Anti-Androgens in Feminizing Hormone Therapy (Puberty Blockers)

While Estradiol promotes the development of feminine secondary sex characteristics, it does not fully suppress testosterone in most transfeminine individuals, especially early in treatment. For this reason, feminizing hormone therapy often includes an anti-androgen, also known as a testosterone blocker, to reduce or counteract the effects of endogenous testosterone. Anti-androgens reduce or block the effects of testosterone, which slows or stops masculinization and allows Estradiol to do its job more effectively.

Effects of Anti-Androgens

By blocking testosterone or reducing its levels, anti-androgens:

  • Drop testosterone levels closer to the female physiological range
  • Or block testosterone receptors entirely
  • Slow or stop facial/body hair growth (or prevent it from getting thicker/coarser)
  • Reduce acne and oily skin
  • Lower libido and spontaneous erections
  • Reduce testicular size and sperm production
  • Can soften muscle tone slightly (testosterone supports lean muscle mass)

Changes in Hair Growth

Anti-androgens (like Spironolactone) do not truly decrease existing body or facial hair in most cases — at least not dramatically. Instead, they mostly:

  • Slow the rate of new hair growth
  • Prevent new terminal (thick, coarse) hair from developing
  • Partially reverse recent androgen-driven changes (if caught early)
  • Soften or thin existing hair very slightly over time

For most transfeminine people:

  • Facial hair may become a bit finer or lighter, but usually persists without electrolysis or laser
  • Body hair (arms, legs, chest, etc.) often grows more slowly, and may lighten or thin over time — particularly on estrogen plus a blocker
  • Scalp hair may improve (especially if taking finasteride or dutasteride), but regrowth varies

Two of the most commonly used anti-androgens in transfeminine HRT are Spironolactone and Bicalutamide, though other medications like cyproterone acetate are used in some countries.

Spironolactone

Spironolactone is a potassium-sparing diuretic originally developed to treat conditions such as high blood pressure, heart failure, and edema. It is also classified as an anti-androgen, as it competes with androgens (including testosterone) for receptor sites in the body and reduces testosterone production by inhibiting enzymes involved in androgen synthesis. Essentially, most of the effect of Spironolactone is not necessarily the decrease in testosterone, but the affection of the hormone receptors.

In transfeminine hormone therapy, Spironolactone is used off-label to reduce the masculinizing effects of testosterone, such as facial and body hair growth, acne, and muscle mass maintenance. It is most often prescribed in conjunction with Estradiol.

Safety Profile

Spironolactone is generally considered safe and well-tolerated when appropriately dosed and monitored. However, its diuretic and potassium-sparing properties can pose certain risks, particularly if not regularly assessed.

The most notable risks include:

  • Hyperkalemia (elevated potassium levels), which can lead to serious cardiac complications
  • Hypotension (low blood pressure), especially in individuals who are dehydrated or on other blood pressure medications
  • Electrolyte imbalance, requiring periodic blood testing
  • Dehydration, due to increased urination

For these reasons, regular monitoring of serum electrolytes (especially potassium) and renal function is recommended every 3–6 months during therapy.

Research and Clinical Use

Spironolactone is the most commonly prescribed anti-androgen in transfeminine HRT in the United States. Although its use is off-label for gender-affirming care, it is included in clinical practice guidelines from leading transgender health organizations (e.g., WPATH, Endocrine Society).

Convenience and Considerations

Spironolactone is an oral medication, making it highly convenient and accessible for most individuals. It is widely available and generally affordable.

However, individuals must be prepared for:

  • Frequent urination, particularly in the first weeks of use
  • The need for regular bloodwork
  • Potential dietary considerations (e.g., avoiding high-potassium foods in some cases)
  • Possible interactions with other medications that affect renal function or blood pressure

Because Spironolactone can interfere with testosterone signaling without eliminating testosterone itself, some individuals may experience emotional or libido-related side effects more significantly than with other blockers or surgical options.

