TABLE OF CONTENTS

Gender-affirming hormone therapy (GAHT, sometimes also called HRT or hormone replacement treatment) can be an essential aspect of gender transition. Estrogen is especially important for many transgender women and transfeminine people because estrogen creates physical changes that are aligned with a more “feminine” body shape. 


The changes E creates in your body can help align your gender expression (the way you look) with your gender identity (the way you feel). Transfeminine/transfem people, nonbinary people, and trans women who take estrogen or other associated medications like spironolactone and progesterone will experience the same changes to varying degrees. Some of these changes are a redistribution of body fat, changing hair texture and growth patterns, and breast growth and nipple development, which promotes a more culturally feminine appearance. This Guide explains the basics of estrogen GAHT so that you can decide whether E is right for you. 


Estrogen 101

Estrogen is a naturally occurring hormone that is typically produced in all bodies, but in different amounts for different bodies. For gender-affirming hormone therapy (GAHT, sometimes also called HRT or hormone replacement therapy), our Care Team prescribes synthetic bioidentical estrogen, also known as 17-beta estradiol. 


People who identify as trans women, transfeminine, transfem or transfemme, or MTF can take different amounts of estrogen as a gender-affirming hormone. Taking E and other medications should simply give you a sense of comfort and ease in your body. Some people take estrogen because they want to look and feel “womanly,” while others like the effects of the medication. Everyone takes E for different reasons and results for their gender transition.


People can take estrogen through three main methods: a daily or twice daily tablet taken by mouth (or under the tongue), a weekly shot (usually into the thigh muscle), or a patch on your skin which is changed once or twice a week. 


Most people start noticing changes from estrogen within 2-3 months with chest development and nipple tenderness. Mental health, especially anxiety and depression, can also improve soon after starting estrogen. Some of the other changes that occur more gradually include body fat redistribution to the outside of the body (hips, thighs and glutes), softer and less oily skin, thinning and slowed growth of coarse body and facial hair, decreased libido and sexual function, and decrease in the size of some parts of the genitals.


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. 


While estrogen is usually a major part of someone’s gender-affirming regimen, other medications can be used, generally alongside estrogen. These medications include “testosterone blockers” (such as spironolactone, finasteride and dutasteride), as well as progesterone, another hormone that can be used during someone’s gender transition. 


If you’re considering starting estrogen or another gender-affirming medication, it is really helpful to think through your goals and preferences. Before your visit with your Care Team at Plume, you might want to write down any questions you want to ask during your visit—it's easy to forget them all when the visit starts! Here are some important questions to consider, but don't worry if you don't know the answers yet:


  • What physical changes, if any, feel affirming for you?
  • If you want to take estradiol (estrogen), how do you want to take your medication? A tablet you take daily, an injection you take once every 1-2 weeks, or a patch you change once or twice weekly? 
  • Do you want to start at a typical starting dose, or perhaps a lower dose? 
  • Do you want to take a T blocker or not? If yes, which one? 
  • Do you have questions that we haven’t addressed?


What is estrogen?

Estrogen is a naturally occurring hormone that is typically produced in all bodies. Different bodies produce different amounts of estrogen. The type of estrogen most commonly prescribed for gender-affirming hormone therapy is called estradiol (or 17-beta estradiol); it is structurally identical (“bioidentical”) to the hormones produced naturally by the body. 


Taking estradiol will decrease the amount of testosterone your body makes, and will lead to specific changes to your body that we’ll detail below. These changes may seem small at first, but can help you to live as your authentic self. Estradiol is vital for many people’s gender identity and gender expression. 


It is important to note that bioidentical estradiol is different from estrogen in birth control pills or conjugated equine estrogens (an older form of estrogen that was commonly used to treat menopause in cisgender women). These medications have a higher risk of certain complications (like blood clots) and are not recommended for gender-affirming care.


What physical and psychological changes are possible?

Everyone’s journey is different, and everyone’s body will change at its own pace. While we offer some general guidelines for when to expect various changes, it’s important to be patient with yourself and the process. Many folks start to notice changes within the first 2-3 months. The first physical changes most people notice are chest development and nipple tenderness. 


