The former life and death of gynecomastia.
Gynecomastia (vx: 13802061280) is a clinical condition in which abnormal development of male breast tissue and abnormal hyperplasia of the connective tissue of the breast are caused by an imbalance in the ratio of estrogen to androgen due to physiologic or pathologic factors.GYN is the most common male breast disease, accounting for about 80% to 90% of male breast diseases. GYN is physiologic in 50% of cases, most common in neonatal and adolescent years, when it is transient and usually benign, but is considered abnormal if it occurs in prepubertal, young, and middle age, and requires further testing to rule out the possibility of breast cancer or other neoplastic organisms.
Epidemiology:
GYN can occur at any age, with the majority occurring between the ages of 12 and 17. In recent years, as people’s standard of living has improved and their lifestyle has changed, the incidence and consultation rates for this disease have increased significantly. The reported incidence varies from 30% to 70%, and the incidence varies by age. Rohrich reported the incidence of GYN in male population as 32%-65%, Chen Zhangqing et al. reported the incidence of GYN in neonates as 50% or more, in adolescents as 39%, and in the elderly as 40% or more.
Pathogenesis:
It is believed that GYN is mainly caused by the disturbance of sex hormone levels in blood circulation, and there are basically two types of sex hormone level disturbance: one is the increase of estrogen, and the other is the increase of estrogen/androgen ratio. On the one hand, elevated estrogen can promote male breast growth and development, on the other hand, increased estrogen/androgen ratio can also stimulate the synthesis of sex hormone binding protein (SHBG), which has a much greater affinity for androgens than estrogen, thus increasing the ratio of biologically active free estrogen/androgen in the blood and promoting breast enlargement. In addition, it is thought that the occurrence of GYN is also related to the local estrogen/androgen ratio in the breast and the response of the breast to hormones. In some cases, the local aromatase activity in the breast increases, resulting in the conversion of more androgens to estrogens, resulting in a local excess of estrogen and causing GYN. The effect of androgens is reduced, while the effect of estrogen is relatively enhanced, resulting in breast enlargement. For example, Xu Peiheng et al. reported that there was no significant difference between the serum level of testosterone and water level in patients with GYN, but the AR binding capacity was significantly lower than that of the control group, which was thought to be caused by the decrease of AR, so that the biological effect of testosterone could not be played normally.
Pensler et al. studied 34 adolescent GYN patients with Klinefelter’s syndrome who had increased expression of ER and progesterone receptors (PR) in the breast, suggesting that the occurrence of GYN is related to the expression of local hormone receptors in the breast. Qin Jun et al. applied immunohistochemistry to detect the expression of heat shock protein 70 (HSP70) in breast tissues of 25 GYN patients and found that the positive rate of HSP70 was 72%, which was similar to the expression rate in breast cancer tissues, suggesting that the occurrence of GYN is closely related to cell proliferation. Zhao Guofa et al. concluded that GYN is actually a chronic inflammatory reaction (non-infectious) in the target organ (breast tissue) under the influence of estrogen stimulation or other factors, and can be better treated by local injection of prednisolone acetate suspension.
Disease classification:
Clinically, GYN can be classified into physiological according to the etiology
The disease is classified as physiological. Pathological and idiopathic three categories.
Physiological GYN
includes neonatal, adolescent and old age
GYN.
1, the neonatal period GYN: its incidence is 60% to 90%, manifested as an increase in breast nodules at birth, this is due to the maternal or placental estrogen into the fetal circulation, caused by the action of the breast tissue. Usually fades within 1~3 weeks, occasionally it can last for months or even years, if it lasts too long, you need to be alert to endocrine and genetic diseases.
2, puberty GYN: male puberty stage can appear 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 a peak, the duration of a few months, a long 2 years, most of them can return to normal within a year, less than 5% of adolescent male GYN performance is persistent. In most boys, the degree of breast enlargement on both sides is asymmetrical, one side is larger than the other, and the time of appearance of breast enlargement on both sides may not be the same, and may be accompanied by pain, without redness or swelling. The exact cause of GYN during puberty is still unclear, but it is thought that it may be due to the high secretion of sex hormones during puberty, with anterior pituitary gonadotropins stimulating the production of testosterone and estrogen, and the testes synthesizing a large amount of estrogen before secreting a large amount of testosterone, thus causing an increase in the serum estrogen/androgen ratio and producing transient male breast development and hyperplasia. It has been found that in boys, plasma estradiol concentration reaches adult levels before plasma testosterone reaches adult levels, resulting in an increased estrogen/androgen ratio. In addition, the average plasma estradiol level was higher in boys with mastopexy. In addition, the local aromatase action in the mammary gland is enhanced during puberty, resulting in increased local estrogen formation, which leads to adolescent breast hyperplasia. It has also been suggested that this may be due to increased sensitivity of breast tissue to physiological levels of free estrogen.
