5 Major Causes of Gynecomastia

Gynecomastia in Neonates and Adolescence

Gynecomastia in Neonates and Adolescence are two of the more common causes of non-obesity and non-medication-related gynecomastia. In the earlier years of life, gynecomastia commonly presents in male neonates as a consequence of the mother’s naturally elevated estrogen hormone levels whose effects are passed on to the baby via the placenta and breastfeeding 1. This is classically known as “ witches milk”, and normally resides after a few weeks when the mother’s hormone levels begin to normalize following childbirth. Likewise, gynecomastia is common during adolescence and is attributed to the natural elevation of male hormones, which, ironically, leads to increased production of the female hormone estrogen, a common culprit of gynecomastia.

Beyond these changes which are typically attributed to normal physiology and puberty, there are four additional major causes of gynecomastia. These include testosterone replacement therapy, side effects from the treatment of prostate cancer, the use anabolic steroids, and obesity.

Testosterone Replacement Therapy

Testosterone replacement therapy (TRT) has become more common as health professionals begin to recognize the prevalence of andropause in the aging male. Andropause in men is analogous to the menopause in women; however, in andropause, men begin to produce less and less testosterone, not estrogen, over time 2. Reduced physiologic levels of testosterone lead to many clinical changes in the male, including erectile dysfunction, reduced libido, fatigue, loss of muscle mass, and even obesity. To combat the naturally decreasing levels of testosterone with age, following thorough clinical workups by physicians trained in endocrinologic medicine, men with abnormally low levels of testosterone may be candidates to receive testosterone supplementation – these testosterone supplements are most commonly administered in the form of injections, pellets, patches, or gels – the goal being to normalize testosterone levels and decrease symptoms of andropause. Unfortunately, this artificial surge of male hormones can lead to unwanted side effects, one of them being gynecomastia. In men, testosterone from TRT is generally converted to its active form by the body. However, excess free testosterone can inadvertently be converted into estrogen. This indirect estrogen increase can stimulate the growth of glandular breast tissue, leading to growth and the formation of male breasts or gynecomastia.

Prostate Cancer Treatment

Gynecomastia is a common side-effect seen with prostate cancer treatment. Because testosterone can stimulate the proliferation of prostate cancer cells, men with prostate cancer often undergo Androgen Deprivation Therapy (ADT), a treatment that decreases the production and physiological effects of testosterone 3. Common drugs used for androgen deprivation therapy include the LHRH ( leutenizing hormone-releasing hormones ) family of drugs including Leuprolide, Goserelin, Triptorelin, and Histrelin. This therapy can lead to an imbalance of estrogen and testosterone, with estrogen progressively becoming the dominant hormone. In these clinical scenarios, estrogen accumulates and begins to stimulate the development of breast tissue, thereby leading to gynecomastia. This adverse effect is a common concern for this patient population. In fact, studies indicated that up to 70% of men undergoing ADT are affected by gynecomastia and require medications to inhibit estrogen formation 3. In cases where medications are not successful at reversing the gynecomastia secondary to ADT therapy, these men often resort to surgery to permanently correct the gynecomastia.

Misuse of Anabolic Steroids

Anabolic steroids are synthetic variations of testosterone. These products are very popular in the competitive athletic arena, and are typically misused by male weightlifters, bodybuilders, and professional athletes in their 20s and 30s because they stimulate muscle growth at a remarkable rate. However, the consistent misuse of anabolic steroids can also lead to gynecomastia. This association is more complex and nuanced than that of TRT and ADT. In short, the excess introduction of synthetic testosterone leads to a hormonal imbalance in the body. In turn, excess testosterone is converted to estrogen through normal physiologic processes, increasing the systemic concentration of estrogen beyond normal levels. In addition, anabolic steroids promote the growth of not only muscle tissue but also glandular breast tissue 4. Coupled together, these effects enhance breast tissue overgrowth and lead to gynecomastia. Interestingly, seasoned bodybuilders often take estrogen blockers such as Arimidex, to decrease the likelihood of developing gynecomastia. This treatment too, comes with risk, as the male body is not designed to function with critically low levels of estrogen – one reason being that estradiol has several protective functions for men in the normal physiologic setting.

Obesity

Obesity in men can both predispose and exacerbate the presence of gynecomastia. The mechanism linking obesity to gynecomastia is a complex one and still not fully understood. It is theorized that excess body fat can lead to a hormonal imbalance that increases estrogen and decreases testosterone, thereby promoting the growth of glandular breast tissue 5. Moreover, excess fat in men has a tendency to accumulate in breast tissue, thereby accentuating its size. This is known as pseudogynecomatia. With this in mind, it is important to note that obesity is not equivalent to gynecomastia. Occasionally, weight loss can reduce fat concentrations and reduce breast size in obese men. However, most cases of true gynecomastia cannot be resolved with weight loss alone. In fact, weight loss can make gynecomastia seem more prominent. This is because weight loss does not directly decrease the size of male glandular breast tissue, but instead reduces fat concentrations. Therefore, men with gynecomastia still have prominent breasts containing overgrown glandular breast tissue, even if they are not surrounded by excess fat.

References:

1. Dickson GMDMBA. Gynecomastia. AM FAM PHYSICIAN. 2012;85(7):716-722.
2. Rhoden EL, Morgentaler A. Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole. International Journal of Impotence Research. 2004;16(1):95-97.
3. Fagerlund A, Cormio L, Palangi L, et al. Gynecomastia in Patients with Prostate Cancer: A Systematic Review. PloS one. 2015;10(8):e0136094-e0136094.
4. Calzada L, Torres-Calleja J, Martinez JM, Pedrón N. Measurement of androgen and estrogen receptors in breast tissue from subjects with anabolic steroid-dependent gynecomastia. Life Sciences. 2001;69(13):1465-1469.
5. Rosen H, Webb ML, Divasta AD, et al. Adolescent gynecomastia: Not only an obesity issue. Ann Plast Surg. 2010;64(5):688-690.