Several years ago I wrote about bicalutamide as an emerging option in gender affirming hormone therapy. At the time there was very little published literature, very little collective clinical experience, and a lot of strong opinions.

You can read that original article here.

Since then, both the literature and my clinical practice have evolved.

This article is an update on how I currently prescribe bicalutamide, how I discuss risks and benefits with patients, and why I continue to offer it despite WPATH Standards of Care Version 8 recommending against its routine use.

As with most things in transgender medicine, I don't think the question is whether bicalutamide is "good" or "bad."

I think the better question is:

For which patients does bicalutamide offer benefits that justify the known and theoretical risks?

That is ultimately the conversation I have with patients every day.

What Changed Since I Wrote the Original Article?

The biggest change is that I have become substantially more conservative with dosing.

Earlier in my prescribing career I used 50mg daily because that was where much of the published literature lived. Over time I wasn't convinced I was getting meaningfully better clinical outcomes from higher doses, but I was increasing medication exposure.

Today I generally prescribe 50 mg twice weekly. I transitioned all my patients from daily to twice and week and no one felt a change in efficacy.

This dose has worked remarkably well in my practice. Patients continue to achieve the desired changes they are seeking, and I have not had patients develop clinically significant transaminitis using this regimen.

That does not mean liver injury cannot occur. It means my own clinical experience has become more reassuring over time, particularly when using lower doses and selecting patients thoughtfully.

I think it is important to separate two questions:

1. Can bicalutamide cause serious liver injury?

2. Is the risk of serious liver injury high enough that we should never prescribe it?

The answer to the first question is clearly yes.

The answer to the second question for me is no.

Who I Currently Consider a Good Candidate for Bicalutamide

I generally avoid prescribing bicalutamide in patients with:

• Patients over the age of 40
• Active liver disease or significant medical fragility
• Any transaminase elevations
• Heavy alcohol use or other recreational substance use that may cause more hepatic stress
• Concurrent medications with substantial hepatotoxic potential
• Situations where reliable laboratory monitoring is unlikely to occur

Before prescribing I obtain:

• AST
• ALT

I continue monitoring liver function during treatment and discuss symptoms that should prompt immediate discontinuation of medication and evaluation, including jaundice, dark urine, persistent nausea, severe fatigue, or right upper quadrant abdominal pain.

My goal is not to eliminate risk. My goal is to help patients understand risk well enough to make informed decisions about their own bodies.

Why Do Some Patients Prefer Bicalutamide?

One of the reasons I continue to prescribe bicalutamide is that many patients simply feel better on it.

Spironolactone is inexpensive, familiar, and effective. It is also a diuretic. Some patients tolerate that beautifully. Others spend all day peeing, struggle with hydration, notice exercise intolerance, or describe feeling mentally foggy.

I also think we often underestimate the social consequences of prescribing a diuretic to transgender people.

Many trans and gender diverse people spend a tremendous amount of energy navigating restroom access and restroom safety. For some patients, using a public restroom is merely annoying. For others, it is anxiety-producing, dysphoria-inducing, or genuinely unsafe.

Asking someone to urinate more frequently is not a neutral intervention.

We don't talk about that nearly enough in gender affirming care.

Every medication exists within a social context. Prescribing a diuretic to a population that is routinely harassed, questioned, or threatened in public restrooms deserves more consideration than it often receives.

Bicalutamide offers a very different experience for some patients.

In my practice, patients commonly report:

• Less urinary frequency

• Less dehydration

• Less dizziness

• Less brain fog

• Better exercise tolerance

• Less impact on erectile function

Not every patient has this experience. Some patients do very well with spironolactone and have no interest in changing. Others strongly prefer bicalutamide after trying both.

One of the recurring themes I hear from patients is that they feel more like themselves while still moving toward their goals.

Remember: Bicalutamide Does Not Lower Testosterone

One of the most common misconceptions about bicalutamide is that it should lower testosterone levels.

Like many anti-androgens, bicalutamide primarily works by blocking androgen receptors. It does not reliably suppress testosterone production.

In fact, testosterone levels may stay the same or even increase.

That does not mean the medication isn't working.

The medication is preventing testosterone from effectively activating androgen receptors throughout the body.

This distinction is important because clinicians unfamiliar with bicalutamide sometimes become concerned when they see testosterone levels that remain elevated despite clear clinical evidence that androgen effects are being reduced.

I spend a lot of time talking about this with both patients and clinicians.

The lab value is not the whole story.

Does Bicalutamide Help Patients See Desired Changes Faster?

Maybe.

I think this is one of the places where we need to be honest about what we know and what we don't know.

Do I think patients often achieve a softer, curvier appearance more quickly with bicalutamide than with estradiol alone?

Probably.

Do I have a high-quality randomized trial proving that?