3, GYN in old age: GYN in old age is most common between the ages of 50 and 80. Older men are mostly accompanied by different degrees of testicular function decline, the metabolism of estrogen and androgen has changed, including a decrease in plasma total testosterone levels, a decrease in plasma free testosterone levels, and an increase in SHBG levels. In addition, the increased fat content in the body tissues of the elderly increases the action of aromatase in the peripheral tissues, and these changes are sufficient to increase the estrogen/androgen ratio in plasma and breast tissues, resulting in hyperplasia of breast tissues, and this phenomenon increases with age. However, in elderly people, it is important to exclude organic diseases such as estrogen-secreting tumors, cardiovascular disease, liver disease, kidney disease, or the frequent use of multiple medications, which may also cause breast enlargement.
Pathological GYN
1. Increased estrogen levels: ① Testicular tumors: Some testicular tumors (such as choriocarcinoma, teratoma and a few seminoma) can produce chorionic gonadotropin (HCG), which can increase the synthesis of testosterone and estradiol in residual testicular tissues. At the same time, the increased concentration of aromatase in cancerous tissues can cause excessive conversion of androgens to estrogens. The increased production of estrogen by testicular tumors suppresses gonadotropin secretion and leads to a secondary decrease in androgen secretion. The increased secretion of estrogen also has an effect on testosterone synthesis enzyme, which further reduces testosterone synthesis, resulting in a significant imbalance of estrogen/androgen ratio and mastocytosis. Adrenal tumors: Some adrenal cancers produce large amounts of estrogen or its precursor, androstenedione, which can be converted into estradiol by aromatase in the surrounding tissues. At the same time, pituitary gonadotropin secretion is inhibited by feedback, and testosterone secretion is reduced, resulting in an increase in the estrogen/androgen ratio. (3) Cirrhosis and alcoholism: When liver function decreases, estrogen degradation decreases, while androgen aromatization increases, resulting in a relative increase in estrogen. ④Other: true hermaphroditism and congenital adrenal hyperplasia increase estrogen secretion by testes. Some rare genetic mutations and autosomal dominant genetic diseases may enhance aromatase activity, resulting in a relative or absolute increase in estrogen production.
2.Low androgen secretion: In patients with primary or secondary testicular hypofunction, such as Klinefelter syndrome, orchidrosis and orchitis, testicular hypofunction is reduced and androgen secretion is reduced; at the same time, gonadotropin feedback is increased, stimulating Leydig cells to secrete testosterone, some of which is converted into estrogen in the periphery; gonadotropin can also enhance Leydig cell aromatase activity, causing the testes to produce estrogen. The final result of the above changes is an increase in the estrogen/androgen ratio, leading to GYN.
Androgen receptor insensitivity: Although the level of sex hormones in the blood circulation is normal in patients with testicular feminization, the androgen receptors are insensitive to testosterone, resulting in a local imbalance of the estrogen/androgen ratio in the mammary gland, where the effect of androgens is weakened while the effect of estrogen is relatively enhanced, leading to breast hyperplasia.
4, karyotype abnormalities: some male breast development is due to clonal karyotype abnormalities, such as: 12p deletion, 9, 17, 19 and 20 chromosome monosomy, some patients with benign or malignant tumors of the breast.
