What To Expect When You're Injecting

A comprehensive guide for injectable HRT

Foreword: I am not a medical doctor, and this should not be considered medical advice. PLEASE consult with your own provider. This guide is meant as a preview of what to expect for those considering injectable HRT and a reference guide for those who want to make sure they’re following safe, sanitary injection procedures.

You’re looking at injections for your HRT. Needles. Ugh, needles! 😖

If you’re anything at all like me, you hate needles. The idea of stabbing yourself once a week for the rest of your life? Y-I-K-E-S! I was scared as heck when I had to turn to injections. It’s been more than two years now, and things are way better for me—and I want to help you over that initial hump if injections are in your future too.

And I promise, we’re gonna talk about how to make the whole stabbing yourself thing way, way better too.

Why injections?

Realistically, there are two reasons why you might be looking at injections: either you’re transmasculine or you’re transfeminine and estradiol pills aren’t a good option for you.

Transmasculine folks

If you’re transmasculine, oral testosterone isn’t an option for you right now because, historically, pill versions of testosterone have been really bad for your liver. Now, that might be changing, but given the history of liver destruction on long-term oral testosterone in the past, regulators are going to want to see a mountain of evidence before they approve a new oral version, especially for lifelong use.

So right now, for you, that means you either need to be on testosterone gel or injections. If you live with small kids, if you’ve got a partner who’s running on estrogen, if you’ve got a dog—topical gel can get into them from touching you, so it might not be a safe option. For this reason, a lot of transmasculine people who use HRT prefer injections. They’re just safer for your family.

There are four different formulations of injectable testosterone, but by far the most commonly prescribed is testosterone cypionate, which can come in 100 mg/ml or 200mg/ml concentrations. It’s more desirable than testosterone enthanate, the next most commonly-prescribed testosterone, because it has a much longer half-life (we’ll get to this later). As with any other form of prescription testosterone, it is a controlled substance in many countries, such as the U.S., so there will likely be a few annoying hoops that you need to jump through as you’re getting your prescriptions.

Transfeminine folks

If you’re transfeminine, there are a few reasons why you might be put on injections. The most common is that you can’t maintain cisfeminine estradiol levels on pills alone. The second most common is that you’re a little bit older. Oral estradiol is heavily processed by the liver, so WPATH guidelines recommend that you not be on oral estradiol if you’re over 50. In either case, they may have had you try patches, which can have adhesion problems, or topical gel, which can be risky for your family if you live with kids, a partner who’s running on testosterone, or cats. For these reasons, most transfeminine people who aren’t on pills go for injections. Like with testosterone, it’s just safer for your family.

Injectable estrogen can come in three forms, estradiol cypionate, estradiol valerate, and estradiol enthanate. E enthanate is, to my knowledge, rarely prescribed, but is commonly used in DIY HRT. As a result, I will not be discussing it in this article. While I support DIY HRT when it’s necessary, I feel it should always be used as a bridge to some form of traditional, medically-supervised HRT, because while HRT is very safe when supervised, there are quite a lot of very serious long-term problems that can crop up when unsupervised, including ones that can kill you. At the very least, if you’re on DIY HRT, please get regular blood estradiol and testosterone tests at a private lab. You can pay out of pocket for them if privacy is important.

E valerate is the most common injectable estradiol, though e cypionate is commonly used and safe too. E valerate is more common simply because it’s more available; shortages of e cypionate are all but endemic in the U.S., for example. E valerate comes in three concentrations—10 mg/ml, 20 mg/ml, and 40 mg/ml—while e cypionate comes only in 5 mg/ml. Despite the disadvantages, e cypionate is desirable for transfeminine people because it has a longer half-life (again, we’ll get to this in a minute), which means you can go longer between injections.

Stay on target

Before we get to the nuts and bolts of what we’re doing and how to do injections right, let’s talk objectives. What we want, at all times, is to be within typical testosterone and estrogen levels for cis people of our gender—these are the levels the body expects to be working with, and as such they’re the safest. If you’re too low for a long time, there’s an increased risk of osteoporosis and dementia, and if you’re high, there are risks too, though those differ depending on whether you’re using testosterone or estrogen.