Over time, physical changes will continue gradually, with shifts in where body fat sits (from your belly to the hips and butt area), a decrease in strength and muscle, softening of the skin, decreased body hair growth and ongoing chest growth. Most folks will continue to see physical changes for the first 2-5 years, after which point changes will start to plateau. At this point, people continue taking estrogen to maintain the changes that have occurred.


While there are many things that contribute to our mental health, many folks notice feeling better emotionally after starting estrogen. In particular, people notice decreased anxiety, improved mood, and increased confidence. With that said, estrogen has the ability to negatively impact mood. For people who have a history of depression or other mental health concerns, E can destabilize mood, making people feel unexpectedly more down. This is something your medical provider will discuss with you at your visit.


Many of the changes that come with estrogen are reversible. This means that when you stop taking it, things will start to go back to the way they were before starting. However, it’s important to point out that some changes are irreversible (though the extent can vary for each individual). Changes that can be irreversible are chest/breast growth, genital changes (a decrease in testicular size), and reduced fertility or infertility (discussed in more detail below).


The effects of E that people most commonly experience include: 

  • Body fat redistribution (decreased in the belly, increased in the buttocks/hips/thighs) 
  • Redistribution of facial fat / changes in facial structure
  • Softer, less oily skin 
  • Nipple tenderness
  • Breast development
  • Thinning and slowed growth of coarse body hair and facial hair 
  • Slowing down of hair loss (at front and top of head) 
  • Decreased libido (sex drive) 
  • Changes in sexual function (decreased spontaneous erections)
  • Decreased muscle mass / strength 
  • Decrease in size of some parts of the genitals (ie: smaller testicles)
  • Mood changes


Estrogen does not cause any voice changes, but you can learn to modify your voice with a speech therapist or through vocal exercises if desired. 


How can I take estrogen?

Estrogen can be taken in several forms. The most common forms include tablets taken once or twice daily (by mouth or under the tongue), weekly injections, and a patch placed on the skin (changed once or twice a week). Plume’s Care Team guides dosing by how you are feeling and progressing. In addition, we keep an eye on lab values to ensure we are prioritizing your safety. 


The estrogen levels in your body are constantly being sensed by your brain. When your brain senses a certain estrogen level, it will tell the body to make less testosterone (T)!  For people who want to maximize the physical changes that estrogen brings, we aim for you to be on a dose of estrogen that will keep your T levels nice and low (ideally under 40-55). 


Estrogen levels measured in your blood are not as reliable as T levels. Estrogen levels can vary greatly depending on what time they are drawn and when your last E dose was. Even though they aren’t super helpful in determining how effective your dose is, estrogen levels are important to check to make sure they aren’t too high. Your Care Team typically aims to keep estrogen levels around 50-200. These levels are shown to maximize efficacy while minimizing risk. Here are the methods your Care Team will likely recommend.


Tablet (oral or sublingual)

Estradiol tablets are generally the most affordable estrogen option and are a popular choice for people who don’t like injections or find a patch undesirable. A typical starting dose is 2-4 mg per day, with a typical maximum dose of 8 mg. Tablets are usually taken once a day (if you’re taking 2 mg) and twice a day (if you’re taking more than that). With a GoodRx coupon, a one month supply costs anywhere from $8-15, depending on your dose.


Estradiol tablets can either be swallowed by mouth or dissolved under the tongue (sublingual). The tablets are made to be swallowed by mouth. However, your Care Team might recommend trying to take the tablets sublingually. When a medicine is dissolved under the tongue (instead of swallowed into the stomach), it skips passing through the liver until later in the digestion process. The recommendation for sublinguals is based on very weak evidence that this might reduce the risk for blood clots. For now, it’s unclear whether there’s any real benefit to taking the tablets sublingually as opposed to swallowing them, but it’s OK to give it a try if you want! 


If you do want to take estradiol sublingually, the tablet can take about 5-10 minutes to completely dissolve. A little bit of the pill might get swallowed, but that is fine. You should avoid drinking or eating anything while letting the tablet dissolve. If your pharmacist is not familiar with the sublingual method, you can let them know you discussed it with your medical provider and have their approval. 