5, other diseases: ① hyperthyroidism: about 10 male patients with hyperthyroidism have mammary gland development, but its cause is not known. It may be due to elevated thyroid hormones in patients, which increase the concentration of plasma SHBG and increase the combination of testosterone, thus increasing the ratio of free estrogen/androgen. In addition, hyperthyroidism can cause a decrease in Leydig cell function, resulting in an increase in the estrogen/androgen ratio. (2) Hypothyroidism: Hypothyroidism with GYN may be related to excessive secretion of prolactin (PRL) and insufficient estrogen. Chronic renal failure: Toxic accumulation can inhibit testicular function, lower testosterone levels, and increase pituitary gonadotropin and PRL levels. ④Malnutrition: can cause androgen synthesis to decline, pituitary gonadotropin synthesis and secretion is inhibited, when nutrition improves, this inhibition disappears.
6, drugs: in addition to estrogen and its analogues, chorionic meow sex kinase and male kinase methotrexate antidote Dan lead to breast enlargement: cimetidine, spironolactone, androgens, isoniazid, reserpine, white elimination of an (Maryland), calcium antagonists, ACE inhibitors, phenytoin sodium, tricyclic antidepressants, penicillamine, diazepam (Valium), marijuana, heroin, etc., these drugs can lead to an increase in the ratio of estrogen / androgen, However, the exact mechanism of action is not clear.
Idiopathic GYN
About half or more of the cases of gynecomastia for which no clear cause can be identified and all hormone measurements are normal are called idiopathic GYN, but it is important to note that some of these patients may have had transient feminizing factors that are no longer present at the time of presentation. They may have been exposed to small amounts of estrogenic or anti-androgenic substances in their work and living environment or may have had mild endocrine dysfunction. Some environmental pollutants are estrogen-like compounds, such as organochlorine pesticides and dioxin compounds, which can enter the body and produce sex hormone-like effects.
In patients with GYN due to the above mentioned causes, plasma PRL levels are usually normal, so PRL does not play a direct role in the development of this disease. The majority of men with pituitary PRL tumors do not develop mastocytosis, but the few who do develop mastocytosis often do so because of pituitary tumor compression or high PRL levels that directly affect gonadotropin secretion and secondary hypogonadism. Some patients with mastocytosis may have mildly elevated PRL levels, but this is a consequence of hyperestrogenemia.
Pathological changes
The histopathology of GYN differs from that of the female breast in that there are no milk-secreting lobules, only hyperplasia and cystic dilatation of the milk ducts, along with hyperplasia of fibrofatty tissue (Figure 1). GYN 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 ductal bracts and branches, and proliferation of fibroblasts in the stroma. In the late stage (after several years), the epithelium degenerates, with progressive fibrosis and hyaline degeneration, and the number of ducts decreases with mononuclear cell infiltration. When the disease progresses to the stage of extensive fibrosis and hyaline degeneration, complete regression of the breast is difficult. Histological changes in male breast development
Cohan divided the enlarged breasts into three types according to the degree of hyperplasia of breast parenchyma and adipose tissue: (1) glandular: the enlarged breasts are mainly hyperplasia of breast parenchyma; (2) adipose: the enlarged breasts are mainly hyperplasia of adipose tissue; and (3) glandular adipose: the enlarged breasts have hyperplasia of both breast parenchyma and adipose tissue. Bannayan and Hajdu classified breast hypertrophy in GYN patients into 3 types according to the degree of hyperplasia of the interstitial and ductal tissues: ① exuberant male breast hyperplasia: the duration of the disease is less than 4 months, characterized by significant epithelial hyperplasia of the glandular ducts, with a large number of fibroblasts in the interstitium, containing adipose tissue, and a mild lymphocytic infiltration with capillary hyperplasia; ② fibrous or sclerotic male breast hyperplasia: the duration of the disease is more than 1 year, characterized by a lesion consisting mainly of collagen fibers, with scattered lymphocytes. (2) Fibrous or sclerotic gynecomastia: the disease duration is more than 1 year, characterized by lesions mainly composed of collagen fibers, with scattered dilated ducts and mild or moderate epithelial cell hyperplasia; (3) Intermediate gynecomastia: the disease duration is between 5 and 12 months, and interstitial fibrosis has begun, which is an intermediate stage between the above two types. Most scholars believe that these 3 types reproduce the duration of breast enlargement and the evolution of mammary gland developmental disease associated with its symptoms in men.
Clinical presentation:
The main manifestation is breast enlargement, either unilateral or bilateral, sometimes with enlarged nipples and areolas. Localized discomfort or tenderness may be felt,
In a few patients, a small amount of white discharge can be seen when the nipple is squeezed (Figure 2).
