Can Estradiol Monotherapy work for you? Will you need antiandrogens?

A lot of people start HRT using blockers such as Spironolactone to suppress Testosterone with the goal of achieving typical cis women levels for optimum feminization. Some people even try a “low and slow” method of antiandrogen monotherapy for several months before starting Estradiol therapy.

One frequent question is whether Estradiol Monotherapy (only dosing Estradiol without antiandrogens) is enough to suppress Testosterone without “unnaturally” high dosage. There is an interesting study on the efficacy of Estradiol Monotherapy and also whether antiandrogens like Spironolactone are effective in suppression.

1. Hormonal Treatment of Transgender Women with Oral Estradiol

Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels.

Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

I really love this particular study because it brings into question the efficacy of Spironolactone, which is often considered “the standard” antiandrogen in the USA. Finasteride increasing Testosterone is not news – it prevents conversion of Testosterone to DHT, so there will be more serum Testosterone as a result.

My personal experience with Finasteride/Dutasteride is that reduced DHT binding results in a type of feminization; specifically in my case it increased facial fat distribution and increased breast development; but did nothing to increase fat distribution to hips and reduced fat in waistline. On the other hand no matter what my serum Estradiol levels were, I could not get much breast development or facial fat distribution; however, my hips and waistline became more feminine on Estradiol approaching 200pg/mL. In my case reduced DHT and increased Estradiol were almost like picking and choosing feminization characteristics.

My particular observations were from 2 labs and varying dosages.

  • Waistline/Hip fat distribution very feminine, little facial rounding, low breast development: Peak serum Estradiol 647pg/mL, Testosterone 8ng/dL, DHT unknown
  • Waistline/Hip fat distribution less feminine, little facial rounding, breasts shrinking; Dramatically reduced Estradiol dosage: Peak serum Estradiol 81pg/mL, Testosterone 18ng/dL, DHT 3.3ng/dL.
  • Waistline/Hip fat distribution very feminine, little facial rounding, low breast development but restarted; increased Estradiol dosage: Estradiol ~160pg/mL
  • Waistline/Hip fat distribution very feminine, sudden facial rounding, sudden increase in breast development; Estradiol ~160pg/mL, added 0.5mg Dutasteride

My DHT ratio to serum Testosterone is within normal range; ~18% of Testosterone. I may just be an edge case, but in my experience DHT blocking was a missing element despite the low serum levels. I also wanted to note that I have primarily done Estradiol Monotherapy other than Dutasteride, which would increase Testosterone as a result of blocking DHT conversion.

I also want to point out there are health risks with taking Finasteride/Dutasteride long term, and frankly that is probably true of most if not all antiandrogens. Our bodies need some amount of androgens to function and androgen deprivation over a long period of time can have consequences. I say this knowing full well there are androgen insensitive people who may be immune to all androgen activity and be running solely on Estrogens. I’m not sure if there is an explanation for the differences or maybe it is a genetic dice roll. Another good example is a lack of progesterone being required for full Tanner 5 breast development with rounding for some androgen insensitive people. It is commonly believed that progesterone is required for the final stages of breast development in trans women to round out the breasts.

Clearly individual people tolerate androgens, antiandrogens, estrogens, etc. uniquely. Getting back to whether you will be able to use Estradiol Monotherapy or need to take antiandrogens, it is largely a genetic dice roll.

Based upon the study referenced[1]; your odds of being able to suppress serum Testosterone without antiandrogens is something like 70%. That study is also based upon oral Estradiol, which is less effective (bioavailable) than other methods of administration. For example, patches, gels, injections, pellets/implants; are all more bio available forms of Estradiol. So I’d wager that 70% is closer to a bottom in terms of the odds.

The question becomes whether you should immediately start with an antiandrogen or gradually use Estradiol alone to moderate Testosterone production. Personally I am glad I used Estradiol Monotherapy for the first ~5 months of HRT. My Testosterone has been under castration levels even with less than 200pg/mL serum Estradiol. I estimate my maximum feminization based upon observations and how good I feel is around 300pg/mL. When my Estradiol gets much higher I have issues with joint pain and feel less physically well/good. For people who want to color by number, the best method is measuring SHBG to find the most effective dosage (ie how much your body is actually using).

2. Early leak of some V 7.0 powerpoint changes: The Magic E2 Number

I will no longer be recommending a “range” for estradiol. I have come to realize this is foolish, as there appears to be what I will now call “The magic number” for everyone. That magic Estradiol total value is the value at which SHBG remains under 115, LH and FSH are zero, and the patient has a free estradiol greater than 1% without boron. Optimized further, its the Estradiol value with those before things and whatever produces the greatest fraction of free E2.

After collecting about 200 labs with my new order set, I can now confidently say that the amount of SHBG produced at different levels varies wildly by humans. Almost never does an estradiol over 700pg/ml seem to benefit the patient. Above that threshold, SHBG goes crazy and the free estradiol level drops. Pushing E2 above that level almost NEVER seems to increase the % free, thereby I have to admit, the old adage from conservative docs of “If you use too much Estradiol it will slow down your transition” is probably true. No, it wont convert into testosterone, and no, thats definitely not happening at an E2 around 150pg/ml, but it does happen to most people over 700 (but not all).

