Gynecomastia is the abnormal proliferation of glandular tissue located behind the areola in males and is a very common condition in humans of all ages. The deformation that it might cause to the whole breast can be referred to as “puffy nipples,” which is one of the reasons for great social embarrassment and a serious psychological consequence. It may have a negative impact on body image and quality of life during puberty in eventual partner relationships. One of the causes of gynecomastia is a pathologic development of one or both mammary glands, the cause of which is a physiologic imbalance between the male sex hormone and the female sex hormone. The final effects of sexual development in both males and females are conditioned in humans by the respective balance of circulating steroids in the bloodstream.
Gynecomastia hormonal imbalance needs to be differentiated from pseudogynecomastia, wherein the increase in the male breast is independent of the augmented size of the glandular element but rather of the fatty one, and from pseudo-pseudogynecomastia, which is obesity per se, wherein the subcutaneous layer is already hypertrophic and with the increase of mammary glands. In cases of gynecomastia, one factor is, from an anatomical standpoint, the associated skin redundancy, which most objectively worsens the aesthetic result to be pursued. Surgical treatment, therefore, plays a very important role in developing a “conservative” attitude to exclude those obese subjects who can be subjected to conversion techniques and those with genuine hypertrophy of mammary glands or mammary hypertrophy to be re-established.
Both excessive and reduced testosterone production, as well as increased estrogen levels compared to testosterone, have been well associated with the onset and development of gynecomastia. Testosterone deficiency is one of the key factors that determine gynecomastia hormonal imbalance in an adult population. In physiological gynecomastia, such as pubertal gynecomastia and gynecomastia in the elderly, but also in pathological causes of gynecomastia, such as liver or kidney disease, there are common variable decreases in testosterone. Fluctuations in estrogen serum concentrations may give rise to clinical gynecomastia in isolated cases. In hypogonadal individuals, serum levels of estrogens may also be low, therefore giving low estrogen/androgen ratio in body tissues. However, this may mislead us because estrogen levels depend not only on the testosterone:estrogen ratio but also on peripheral aromatization. The relatively common clinical manifestations of pubertal gynecomastia, which is transient breast tissue growth found in boys, and gynecomastia hormonal imbalance in the elderly is seen among men with deviations in the balance between testosterone, estradiol, and estrogen. Antiandrogens, antihypertensive drugs, drugs used for treating cardiovascular conditions, and leading antineoplastic drugs disrupt normal hormonal regulation. Although these pharmaceutical agents have other primary indications, occasional reports of gynecomastia are associated with their usage. In addition, several drugs and prescribed medications, as well as environmental endocrine disruptors, have been recognized as a cause of gynecomastia hormonal imbalance development. The gradual onset of gynecomastia may be associated with significant changes in testosterone-to-estrogen ratios, caused by several factors, in which multifunctional treatments, including surgical therapies that block estrogen production or action, are required. Do hormonal changes really influence the development of gynecomastia so much?
Another important factor related to what causes male breast growth is obesity. Overweight and obese people were found to have higher levels of endogenous estrogens, since estrone can be synthesized in adipose tissues. Male breast enlargement causes are complex phenomena and the main etiology is idiopathic (about 75% of cases), but there are many cases where it can be related to other factors, justifying its multifactorial origin.
This disease is also related to the use of some medications; of particular note is spironolactone, which competitively inhibits androgens from binding to the androgen receptor and is also a potent inhibitor of the biosynthesis of dihydrotestosterone. Finasteride, a 5-alpha-reductase inhibitor, is used in men to delay puberty, reduce the size of the prostate, and assist them in differentiating their sexual organs. As a result, the gynecomastia risk factors exists, and this can be enough of a cause for them to escape diagnosis. Other drugs utilized but not universally deployed, such as verapamil, cimetidine, and amlodipine, are linked to male breast enlargement causes and, in theory, can be used for diagnostic purposes. Also, the use of illicit drugs like cannabis, heroin, amphetamines, and anabolic steroids could induce this disease. There is an association between inadequate diet in adolescence and the development of gynecomastia, particularly surplus caloric intake via sugar-rich and high estrogenic compounds in fast food chains. Gynecomastia can be associated with diseases such as hepatic cholestasis, cirrhosis, leukemia, renal failure, myopathies, malnutrition, and hyperthyroidism. Taken overall, gynecomastia is a multifactorial disorder and, for this reason, one that is hard to control both from a preventive and therapeutic standpoint. Moreover, it is also possible that a combination of genetic and exogenous factors could be the root of this phenomenon. Age and surgical approach are also indicated as potential gynecomastia risk factors for disease progression in the delay or failure of treatment. Conventional treatment strategies tend to focus merely on hormonal pharmacological therapies, surgery, and associated drugs.