Injection 

Injectable estrogen can be a great option for those who don’t want to (or can’t remember to!) take a pill once or twice a day. There are two forms of injectable estrogen: estradiol valerate and estradiol cypionate. Either of these can be given weekly or every two weeks. The most common starting dose of estradiol valerate is 4-6 mg per week (which is 0.2 - 0.3 mL of a 20 mg/mL concentration). The most common starting dose of estradiol cypionate is 1-2 mg per week (which is 0.2 - 0.4 mL of a 5 mg/mL concentration). A 2.5 month supply of this medication is usually one 5 mL vial, depending on your dose. With a GoodRx coupon, this typically costs $45-50 for estradiol valerate and $120 for estradiol cypionate.


Injections are given both intramuscularly (IM) and subcutaneously (SC/subQ). Estrogen is more commonly prescribed IM, but there is evidence that similar estrogen levels can be achieved with subcutaneous injections. You can talk to your Care Team about which injection method is best for you. 

  • Intramuscular (IM) injection is an injection into the butt, glute, or thigh area. The needle is long, so that the medication reaches the large muscles underneath layers of skin and fat. If you choose this method, you’ll alternate your injections between each of those areas and change sides of your body for each injection.
  • Subcutaneous (SC/subQ) injection uses a shorter, thinner needle similar to an insulin needle or a dart. This type of injection is given just under the skin of the belly or front of the thigh. SubQ injections are generally less painful, but can sometimes lead to more local skin irritation and discomfort. 


Studies 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. 


Injection supplies for your medication

When you are ready to begin hormone therapy, your Care Team will send prescriptions for your syringes and needles to the pharmacy so you have everything you need. If you are not using your insurance for supplies, it can be cheaper to buy supplies online in bulk. You can ask your Care Team for recommendations on where to find these. 


You will get a larger, wider needle to draw up the estradiol because it is suspended in a thick oil. The larger needle enables you to draw the liquid out of the vial quicker, with fewer bubbles. You will also get a thinner needle. After you have drawn up your medication, you will switch over to the thinner needle to inject it. 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 and ask for a 1 mL syringe instead!) 


We know some folks can be anxious about injections. Don’t worry! If you choose to do injections, our teaching videos will clearly walk you through how to safely get started. You can also meet with a Care Team member and they will walk you through your injection in real time so you feel comfortable and supported.


Patch

Patches come in two 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 keep on, especially if you sweat a lot, swim for fitness, or exercise intensely. Most people use one or two patches at a time, each dosed at 0.1 mg/day. With a GoodRx coupon, a one-month supply will cost around $30-115, depending on your dose.


The data comparing the safety of different estradiol forms is limited. There is some evidence to suggest that patches are the safest form of estradiol and carry the lowest risk for blood clots. This is particularly true if you use tobacco, have a personal or family history of blood clots, or have any pre-existing heart conditions. 


If you opt for our delivery pharmacy, you may be able to get your medication at a lower price! You can check the pricing of these medications here.


What is “microdosing”? 

Microdosing is a newer term that describes using a smaller amount of a medication to achieve subtler or different effects from more common dosing recommendations. For example, some nonbinary people do not want to look like “women,” but want more feminine features such as softer skin or breast growth. A microdose of the correct medication may achieve these changes over a longer period of time. The changes will be less dramatic than the ones someone might notice on the full dose.


Microdosing is a very individualized process. We cannot pinpoint exactly which physical changes will occur, or how quickly they will happen. It’s impossible to pick and choose exactly which effects of E you want, and which you don’t. So do be sure you can accept all the changes that could come with estrogen before starting (especially the ones that are irreversible). Some people decide to avoid estradiol altogether and use only testosterone blockers. 


We can support you while you find the dose and regimen. Just let your Care Team know what feels right for you and we will help you reach your transition goals!


Are there any possible risks to taking E?

When used appropriately under the supervision of a medical provider, estradiol has been shown to be a relatively safe medication. Every medication has its risks (even those you can pick up without a prescription!). Before you start, your Care Team wants to ensure you have a clear understanding of the benefits and the risks, so that together, you can make an informed decision about whether or not E feels right for you. 


Here’s a more comprehensive list of the potential risks of E. Our goal is to empower you with as much information as possible to choose what is best for you. In addition to those risks discussed in more detail below, E can cause an increase in the risk for: 

  • Gallstones
  • Liver inflammation
  • Weight gain
  • Elevated triglycerides (or fats) in your blood
  • Elevated blood pressure
  • Benign (non-cancerous) tumors of the pituitary gland in your brain
  • Migraine headaches


It’s important to tell your Care Team if you’re taking any other medications or over the counter supplements, as it’s common for these to interact with E. For people with additional risk factors (related, for example, to your personal or family history), there’s also a possibly increased risk of heart disease, Type 2 diabetes, and breast cancer. 


