What are the best Antiandrogens? Limited studies exist.

When I asked my Doctor about whether Spironolactone actually worked, he said it worked well for some people. I mentioned the lack of consensus in studies about efficacy and he simply stated that antiandrogen studies were very limited and pointed to this reference:

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cen.14329

5 | CONCLUSION
Antiandrogens are frequently added to estradiol to assist with
feminization and suppression of testosterone. Spironolactone,
CPA, GnRH analogues and MPA all have antiandrogenic effects and
despite less suppression of total testosterone with spironolactone,
there are inadequate data to support enhanced feminization with
any particular antiandrogen. Serum total testosterone is a flawed
surrogate marker of antiandrogen therapy given some medications
work predominantly through androgen receptor antagonism rather
than by decreasing testosterone levels. The comparative effects on
breast development, body fat redistribution and reduction in facial
and body hair are unclear. Further research is needed with clinically
relevant endpoints to optimize the care of transgender women.

Yikes, that is a useless conclusion.

TransfeminineScience has some interesting references about antiandrogens:

https://transfemscience.org/articles/

If you look at antiandrogens on Wikipedia you’ll find there are many:

https://en.wikipedia.org/wiki/Antiandrogen

And if you look at Plume’s website, they support a total of 3:

https://getplume.co/estrogenfaq/

Finasteride, Dutasteride, and Spironolactone. Why so few on Plume? Because they tend to not kill people based upon studies, regardless of efficacy or transitional results.

The line I see repeated many times is that most antiandrogens exist for the treatment of prostate cancer, which is a life threatening condition where the pay off of a highly effective antiandrogen may save a life, and if a rare and severe complication occurs, the patient might well have died from the cancer regardless. So the risk of a rare complication that can save a life from cancer is worth it.

What about for transgender populations? They tend to be younger and otherwise healthy, so the risk of a life threatening complication is unnecessary for a potentially improved transition result or to avoid certain common but unpleasant side effects of more mainstream antiandrogens.

I can understand the temptation to take antiandrogens off the table if they are too risky potentially; however, transgender populations have over 10 times the suicide risk as the general population which places it in a very high risk group indeed. Much as is the case with informed consent, I believe trans people should be able to choose their own risk level and monitor their ongoing risk with labs accordingly.

Some antiandrogens are also inaccessible in different regions of the world – particularly CPA in Europe vs. the USA.

Here is a rough breakdown of common antiandrogens, risks, and benefits:

• CPA – Cyproterone Acetate; used heavily in Europe; developed in 1973, efficacy as an antiandrogen is good; used at low dosage to avoid risks; fatigue, blood clots, benign brain tumors, and liver damage; https://en.wikipedia.org/wiki/Cyproterone_acetate#Hormone_therapy; https://transfemscience.org/articles/cpa-meningioma/
• Bica – Bicalutamide; approved for medical use in 1995; efficacy as an antiandrogen is excellent; Bicalutamide causes elevated liver enzymes in around 1% of people.[19][20] Rarely, it has been associated with cases of liver damage,[10] lung toxicity,[3] and sensitivity to light. https://en.wikipedia.org/wiki/Bicalutamide#Medical_uses; https://transfemscience.org/articles/bica-adoption/; https://transfemscience.org/articles/bica-faq/
• Spiro – Spironolactone; introduced in 1959; not approved as an antiandrogen by the FDA (used off label for this purpose); efficacy has mixed results in studies; anecdotally may limit breast development via premature breast bud fusion (limited studies); https://en.wikipedia.org/wiki/Spironolactone#Transgender_hormone_therapy; https://transicarus.com/maximum-transfeminine-breast-development-what-is-the-hard-evidence/
• Buserelin; GnRH agonist; approved in 1985; not available in the USA; suppresses gonadal testosterone production; puberty blocker; https://en.wikipedia.org/wiki/Buserelin#Medical_uses; https://transfemscience.org/articles/buserelin-inexpensive/
• Fin – Finasteride; approved in 1992; limited efficacy for transgender therapy; possible elevated risk of depression and suicidal ideation; https://en.wikipedia.org/wiki/Finasteride#Transgender_hormone_therapy
• Dut – Dutasteride; approved in 2001; limited efficacy for transgender therapy; possible elevated risk of depression and suicidal ideation; a more complete 5α blocker than Finasteride; https://en.wikipedia.org/wiki/Dutasteride#Transgender_hormone_therapy

What is the right antiandrogen for you? That probably depends on what is available, what you can afford, what you can get a prescription for, and what side effects are most tolerable to you.

In the USA Spironolactone is a low risk general purpose antiandrogen; however, the side effects may be intolerable; anecdotally it has been said to also lower the voice, which is non ideal for transfeminine people. If your liver can handle it and you can get regular testing, Bicalutamide may be a good option. If Spiro and Bica are off the table your best bet would be Dutasteride; however, it also has strong side effects potentially and only blocks DHT, not Testosterone. Finasteride similarly to Dutasteride blocks DHT, but is a less complete blocker.

Buserelin appears to be an excellent option if you can get it. CPA is widely used in Europe but may have strong side effects or health implications. A study about use of CPA at lower dosage exists which has good blocking effects with lower health risks; https://transfemscience.org/articles/cpa-dosage/.

Estradiol itself also reduces testosterone production without the aid of an antiandrogen, so if no antiandrogens are agreeable, Estradiol can still do its work with monotherapy. It should be noted that if you have no interest in reproduction, orchiectomy (castration) can reduce testosterone by about 95%. This does necessitate hormone therapy for life to prevent issues with bone density and other potential health complications. If you do opt to remove testicles, the scrotal skin should be intact for the possibility of use in GRS (Gender Reassignment Surgery).