastia is caused by excessive estrogen action or a disturbed balance between androgen and estrogen supply or action. This results in hypertrophy of the male mammary gland, usually occurring on both sides. This must be distinguished from pseudo-gynecomastia, which occurs due to lipomastia (fatty growth) (unilateral) or obesity (bilateral). Furthermore, lipo-gynecomastia exists as a mixed type. The mammary gland growth of true gynecomastia is a proliferative process, which in the course of time may pass into an irreversible stage of fibrosis (pathological proliferation of connective tissue). Idiopathic gynecomastia is present in approximately 50% of pathologic gynecomastia.

Etiology (causes) of true gynecomastia

Biographic causes

  • Genetic burden from parents, grandparents.
    • Genetic diseases
      • Klinefelter syndrome – genetic disorder with mostly sporadic inheritance: numerical chromosomal aberration (aneuploidy) of the sex chromosomes (gonosomal anomaly) occurring only in boys or Men occurs; in the majority of cases characterized by a supernumerary X chromosome (47, XXY); clinical picture: large stature and testicular hypoplasia (small testis), caused by hypogonadotropic hypogonadism (gonadal hypofunction); here usually spontaneous onset of puberty, but poor pubertal progress.
      • McCune-Albright syndrome (MAS) – belongs to the neurocutaneous syndromes; clinical triad: fibrous bone dysplasia (FD), café-au-lait spots of the skin (CALF; light brown, uniform skin patches of varying size) and pubertas praecox (PP; premature onset of puberty); later endocrinopathies with hyperfunction appearing, eg. For example, hyperthyroidism (hyperthyroidism) and increased secretion of growth hormone, Cushing’s syndrome and renal phosphate loss.
  • Childhood: gynecomastia is common in this phase of life and usually disappears spontaneously usually during the first year of life (physiological gynecomastia: about 90% of newborn males = neonatal gynecomastia).
  • Hormonal factors
    • Puberty (pubertal gynecomastia; pubertal gynecomastia; prevalence (incidence of disease) at age 14 60%; regresses spontaneously within 2 to 3 years).
    • In old age due to increasing body fat and strong aromatase activity.

Behavioral causes

  • Drug use
    • Cannabis (hashish and marijuana)
  • Use of shampoos, soaps, lotions, balms, gels, etc. containing lavender/tea tree oil cause gynecomastia in prepubertal boys; cause: ingredients have estrogen-like effect
    • Eucalyptol, terpin-4-ol, dipentene/limonene, and alpha-terpineol were present in both lavender and tea tree oils
    • Linalyl acetate, linalool, alpha-terpinene, and gamma-terpinene were present in one of the two agents

Disease-related causes.

Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99).

  • Klinefelter syndrome (see below “Biographic causes”).
  • Cryptorchidism (absence of one or both testes in the scrotum (not palpable) or the testis has an intra-abdominal location (retentio testis abdominalis; abdominal testis) or is absent (anorchia)), associated with hypogonadism (gonadal hypofunction)
  • McCune-Albright syndrome (MAS) (see below “Biographical causes”).
  • Reifenstein syndrome – genetic disease (see above under partial androgen resistance).
  • Pseudohermaphroditism – conditions in which chromosomal sex and gonadal sex (which determine internal genitalia) do not match genital sex (external genitalia) and secondary sexual characteristics.

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Androgen inactivity syndrome
  • Acromegaly – hypersecretion of growth hormone; there is an increase in the size of the body end limbs or acra.
  • Hyperprolactinemia – pathological (pathological) increase in the level of prolactin.
  • Hyperthyroidism (hyperthyroidism).
  • Hypogonadism (gonadal hypofunction: primary (hypergonadotropic) hypogonadism; secondary and tertiary (hypogonadotropic) hypogonadism).
  • Hypothyroidism (hypothyroidism).
  • Graves’ disease – form of hyperthyroidism (hyperthyroidism) caused by autoimmune disease.
  • Partial androgen resistance (synonyms: Partial androgen insensitivity syndrome, PAIS; Reifenstein syndrome) – genetic disease in which, due to a mutation in the genome of the diseased male, the androgen receptor functions inadequately. This leads to the fact that the individual is genetically a man (XY sex chromosomes), the sex organs are differentiated male, and androgens are also produced; however, the site of action of these hormones, the androgen receptor, functions insufficiently or not at all.Symptoms: Gynecomastia, hypospadias (congenital anomaly of the urethra; this does not end at the tip of the glans but depending on the severity of the degree at the bottom of the penis), micropenis (small penis), azoospermia (absence of spermatozoa in the semen) or / and cryptorchidism (undescended testis) or inguinal testis.
  • Malnutrition

Skin and subcutaneous tissue (L00-L99)

  • Lymphadenosis cutis benigna (Bäfverstedt syndrome) – occurrence of nodular or areal skin infiltrates; occur after tick bite, injury, or viral infection.

Cardiovascular system (I00-I99).

  • Venous/lymphatic outflow disorders in the chest region.

Infectious and parasitic diseases (A00-B99).

  • Inflammatory reactions in the region of the mamma (breast).
  • Leprosy (due totesticular atrophy; “shrunken testicles“).

Liver, gallbladder, and bile ducts-pancreas (pancreas) (K70-K77; K80-K87).

Neoplasms – tumor diseases (C00-D48).

  • Bronchial carcinoma (lung cancer; in the setting of a paraneoplastic syndrome).
  • Benign neoplasms of the mamma (breast) such as fibromas, lipomas, cysts.
  • Testicular carcinoma (7% of cases, mainly non-seminomas).
  • Hypernephroma (renal cell carcinoma).
  • Germ cell tumors: chorionic carcinomas, embryonal carcinomas, teratomas.
  • Hepatocellular carcinoma (liver cancer)
  • Leydig cell tumors of the testis
  • Mammary carcinoma (breast cancer)
  • Adrenal tumor, unspecified

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

Injuries, poisonings and other consequences of external causes (S00-T98).

  • Injury to the chest resulting in the formation of a hematoma (bruise)

Medication

  • Antidepressants
  • Antihypertensives
    • ACE inhibitors
    • Nifedipine (calcium antagonist)
  • Antifungal agents (itraconazole).
    • Azoles (voriconazole)
    • Triazole derivatives (fluconazole)
  • Captopril (ACE inhibitor)
  • Cimetidine (H2 antihistamine)
  • Diazepam
  • Cardiac glycosides (digitalis) – digitoxin, digoxin
  • Hormones
  • Finasteride
  • Ketoconazole (antifungal agent)
  • Methadone (opioid; heroin substitute).
  • Metoclopramide (antiemetic)
  • Metronidazole (antibiotic)
  • Omeprazole (proton pump inhibitor)
  • Phenytoin (anticonvulsant)
  • Psychotropic drugs, unspecified
  • Spironolactone (diuretic)
  • Tuberculostatics (INH) and others
  • See also under drug side effects “Hyperprolactinemia due to drugs“.

Other causes

Etiology (causes) of pseudo-gynecomastia

Disease-related causes.

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • Obesity (obesity)

Neoplasms – tumor diseases (C00-D48)

  • Lipoma (fatty tumor)
  • Fibroma (connective tissue tumor)