The FTO gene was identified as contributing to the survival of adipose cells and consequently to their accumulation, and people with susceptibility gene variants may have a higher probability of getting gynecomastia caused by excessive fat mass accumulation. As many as 1 in 3 have excessive adipose cells. Predisposition for early breast development can also lead to more severe gynecomastia in susceptible young men. Several environmental activities can encourage harmful epigenetic changes in the chest, not to mention greater lifetime possibilities of getting cancer. Breast growth normally begins in boys between 10-12 years of age and persists for 1-2 years, and these days tends to be smaller, at an adult age, and to generally resolve without interventions at 16. Estrogen is essential as a puberty ‘muter’ since it halts bone-forming elements and triggers bone closure, which normally takes place in the chest 1 year after peri-puberty. In puberty, the prevailing condition is so thoroughly described and generally considered that it is of little therapeutic interest. Furthermore, benign pubertal gynecomastia for teenagers identified in various studies appears to be more of an enhancement than a problem. Only those teens troubled by gynecomastia as a result of puberty or those whose condition deteriorates after puberty should initiate gynecomastia therapy. For all others, a follow-up plan may be recommended, which offers support for patient anxiety and tracks enhancement.
A detailed history should be taken in patients with gynecomastia. The history should consist of drug, social, and life-style history, the duration of onset and progress of the breast swelling, social habits, and the degree of embarrassment and concern of the patient. Physical examination for gynecomastia includes inspection and palpation. It is also useful to assess the density of breast tissue and for making a potential carcinoma diagnosis. The diagnostic workup, mainly excludes the secondary causes of gynecomastia. Often a mild non-palpable, painless, and bilateral enlargement of the breasts is physiological, and reassurance suffices. In symptomatic cases or with palpable breast mass, mammogram or ultrasound scan can be done to exclude the cancer of the breast and also to distinguish the presence of glandular tissue from the fatty tissue of the breast. Available medical history could distinguish physiological gynecomastia from pathological gynecomastia. The higher the score of the patient in a checklist for pathological signs and symptoms, the greater the chance to have pathological gynecomastia. Diagnosis is based on available physical examination and/or imaging or laboratory tests. Treatment for Gynecomastia comes in the form of either surgical or non-surgical. Treatment can be conducted in symptomatic alleviation, alteration of appearance, or normalization of hormone levels.
For the majority of patients, clearly visible gynecomastia is the most important reason to seek help for their complaints. Especially for pubertal breast enlargement, lack of response to reassurance may be the main argument for surgery. In an individualized treatment plan, the underlying cause, potential gynecomastia risk factors, hormone levels, and the progression or involution of the breast swelling should be taken into account. This should be discussed with the patient. Optimal support and information about the options, limitations, gynecomastia risk factors, and benefits of treatment are important. Ongoing physician contact and support for this vulnerable group of patients are mandatory.
The management of male breast enlargement causes in patients is complex, and the available literature on the pathophysiology of gynecomastia to date has many gaps. Thus, the management of gynecomastia in patients is challenging, with no clear guidelines to help guide management decisions. With these gaps in knowledge about pathophysiological and associated mechanisms of gynecomastia, it is important to conduct longitudinal, post-treatment outcomes studies to examine the long-term effects of delaying specific treatment options. Furthermore, deformity assessment and post-gynecomastia reconstruction aesthetic studies have emphasized the lack of research on the psychosocial impact of gynecomastia on patients before and after surgery, and the extent of depression in gynecomastia cases needs further exploration in the social environment. Pathophysiological changes in gynecomastia are related to both depression and severity of disease.
The first is the emerging interest in the advantages of a multi-specialty approach by combining the knowledge of plastic surgeons and endocrinologists in relation to gynecomastia surgery and patient work-up. In our experience, combining this knowledge of hormonal abnormalities and artistic plastic surgery regarding body contouring with gynecomastia was a superb experience for creating a complete picture of the patient from both health and aesthetic perspectives. Second, persons with gynecomastia need to be evaluated in terms of the chronic pattern of physical, psychological, and social outcomes to develop a more multidimensional or “whole-person” approach in terms of understanding the potential impact. Third, there are many misconceptions and uncertainties regarding gynecomastia; therefore, it is absolutely necessary to utilize different resources to develop a comprehensive assessment of people with gynecomastia, encompassing self-selected individuals from different countries, languages, and cultures integrated with healthcare professionals. The patients’ points of view are evident when reviewing the comparisons. The core challenges for successful progress in these future directions are the heavy stigma and frequent lack of support and validation towards gynecomastia patients from the general public, which requires a coordinated multi-stakeholder effort to address.
