What do hormones do?
Hormones are chemical messengers in the body. Testosterone and estrogen are heavily involved in how our internal sense of gender develops and how our external presentation of gender manifests. Using estrogen hormone replacement therapy (HRT) to affirm your gender identity involves shifting from a testosterone-based system to an estrogen-based system. Estradiol is the safest and most commonly prescribed estrogen for gender-affirming care.
Gender-affirming estradiol therapy works in two ways. First, it sends a signal to the brain that stops the testes from secreting testosterone. With lower testosterone levels, the estradiol you take has more room to work. Estradiol—whether produced by the ovaries or supplied externally via pills, patches, or injections—travels through the body to different tissues and organs that have estrogen receptors.
Hormones change signals in the cell membrane to produce different proteins and functions. For example, more estrogen means skin cells will produce less oil, and hair will not grow as thick or dark. Increased estradiol also contributes to an increase in the size of chest tissue, producing breasts. Estradiol also creates changes in your body and shape as muscle and fat cells also change and increase around the hips, butt, and thighs. These are a few examples of how estrogen HRT can change your body through gender-affirming hormone therapy (GAHT).
Why do we need labs?
Gender-affirming hormones are used to meet our members' gender goals, which are different and unique to each person. We use labs as tools to assess the safety and effectiveness of the medication. Many people take estrogen HRT for the internal and external changes they will experience; labs are just one piece of data that can help you and your clinician determine the next steps. When your clinician orders labs for those on estradiol, they check on a couple of things.
We test your estradiol (estrogen) levels
An estradiol lab checks the amount of estrogen in the bloodstream at a single point in time. The result is affected by many things, including when you last took your dose, how much you take, how often you take or miss doses, and your metabolism. Labs aren't a perfect source of truth but are impacted by multiple variables, and hormones are challenging to measure accurately for many reasons. While that single number may offer helpful additional information, it's more important to focus on what estradiol is doing for you and how it may or may not meet your specific goals.
Let's talk about how we use estradiol levels as a tool to help you get the results you want and need. Higher estradiol levels can cause changes more quickly, whereas lower estradiol levels might create slower and more subtle changes, resulting in a more androgynous or less feminizing outcome. There is a wide range for both estradiol doses and the lab levels we expect to see.
When estradiol levels are too high, we may see negative effects and increased risk. Extremely high estradiol levels do not necessarily mean faster, more, or better changes. Change might be affected by age, previous exposure to testosterone, and family and genetic tendencies. Talk with your clinician if you are still waiting to see the changes you desire on GAHT. Part of that conversation might include what gender-affirming surgical options might offer to meet your specific goals.
While it is fairly uncommon, high levels of estrogen may increase risks for blood clots, which in turn, can lead to risk for venous thromboembolic events (VTE). VTE are blood clots in the veins that can lead to stroke or pulmonary embolism. Lots of other health and lifestyle issues also create a risk for blood clots, such as high blood pressure or high cholesterol, diabetes, heart disease, lack of exercise, and smoking or vaping.
We check your labs to try and keep estradiol at a reasonable level where there is less risk for a blood clot, stroke, or pulmonary embolism. If levels are very high, increasing estradiol may not be effective or healthy for you.
We check labs because it gives us important data for adjusting your dose. Remember, goals are much more important than specific labs and numbers. This is because labs and levels are not always accurate measures nor direct indicators of how much and what effects you get from estradiol. Many factors can impact labs, so we expect them to be imperfect estimates. Sometimes, your clinicians may ask you to repeat them to double-check.
Consider your risk in context when you think about keeping your levels "within range." Avoiding smoking tobacco and long periods without movement will significantly reduce your risk of blood clots.
What estradiol range is normal?
