The mammary glands originate from the primitive ectoderm, and during the fifth and sixth weeks of embryonic development, a pair of cord-like primitive milk lines are formed on the ventral surface of the embryo from the axilla to the groin, and this milk line gradually forms the so-called milk ridge in the chest, while the milk lines in other parts gradually degenerate and disappear. In the 1-2 weeks after birth, due to the action of various placental hormones brought from the mother, the mammary duct epithelium secretes a little milk-like material into the duct lumen, and the nipple can overflow, which is a normal physiological phenomenon, and this phenomenon will generally disappear in about 3-4 weeks as the concentration of placental hormones from the mother gradually decreases in the newborn. The mammary glands remain relatively stable and still during this period until the onset of puberty, during which there are basically no essential physiological and anatomical differences between the mammary glands of boys and girls. During the onset of sexual maturity, the female breast continues to develop, while the male breast generally ceases to develop. The abnormal development of male breast tissue and abnormal hyperplasia of the connective tissue of the breast caused by an imbalance in the ratio of estrogen to androgen due to physiological or pathological factors in some men is called gynecomastia. There are 2 types of gynecomastia: physiological and pathological. Physiological (also known as primary) gynecomastia is mostly caused by physiological endocrine disorders and is most common in adolescence. Pathological (also known as secondary) gynecomastia is mostly caused by endocrine organ diseases or endocrine dysfunction caused by diseases of other organs. About half or more of the gynecomastia cannot find a clear cause, and all kinds of hormone measurements are normal, called idiopathic gynecomastia, gynecomastia is mostly benign, and malignant changes are rare. Guo Guangcheng, Department of Breast Surgery, First Affiliated Hospital of Zhengzhou University
(A) Etiology
1. Physiological breast hypertrophy
Male breast development is mostly thought to be due to increased secretion of estrogen or a lower androgen/estrogen ratio. Excessive estrogen is the main cause of gynecomastia in men.
(1). Male breast development in the neonatal period: Its incidence is 60% to 90%, and it manifests as enlarged breast nodules at birth, which is caused by estrogen from the mother or placenta entering the fetal blood circulation and acting on the breast tissue. It usually subsides within 3 to 4 weeks, but if it lasts too long you need to be alert to endocrine and genetic diseases.
(2). Adolescent male mammary gland development: male adolescence can be a transient breast enlargement, the incidence of about 30% to 60%, usually from the age of 10 to 12 years old, 13 to 14 years old to reach the peak, the duration of a few months or 2 years, most of them can return to normal within a year, can not be regarded as a pathological state. Less than 5% of adolescent males exhibit persistent mammary gland development. In most boys, the degree of breast enlargement on both sides is asymmetrical, with one side larger than the other, and the time of appearance of breast enlargement on both sides may not be the same, and button-like lumps may be palpated under the areola area with pain, usually without redness or swelling.
(3). Geriatric male breast development: Geriatric male breast development is most common between the ages of 50 and 80. Most elderly men are associated with varying degrees of decreased testicular function and lower plasma free testosterone levels. In addition, the increased fat content in body tissues of elderly people enhances the action of aromatase in peripheral tissues. The above changes are sufficient to increase the estrogen/androgen ratio in plasma and breast tissues, causing breast tissue hyperplasia, and this phenomenon increases with age. However, for elderly people, we should first rule out the possibility of organic diseases, such as estrogen-secreting tumors, cardiovascular diseases, liver diseases, kidney diseases, etc. These conditions may also cause mastopexy.