Before I continue: no matter how you feel about your natal sex hormone, it can be very dangerous to reduce it to extremely low levels. All bodies require both testosterone and estrogen for their survival.

I’m giving measurements for each level in two units, because different health systems use different units of measurement.

A note on nonbinary regimens

I want to start here with a note on HRT regimens often used by nonbinary folks, who sometimes will work to balance testosterone and estrogen levels, or to microdose hormones for more incremental effects. Unfortunately, zero serious research has been performed on these HRT regimens, so I’m not comfortable offering advice. I’d strongly recommend working with your prescriber if you’re looking at target hormone levels that are not typical of cis men or cis women.

Transmasculine target levels

Transmasculine folks on HRT have wide, easy-to-hit, well agreed-upon target ranges:

• Testosterone: 300-1,000 ng/dl, or 3,860-12,870 pmol/l

• Estrogen: 10-50 pg/ml, or 37-184 pmol/l

Transfeminine target levels

Transfeminine folks on HRT generally have to deal with conflicting target ranges for estrogen, which are often very narrow. The Endocrine Society recommends a very tight band, aimed at minimizing patients’ risk of a blood clot, which could kill a patient. The problem here is that that recommendation was designed based off of the use of Premarin, an estrogen which is no longer in use and which has a very high risk of blood clotting. Modern estradiol does not carry this risk to a significant degree beyond the first year of use, and carries it most significantly in its oral form. There is currently no high-quality evidence that I’m aware of that suggests that injected estrogen significantly increases risks for blood clotting among people without blood clotting disorders (again, outside of the first few months of use). Several other standards of care, such as UCSF’s, endorse estrogen levels anywhere within the range that cis women typically have for this reason.

Because of this conflict, I will be presenting the Endocrine Society’s target ranges and typical premenopausal ranges for cis women. I encourage you to consult with your prescriber about what’s right for you.

• Estrogen, Endocrine Society: 100-200 pg/ml, or 370-730 pmol/l

• Estrogen, cisfeminine range: 30-400 pg/ml, or 110-1470 pmol/l

• Testosterone: 15-70 ng/dl, or 190-901 pmol/l

Because large portions of the cisfeminine estrogen range fall within the range for cis men—this is because cisfeminine estrogen levels vary over the course of the menstrual cycle—I personally use a hybrid of this range to guide my own treatment, taking the bottom of the recommended range from the Endocrine Society and the top of the typical range for cis women as my acceptable target range. That, for me, is a range of between 100-400 pg/nl. That way I’m never in cismasculine ranges, and never at a higher level than cis women have.

Injection frequency and testing

The biggest advantage of being on hormone injections is that you only need to fuss with your HRT every so often. That said, I strongly recommend some patient self-advocacy when you’re working with your HRT prescriber, because standard dosing regimens are not based in smart science—which may explain the low, but increased, blood clotting risks estradiol runs, for instance. All standard regimens for both testosterone and estrogen recommend injecting once every 14 days, and testing in the very middle of that dosing cycle. While this is a bad idea for all forms of HRT, it’s most apparent when we look at e valerate.

Estradiol valerate and why biweekly injections are dumb

Transfem Science offers a lovely tool to simulate levels of estradiol when someone’s injecting, and while there are major problems with using it as a definitive predictor—for instance, it can’t account for the estrogen a transfeminine person’s body naturally produces, and each body processes estrogen at different rates—it’s a handy device to show how a body will process medicine over time.

This picture is an example dose of how a body will use up a single, 1ml (20 mg/ml) injection of estradiol valerate over time, which is the standard starting injection dose recommended by the Endocrine Society.

The problem here is that if you follow ES recommendations and test yourself at day 7, you’ll have a reading of about 120 pg/ml—and almost seven days where your estrogen levels will be below your target range. What’s worse, you’ll have estrogen levels in the normal range for cis men four days out of every 14, or about 28% of the time!

The reason this happens is that estradiol valerate has a half-life of about five days, which means that every five days, half of the estrogen that gets injected is used up. That means, in turn, that a transfeminine person’s estrogen levels on day 14 of their injection cycle is only about 12.5% of what it was at its peak!