The patient is placed in a supine position and the examiner places the thumb and index finger on the base of the breast and slowly brings them together. A disc-shaped nodule or diffusely enlarged tissue with a more rubbery texture can be palpated, such as stage 3 to 5 according to Turner staging. At present, there are two grading criteria for GYN, see Table 2, and the clinical decision on surgery is based on this grading. Pathological GYN caused by organic disease also has clinical manifestations of the primary disease.
Table 2 Simon and Rohrich classification of gynecomastia
Simon’s classification Rohrich’s classification
! Class Mild breast enlargement Class Mild hypertrophy No
Sagging (<250g)
No excess skin A glandular dominant B fibrous dominant
A gland dominant B fibre dominant
Class IIA moderate course Class 1 moderate hypertrophy no
moderate breast enlargement with sagging (250-500g)
No excess skin A glandular dominant B fibrous dominant
predominantly
Class llB moderate degree Kawasaki class severe hypertrophy with
Breast enlargement with mild sagging (>500g)
with excess skin glandular or fibrous
Class I severe breast Class IV severe hypertrophy with
Enlargement with severe sagging
Significant excess skin (Type I or old Type I)
Skin glands or fibers
Similar to a sagging gynecomastia
Disease Screening
1. Gonadal and related hormone tests: Luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, testosterone, HCG, PRL (especially if there is breast overflow). Elevated HCG levels in testicular or non-gonadal germ cell tumors or ectopic HCG-secreting non-trophoblastic tumors; elevated LH concentrations combined with decreased testosterone levels in primary hypogonadism; decreased testosterone levels and LH levels in secondary hypogonadism due to hypothalamic or pituitary abnormalities. Plasma estradiol levels are elevated when tumors of the testes or adrenal glands secrete estrogen and are accompanied by normal or suppressed LH concentrations.
2.Imaging examination: Ultrasound of breast is the first choice, which typically shows a fan-shaped hypoechoic area centered on the nipple, clearly demarcated from the surrounding tissues, with small ductal lumen and thick glandular tissue. The typical presentation is a subareolar round, nodular or lumpy homogeneous dense shadow with a diameter of 2-4 cm, smooth margins or burrs, and rarely lobar changes, sometimes with fine sand-like calcifications in or around the hyperplastic breast tissue, clear vascular structure, and clear demarcation from the surrounding tissue. For patients with elevated HCG, MR| or CT of the brain, chest, or abdomen and ultrasound of the testes are needed to rule out any HCG-secreting tumors. If dehydroepiandrosterone sulfate is elevated, an ultrasound of the adrenal glands is required.
3.Chromosome examination: If the penis is shorter than 3cm or the testicular volume is less than 6mL, karyotype analysis should be done to exclude Klinefelter syndrome. At the same time, karyotype testing can exclude GYN due to karyotype abnormalities.
4, Other: If necessary, check liver function, kidney function, thyroid function to rule out whether these chronic diseases cause breast development.
Diagnostic differentiation
Clinically, it is usually recognized that glandular tissue >0.5cm is the diagnostic criterion for this disease. The first step in diagnosing GYN is to distinguish between true GYN and pseudo-GYN, which is an enlargement of the breast due to fat deposits rather than glandular hyperplasia. Patients with this condition are generally obese and have no breast pain or tenderness. The distinction between the two can be made by breast palpation. In true GYN, patients can palpate elastic or firm discoid tissue, with the nipple as the center extending around the mammogram of male breast development and breast cancer, and can feel resistance when the fingers are closed, while in pseudo-GYN there is no resistance when the fingers are closed. If you can’t distinguish them by examination, you can perform breast ultrasound, which can visually show the size, shape and internal echo of the breast, and also visually show whether there is a lump in the breast, as well as the nature, location, size, shape, boundary and blood flow signal of the lump, which is accurate and reliable in distinguishing true from false GYN, with an accuracy rate of almost 100%. Secondly, it should be distinguished from breast cancer; GYN has elastic tissue texture, patients are mostly bilateral and rarely have nipple overflow; while male breast cancer is usually seen in older men, often as an isolated lump in unilateral breast, with firm texture and unclear borders, often without tenderness, and there may be skin adhesions in the areola and enlarged axillary lymph nodes, with skin changes such as nipple overflow, depression or deviation. If local ulcers or adjacent lymph glands are enlarged, it is a sign of advanced breast cancer. If clinical examination alone cannot differentiate GYN from breast cancer, mammography should be performed (Figure 5), which has a sensitivity and specificity of 90% in differentiating benign and malignant breast lesions. Breast cancer x-ray shows a lump mostly located in the upper outer quarter of the breast, eccentric, with indistinct margins and burr-like extension. The sensitivity and specificity of breast ultrasonography for identifying benign and malignant breast lesions can also reach over 90%. Ultrasound shows that breast cancer lumps are often deviated from the areola, with poorly defined borders and posterior attenuation. For patients with high suspicion of breast cancer, fine needle aspiration cytology and pathological biopsy should be performed as early as possible to confirm the diagnosis.