2. Pathological breast hypertrophy
(1). Increased estrogen levels: ① Testicular tumors: Some testicular tumors (e.g. choriocarcinoma, mesenchymal cell tumors) can produce chorionic gonadotropin (HCG), which can increase the synthesis of testosterone and estradiol in residual testicular tissues. Also, due to the elevated concentration of aromatase in cancerous tissues, excessive conversion of androgens to estrogens can occur. Increased estrogen production by testicular tumors feeds back to inhibit gonadotropin secretion, leading to a secondary decrease in androgen production. This leads to a significant imbalance in the estrogen/androgen ratio and mastocytosis. (ii) Adrenocortical tumors: Some adrenal cancers can produce large amounts of estrogen, leading to an elevated estrogen/androgen ratio. ③Liver disease: Estrogen inactivation is weakened when liver function is diminished, while androgen aromatization is enhanced, resulting in a relative increase in estrogen. (iv) Others: True hermaphroditism, hypothalamic and anterior pituitary tumors or hyperplasia, and acromegaly can lead to a relative or absolute increase in estrogen production.
(2). Androgen hypersecretion: In patients with primary or secondary hypogonadism, such as Klinefelter’s syndrome, cryptorchidism, orchitis, and testicular trauma, testicular function is reduced and androgen secretion is decreased; at the same time, gonadotropin feedback is increased, stimulating Leydig cells to secrete testosterone, some of which is converted into estrogen in the periphery, and the end result of the above changes is an increased estrogen/androgen The final result of the above changes is an increase in the estrogen/androgen ratio.
(3). Other diseases: ① Hyperthyroidism: About 10% of male hyperthyroid patients have mammary gland development, but its cause is unknown. It may be caused by elevated thyroid hormones in patients, which increase plasma SHBG concentration and increase bound testosterone, thus increasing the free estrogen/androgen ratio. (ii) Chronic renal failure: The accumulation of toxic substances can inhibit testicular function and decrease serum testosterone levels. (③) Malnutrition: mostly seen in chronic wasting diseases, which can lead to decreased androgen synthesis and inhibition of pituitary gonadotropin synthesis and secretion.
(4). Drugs: In addition to estrogens and their analogues, androgen antagonists, etc., the following drugs have also been reported to cause breast hypertrophy: chorionic gonadotropin, cimetidine, spironolactone, androgens, chlorpromazine, reserpine, penicillamine, leucovorin (Maryland), calcium antagonists, isoniazid, ACE inhibitors, phenytoin sodium, tricyclic antidepressants, diazepam (Valium), marijuana, etc. These drugs can cause breast hypertrophy. All these drugs can cause the disease through different mechanisms.
Mammary gland development in men of different etiologies has the same histological changes. The early stage is characterized by hyperplasia of the ductal system, lengthening of the ducts, appearance of new bracts and branches, and proliferation of fibroblasts in the stroma. In the late stage (after several years) there is proliferative degeneration of the epithelium, progressive fibrosis and hyaline degeneration, reduction in the number of glandular ducts, and infiltration with mononuclear cells. When the disease progresses to the stage of extensive fibrosis and hyaline degeneration, complete regression of the mammary gland is not possible. The hormone levels are normal, except for some pathological gynecomastia, and PRL levels are also normal. PRL is not a growth hormone of the breast and has no direct effect on the development of the male breast.
(2) Clinical manifestations
The main manifestation is breast enlargement, depending on the etiology, the developing breasts show bilateral symmetrical or asymmetrical enlargement, or unilateral enlargement. Generally, disc-shaped nodules or diffuse enlargement can be palpated in the breast, with a tough texture and a certain degree of mobility, without adhesions to the skin, and local discomfort or tenderness can be felt.
(iii) Diagnosis
1. Detailed medical history to understand the history of medication and special diseases (such as liver cirrhosis).
2. physical examination, to understand the state of physical development, the presence of abnormal testicular development, thyroid nodules, etc.
3. laboratory tests, ⒈ sex hormone assay, gonadotropin assay. It helps to diagnose whether there is primary or secondary hypospadias. ⒉Liver and kidney function tests. Helps to diagnose liver and kidney failure. Cortisol and ACTH, 17-OHP, 17-ketosteroids and 17-ketogenic solid ketones assay. Can evaluate congenital and congenital adrenal cortical hyperplasia. Other ancillary tests: ⒈ breast B-ultrasound, mammography. They can differentiate between fat and breast tissue to rule out breast cancer in time. Pelletizing histopathological examination of the breast to further confirm the diagnosis.
