There are a number of drugs that cause gynecomastia. In order to understand how drugs, cause gynecomastia, were first must understand what gynecomastia is as well as the physiological process of how hormones are created.
Gynecomastia is the development of breasts in a male patient. Specifically, it is the growth of glandular tissues in the breast. Well, how do they get breasts? It is the same process on how females get breasts, by their dominant hormone estrogen. It is important to understand that both females and males carry both hormones, estrogen and testosterone. As you know, estrogen is dominant in females, giving the breast growth, pubic hair, and a menstruation cycle. In males the dominant hormone is testosterone, allowing for penile growth, muscle masculinization (growth), deepened voice, and facial/body hair. For some reason there is an imbalance of testosterone to estrogen ratio in males. Either testosterone is depleted and there is more estrogen, or estrogen is increased and there is less testosterone. Whatever the cause may be, there is more estrogen in the bloodstream causing gynecomastia to occur.
Now before we get to the type of drugs that can cause gynecomastia, it is important to understand the breakdown of how hormones response to each other as well as how they are produced and circulated throughout our blood vessels.
Our endocrine system is a system in our body that has a presence of a number of glands. The major role of all these glands is to work together to keep our hormones balanced. They do this by alerting each other if a certain hormone is low or if a certain hormone is high. Let’s talk about the male productive endocrine axis to get a better understanding. The master gland, also known as the hypothalamus, is an autoregulator. When it realizes a specific hormone is low it sends its own hormone to another gland to produce that specific hormone. In the same way, when it realizes a hormone is being produced too much, it stops producing that specific hormone that causes it to increase. In males, when the hypothalamus realizes that testosterone in males is low it sends out the GnRH hormone (gonadotropin-releasing hormone). The GnRH hormone then goes to the anterior pituitary gland which gets triggered to release the hormones FSH and LH. FSH and LH are then led to the testes of males which then triggers the production of testosterone.
Males testes have a specific cell that gets triggered by LH and FSH called the Leyid cell. This cell then produces testosterone and testosterone is spilt up into two major final hormones. These hormones are dihydrotestosterone and estradiol. Dihydrotestosterone is much more dominant than estradiol in males. Two specific enzymes are used to convert testosterone to its final products. 5-alpha-reductase is an enzyme that is the conversion of testosterone to dihydrotestosterone, and aromatase is the enzyme that helps it convert to estradiol. Finally, as you know, these hormones help produce a lot of our bodily functions and features, such as hair growth, breast growth, and etc, therefore, these hormones circulate the bloodstream by attaching to two specific protein to help their transportation. These proteins are sex hormone-binding globulin and albumin.
Now that we understand that process of how hormones regulate, how they are made, and how they are transported, we can now understand which drugs cause gynecomastia.
There are a number of drugs that can cause gynecomastia. From antibiotics to acne medication to pain killers and acid reflex medication, it is important to understand that when you are prescribed these drugs to make sure you get an accurate explanation for its side effects. Some type of antiandrogen drugs is finasteride, spironolactone, ketoconazole; examples of antibiotics are isoniazid (typically used for tuberculosis), Antiulcer drugs or drugs used for GERD like omeprazole can also cause Gynecomastia. Drugs that are used to depression and seizures can also cause gynecomastia such as tricyclic antidepressant drugs and atypical antipsychotics. There is also a number of abusive drugs that can lead to gynecomastia, such as alcohol, amphetamines, heroin, marijuana, and methadone.
Let’s talk about finasteride. Finasteride is a drug that can be prescribed for male pattern baldness or benign prostate hyperplasia also known as BPH. Both are caused by an increase of dihydrotestosterone. As I mentioned above, dihydrotestosterone is converted from testosterone from a specific enzyme called 5-alpha-reductase. Finasteride is a 5-alpha-reductase blocker. It attaches to the enzyme and prevents the conversion of testosterone to dihydrotestosterone. Therefore, we have a decrease in dihydrotestosterone and a stable increase of estrogen production leading to an imbalance of the testosterone to estrogen ratio which can lead to gynecomastia.
Another type of drug that can cause gynecomastia is spironolactone. Spironolactone is an antiandrogen drug. It specifically goes to androgen receptors, where testosterone and dihydrotestosterone like to attach to and react. Specifically, dihydrotestosterone during puberty ages can cause acne. When the route cause is found that dihydrotestosterone is causing the acne Spironolactone can be prescribed. It is important to understand that when you take this medication just like almost all medications, that it targets the entire body and just not where you are having acne. Also, spironolactone causes an increase of aromatase, the enzyme that converts testosterone to estrogen. Therefore, all of your androgen receptors throughout your body end up being blocked as well as an increase of estrogen leads to an imbalance ratio of testosterone to estrogen.
Some antiseizure medications cause an increase in sex hormone-binding globulin (SHBG). SHBG is known to have a higher affinity or a higher attraction, to binding to androgen hormones, which is our testosterone and dihydrotestosterone hormones. When our body has substances bounded to each other they are considered inactive and do not perform the functional duties. Therefore, we might have normal values of testosterone, but it is important to check the value of SHBG as well as free testosterone, the testosterone that is not bounded to a protein, which would be low because of other the other testosterone is bounded to SHBG.
In sum, there are a number of drugs that can caused gynecomastia which all have different roots of causing the condition. These drugs range from your over-the-counter anti-reflux drugs like cimetidine (Histamine blocker) to drugs like diazepam that are used for severe anxiety and psychotic behaviors. It is vastly important to understand what drugs you take and always contact your healthcare provider for any questions you may have.