After the clinical diagnosis of GYN is made, a detailed history, physical examination, and relevant hormone tests should be performed to determine the etiology of the disease. Secondary sexual characteristics, testicular volume, body size, sex hormones, and gonadotropins are useful in the diagnosis of primary or secondary hypogonadism. Measurements of adrenocorticotropic hormone, cortisol, 17-hydroxyprogesterone, 17-ketosteroids and 17-ketogenic steroids can assist in the diagnosis of congenital adrenocortical hyperplasia. Testicular tumors, germ cell tumors, or ectopic non-trophoblastic tumors should be investigated with testicular ultrasound, abdominal and chest CT. When the plasma estradiol level is elevated and the LH concentration is normal or decreased, estrogen-secreting testicular or adrenal tumors are considered. In addition, a history of liver and kidney disease and hyper- and hypothyroidism should be carefully investigated, and liver and kidney function tests and thyroid function tests should be performed if necessary. If necessary, liver and kidney function tests and thyroid function tests should be performed. The patient should be asked about the use of sex steroids and their precursors, anti-androgen drugs, anti-ulcer drugs such as cimetidine, cancer chemotherapy drugs, especially alkylating agents, cardiovascular drugs such as spironolactone, psychotropic drugs and drug abuse. If the above tests are normal, the diagnosis of idiopathic GYN can be made, and the diagnostic and differential diagnostic procedures for GYN can be made with reference to Figure 6.
Disease treatment:
The treatment of GYN should be based on its etiology, length of history, presence of concomitant symptoms, and breast size to make a reasonable choice. Treatment should first be directed at the cause. In general, most patients have a clear pathogenic factor, and for those with a definite pathogenic factor, the symptoms of breast enlargement will fade after the original cause is removed. If the symptoms are caused by medication, the medication should be discontinued, and most of them will recover on their own. Most GYN can subside on their own (the most common is transient GYN in adolescence), so most of them do not require treatment, and can be observed clinically after patient and careful explanation. However, clinical intervention is needed for those with clinical pain or tenderness in the breast, and for those with persistent large breast development affecting the patient’s physical appearance and psychology.
I. Drug treatment
In the rapid proliferation phase of GYN (early onset), the histology shows ductal epithelial proliferation, inflammatory cell infiltration, increased stromal fibroblasts and increased vascular distribution, often accompanied by clinical breast pain or tenderness, at this time, drug therapy can not only relieve the symptoms. It can also promote the fading of the developing breast. In addition, for hard nodes within 5 cm or limited to the areola, drug treatment is feasible. The following drugs are commonly used:
1, androgen preparations ① testosterone: good effect on patients with testicular hypofunction. Testosterone enanthate is commonly used to increase the level of testosterone in the body, while not being converted into estradiol by aromatase. It is usually administered at 200mg, once every 3-4 weeks by intramuscular injection. Some studies reported that after 3 months of treatment, the breast size was reduced by 67%-78%. During the treatment period, the plasma level of dihydrotestosterone increased, and the level of LH, FSH, testosterone and estradiol was suppressed. (2) Dihydrotestosterone heptane salt: it acts directly on the target cells and is not affected by aromatase, so it is more effective.
2.Tamoxifen (triamcinolone)
It is an estrogen antagonist, which can combine with ER of target tissues to block the effect of estrogen. It is commonly used at a daily dose of 20 mg orally, and some people report that the breast gland shrinks significantly after 1 month of taking the drug, and the dose can be increased if the effect is not obvious. In the literature, it has been reported that oral tamoxifen, 20mg daily for 3 months, partially regressed breast development in 80% of men and completely regressed in 60% of patients, and breast pain or tenderness was reduced within one month in patients with effective tamoxifen.
