Estrogen and T Blocker (Estrogen+) Information

By Dr. Jerrica Kirkley | June 16, 2020


Thank you for scheduling with one of our trans-specialist medical providers. Please take the time to read this complete document before your first appointment. This information will help you decide what medications may support your unique needs and desires. Knowing what medications you have in mind or questions you have at the time of your appointment will free up both you and the provider to more effectively address your needs.

Some things to think about as you read the information in this document:

  • What physical changes, if any, are affirming for you? If you don’t know what changes might occur, this document should help.
  • If you want to take estradiol – which uptake method? Tablet that dissolves under the tongue, injection, or patch?
  • Do you want a low dose or not?
  • Do you want to take a T blocker or not? If yes, which one?
  • What questions do you have that this document hasn’t addressed?

We look forward to meeting you!

~ Your Plume Care Team


Estrogen is a naturally occurring hormone that is typically produced in all bodies, but in different amounts for different bodies. Synthetic bioidentical estrogen, also known as 17-beta estradiol is what we use when we prescribe it to encourage physical changes in the body to live our authentic selves in respect to our gender identity or lack thereof. It is important to note that bioidentical estradiol is different from estrogen in birth control pills or premarin (a conjugated estrogen from horse urine), both of which are known to cause significant complications like blood clots, so we do not use those for gender-affirming care.


Blood clots – When used appropriately under supervision of a medical provider, estradiol has been shown to be very safe, but every medication is not without its risks. There was a study that came out in 2011 which showed that there was a significantly higher proportion of blood clots in a group of trans folks taking estrogen compared to the general population (meaning everybody, not just one subset of the population) which created quite a scare and is unfortunately where the concern for blood clots comes from. In that same study, they went back and removed all the people from the analysis that were taking estrogen by birth control pills or premarin and none of the folks in the study who were taking bioidentical estradiol had any blood clots. More recent review studies looking back over 30-40 years have shown trends that estrogen might lead to more blood clots, strokes or heart attacks relative to the general population but these studies don’t separate out well for the different types of estrogen being used and other risk factors like smoking or pre-existing heart disease and other medical problems. These studies also show trends that higher blood levels of estradiol and large dose increases tend to be correlated with more events of blood clots, so that is why we try to keep levels between 50 to 200 more or less in the blood. So far, we do not have evidence that higher levels correlate with different levels of physical change.The bottom line is that there might be a small increased risk of blood clot, stroke, and/or heart attack when taking estrogen, but it doesn’t seem significantly higher than the general population when using bioidentical estradiol and regular lab monitoring.

Estrogen could cause infertility – Over time estrogen causes the levels of testosterone in the body to drop which then causes changes to other body parts that are important in allowing pregnancy to occur. We can’t predict who this will occur in and there are many factors that can contribute to infertility outside of taking estrogen. If preserving fertility (having children with your own genetic material in some way) is important to you, we strongly encourage you to see a reproductive specialist regarding freezing of certain body parts that can be used to make a pregnancy later.

Expected Changes

The first changes most people notice start at around 2-3 months with chest development and nipple tenderness.

While there are many things that contribute to our mental health, many folks notice feeling better emotionally shortly after starting estrogen – in particular, decreased anxiety and depressed mood and increased confidence. Other changes that can occur and tend to be more gradual include:

  • Body fat redistribution to the outside of the body instead of more centrally and increased subcutaneous fat, including more fullness in your cheeks
  • Softer, less oily skin with less acne
  • Thinning and slowed growth of coarse body hair and facial hair
  • Decreased libido and sexual function
  • Decrease in size of some parts of the genitals

Estrogen does not cause any voice changes, but you can modify your voice with a speech therapist. Most folks will max out on physical changes after taking estradiol for 2-5 years, at which point it is typically continued to maintain the changes that have occurred.

Uptake Method, Dose, and Frequency

Sublingual Tablet – We recommend taking estradiol tablets sublingually, which means to let it dissolve under the tongue rather than swallowing them. This typically takes about 5-10 minutes for the tablet to completely dissolve. We recommend taking the tablet sublingually so it avoids going through the liver, which we think is safer and reduces the risk of blood clots. A little might get swallowed, but that is OK. You should avoid drinking or eating anything while letting the tablet dissolve. The pharmacist might not be familiar with the sublingual method but you can let them know you discussed it with your medical provider and it is OK. The typical starting dose is 2-4 mg per day. With a goodrx coupon, a one month supply costs anywhere from $8-15 depending on your dose.