That sucks. Basically, it’ll put you through menopause every other week.

If, instead, that same person does a smaller injection of estrogen every five days—at the half-life of e valerate—their levels will be much more stable, and will be within the Endocrine Society’s recommended range at all times.

A strategy like this is much safer and more effective at delivering appropriate amounts of estrogen to a transfeminine person at all times, as you can see.

Personally, I test right before re-dosing myself, a strategy known as trough testing, which provides more consistent tracking data. I prefer trough testing to midcycle testing because of e valerate’s quick half-life; a difference of a few hours at mid-cycle can have a meaningful effect on your test levels, which makes those test readings too unreliable for my preference. Since I inject first thing in the morning, trough testing just means that I head over to the lab bright and early on testing day, right before I inject. A big advantage of trough testing when you dose at the half-life of your hormone is that you can simply double your test results and know just about what your maximum level was.

Talk to your provider to develop a strategy that you prefer.

Half-life reference table

We’ve spent a lot of time looking at e valerate because it’s a good example, and because Transfem Science offers us a handy tool to see the difference time and dose strength makes, but these same principles apply identically to all forms of injectable HRT. Here’s a reference chart you can use, so you know how quickly your HRT gets used up:

• Testosterone Cypionate: 8 days

• Testosterone Enthanate: 4.5 days

• Estradiol Valerate: 5 days

• Estradiol Cypionate: 10 days

You may notice that, if you look up some of these that the listed elimination half-life is shorter than what I’m quoting—e valerate, for instance, has an elimination half-life of 3.5 days. The reason for this is that elimination half-life is measured not from the moment of injection, as simple half-life is, but from peak dose strength. All injectable drugs need a much longer ramp-up time before they hit their peak doses—usually a day or two—because the body absorbs the carrier oil that your hormones are suspended in, causing the hormones to condense into a tiny crystal in your body. Only then can it be absorbed at its peak rate. If you’re a dork, like I am, you might even hum a little ditty while you inject some weeks because of this.

If you want to, you can inject even smaller amounts of your HRT even more frequently if you prefer extremely stable levels and don’t mind repeated injections, but less-frequent injections are a little safer in principle—there’s always a low chance that something goes wrong when you inject.

One additional note: stop taking multivitamins or biotin at least three days before going in for a levels test! Biotin is used as a reagent in estrogen level tests, and if your blood level of biotin is outside of normal ranges, it’ll give you wildly incorrect test results.

Let’s talk about how you can keep your injections as safe as possible!

Get your gear

To inject safely, you’re going to need some specific stuff. Here’s a full list:

• A vial of your hormones

• A STERILE syringe

• A STERILE needle

• An alcohol swab

• A band-aid

• A container to put your needle in after you’re done

• (Optional) An autoinjector needle guide, if you’re needle-shy like I am

You’ll get your hormones from your pharmacy, obviously. The alcohol swab, band-aid, and sharps container can be gotten anywhere you prefer; you can even use an old soda bottle for your sharps container, but sharps containers are pretty cheap. I like the professional ones because I can drop them off at the local health department for safe disposal when they’re full. They’re not very expensive.

You can get your needles and syringes at a pharmacy too—but they’re usually much more expensive there than they would be if you bought them yourself from a hospital supply company. Some states and countries have laws that prevent these companies from selling needles and syringes directly to patients, but the suppliers’ websites should stop you if that’s the case. If you’re getting your own needles and syringes, you’ll need slightly different equipment, depending on whether you’re injecting intramuscularly or subcutaneously—just check your vial. It’ll tell you how you’re supposed to be injecting.

If you’re injecting subcutaneously, you’ll want a needle between 1/2” and 5/8”.

If you’re injecting intramuscularly, you’ll need a needle between 1” and 1.5”.

You’ll notice that each needle also has a gauge, which describes how big around the needle is. A smaller gauge number is larger, which is good for getting your hormones into the syringe quickly, but it’ll hurt more when you actually go to inject, while the opposite is true for high-gauge needles. Because of this, some people like to use a larger needle, like an 18ga, to fill your syringe, and a smaller, like a 23 or 25ga needle, to inject.

