Estrogen and Testosterone HRT/GAHT: Subcutaneous vs. Intramuscular Injections

Learn about the differences between subcutaneous (Sub-Q) and intramuscular (IM) hormone injections for HRT/GAHT, including how and where to inject.

July 3, 2023
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Some transgender, nonbinary and gender-diverse people will begin hormone replacement therapy, also known as gender-affirming hormone therapy (GAHT) as a way to begin to live their lives authentically. Some people choose injections as their method for taking testosterone or estrogen/estradiol. There are other methods to deliver hormones and desired results which might include: topicals or transdermals, pills that can be swallowed or placed under the tongue, and long-acting testosterone injections and implants. Whatever method you choose, feel free to discuss the pros and cons of these options with your healthcare provider. It's important to know that if desired, the method can always be changed at any point during your journey.

Some people feel they notice faster changes when using injections rather than patches, pills, or gels (more on the differences in those routes for estrogen/estradiol here and testosterone here). The active hormones in all HRT/GAHT routes are 17-B estradiol and testosterone, depending on which hormone you take. Taking medicine once weekly might make it easier to remember and help keep levels constant in the long run; this might partly explain why it is more effective for some people who struggle with daily dosing.

There are two methods for delivering testosterone or estrogen with needles: subcutaneous (Sub-Q) injections or intramuscular (IM) injections. Both of these can be self-administered at home by yourself or with the help of a friend or family member. No matter your feelings towards shots or needles, there are ways to navigate the injection process to help it feel simple and safe. 

FOLX clinicians can offer training on how to self-inject and are here to answer any of your questions along the way. You can also sign up for nurse-led trainings on the FOLX Community Platform.

Forms of estrogen/estradiol in injections

There are two different types of injectable estrogen: estradiol valerate and estradiol cypionate. Both of these are precursors to estradiol and have similar affinity for estrogen receptors in the body, meaning they're equally effective. 

Injectable estradiol comes in two versions. Estradiol cypionate is suspended in cotton seed oil in concentrations of 5 mg/ml. Estradiol valerate is suspended in caster oil and comes in concentrations of both 20 mg and 40 mg per ml. Dosing is more dependent on whether you want to inject once weekly or biweekly (every two weeks). Self-injecting weekly means more injections per year, but more constant levels, and fewer side effects due to higher peaks and lower troughs. The released hormone in both versions is the same and equivalent for most people.

Injecting testosterone

Similarly, there are two types of injectable testosterone: testosterone cypionate and testosterone enanthate. Testosterone cypionate is suspended in cottonseed oil in a concentration of 100 or 200 mg per ml; while testosterone enanthate is suspended in sesame seed oil at 200 mg/ml. The most common injectable testosterone used in the US is testosterone cypionate which is the version that FOLX usually prescribes. 

Both testosterone and estradiol injectables can be dosed once weekly for subcutaneous injections or spread apart every two weeks with intramuscular injections.


Types of injections for hormone therapy

IM and SubQ injection sites on multi-colored bodies.

Subcutaneous (Sub-Q) injections for testosterone or estradiol

A subcutaneous injection sends a sterile liquid form of testosterone or estrogen (suspended in oil) into the fatty tissue under the skin. After drawing the correct volume of hormones into a syringe and sterilizing the injection site, insert the needle at a 45° angle into an area of the body with some fatty tissue. Common sites to inject Sub-Q include the belly, fatty parts of your arm, or outer/front facing parts of your thighs. If injecting around the belly, avoid the belly button or bony areas.

For most folks, this is a more comfortable and less painful method than intramuscular injections. Needles are relatively thin and short (typically a 25G needle, and ⅝ inches in length) since they go right underneath the skin into fatty tissue. It may take a bit of force to push the oil-based medicine through the tiny needle.

Make sure you throw away your needles in a sharps container after your injection. Do not reuse needles if you can, and call your provider if you run out of the necessary injection supplies.

Steps to prepare your injection:

  1. Gather all supplies, one of everything (injection needle, draw-up needle, medication vial, syringe) and two alcohol wipes.
  2. Remove the cap from the vial of medication.
  3. Wipe dark grey rubber in the center of the top of the vial with an alcohol wipe. Leave wipe on top of the vial until ready for use.
  4. Note different sizes on needles. Rule of thumb for sizing: the bigger the number, the smaller the needle.
  5. Open the larger needle (draw-up needle) to draw up medication.
  6. Open the syringe and gently screw on the open draw-up needle. Make sure it is not screwed on too tight.
  7. Draw up the same amount of air as the dose prescribed.
  8. Inject the air into the vial of medication and turn the vial upside down with the needle inside.
  9. Slowly draw up your dose. The key to minimizing air bubbles is to go slowly.
  10. Remove the needle from the vial. Slowly pull back on the plunger until you see air in the colored part of the syringe.
  11. Carefully replace the cap on the needle and remove the needle from the syringe.
  12. Open the other needle (the smaller one you will use for injection) and firmly screw it onto the syringe.
  13. Slowly push medication through the new needle until you see a drop at the tip of the needle to prime it.