We typically are looking for levels in a range from 50 to 500 pg/mL (picograms per milliliter). We use these as estimates to give us an idea of your hormone levels at a particular time. When levels are on the lower end, they can be increased and still stay within a safe and acceptable range. If levels are very high, this can increase the risk for side effects such as extreme moods, irritability, fatigue, and a potential risk of blood clots to the brain or lungs. We think people using GAHT may need and deserve wider ranges than their cisgender peers. The typical estradiol range for cis women is 100-350 pg/mL. We use a broader range for GAHT. Whether or not this is the right range for you is something you and your clinician should discuss. Estradiol levels are not always accurate and can differ for many reasons.
When estradiol and testosterone are both very low (at postmenopausal levels), a person can experience low energy, low mood, depression, irritability, difficulty concentrating, difficulty sleeping, and low sex drive. Very low levels of estradiol and testosterone might also increase the risk of problems with cholesterol, heart disease, and bone health problems. Studies are ongoing to determine how low is safe.
If your estradiol level came back lower than usually expected (except for someone on a microdose), be aware of common reasons for a low estradiol level. The most common reasons for low estradiol levels are: microdosing, getting levels right before your next dose, missed or skipped doses, or doses that are too low.
Do you ever check testosterone levels?
We think that for estradiol to have a maximal effect, it is important to have very low levels of testosterone (< 100). We will likely want to check to ensure your testosterone levels are suppressed if you want maximal estrogen effects. Testosterone only needs to be checked once or twice a year to confirm that testosterone is not getting in the way of estrogen effects. For most people on higher doses of estrogen, we know that testosterone is likely suppressed when people both report getting the changes they desire and are taking average to higher doses of estradiol. For people who are on lower doses or are not meeting gender goals despite higher doses of estradiol, we can use testosterone levels to more directly estimate what is going on with testosterone production and its effects. However, most people don't need both estradiol and testosterone checked multiple times every year.
Some people may feel better with higher levels of testosterone (> 100 to 400). This is a healthy option as well. Some people on estradiol feel more energy, have better moods, better sex drive, and concentration with higher testosterone levels. Not everyone "has to have" super low testosterone levels. Again, it is about your response to estradiol and what you and your body tell us is working. This is why checking in on how you feel and are doing is more important than estradiol or testosterone numbers.
What about "androgen blockers?"
People can often be confused by the name "androgen blockers." When people take androgen blockers, they mostly take these medications to block any remaining testosterone effects on the skin and hair. Spironolactone, finasteride, and dutasteride mostly block male-pattern hair growth, while estradiol is the main hormone that decreases testosterone levels. Spironolactone can decrease testosterone levels a little bit, but that is not the main driver for suppressing testosterone production from the testes. We can see some minor decreases in testosterone levels with either spironolactone or progesterone. Still, we use these medications to support using estradiol, which is mainly responsible for lowering testosterone and increasing feminizing changes.
Typically, we do not adjust these medications to lower testosterone levels. How well spironolactone or finasteride/dutasteride reduces male pattern hair growth is a better way to adjust these medications, rather than measuring either estradiol or testosterone.
What labs do you measure for someone on spironolactone?
Spironolactone is a medication that can affect how the kidneys work. If your kidneys are young and healthy, spironolactone rarely has adverse effects. It may lower blood pressure and make you have to pee more frequently.
For folks on spiro, we check your creatine and potassium to make sure your electrolytes and kidneys are working properly.
If your kidneys don't work as well, this medication might lead to your kidneys retaining too much potassium. While rare, if the potassium levels are too high, it can lead to hyperkalemia. This is not common when taking medically prescribed GAHT. Still, it is a serious condition that can cause irregular heartbeats, trouble breathing, paralysis, and even death, and requires immediate medical intervention.
What about all the other labs that some providers run?
At FOLX, we run standard labs associated with GAHT/HRT to ensure that these medications are safe, effective, and meeting your goals. We only run labs that are necessary for the care we are providing. These labs include estradiol and sometimes testosterone, depending on your symptoms and care plan.