The clinical diagnosis of the disease is usually determined as glandular tissue >0.5 cm. To diagnose breast hypertrophy, we must first distinguish between true breast hypertrophy and pseudobreast hypertrophy. Pseudobreast hypertrophy is an enlargement of the breast due to fat deposition rather than glandular hyperplasia. Patients with this condition tend to be generally obese and have no breast pain or tenderness. The distinction between the two can be made by palpation of the breasts. Patients with true breast hypertrophy can palpate elastic or firm disc-like tissue that extends around the nipple.
The diagnosis of breast hypertrophy also requires differentiation from breast cancer. In contrast, male breast cancer is usually seen in older men and is often an isolated lump in one breast with firm texture and unclear borders, often without tenderness, and may present with areolar skin adhesions and enlarged axillary lymph nodes, with skin changes such as nipple overflow, depression or deviation.
(iv) Treatment
Treatment of breast hypertrophy begins with finding the cause and treating it according to the cause. In general, for patients with exact pathogenic factors, the symptoms of breast enlargement will fade after removing the primary cause. If the symptoms are caused by medication, the medication should be discontinued and most of them can recover on their own. Most of the adolescent male breast growths can subside on their own, so most of them do not require treatment, and simple clinical observation after patient and careful explanation to the patient is sufficient. For those with clinical pain or tenderness in the breasts, or those with large breasts that affect their appearance and psychological well-being, clinical intervention is required. The common treatments for breast enlargement include medication and surgery.
1. Pharmacological treatment
(1). Androgen preparations
Testosterone: It is effective for patients with hypotrichosis. Testosterone enanthate is commonly used to increase the level of testosterone in the body without being converted into estradiol by aromatase. Generally, 200 mg is used and injected intramuscularly once every 3-4 weeks. (2) Dihydrotestosterone heptane salt: It acts directly on the target cells without the effect of aromatase and has better efficacy.
(2). Tamoxifen (triamcinolone)
It is an estrogen antagonist, which can bind to ER of target tissues and block the effect of estrogen. The usual dose is 20 mg orally daily. tamoxifen is effective in reducing breast pain or tenderness within one month.
(3). Clomiphene (clomiphene)
It is an anti-estrogenic drug with significant effects and can reduce breast development in middle-aged people, but it can also cause breast development itself and has greater side effects. It can reduce breast development in middle-aged people, but it can also cause breast development itself, and has a large side effect. 50-100 mg per day orally, about 70% of patients have different degrees of efficacy.
(4). Danazol (danazo1)
It is an anti-chorionic gonadotropin drug at a dose of 200 mg three times a day for 3-9 months. It is effective in both adult and adolescent mastocytosis and can reduce pain and breast development, but has side effects such as edema, nausea, seborrheic dermatitis, and weight gain.
2. Surgical treatment
If medication does not work over time or if the breast has been enlarged for many years and has become a mental burden for the patient, or if there is a large gynecomastia or suspected cancer, surgical removal is required. The indications include: (1) males with breast development at the end of puberty or after puberty, with breast diameter >4 cm, where medication has failed; (2) males with serious aesthetic problems; and (3) males with suspected malignant changes.
Modern mammaplasty can be broadly divided into three types, namely fat aspiration, open excision and fat aspiration combined with open excision. The open surgical approach generally uses subcutaneous excision of the gland (preserving the nipple and areola). Subareolar mammary tissue is usually removed using a circumareolar approach. In recent years, the application of lumpectomy technology has improved the safety of the procedure, and some scholars believe that total lumpectomy with subcutaneous glandular excision of the breast has fewer complications and good cosmetic results, and is the best surgical method for most gynecomastia. Removal of glandular tissue needs to be sent for pathological examination to clarify the diagnosis.