No.

I also want to be careful not to overstate what I'm seeing clinically. I don't know that bicalutamide ultimately results in someone becoming more soft or more curvy than they would have become with estradiol alone. I suspect the final destination is still heavily influenced by genetics, duration of treatment, age, prior testosterone exposure, and factors we don't fully understand.

What I do think I see is that some patients appear to get to their desired changes more quickly.

Is that because of more complete androgen receptor blockade? Increased aromatization of testosterone to estradiol? Selection bias? Something else entirely?

I don't know.

What I do know is that many experienced gender medicine clinicians have made similar observations, and I think it is reasonable to discuss that possibility during informed consent while being transparent about the limitations of the evidence.

As always, I am much more confident discussing the possibility of a different rate of change than I am making claims about a different ultimate outcome.

I also suspect that preserving circulating testosterone while blocking androgen receptors may have advantages for some patients.

There are theoretical reasons this could be beneficial for:

• Bone health

• Energy

• Exercise tolerance

• Sexual function

The evidence here remains limited, but I think these questions deserve more attention than they currently receive.

Why I Do Not Consider Bicalutamide a Forever Medication

This is probably the biggest shift in my current practice.

I increasingly frame bicalutamide as a medication for years rather than decades.

When I review the available literature, I see reassuring data from younger populations receiving doses that are much closer to what we use in gender affirming care.

I also see case reports of fulminant hepatic failure and death in older cisgender men receiving substantially higher doses for metastatic prostate cancer.

These populations are not comparable.

The dose is different.

The age is different.

The underlying health conditions are different.

The goals of treatment are different.

At the same time, those reports remind us that bicalutamide is not a completely benign medication.

For that reason I generally view bicalutamide as a bridge medication rather than a destination medication.

For many patients the long-term plan involves one of several pathways:

• Estradiol eventually suppresses testosterone production sufficiently that an anti-androgen is no longer needed.

• Estradiol and progesterone together provide enough suppression that an anti-androgen is no longer needed.

• Orchiectomy eliminates the need for ongoing anti-androgen therapy.

• A different anti-androgen becomes a better fit.

None of those pathways are inherently better than the others.

The point is simply that I do not usually present bicalutamide as a medication someone will necessarily take forever.

When I Consider Lowering the Dose or Stopping It

One of the mistakes I occasionally see clinicians make is assuming that more androgen blockade is always better.

It isn't.

If a patient develops:

• Fatigue

• Low mood

• Low libido

• Exercise intolerance

• Reduced quality of life

I start thinking about whether the anti-androgen may be contributing.

Sometimes the answer is increasing estradiol.

Sometimes the answer is adjusting progesterone.

Sometimes the answer is reducing or discontinuing the anti-androgen.

The goal is not to eliminate every trace of testosterone activity.

The goal is helping patients feel good in their bodies while moving toward the changes they want.

What About WPATH?

WPATH Standards of Care Version 8 recommended against routine use of bicalutamide because of concerns regarding limited evidence and potential hepatotoxicity. That recommendation deserves respect. It was based on the evidence available at the time.

I also think it is important to acknowledge that the evidence landscape has changed since SOC8 was developed.

We now have additional case series, retrospective reviews, adolescent data, and substantially more collective clinical experience than we did several years ago.

Do we have perfect evidence?

Absolutely not.

Do we have enough information to support a thoughtful informed consent discussion with appropriately selected patients?

I believe we do.

I also find it interesting that we are often comfortable prescribing medications with known risks and limited trans-specific data until the medication is bicalutamide. Then suddenly many people become deeply concerned about evidence quality.

The reality is that much of gender affirming care is built on extrapolation, physiologic reasoning, clinical experience, observational data, and informed consent. That doesn't mean we shouldn't ask hard questions about bicalutamide. We absolutely should. It does mean I want us to apply the same evidentiary standards across all of gender affirming care rather than treating bicalutamide as uniquely controversial.

The question is not whether uncertainty exists.

The question is whether we are discussing that uncertainty honestly with our patients.

So Why Do I Still Prescribe Bicalutamide?

I still prescribe bicalutamide because I think it fills an important gap in gender affirming care.

I prescribe it at lower doses than I used to.

I monitor liver function.

I discuss uncertainty openly.

I generally view it as a temporary medication rather than a lifelong medication.

And I continue to have patients who strongly prefer it over spironolactone because it allows them to move toward their goals with fewer unwanted side effects.

Will my practice continue to evolve as new evidence emerges?

I hope so.

Good transgender medicine requires curiosity, humility, and a willingness to change our minds when better data become available.

For now, bicalutamide remains a medication that I continue to discuss, prescribe, and monitor thoughtfully with appropriately selected patients as part of an informed consent model of gender affirming care.

References

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