Some people may have other chronic medical conditions that may benefit from closer lab evaluation, and these are reviewed during our Informed Consent process so that members can decide how to proceed. If you have certain medical conditions, we recommend you discuss them with your FOLX clinician, who can also be your primary care provider (PCP). In addition to GAHT, your care team can help you assess or manage other conditions.
FOLX pairs lab results with our members' lived experiences to make medical decisions
At FOLX, we want to help you meet your gender journey goals. We offer excellent care and provide evidence-based medical updates and information. The most important part of this process includes listening to what your specific gender goals are so that we can adjust your plan accordingly. While labs are important tools, we do not base medical decisions solely on lab numbers. We take a holistic perspective to assess the safest and most effective plan for you.
It's important for us to hear from our members about how they are feeling. We will communicate if there are any concerns about your lab results from a medical perspective, but we may not adjust dosages solely based on these results. We want to hear from our members themselves about what feels right in their bodies and how they want to move forward before finalizing any changes.
Lab results can vary
The time you get your labs done in relation to when you took your last dose of estrogen HRT greatly impacts your lab results. Levels also depend on how often you miss doses, how much medication you give yourself, and the way your body metabolizes medication.
Timing of labs based on route:
- Pills: We recommend getting your blood drawn 6-12 hours after your last dose.
- Injectables: We recommend getting your blood drawn mid-injection. "Mid-injection" means day three or four after weekly injections or day seven or nine after biweekly injections. Getting your blood drawn at the end of your injection cycle gives us a falsely low number that isn't your true weekly average. Getting your blood drawn right after an injection captures a falsely elevated number that, again, is not your average weekly level.
- Patches: You can keep your patch on when you go to get your labs done. However, we do not recommend getting your labs done on the first day of your patch application, but waiting until day two or three after applying.
It can be harder to measure an accurate estrogen level in the bloodstream for people who take weekly or biweekly injections because the level of estrogen cycles from very high immediately after injection to very low right before the next injection.
Labs need to happen more frequently when starting or restarting estrogen
We follow people starting hormones more closely during the first year of treatment. This looks like checking in with your clinician every three months during the first year to assess if your goals and needs are being met.
We don't necessarily need to check your hormone levels every three months, but getting labs and levels around five to six months after starting E can be helpful. For people without chronic medical conditions or side effects, or those happy with their medication and meeting their gender goals, we usually do once-a-year blood work after the first year on estradiol.
FOLX wants to make getting labs done easy
FOLX orders lab draws at a member's nearest Quest Diagnostics Patient Service Center. Lab draws require going in person and having a vial of blood drawn through a needle. If you choose to go to Quest, it's important to know that they are required to use members' legal names on the lab requisition form. We know that this may lead to deadnaming or lab technicians using incorrect pronouns. If you experience anything like this at a Quest location, please let us know so that we can work on additional training and follow-up.
Read our Library article for more information on how to get your labs drawn at Quest or non-Quest locations.
Finally, for those switching over from a previous provider to FOLX for GAHT/HRT care, we can accept labs drawn within the last year, as long as they were done while on the same route and dosage requested from FOLX.
For those ready to get started with FOLX for estrogen, the process begins here. For existing FOLX members with additional questions about labs, don't hesitate to schedule time with a clinician. And for those who've just got some more questions, feel free to reach out to our Member Navigators at the FOLX Help Center.
FOLX Health is the first digital healthcare company designed by and for the LGBTQIA+ community. Our services include virtual primary care, gender-affirming hormone therapy including estrogen and testosterone (HRT), mental health care, sexual and reproductive health care, preventive care, and fertility consultations. FOLX memberships give you access to LGBTQIA+ expert clinicians, peer support, thousands of LGBTQIA+ resources, and more. Whether you’re lesbian, gay, bisexual, transgender, queer, gender non-conforming, or nonbinary, you can find LGBTQIA+-specialized health care that helps you meet your wellness goals. FOLX Health is health care that's queer all year. Get all the benefits of becoming a FOLX member and sign up today!