Antiandrogen Drugs / Testosterone Blocker Pills For Transgender
Androgens are hormones that control the development of secondary sex characteristics. People born with male sex characteristics typically have high androgen levels, while people born with female features have low androgen levels, and they have high estrogen levels. Androgens may be called “male hormones, and the principal ones include testosterone and androstenedione.
Anti-androgen pills work by either blocking the production or functioning of androgens, like testosterone. They do this by binding to specific proteins in the body called “androgen receptors.” They bind to these receptors in order to prevent androgens from doing so.
There are a variety of anti-androgens forms, including pills, injections, and subdermal implants. Typically, they are administered with other drugs or during certain surgical procedures. The following are some of the most commonly used antiandrogens or testosterone blockers on the market.
Testosterone Blocker Drugs
Testosterone blockers, also known as antiandrogens or androgen antagonists, are a class of medicines that inhibit the regulation of biological effects in the body by androgens such as testosterone and dihydrotestosterone (DHT). Antiandrogens include medications that inhibit testosterone production, block androgen receptors or prevent testosterone conversion to its more active form, dihydrotestosterone.
Several medications have antiandrogenic effects. Some have been specifically designed for this purpose, but others have been created for another therapeutic purpose. For example, an antifungal drug “ketoconazole”, blocks steroid synthesis, including cortisol and testosterone. In addition to several other applications, most antiandrogens are also used as puberty blockers in transgender girls and by transgender women as a part of feminizing hormone therapy.
Some of the effective antiandrogens currently being used as a part of transgender feminizing therapy. Most of them are not approved by the FDA yet and prescribed only in certain countries for specific treatments.
These Testosterone Blocker Drugs include;
Spironolactone (Antiandrogen Drug)
Spironolactone (or also known as “spiro” or “Aldactone”) is the most common anti-androgenic hormone used in the United States. It is a potassium-sparing drug used to treat various body conditions such as heart failure, liver disease, and high blood pressure. Nevertheless, as it has testosterone-blocking effects, it has also been considered useful for seborrhea, hirsutism, and acne.
Scientific studies and clinical trials suggest that spironolactone is one of the safest and most effective ways to lower testosterone levels. A recent study concluded that MTF transgender people who are using this drug for more than six months had reported positive effects in terms of physical appearance and sexual changes. Since it is a diuretic (water pill), the use of spironolactone as an anti-androgen may require frequent urination by some transgender women.
Cyproterone Acetate (Antiandrogen Drug)
Cyproterone acetate is widely used as anti-androgenic for transgender women in Europe. Some research and statistical data suggest that it is more effective than spironolactone when it comes to reducing testosterone levels. It may also improve transgender women’s breast development. Some studies also suggest the combined use of both spironolactone and cyproterone acetate for greater safety and efficacy.
Cyproterone acetate, however, is not certified to be used in the United States. It is not approved by the FDA because the drug is associated with an increase in metabolic liver disease and the possibility of liver cancer. Cyproterone acetate may also cause other adverse health effects by decreasing HDL cholesterol and increasing the production of prolactin (a hormone that helps produce breast milk).
Finasteride and Dutasteride (Antiandrogen Drug)
Finasteride and dutasteride are the testosterone blocker pills that fall in the category of 5-alpha reductase inhibitors. They block type two and three 5-alpha reductase mediated testosterone conversion to its more potent form called androgen dihydrotestosterone. Dutasteride more efficiently blocks the type 1 isozyme of testosterone that is present in the pilosebaceous system and may, therefore, have more dramatic feminizing effects. Because these drugs do not inhibit and block testosterone production or action, their testosterone-blocking effect is lower than that experienced with spironolactone or cyproterone acetate.
5-alpha reductase inhibitors may be the right choice for those unable to tolerate spironolactone. They may also be an alternative option for use as a single agent in transgender people seeking partial feminization, or for those who tend to show virilized characteristics or other complications such as hair loss following orchiectomy or total androgen blockade.
Progestogens (Antiandrogen Drug)
Well-designed studies have not proved the role of progestogen pills in feminizing hormone regimens. Many transgender women and providers report improved breast and areolar development, mood, or libido with the use of progestogens. Clinical trials provide no evidence that the use of progestogens in transgender care is harmful. In reality, some patients may respond well to progestogens, while others may experience adverse mood effects. While progestogens do have some anti-androgen effect through the central gonadotropin blockage, there is also a theoretical possibility of progestogens having a direct androgenizing effect.
Transgender women may experience tenderness of the breast with these changes in testosterone. Drop-in blood pressure, high potassium, and excessive urination are the most common side effects. Your provider will monitor your levels of potassium. If this drug is not well tolerated, consult your physician or provider for better alternatives.