Injection – Injections are given intramuscularly, most commonly in the outer thigh or upper outer glute/butt area. They are given once a week, more or less, the same time each day you inject. All studies seem to suggest all forms of estradiol are equal in their ability to cause changes in the body, but some people report that injections seem to cause more prominent and perhaps quicker change. We send prescriptions for your syringes and needles to the pharmacy so you have everything you need.

You will get a larger, wider needle to draw up the estradiol because it is in a thick oil. The larger needle enables you to draw the liquid out of the vial quicker. You will also get a thinner needle to switch over to that you will inject with and a syringe as well. We recommend and prescribe a 1 ml syringe because it is easier to see all the measurement markings. Often, the pharmacy will try to give you a 3 ml syringe, so be aware. We know some folks can be anxious about injections. Don’t worry, we will provide you with teaching videos and walk you through how to inject if you choose to do injections.

While injections are convenient, effective, and safe, one downside is the availability can be spotty and often pharmacies do not carry injectable estradiol. If we are having trouble accessing injections for you, we can always use the tablets or patches until we are able to obtain the injectable form. The two main forms are estradiol valerate and estradiol cypionate (also known as Depo-Estradiol). The most common doses are 10 mg or 0.5 ml per week of the estradiol valerate (usually a 20 mg/ml concentration which comes in a 5 ml vial) and 2.5 mg or 0.5 ml per week of the estradiol cypionate 5 mg/ml concentration (also comes in a 5 ml vial). With a goodrx coupon, a 2.5 month supply (usually one vial depending on your dose) typically costs $45-50 for estradiol valerate and $120 for estradiol cypionate.

Patch – Patches are considered the safest form of estradiol. They are good if you have any pre-existing heart related conditions like a prior heart attack, stroke, or blood clot; high blood pressure, or tobacco use among others. They come in 2 versions – one that is applied once a week and one that is applied twice per week. The patches work well for many people, but sometimes can be difficult to stay on, especially if you sweat a lot. Most people use 1 or 2 patches at a time, each dosed at 0.1 mg/day. 2 patches are equal to about 4-6 mg of tablets and 10 mg of injectable estradiol. With a goodrx coupon a 1 month supply will cost around $30-115 depending on your dose.

Determining The Right Dose

Most people do quite well on the common doses listed above when seeking the maximal physical change their bodies are capable of. We guide dosing by how you are feeling and progressing but also have to keep safety in mind, typically maintaining estradiol levels in the blood around 100-200 more or less. If you are looking for more subtle or gradual change, then we can work on the lower dose end of the spectrum, or could consider using only testosterone blockers if you wanted to avoid estradiol altogether. You can talk with your provider about how this might work.

T Blockers

It is important to know that estrogen, and not testosterone blockers, is primarily what lowers testosterone in the body. T blockers block the effects of testosterone in different ways, but do not typically have a direct lowering effect. In fact, often at least initially, they increase the levels of testosterone in the body because there is more floating around with nothing to do. Once the T drops to very low levels, like less than 30 (T is usually somewhere between 400-800 pre-HRT for most folks), most people don’t need to be on T blockers anymore, because there is hardly any T to block anymore! Whether to go on T blockers or not is totally up to you. You could be on none, one or all of these at the same time depending on your personal situation. While T blockers can help limit the effects of testosterone on the body, you will have to weigh the different side effects as listed below. Ultimately, the only way to know how a medication will affect you is to try it, so if you are interested in a T blocker, I would recommend starting with one, to make sure you tolerate it well.


Spironolactone, or spiro for short, is a medication that has been around for a long time and was first used for heart failure and blood pressure control. Over time we realized that it has the side effect of blocking testosterone receptors and making changes in the body like breast development, decreased facial hair and body hair growth, decreased acne, and decreased libido and sexual function (like the ability for genital parts to become erect and decreased fluids related to orgasm). It can be used as a supplement to estrogen for gender-affirming care. Blocking the effects of testosterone can enable the estrogen to work quicker while the testosterone is gradually dropping.

Spiro is a steroidal anti-androgen, meaning it blocks the testosterone receptors in the body. It might have some direct effect in blocking the production of the precursor hormones to T so could have a direct lowering effect of T, although slight.

Uptake Method, Dose, and Frequency – We usually start dosing at 50 mg once daily and can go all the way up to 400 mg per day in some cases. It is usually taken twice daily once you get over 50 mg, but can be taken in one dose if tolerated OK. The dose is different for everybody and depends on what changes you desire and the progress made towards those changes.

Risks – Spiro is a diuretic which means it makes you pee more often so it is important to stay hydrated. It can cause high potassium and low sodium so it is important to tell your Plume provider about all medications you are taking to make sure they don’t interfere, and get your blood work done every 3 months to make sure everything is in a healthy range.

