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

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FOLX Health

Jan 21, 2022

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Some transgender, non-binary and gender diverse people will begin hormone replacement therapy/gender-affirming hormone therapy (HRT/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 the method can always be changed at any point during your journey, if desired.

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 exactly the same— 17-B estradiol and testosterone. However, taking a medicine once weekly might make it easier to remember and help to keep levels constant in the long-run; this might explain in part 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 what feelings you have towards shots or needles, there are ways to navigate the injection process to help it feel simple and safe. 

FOLX clinicians can offer training for how to self-inject and are here to answer any of your questions along the way.

Forms of estrogen/estradiol and testosterone used 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 5mg/ml.  Estradiol valerate is suspended in caster oil and comes in concentrations of both 20mg and 40mg 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.

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 200mg/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 to every two weeks with intramuscular injections

Types of injections for hormone therapy

Subcutaneous (Sub-Q) injections


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, the needle is inserted at a 45° angle into an area of the body where there is some fatty tissue (some common areas include the belly, buttocks, outer or front facing thighs).

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. It takes a bit of force to push the oil based medicine through the tiny needle, so that should be expected. 

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.

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 hormones into a syringe and sterilizing the injection site, the needle is inserted at a 90° angle into an area of the body that has a good sized muscle (thigh, buttocks).

Since you are injecting directly into the muscle, and the needle is longer (22G or 23G and 1 to 1.5 inches in length) IM injections can be a more painful method for folks. 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, it might just mean the needle hit a small blood vessel.  If this happens, just use a tissue, cotton, or gauze to hold some pressure.

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.

Frequency of injecting hormones

With intramuscular injection, you have the option to either inject weekly or bi-weekly, as the large muscle can hold more supply. 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 site of injection. 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 type of suspension is one way to deal with these minor local reactions of swelling, firmness, 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 side effects of hormone replacement therapy are 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 on estradiol and get worse on testosterone. 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. Estradiols studied in cisgender woman and birth control have been shown to increase 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.

For each person, which route and dosage of hormones will change depending on your goals, body, and health history. You might prefer subcutaneous shots to intramuscular ones if you have a fear of needles, or opt for the biweekly frequency of intramuscular shots. For existing FOLX members with questions about self-injecting, don't hesitate to schedule time with a clinician. And for those who’ve just got some more questions, feel free to book a virtual visit with a FOLX provider
here or read up more on self-injecting here.

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