Personally, I don’t like to be wasteful, so I split the difference with a 21ga needle that I use to both fill and inject, and I just have a little patience while I fill the syringe.

Safety first!

The single most important part of injecting is doing so safely—there are more spots where things can go wrong, which translates to more risk of a patient getting hurt, than with pills. That’s why doctors prefer pills over injections whenever they can.

Please understand that following safety procedures religiously makes a huge difference in staying safe when you’re injecting.

Our enemy when injecting is bacteria. Unfortunately, bacteria are everywhere, even in the air, so there’s no such thing as a sterile injection, only a sanitized one. The moment you open the sterile pack that your syringe came in, it’s no longer sterile—same for your vial of hormones. As such, here is a process to get yourself ready to inject that’ll keep things as safe as possible:

1. Check your hormone vial for anything in the fluid of your hormones. If you see any cloudiness at all, any grainy bits at the bottom, or anything floating in the fluid, throw the vial away immediately and contact your pharmacy for a replacement.

2. Open your alcohol swab.

3. Sanitize the top of your vial of hormones by pressing the alcohol swab into the rubber nipple in the middle and turning it back and forth 20-30 times, so the alcohol swab thoroughly scrubs everything on top of the vial that isn’t glass, including the metal part that holds the rubber nipple.

4. Set the vial down without letting any part except the glass touch anything, including your hand.

   1. If you do, go back to Step 3 and try again.

   2. Don’t throw away your alcohol swab. You’ll need it again in a minute.

5. Open the blister pack that your needle and/or syringe is in.

   1. If your needle and syringe are separate, twist the needle onto the syringe without letting either touch anything except each other. If they do, throw both away and try again.

6. Take the cap covering your needle off and throw it away.

   1. NEVER put a cap back on a needle. That’s the #1 way to hurt yourself while injecting.

7. Pick up your vial in one hand and your syringe in the other.

8. Carefully stab the needle through the middle of the rubber nipple.

   1. There’ll be a little circle raised on most of them, to show you where the best spot to poke it is.

9. Turn the vial upside down, so the fluid is concentrated near the cap.

10. Pull the plunger of the syringe farther than your dose.

    1. For instance, if you need to inject 0.3ml, pull the plunger to 0.5 or 0.6ml.

11. Wait patiently as the syringe fills.

    1. It will probably stop filling with a bubble of air in the barrel of your syringe. This is normal, and why we pulled the plunger back farther than we needed.

12. Keeping the vial upside down and the syringe pointing straight up, push the plunger back in to squeeze any air and any extra fluid back into your vial.

13. Carefully pull the needle out of the vial and set them both down, making sure that the needle doesn’t touch anything.

14. If you’re changing needles, carefully unscrew your draw needle and screw on a fresh injecting needle, making sure that the needle doesn’t touch anything, and repeat Step 12, except without the vial, until a tiny bit of fluid comes out the end.

An optional step 15, if you’re needle-shy, like me

I can’t poke myself with a needle if I can see the needle. Just can’t. I’ve been injecting for years, and I absolutely, positively can’t. If you’re like me and you need to inject, the good news is that there’s a tool that’ll help you.

I use this autoinjector every week when I inject, because I do intramuscular injections. If you’re doing subcutaneous injections, you’ll want the 45 degree angle one. Yes, I know the website looks sketchy as hell. It’s legit, and their customer service is actually top-notch. And no, they haven’t paid me a cent or asked me for this plug. I just think their stuff is amazing.

The autoinjector works by using a spring-loaded plunger to jab the syringe into your body for you—all you have to do is clip the syringe into it and push a button. It’ll even hide the needle from you while it does it. The only downside is that you’re stuck with the type of syringe you order it with—both needle length and barrel type. One big advantage of these devices is that they jab the needle into you faster than any human possibly could unless someone’s basically playing darts with the syringe, and fast means less pain.

So, if you use this device, for step 15, prime it by pulling the top back until you hear the little latch inside catch and clip your syringe in, being careful to keep the needle from touching the autoinjector.

