by Anaïs Di Via Ioschpe, Itay Wiser
It should come as no surprise that anabolic steroids, which are known to improve athletic performance, have numerous negative side effects. This article will unravel the mysteries that link this drug to gynecomastia, a condition characterized by increased male breast size.
Gynecomastia is physiologically normal during three time periods in a male’s lifetime: as a baby, during puberty, and after around 65 years old. There are many reasons why it may happen outside of these time periods, yet the mechanism of how breast tissue develops is a complex interaction of hormones. One of the key hormones that play a large role in developing gynecomastia is estrogen.
Estrogen levels dictate a cascade of events that lead to the development of breast tissue in both men and women. In men, decreased testosterone levels can cause an elevation in the estrogen-to-androgen ratio, thereby producing gynecomastia. On the other hand, increased testosterone can be converted to estrogen by the enzyme aromatase, also leading to gynecomastia. This highlights the complexity of the topic at hand.
About 20% of gynecomastia is drug-induced. Some drugs may increase estrogen levels in the body by several mechanisms: 1) They have properties that are similar to estrogen, 2) They cause the body to make more estrogen, or 3) They give the body too much of an estrogen precursor (like testosterone or androstenedione) that can be turned into estrogen.
Anabolic-androgenic Steroids (AAS) include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects to testosterone. They have been heavily reported to cause the side effect of gynecomastia due to excess testosterone being converted into estrogen by the enzyme aromatase.
There are three major classes of AAS: oral, oil-based injectables, and injectable water-based agents.
Male breast reduction for the treatment of gynecomastia has risen by 181% from 1997 to 2016
The reported mean age at the time of first AAS use is 24 years (range, 16–39 years)
The mean duration of AAS use (1 month to 12 years) and the number of AAS cycles (mean, 2.7; range, 1–16)
The most commonly used androgens reported are single or mixed testosterone esters (eg, Testaviron, Sustanon 250, Depo-T, Virormone, Andriol), nandrolone deconate (Deca-Durabolin), stanozolol (Winstrol), methandrostenolone (Dianabol), and oxandrolone (Anadrol)
There is more than a 50% chance that gynecomastia will return following breast reduction surgery if AAS is continued
Even with various cycling strategies and use of post-cycle therapy agents to combat hormone imbalance, many AAS users continued to experience persistent gynecomastia
AAS users are at higher risk of surgical bleeding complications
Other risks of using anabolic steroids
Testosterone Replacement Therapy (TRT) refers to androgen supplements for people that suffer from testosterone deficiency, commonly due to genetics and aging. TRT treatment can lead to gynecomastia through its aromatization to estradiol. Some sources suggest that this is a rare side effect and possibly reversible.
The benefits and risks of TRT are largely age-based. Testosterone produces substantial anabolic effects in young and middle-aged hypogonadal men, yet inconsistent results in older men. Hypogonadal men are those who are symptomatic and have a serum testosterone concentration below 200 ng/dL.
The major methods of taking TRT are: oil-based injectables, transdermal, buccal, and oral testosterone.
Testosterone supplementation in the United States has increased substantially over the past several years, with an increase of more than 500 % in prescription sales of testosterone products since 1993.
There is a lack of evidence on the dose-response relationship of TRT and its side effects.
One study reports that gynecomastia was the most common side effect reported in young hypogonadal thalassemic men that are taking TRT. 43.1% experienced mild to moderate gynecomastia. None of the patients received aromatase inhibitor therapy
Gynecomastia does not need to be treated unless it causes physical or psychological distress. In this case, the following reasons may warrant a consultation at the WiserMD clinic:
What does gynecomastia treatment entail? This is something that consultation with WiserMD will cover in great detail after a discussion of your medication history and evaluation with a physical exam and laboratory tests. The mainstay of treatment is discontinuing contributing medications, treating the underlying disease, and making lifestyle changes. In some cases, medications and surgery can help treat gynecomastia.
Medication options include androgens (testosterone, dihydrotestosterone, danazol), anti-estrogens (clomiphene citrate, tamoxifen), and aromatase inhibitors such as letrozole and anastrozole. One study suggests that 20 mg of tamoxifen daily will block the breast estrogen receptors and stimulate hormonal recovery for patients with AAS-induced hypogonadism. After 4 weeks of medical treatment, repeated hormone panels should be obtained.
Longer duration of symptoms, higher-grade disease, or inability to tolerate medications may prompt surgery as a first-line option. Surgical options include liposuction, a procedure that removes breast tissue via a small incision site.
Obesity is another common cause of gynecomastia (pseudogynecomastia). It is caused by excess fat that converts naturally occurring testosterone and androgens into estrogen.
Cannabis use is also linked to gynecomastia. Crude marijuana extracts interfere with estrogen receptors, suggesting that marijuana-associated gynecomastia may reflect the presence of plant estrogens.
Hypothyroidism. Gynecomastia occurs in 10- 40% of men with hyperthyroidism, although it is rarely the only symptom at presentation
Liver Cirrhosis. Cirrhosis is linked to a higher level of SHBG, a protein that binds testosterone more strongly than estrogen, lowering the ratio of androgens to estrogens.
Tumor. Although testicular tumors are rare, approximately 10% of people with testicular tumors present with gynecomastia alone.
Borst SE, Mulligan T. Testosterone replacement therapy for older men. Clin Interv Aging. 2007;2(4):561-6. doi: 10.2147/cia.s1609. PMID: 18225456; PMCID: PMC2686341.
Corona, Giovanni, et al. “Consequences of Anabolic-Androgenic Steroid Abuse in Males; Sexual and Reproductive Perspective.” The World Journal of Men's Health, vol. 40, no. 2, 2022, p. 165., https://doi.org/10.5534/wjmh.210021.
De Sanctis V, Soliman AT, Daar S, Di Maio S. Adverse events during testosterone replacement therapy in 95 young hypogonadal thalassemic men. Acta Biomed. 2019 May 23;90(2):228-232. doi: 10.23750/abm.v90i2.8477. PMID: 31125000; PMCID: PMC6776204.
Dickson G. “Gynecomastia.” Am Fam Physician. 2012 Apr 1;85(7):716-22. PMID: 22534349.
Eckman A, Dobs A. Drug-induced gynecomastia. Expert Opin Drug Saf. 2008 Nov;7(6):691-702. doi: 10.1517/14740330802442382. PMID: 18983216.
Maseroli, E., et al. “Gynecomastia in Subjects with Sexual Dysfunction.” Journal of Endocrinological Investigation, vol. 37, no. 6, 2014, pp. 525–532., https://doi.org/10.1007/s40618-014-0055-z.
Ng, Jason C. M., and Ronald S. Swerdloff. “Gynecomastia.” Male Reproductive Dysfunction, 2007, pp. 519–528., https://doi.org/10.3109/9781420018813-48.
Rahnema CD, Lipshultz LI, Crosnoe LE, Kovac JR, Kim ED. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014 May;101(5):1271-9. doi: 10.1016/j.fertnstert.2014.02.002. Epub 2014 Mar 14. PMID: 24636400.
Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med. 2004 Jan 29;350(5):482-92. doi: 10.1056/NEJMra022251. PMID: 14749457.
Vojvodic, Miliana, et al. “Anabolic-Androgenic Steroid Use among Gynecomastia Patients.” Annals of Plastic Surgery, vol. 83, no. 3, 2019, pp. 258–263., https://doi.org/10.1097/sap.0000000000001850.