Histrelin (Antiandrogen Drug)
Histrelin is an agonist of gonadotropin-releasing hormone (GnRH), which is used as a puberty blocker for transgender teenagers. It is available in various forms, including an implant (supprelin) that can last up to a year. Since histrelin is an effective way to reduce the production of testosterone, it is sometimes also used as part of feminizing hormone therapy.
Histrelin and its analogs are used less often as a testosterone blocker for MTF transgender adults after puberty, but they are an option. Similar to other testosterone blockers, histrelin/supprelin can cause some side effects, including mood swings, headache, irritation at the implant site (redness, bruising, pain), and hot flashes (flushing).
Megestrol Acetate (Antiandrogen Drugs)
Megestrol acetate is a well-known antiandrogen that is commonly used as an appetite stimulant to facilitate weight gain in a number of situations. If given at high doses, megestrol can act similar to a natural substance produced by the body called progesterone and inhibits steroid production, like testosterone and other androgens. Nevertheless, studies and clinical trials have shown that it only causes detectable androgenic effects in animals at a dose that is approximately 200 times the amount that is usually used in men to treat prostate cancer. According to a study, the most observable clinical sign of feminization caused by megestrol acetate is the development of breasts. At high doses, it may also cause other feminizing effects such as reduced muscle mass and deepening of the voice.
The most common side effect of megestrol acetate is weight gain, with an occurrence of 15 to 70 percent. Other common side effects include nausea, vomiting, diarrhea, altered bowel movements, skin rash and trouble sleeping (insomnia).
Oxendolone (Antiandrogen Drugs)
Oxendolone is a synthetic progestogen that was primarily designed to treat benign prostatic hypertrophy. Currently, this antiandrogen and progestin medication is used in Japan as a treatment option of an enlarged prostate. It works by inhibiting the androgen receptors and thus block the attachment and resultant effect of androgens like testosterone. Some studies also suggest that it may also block 5-alpha reductase mediated conversion of inactive testosterone to its active and potent form – dihydrotestosterone.
Because oxendolone does not inhibit the production of testosterone, its antiandrogen effect is lower than that observed with total blockage. Synthetic progestogens may be a good choice for people who are unable to tolerate spironolactone or other potent antiandrogens. These are also a safe and effective option for use as a single antiandrogen agent in transgenders seeking partial feminization, or for those who continue to have hair loss or other virilized features following full androgen blockage. Oxendolone is ineffective when taken by mouth and must be delivered by intramuscular injection.
There is a little clinical evidence of oxendolone use for full feminization and its evidence of safety or efficacy is also limited. Furthermore, caution is advised when administering oxendolone to transgender people, as it may cause side effects such as anxiety, depression, and suicidal ideation – symptoms that are common in the transgender population.
Chlormadinone acetate (CMA) (Antiandrogen Drugs)
Chlormadinone acetate is also a synthetic progestin with antiandrogen effects. It is usually mixed with other birth control pills to prevent pregnancy. Besides its common use, this anti-androgen agent is also used in conjunction with estrogen as a hormonal treatment of transgender women. Studies suggest that it enables feminization to occur by inhibiting the effects of testosterone. Cyproterone acetate (CPA) is an anti-androgenic agent widely used in European and Canadian feminizing hormone therapy.
Studies have found that when used in combination with prescribed estrogen therapy in transgender women, 25 mg of chlormadinone acetate per day is effective in reducing testosterone levels to the normal female range. However, it has not yet been studied for specific feminization effects such as breast development, reduced muscle mass or thinning of hair.
Flutamide (Antiandrogen Drugs)
Flutamide is a non-steroidal antiandrogen used mainly as a prescription drug in the treatment of androgen-dependent disorders such as acne, premature hair growth and feminizing hormone therapy. Flutamide functions as a potent androgen receptor (AR) antagonist. It competes with androgens such as dihydrotestosterone and testosterone for binding to androgen receptors in tissues such as the prostate gland. This prevents their effects and blocks them from stimulating secondary male characteristics. Flutamide is a more active form of medicine. It remains in the body for a relatively short time – this is the reason why transgender people have to take flutamide multiple times a day.
Because of evidence of hepatotoxicity in men with prostate cancer, the use of flutamide for feminization purposes is discouraged in cisgender women with androgen-dependent dermatological conditions.
Bicalutamide (Antiandrogen Drugs)
Bicalutamide is one of the strongest anti-androgen that is primarily used to treat prostate cancer and prostate enlargement secondary to prostate hyperplasia. It is typically used in conjunction with gonadotropin-releasing hormone (GnRH) analog or surgical intervention to produce feminizing effects. Bicalutamide works by blocking the androgen receptors – on which biological hormones such as testosterone and dihydrotestosterone act and produce effects.