3.Clomiphene (clomiphene)
It is an anti-estrogenic drug with obvious effects, which can reduce breast development in middle-aged people, but it can also lead to breast development itself and has large side effects. Daily oral 50-100mg, about 70% of patients have different degrees of efficacy.
4, aromatase inhibitors ① testosterone lactone: can block the conversion of testosterone into estradiol in the periphery. Some people use 450mg per day, divided into oral doses, have good efficacy, no adverse reactions were found. The level of androstenedione, testosterone, dehydroepiandrosterone and E0 increased slightly, and the ratio of androstenedione/EO increased, while the level of LH, PRL and E2 did not change significantly. Anastrazole is a new type of aromatase inhibitor that has been used in the treatment of postmenopausal breast cancer patients and has been clinically proven to be safe and effective in the treatment of gynecomastia. This drug inhibits tissue estrogen secretion and reduces estrogen production, but does not inhibit pituitary function. Side effects include flushing, thinning of hair, gastrointestinal reactions (anorexia, vomiting, diarrhea), etc.
5.Danazol (danazo1)
It is an anti-chorionic gonadotropin drug at a dose of 200mg 3 times a day for 3-9 months. It is effective for both adult and adolescent breast enlargement and can reduce pain and breast development, but has side effects such as edema, nausea, seborrheic dermatitis and weight gain.
Second, surgical treatment
If medication does not work after a period of time or if the breast has been enlarged for many years and has become a mental burden for the patient, or if large gynecomastia or cancer is suspected, the enlarged breast glandular tissue should be surgically removed. The indications include: (1) men with breast development at the end of puberty or after puberty, with breast diameter >4cm, where medication has failed; (2) men with severe aesthetic problems; and (3) men with suspected malignant changes.
The Simon and Rohrich classifications provide an important clinical basis for the selection of GYN surgery. When selecting the surgical approach, the surgeon must consider not only the cause of the patient’s morbidity, the size of the breast, the tissue composition of the enlarged breast, and the presence or absence of excess skin, but also the patient’s requirements for aesthetic appearance. The first surgeon to report surgical treatment of gynecomastia was Paulus Aegineta, and in 1933 Menvill first considered surgical treatment of gynecomastia from the principles of plastic surgery. Modern mastopexy can be broadly divided into three types, namely fat aspiration, open excision, and fat aspiration combined with open excision. A circumareolar approach is generally used to remove the subareolar breast tissue. In recent years, the application of lumpectomy technology has improved the safety of surgery. In China, Fan Linjun et al. used lumpectomy technology to perform subcutaneous adenomectomy in 65 patients with gynecomastia, and concluded that total lumpectomy with subcutaneous breast adenomectomy has few complications and good cosmetic results, and is the best surgical method for most gynecomastia. However, after mastectomy, the other breast can develop again, so it is important to pay attention to follow-up observation and timely detection. If the other breast develops, medication is effective, and if it does not subside, it can be surgically removed again.
Other
The most convincing data from the Scandinavian randomisedscandinaviantrial shows that prophylactic radiotherapy can significantly reduce the incidence of anti-androgen-induced GYN and breast pain. However, there is a lack of additional clinical evidence.
In summary, two points need to be noted regarding the treatment of GYN: 1, GYN, especially adolescent GYN, can subside on its own in the majority of patients; 2, drug therapy (including traditional Chinese medicine) is often most effective in the early stage of the disease, when the gland is actively enlarged, once the gland enlarges for a certain period of time (usually 12 months), the gland will undergo interstitial vitreous transformation and tissue fibrosis, and the responsiveness to drugs will The response to the drug is severely reduced.
Expert opinion:
GYN can cause varying degrees of physical and psychological damage, so effective treatment is a major issue for clinicians. Surgery is now the mainstay of treatment, and despite the development of surgical theory and techniques, surgeons often find it difficult to choose the best surgical approach for a diagnosed patient. Therefore, it is imperative to explore a systematic approach to the treatment of gynecomastia that takes into account breast size, texture, skin excess, and skin elasticity.