Your Care Team will review your medical history with you during your visit! If you are getting ready for your first appointment, here’s everything you need to know. 


Estrogen, blood clots, and heart disease 

Several review studies looking back over the past 30-40 years have shown trends that estrogen increases the risk for blood clots, strokes, or heart attacks relative to the general population. Bear in mind that much of the data we have about the risks of estrogen comes from studies in post-menopausal, cisgender women at a time when different forms of estrogen were commonly used. We have clear evidence that these other forms of estrogen (like Premarin or ethinyl estradiol, which is the estrogen used in birth control pills) increase the risk for blood clots, strokes and heart attacks. 


At Plume, we prescribe estradiol, a form of estrogen that has a lower risk of blood clots, heart attacks and strokes than other forms of estrogen. Unfortunately, most studies still include people on a mix of estrogen forms, including the forms that we know are higher risk and that we don’t prescribe for GAHT. This makes it really hard to know exactly how much estradiol increases the risk for blood clots and heart disease. But, from the limited data we do have in trans folks, there haven’t been any cases of blood clots, heart attack or stroke as a result of estradiol for GAHT. 


What we do know, however, is that higher blood levels of estradiol and large dose increases are associated with a higher risk of blood clots. So far, we don’t have evidence that higher levels of estradiol correlate with different levels of physical change or increased satisfaction with GAHT. Because of this, we try to keep estradiol levels between 50-200 and ask patients to get blood work done every 3-4 months while taking their medications. Our goal is to maximize efficacy and safety, and our Care Team will work with you to individualize your care. 


Infertility and E

Over time, estrogen causes the levels of testosterone in the body to drop. This then causes changes to other body parts that are important in allowing pregnancy to occur. It is impossible to predict if someone taking E will become infertile and how long that will take. Because of this, it is really important to consider your desires and goals before getting started on E. 


We recognize that there are many ways to build your family, and that using your genetic material is only one of them. However, if preserving your fertility is important to you, or if you would like to have children who share your genes, we strongly encourage you to see a reproductive specialist regarding preserving your genetic material (sperm) before starting on hormones. 


If someone has already started estrogen, it is possible to come off hormones to try and preserve genetic material. This isn’t always successful, however. Those who have been on E longer might have more difficulty. Changes to fertility can happen very soon after starting GAHT. 


Whatever your hopes are for starting a family, know that you have options. The most important thing is to be aware of the impact E can have on your fertility before starting the medication. We understand you might not yet have a clear answer for yourself and your future family, but it is important to know that E can impact your future fertility.


What are T-blockers?

It is important to know that estrogen—not testosterone blockers—is primarily what lowers testosterone in your body. T blockers got their name because they block the effects of testosterone in different ways, but do not typically lower T levels directly. T is usually between 400-800 pre-GAHT for most folks. Estrogen will cause T levels to drop significantly. Once your T drops to very low levels (like less than 30), most people don’t need to be on T blockers anymore, because there is hardly any T left to block! 


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, which are 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, your Care Team may prescribe you one to see if it works for you.


What is spironolactone?

Spironolactone, or spiro for short, blocks the testosterone receptors in the body. It can be used as a supplement to estrogen for gender-affirming care. Blocking the effects of testosterone can allow estrogen to work quicker while the testosterone levels are gradually dropping. It might also have some direct effect in lowering T production, but is far less helpful at lowering your T levels than estrogen.


Spiro is a medication that has been around for a long time. It was first used for heart failure and blood pressure control. Over time, doctors realized that it has the side effect of blocking testosterone receptors. Spiro creates changes in the body like 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).These changes are generally reversible if and when spiro is stopped.


How can I take spironolactone?

Spiro is usually started as one 50 mg tablet per day. The tablets can go all the way up to 400 mg per day in some cases. The medication is usually taken twice daily once you get over 50 mg, but this can be taken in one dose if your body tolerates it. The dose is different for everybody and depends on what changes you desire and how well you tolerate the medicine.


Are there any possible risks for taking spironolactone?