How to inject safely

From here on, everyone’s going to be using one of two strategies, which your prescriber will choose for you. Either you’ll be injecting intramuscular (IM), deep into a muscle, or subcutaneously (SubQ), shallowly into a fatty area. The easy way to think of these options is this: when you get your flu shot, that’s an intramuscular shot, while people with diabetes inject their insulin into their bellies, subcutaneously.

The biggest difference between IM and SubQ injection—even more than where you inject—is the needle you use. IM uses a longer, larger needle, whole SubQ uses a shorter, finer needle, sometimes as tiny as 30ga. That’s great for reducing pain, but it means that you definitely have to change your needle after loading your syringe up. Hormones come in a viscous oil, and it can take a long time to load a fine needle.

From here on, our procedure is going to diverge a little bit, because the procedure for SubQ and IM injection are different.

Intramuscular injections

There are three main spots around the body where you can safely perform an intramuscular injection: in the deltoid (your shoulder), the ventrogluteal (your hip), and the vastus lateralis (your outer thigh). However, the shoulder and hip target spots are small—between the size of a quarter and a silver half-dollar—and if you’re injecting yourself, you have to twist a lot to get at them. Because of this, when you’re self-injecting, it’s really easy to miss the safe target spots on the shoulder and hip. Meanwhile, your thigh has a target area about the size of your whole spread hand, and you don’t need to twist to hit it.

Please do not attempt to self-inject into your shoulder or hip. It’s a bunch of extra risk for no extra benefit. If someone else is doing your injections for you, they’re fine spots to inject, but going for the thigh is still best in general.

To find your injection site, you can use the width of your hand to make an imaginary rectangle on your leg. Sit down on a chair, then put one hand crosswise at the top of your thigh, even with the bottom of your crotch, and the other touching your knee on the bottom side. Everything in between your hands are the top and bottom of the safe target zone. Then, put one hand on the side of your hip so one side is touching the chair you’re sitting on and the other on the top of your thigh so that the outside of it is at the middle of the top of your thigh. The insides of your hands there will tell you the left and right borders of your safe target spot.

We want to target this spot because there are no big veins that you could accidentally spear, and because there aren’t a lot of capillaries, so your hormones won’t be absorbed too quickly.

Once you know where the safe spot is, here’s your plan for safely injecting:

1. If pain is a problem for you, you can hold an ice cube on that spot for a minute or two to numb it.

2. After that, wipe your target spot down with your alcohol swab.

3. Let it dry for a few seconds.

   1. It’s fine to fan it with your hand to speed things up, but don’t blow on it.

4. Carefully pick up your syringe, making sure that the needle doesn’t touch anything, and hold the barrel on your hand like you would a pencil.

5. Rest your wrist a little bit above your target spot and rotate your wrist away from your thigh.

6. With a single, quick snap of your wrist, jab the syringe into your target spot all the way up to the plastic hub of the needle.

   1. Your goal is for the syringe to be at a 90 degree angle to your thigh.

   2. The quicker you jab the needle in, the less painful your injection will be.

7. Holding your syringe barrel in one hand, pull the plunger of the syringe back just a little bit. If you see any blood in the syringe at all, remove the syringe and start over completely.

   1. This should basically never happen, but bodies are weird. Once in a very great while, someone grows a vein where it’s not supposed to be, and it’s a bad idea to inject a week’s worth of hormones straight into a vein.

8. If you don’t see any blood in the syringe, push the plunger of the syringe all the way down with your other hand.

9. With a single, quick pull, remove the needle from your thigh and set it on a convenient table.

   1. If a little blood or fluid leaks out, don’t worry. That’s just the vascular action of your thigh squeezing the hole you just made shut. It won’t be enough to make a difference.

   2. If you get a little more blood, which won’t happen often but which will happen once in a while, you hit one of the few capillaries in the vestus lateralis. Don’t worry! It’s fine. The whole reason we’re going an inch to an inch and a half deep is that there’s nothing at all at that depth. You just speared something on the way in.

10. Put a band-aid on your injection site.

11. Put any needles you used in your sharps container and throw everything else except for the vial of hormones (and autoinjector, if you used one) away.