It does not reduce androgen levels and also has a significant but not completely quantified risk of liver function disorders (including fulminant hepatitis). Multiple scientific studies and clinical trials have shown that the risks are appropriate when considering the benefits of bicalutamide in inducing secondary feminizing characteristics. Bicalutamide, when prescribed in higher doses, can cause thinning of hair and deepening of voice after a treatment course of several weeks to months. However, these are the side effects associated with bicalutamide that limit its use – including hot flashes, breast swelling/tenderness/pain, drowsiness, or dizziness and weight changes.
Nilutamide (Antiandrogen Drugs)
Nilutamide is a nonsteroidal antiandrogen (NSAA) used to treat acne and seborrhea in women and as a part of feminizing hormone therapy in transgender people. Nilutamide functions as a potent androgen receptor antagonist and blocks the body’s production of androgen hormones such as testosterone and DHT.
To asses its feminizing effects, nilutamide has been tested in at least five small clinical studies in treatment-naive subjects. In these studies, 300 mg/day nilutamide monotherapy has been shown to induce measurable signs of feminization in young transgender women within 8 weeks. The major feminizing effects include decreased body hair (although not facial hair), breast development, reduce sexual desire, decreased morning erections, and positive emotional changes.
Within 6 weeks, signs of breast development and enlargement occurred in all subjects and were associated with increased sensitivity to the nipple. Decreased hair growth was also the prominent sign of feminization along with the thinning of hair.
Toplutamide (Antiandrogen Drugs)
Topilutamide, more commonly referred to as fluidic, is another non-steroidal testosterone blocker used in the treatment of male and female pattern hair loss. Topilutamide does not prevent or inhibit the production of androgen hormones in the body (i.e. It does have potent antigonadotropin properties). Therefore, it is only known to mediate its antiandrogenic effects by inhibiting the androgen receptors.
The introduction of ethinylestradiol to tolbutamide treatment is linked to reduced production of LH, estradiol, and testosterone. It also significantly decreases testosterone levels within the normal female range. Nilutamide alone and the combination of estrogen and nilutamide are considered to result in efficient and beneficial antiandrogen activity and stimulation of secondary feminization in transgender women.
Enzalutamide (Antiandrogen Drugs)
Just like nilutamide and toplutamide, enzalutamide is also a non-steroidal antiandrogen that blocks the action of testosterone in certain body tissues. These testosterone blocker pills are indicated for use in the treatment of MTF transition in conjunction with orchiectomy (castration). It mainly works by blocking the activation of androgen receptors that further inhibits the synthesis of proteins involved in muscle growth, bone mineral density, and lean body mass.
Clinical data suggest that the most promising effect of enzalutamide in the development of breast in transgender women. It also causes some other changes in the MTF transgender people such as reduced hair growth and thinning of hair. However, its use as a component of feminization hormone therapy is not well-recognized due to a list of side effects caused by it – including some serious ones such as fulminant hepatitis and risk of liver cancer.
Apalutamide (Antiandrogen Drugs)
It is structurally and pharmacologically similar to the second-generation non-steroidal antiandrogens (NSAAs) such as enzalutamide and toplutamide. However, it has some benefits over them – including higher antiandrogenic activity and multiple-fold reduced distribution in the central nervous system. This latter distinction can minimize its comparative risk of both mild and severe side effects of NSAAs such as seizures. When used as a high-dose monotherapy, apalutamide shows a slightly lower efficacy compared to GnRH analogs and other second-generation non-steroidal antiandrogens in the induction of secondary feminization in transgender females.
Although similar to enzalutamide, it carries a reduced risk of liver side effects (fulminant hepatitis and liver cancer) due to its reduced distribution in the central nervous system. Studies have shown that the risk of other significant side effects is also expected to be lower than other NSAAs.
What are the side effects of Antiandrogen Drugs?
Depending on the dose and type you take, anti-androgens can cause a variety of side effects. Some prominent ones include:
- reduced facial and body hair
- low sex drive
- elevated liver enzymes
- increased risk of depression
- liver injury
- breast pain and tenderness
- hot flashes
- skin rash
- resistance against anti-androgens – meaning the medication stops working
The intensity of side effects can be different for different people. Your doctor or provider can help you choose the right type and dosage of an anti-androgen that comes with the fewest side effects.
Conclusion about Antiandrogen Drugs
Anti-androgens are the group of drugs that bind with androgen receptors and either stop the production or inhibit the functioning of androgens, especially testosterone. The two most widely used anti-androgen pills include spironolactone and cyproterone acetate. Depending on genetics, age, and other factors, testosterone blockers may work differently for each person.
Consider the effects of anti-androgen hormone therapy as a second puberty, and for full effects to be seen, puberty usually takes several years. Taking higher doses of testosterone blocker pills may not necessarily lead to faster changes, but it may put your health at risk. And because everyone is unique, your prescriptions or dosages will vary greatly from those of your family, or from what you might have read in books.