Spiro is a diuretic, which means it makes you pee more often. (It is important to stay hydrated!) The medication can cause high potassium levels and low sodium, so it is important to tell your Plume Care Team about any other medications you are taking to make sure they don’t interfere with one another. Because of these side effects, it’s critical that you get your blood work done every three months to make sure everything is in a healthy range.


Some people report that spiro causes a mental or emotional fog sensation. Some people might experience an increased risk of depression while taking this medication. Spiro is generally well tolerated, and these symptoms are generally reported only at higher doses. Do tell your Care Team if you are experiencing depressive symptoms that consistently disrupt your daily life. Mental health can shift quickly, and hormone levels influence our moods and feelings. Help us support you by being transparent with your Care Team about your emotions.


Finally, it’s important to understand how spiro might impact chest growth. A small study, based on animal models, suggests that spiro might cause premature breast bud fusion. This means that the breast bud may close early, limiting the full extent to which the breasts might develop with estrogen. For this reason, some folks prefer to start spiro 3-6 months after starting estradiol. 


With this being said, breast development is also a common side effect of spiro (though this side effect is different from the permanent breast growth with estrogen). If optimizing breast development from gender-affirming hormone therapy is very important for you, then we recommend holding on spiro for at least 3 months. If you’re still interested, you can always start it later.


What is finasteride/dutasteride?

Finasteride and dutasteride are medications that belong to a class of medications called 5 alpha reductase inhibitors. We call these DHT blockers, because instead of blocking the testosterone receptor like spiro, they block the conversion of testosterone to dihydrotestosterone (DHT), which is the stronger form of testosterone in the body. 


DHT plays a big role in scalp hair loss especially, which is why finasteride is also prescribed for hair loss outside of gender-affirming care. For folks 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. Some people like to take a DHT blocker with spiro, which is totally fine to do.


How can I take finasteride/dutasteride?

Finasteride is taken as one 5 mg tablet swallowed once daily 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. With a GoodRx coupon, a 1-month supply of finasteride is about $10-12 and dutasteride is about $15-17.


Both finasteride and dutasteride are typically well-tolerated, with limited side effects. The side effects are what you would expect from any estrogen-related medication: decreased libido, decreased ability to make genital parts erect, and decreased fluids related to orgasm. There are some anecdotal reports of increased depression, but our Care Team has 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. Because prostate cancer can present with symptoms of an enlarged prostate, taking a DHT blocker could mask the presence of prostate cancer. You should talk with your primary care doctor 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 side effect of DHT blockers will be a non-issue, but important to be aware of.


What is progesterone?

Progesterone is another hormone that can be used during someone’s gender transition. Usually progesterone is used alongside estrogen, and is added on after someone has been on estrogen for at least 6-12 months. 


At Plume, our Care Team generally prescribes bioidentical progesterone. This is called micronized progesterone or Prometrium (the brand name). Progesterone is usually taken as a capsule swallowed in the evenings before bed.


How can I take progesterone?

The progesterone we prescribe 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.


Are there any possible risks to taking progesterone?

Very little medical research exists about the ways progesterone is a useful gender-affirming medication. Because of this, there are mixed recommendations from the medical community as to whether progesterone is a useful addition to a GAHT regimen. However, just because there is no evidence doesn’t mean progesterone doesn’t do anything. We don’t have evidence mainly because the medical community just hasn't done the studies! 


Many folks feel that this hormone helps with changes like breast development (including rounding out the breasts and areolar development), 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 for progesterone 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). At Plume, we prefer to prescribe bioidentical progesterone, called micronized progesterone or Prometrium (the brand name). It is less likely to cause those androgenizing effects than other forms of progesterone such as medroxyprogesterone.


Welcome to this exciting stage of your gender transition

Transitioning with estrogen and other E-related medications is a journey in itself. While the changes you observe may seem small at first, they have a big impact on our sense of self-alignment. They make us feel like we’re finally being seen the way we are. Once you’ve started, you may feel like the changes you’ve yearned for are slow to arrive—but they’ll show up at their own pace.


While you may want to rush through this part of your transition and just get it over with, understand that hormonal changes happen in their own time. You might feel like your transition isn’t happening fast enough, or worry that you aren’t seeing changes as quickly as some of your friends. Don’t sweat the speed of your journey—it’s one day at a time. Keep moving, and you’ll get where you want to be.

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