Potential Side Effects

Common side effects associated with Spironolactone include:

  • Increased urination
  • Fatigue or dizziness (particularly upon standing)
  • Breast tenderness
  • Reduced libido and erectile function
  • Dry skin
  • Gastrointestinal discomfort

More rarely, individuals may experience mood changes, menstrual-like cramping, or gynecomastia, though the latter may be desirable in a feminizing context.

Dosing Protocols

Spironolactone dosing for transfeminine individuals typically ranges from:

  • 100–200 mg daily, usually divided into two doses (e.g., 100 mg in the morning and 100 mg at night)

Higher doses (up to 300 mg/day) may be used in some cases, though the benefits beyond 200 mg/day are unclear and the risk of side effects increases. Dose adjustments are made based on serum testosterone levels, side effect profile, and electrolyte balance.

It is not uncommon for individuals to reduce or discontinue Spironolactone after a year or more on estradiol, once testosterone levels are sufficiently suppressed by estrogen alone, or after gonadectomy (orchiectomy).

Bicalutamide

Bicalutamide is a non-steroidal anti-androgen that is used off-label in feminizing hormone therapy to reduce the effects of testosterone. Originally developed and approved for use in the treatment of prostate cancer, it is most commonly prescribed under the brand name Casodex.

Unlike Spironolactone, which has multiple actions (diuretic, anti-mineralocorticoid, and anti-androgen), Bicalutamide is a pure androgen receptor blocker. It does not lower testosterone levels directly but blocks testosterone from activating its receptors throughout the body. Because of this, testosterone may remain high in the bloodstream, but its masculinizing effects are significantly reduced at the tissue level.

This receptor-specific mechanism gives Bicalutamide a more targeted anti-androgenic effect with potentially fewer systemic side effects compared to agents that affect hormone production more broadly.

Safety Profile

Bicalutamide is generally well tolerated when used at low doses in otherwise healthy adults. However, its primary safety concern is liver toxicity. Though rare, cases of elevated liver enzymes and liver failure have been documented, particularly at higher doses or with long-term use in other populations.

For this reason, liver function tests (LFTs) should be performed before beginning Bicalutamide, and then every 3 to 6 months thereafter during continued use. Other side effects may include fatigue, nausea, breast tenderness, or mild mood changes. Bicalutamide does not affect Potassium levels or cause diuresis.

Research and Clinical Use

There is limited research on Bicalutamide in transfeminine individuals, especially compared to Spironolactone or Cyproterone Acetate. Most studies involving bicalutamide focus on its use in prostate cancer or in cisgender women with androgen excess, such as in polycystic ovarian syndrome (PCOS).

Anecdotal and clinical reports in trans communities suggest that bicalutamide:

  • Is well tolerated at low doses
  • May result in more noticeable breast development in some cases
  • Is effective at reducing the impact of testosterone when combined with Estradiol

However, long-term data specific to transfeminine populations is lacking, and liver safety remains an open question for extended use.

Convenience and Considerations

Bicalutamide is taken once daily as a pill and is generally well tolerated. Because it does not require potassium or blood pressure monitoring, it can be a more convenient option for some people. However, liver monitoring is essential, and the need for off-label prescribing may limit access depending on the clinician or region.

Its stability in the bloodstream and lack of dose titration also make it relatively easy to manage once an appropriate starting dose is chosen.

Potential Side Effects

Most common:

  • Breast tenderness
  • Fatigue or drowsiness
  • Headache
  • Gastrointestinal discomfort (rare)

Less common but serious:

  • Elevated liver enzymes
  • Jaundice or signs of liver damage (seek immediate medical attention)

Unlike Spironolactone, Bicalutamide does not cause frequent urination, dehydration, or changes in blood pressure.

Dosing Protocols

Dosing for transfeminine individuals typically ranges from:

  • 25–50 mg daily, once a day (due to its long half life)

It is generally not titrated up beyond this range, as higher doses significantly increase the risk of liver toxicity without proportional benefit.

Because it does not lower testosterone levels, bicalutamide is rarely used as a standalone agent. It is almost always combined with estradiol, which provides both feminizing effects and some degree of testosterone suppression via negative feedback.