In short, I will now be setting my goal estradiol level for each individual patient at the level at which they have the greatest fraction of E2 free pre-boron and simultaneously have an LH and FSH of zero with a SHBG goal of 115.

That number seems to range from 200pg/ml to 700pg/ml in 95% of my patients, and so I think that in doing so, I can use less estrogen to get more effect if I figure out exactly what that happy number is.

In addition, ALL MTF patients now get a DHT ordered along side their T. While most of my zeroed LH/FSH patients have a Total T of 10-20ng/dl and a DHT below the detectable limit, there appears to be a subset who when testicular T production tanks, the adrenal glands and their swift 5AR gets to work on producing DHT. I had a patient yesterday with a T of 10ng/dl and a DHT of 25ng/dl which literally makes no sense when in cis males the DHT should be 10%. Clearly this falls under the category of “trans people are weird” and have weird enzyme mutations. For these patients I’m using microdosing of 5AR drugs or Bicalutamide, whichever the patient prefers. I prefer bica, and for them I’m doing twice a week dosing due to its long half life.

Reference[2] is by Dr. William Powers, who specializes in Transgender patients and HRT; in case you wanted more details on labs and fine tuning dosage.

Another point I wanted to address is whether Spironolactone is actually effective as an antiandrogen. Unfortunately this seems to be hit or miss for different people. Another point is whether Spironolactone prevents good breast formation for Transgender women; again, evidence is unclear.

3. What are the best Antiandrogens? Limited studies exist.

4. Maximum Transfeminine breast development. What is the hard evidence?

I have tried quite a few mainstream antiandrogens at this point and most did not agree with me within a short time; Finasteride, Spironolactone, Bicalutamide all had intolerable side effects. Dutasteride I have strangely tolerated very well compared to all others.

5. Potential side effects from Finasteride. Is Dutasteride any better?

As noted in the reference[5], there are serious long term health concerns with Finasteride and Dutasteride, so I have decided (at the time of this writing) to take Dutasteride every other day rather than every day; effectively 0.25mg daily equivalent. Since 0.5mg Dutasteride has more efficacy than 2.5mg Finasteride, in theory this may be equivalent if not superior to 1.25mg Finasteride; a common dosage for treating hair loss. Even so, I may discontinue Dutasteride entirely once my Feminization goals are achieved.


Your odds are good that Estradiol Monotherapy can work for you. You may be wondering if there is any advantage to monotherapy? For some people taking antiandrogens causes serious issues with libido and also shrinks the prostate. Antiandrogens are designed for treating prostate cancer to improve the odds of survival, so it’s very possible to have prostate shrinking and loss of libido. In particular DHT functions in the formation of the penis during puberty to reach full development, so blocking DHT can shrink the prostate and the penis. Note that you can treat your penis with a Testosterone cream to improve function while taking antiandrogens and/or Estradiol.

What if Estradiol Monotherapy doesn’t work for you? I would say there are good odds Spironolactone may also be ineffective in that case, since it doesn’t seem to lower Testosterone very effectively for some people. Personally Bicalutamide would be my primary choice of antiandrogen in the USA; though as noted the side effects were problematic in my case. Thankfully Dutasteride has been agreeable and Estradiol is doing the rest to block Testosterone production for me. I may also be able to titrate Bicalutamide in a pinch since I was dosing at 50mg and didn’t need that much antiandrogen blocking; due to already low serum levels of Testosterone/DHT.

Castration will most likely solve over production of Testosterone for the minority of people who require antiandrogens long term. Anecdotally I have also heard that castration completely changes the Transgender experience in terms of the strongest feminization. Since I lean towards nonbinary, my hope is to keep my testicles for the rest of my life as they may be revived in sperm production if I have that interest, and also the Testicles can produce Testosterone and Estrogen hormones. In a crisis situation I like the idea of having sufficient hormones in my body if I cannot get them externally. If a person discontinues HRT and still has their testicles, they can “revert” to full production for the purpose of survival or if they change their mind about transitioning their body.

Many people with gender dysphoria also prefer castration/orchiectomy for the primary purpose of gender identity affirmation.

6 thoughts on “Can Estradiol Monotherapy work for you? Will you need antiandrogens?

  1. Ah, yes. Estrogen monotherapy is actually the main way I prescribe in my own practice for trans medicine. I shoot for a trough level of somewhere between 150-300 (exact number based off of patient response) and rarely ever need any kind of anti-androgen due to the wonderful negative feedback pathway through the hypothalamus/pituitary. Hundreds of patients later: excellent results and no adverse events. Being attentive/adaptive to each individual’s response to the hormones being taken is of utmost importance in developing a regimen that works the best for them. Less than 5% of my feminizing patients require any sort of anti-androgen. And even then, it is for varying reasons, not always due to persistence of elevated T levels.
    Thanks so much for your site. I stumbled upon it today and have enjoyed reading what you have here. 🙂

  2. Wait so you got sudden face fat redistribution and breast growth immediately after starting dutasteride? I haven’t experienced any breast growth since month 10 and I’m very insecure about it, does this actually work? I’ve had lots of body fat redistribution everywhere else just not my breasts so much (my face some)

    My DHT seems to be at a normal level though at 18.6 ng/dL. I do 6mg of EEn IM monotherapy. Is starting dutasteride worth a shot?

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