Self-Injection

If you're a visual person, watch our How to Self-Inject: Sub-Q video:

Intramuscular (IM) injections

An intramuscular injection sends a sterile liquid form of testosterone or estrogen (suspended in oil) straight into the muscle. After drawing the correct volume of estradiol or testosterone into a syringe and sterilizing the injection site, insert the needle at a 90° angle into an area of the body that has a good-sized muscle. The best spot for IM injections is the outer thigh, for when you are self-administering.

IM injections can be a more painful method for folks since you are injecting directly into the muscle, and the needle is longer (22G or 23G and 1 to 1.5 inches in length). Common side effects include muscle soreness, bruising, or a bit of bleeding. There are no big or scary blood vessels in the area to worry about. Bleeding means the needle hit a small blood vessel. If this happens, just use a tissue, cotton, or gauze to hold some pressure until the bleeding subsides.
Throw away your needles in a sharps container (included in the FOLX HRT injection package) after your injection.


If you're a visual person, watch our IM injection guide video:

Disclaimer: FOLX prescribes estrogen and testosterone injectable form. The medication used in this video is progesterone, and not currently prescribed by FOLX in injectable form, and is used for demonstration purposes only.

The gluteal site (buttocks) is no longer recommended as an injection site. Over time, with repeated injections into the incorrect area, inferior gluteal nerve injury can occur. If gluteal location is truly desired, proper placement of injection is key to prevent nerve damage.

Frequency of injecting hormones

With intramuscular injection, you have the option to either inject weekly or bi-weekly, as the large muscle can hold a larger dose of medication. However, for subcutaneous injections, the fatty tissue does not hold onto the injected supply of hormones for the same length of time, meaning weekly injections are typically better.

Most people do weekly subcutaneous or intramuscular injections, but this can change depending on your dose and preference. Be sure to talk with your provider to help determine which frequency, dosage, and method is right for you.

Things to consider when injecting hormones 

Hormone injections can cause fluctuations in hormone levels, and most folks will see a bell-shaped curve, with the peak level occurring five to seven days after their injection. Weekly injections cause less dramatic fluctuations and, therefore, less side effects. Some people might see bruising, tenderness, or redness at the injection site. All injections can cause these symptoms and are related to the needle disrupting a minor blood vessel. 

Injections can also cause local allergic reactions. This is related to oil suspension—not the hormone! Changing the suspension type is one way to deal with these minor local reactions of swelling, firmness, and redness. Some people may also try icing the area before the injection and/or taking an allergy medicine such as Benadryl an hour before injecting to reduce allergic reactions. While unlikely, if you have a severe allergic reaction to injectable hormones, stop your medicine and tell your provider right away. 

Much of what we know about the side effects of hormone replacement therapy is based on limited research and clinical studies of trans people. The risks can often be overstated, and it’s important to put them in perspective. Much of what we know about the risks of hormone therapy often are based on cisgender populations, so the risks will not always be relevant for transgender people on HRT. That said, it’s important to know what risks there might be and always consult with your provider if you have questions or concerns.

Common side effects related to injectable hormones are similar to non-injectable routes of HRT/GAHT. Acne may improve with estradiol injections and get worse on testosterone injections. Sexual dysfunction and lack of menses may occur. Moods typically improve on HRT/GAHT but may easily change or be flatter. So far, research indicates that there are no clinically significant changes in blood pressure or metabolic labs and function. Hormones affect where we gain muscle and fat and can impact weight. Estradiol studied in cisgender women and birth control have been shown to increase the risk of blood clots or stroke but are not common in HRT/GAHT. Staying healthy and avoiding tobacco helps reduce that risk. If you have any predisposed medical conditions or concerns and questions about these side effects, make sure you consult with your healthcare provider to discuss what HRT/GAHT route is best for you and your body. 

The route and dosage of hormones will change for each person depending on your goals, body, and health history. If you fear needles, you might prefer subcutaneous shots to intramuscular ones, or opt for the biweekly frequency of intramuscular shots. Existing FOLX members can join an injection training or check out the resources in the FOLX Community Platform to get their questions answered.

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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!

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