Some people report it causes a mental or emotional fog sensation. There might be an increased risk of depression while taking it. Tell your provider if you are experiencing depressive symptoms that consistently disrupt your daily life.

There was a small study, not based in humans, which suggested that spiro might cause premature breast bud fusion, meaning if the breast bud closes early, the breast might not develop to the full extent it otherwise would from estradiol. For this reason, some folks prefer to not start spiro until 3-6 months after starting estradiol. With this being said, we do know that breast development is also a common side effect of spiro. If optimizing breast development from HRT is very important for you, then I would recommend holding on spiro for at least 3 months and we can always start it later.


These 2 medications belong to a class of medications called 5 alpha reductase inhibitors – say that 5 times fast! We call these DHT blockers, because instead of blocking the testosterone receptor like spiro, they block the conversion of testosterone to dihydrotestosterone, or DHT, which is the stronger form of testosterone in the body. It plays a big role in scalp hair loss especially, which is why finasteride is also prescribed for hair loss outside of gender-affirming care. You didn’t know you would get a biochemistry lesson today, did you? For those that are more worried about scalp hair loss, or concerned about the side effects of spiro, this can be a good option to supplement estradiol with. Some people like to take a DHT blocker with spiro to have a double effect of blocking the changes made by T which is totally fine to do.

Uptake Method, Dose, and Frequency – Finasteride is taken as one 5 mg tablet swallowed once per day and dutasteride is taken as one 0.5 mg capsule swallowed once daily. There is some thought that dutasteride might have a stronger effect because it blocks the type 1 isoenzyme, whereas finasteride blocks type 2 and 3 isoenzymes which are less potent. TMI? More biochemistry – yay! With a goodrx coupon, a 1 month supply of finasteride is about $10-12 and dutasteride is about $15-17.

Risks – They are typically well-tolerated with limited side effects other than what we would expect, like decreased libido, decreased ability to make genital parts erect, and decreased fluids related to orgasm. There are some reports of increased depression, but we have not seen that in the context of gender-affirming care.

DHT blockers are also used to shrink the size of the prostate for folks with enlarged prostate symptoms and could mask the presence of prostate cancer. Because prostate cancer symptoms show up the same as enlarged prostate symptoms, if you were taking a DHT blocker medicine that shrinks the prostate then you might not get symptoms of prostate cancer when you otherwise would. This typically isn’t something to worry about until you are over 50 years old. You should talk with your primary care provider about prostate cancer once you turn 50 and whether or not you need to be tested for it. In general, the medical community is moving away from testing for prostate cancer because in most cases it is a slow growing and benign cancer. For most folks, this will be a non-issue, but important to be aware of.


We unfortunately don’t have any evidence to show that progesterone causes significant changes within gender-affirming care. This is mainly because we just haven’t done the studies, so it doesn’t mean that it isn’t out there. Many people feel plus/minus about progesterone. But there are a fair amount of folks who feel that it helps with things like breast development, rounding out the breasts and areolar development, perhaps adding fullness to the hip area, and possibly improving mood and increasing libido. It appears to be safe, so if you want to try it, there doesn’t appear to be much risk. The most common side effects reported are drowsiness, nausea, and sometimes weight gain. It is important to know that there is some risk of androgenizing effects (i.e. testosterone-like changes such as coarse or dark hair growth on the face or acne) because progesterone sometimes comes from the same family as testosterone precursor hormones.

We prefer to use bioidentical progesterone, called micronized progesterone or Prometrium (the brand name). It is less likely to cause those androgenizing effects as above than other forms of progesterone such as medroxyprogesterone.

Uptake Method, Dose, and Frequency – It is a capsule which is swallowed in the evening before bed with a dose of anywhere from 100 mg to 300 mg at a time. You might have heard of some people taking the oral capsule as a suppository to increase the levels in the body and make it last longer. We have zero evidence to support the effectiveness or safety of this, but it is likely to be safe given what we know about progesterone. We don’t encourage this method, but if you feel this works better for you, it seems to be OK to do this for now.

Thank you!

We know that was a lot of information. Hopefully, it was helpful and educational. We truly look forward to meeting you and assisting you in a personal and meaningful way.

Your Plume Care Team



The information in this document is derived from national and international guidelines on gender-affirming care, expert opinion and the personal practice experience by the medical providers of Plume. Guidelines include the UCSF Transgender Center of Excellence, the World Professional Association of Transgender Health and the Endocrine Society

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