If you need or want to practice the stabby part, get a couple of oranges from the grocery store. They’ve got a resistance very similar to your thigh’s, so they’ll give you good practice at what kind of force you’re going to need to get the needle up to the hub.

It’s also a good idea to go back and forth between your thighs with each injection, just so you don’t build up scar tissue, but if you’re really dominant in one hand, it’s okay to stick to one thigh. Just try to not use the exact same spot over and over.

Subcutaneous injections

Technically, you can do a subcutaneous injection anywhere you’ve got a good amount of fat, but your tummy is a large area that’s really easy to get at, so there’s no good reason to inject anywhere else unless either you’re very thin or you use insulin and want to spread out where you’re sticking needles into yourself—but if that’s you, you won’t need my help with how to do subcutaneous hormone injections, because it’s pretty much the same as with your insulin. If you’re very thin, talk to your prescriber and get some help finding a spot that’s going to work safely for you—or, as a better option, ask to switch to intramuscular injections.

To find a good spot, find your belly button. Anywhere that’s at least the width of a quarter away from your belly button is a good spot to inject, but it’s particularly important to move your injection site from injection to injection when you’re doing subcutaneous injections. Most people who do subcutaneous injections like to quarter their bellies and move from one quarter to the next, in a clockwise rotation, from injection to injection.

Once you’ve picked your spot, here’s your plan for safely injecting:

1. If pain is a problem for you, you can hold an ice cube on that spot for a minute or two to numb it some.

2. After that, wipe your target spot down with your alcohol swab.

3. Let it dry for a few seconds.

   1. It’s fine to fan it with your hand to speed things up, but don’t blow on it.

4. Carefully pick up your syringe in your dominant hand, making sure that the needle doesn’t touch anything, and hold the barrel like you would a pencil, but toward the top of the syringe, well away from the needle.

5. With your non-dominant hand, gently pinch a 2-inch section of your target spot between your index finger and thumb, so you have a little lump of tummy.

   1. If it hurts, you’re pinching too hard!

6. Gently lift the lump of tummy away from your abdomen a little bit.

   1. This helps make sure you don’t accidentally go too far if you’re skinny and inject into your abdominal muscle.

7. With a single, quick jab, insert the syringe into your target spot all the way up to the plastic hub of the needle.

   1. Your goal is for the syringe to be at a 45 degree angle to your tummy.

   2. The quicker you jab the needle in, the less painful your injection will be.

8. Holding your syringe barrel in one hand, pull the plunger of the syringe back just a little bit. If you see any blood in the syringe at all, remove the syringe and start over completely.

9. If you don’t see any blood, push the plunger of the syringe down either with your thumb or index finger.

10. With a single, quick pull, remove the needle from your thigh and set it on a convenient table.

    1. If a little blood or fluid leaks out, don’t worry. That’s just the vascular action of your tummy squeezing the hole you just made shut. It won’t be enough to make a difference.

11. Put a band-aid on your injection site.

12. Put any needles you used in your sharps container and throw everything else except for the vial of hormones away.

Clean-up

While it’s a little freaky to get used to, injecting hormones is safe and pretty easy, once you get into the routine of it—I don’t spend more than five minutes a week on injecting. That said, there are a couple of things that you should keep in mind as you inject:

1. All reusable medication vials are treated with an antimicrobial on their insides, but that antimicrobial is only certified for 28 days after you pierce the vial the first time.

   1. Some American insurance companies will try to weasel out of giving you a new vial every month by claiming that the volume of medication is enough to last you longer. If they do, appeal the decision, because per FDA regulations, they cannot do that, as it is unsafe.

   2. This doesn’t mean that your vial is instantly contaminated on Day 29, and I’ll use a vial that’s a day or two out of certification as long as it’s clear and pure inside. It’s not usually a good idea to use it down to its last drop, though.

2. Sometimes a bit of the nipple will break off and fall into your hormones when you stab through it to draw hormones up for an injection. This is called “coring,” and if that happens, the vial is no longer sterile, and needs to be replaced immediately.

   1. This happens because of occasional microscopic defects in the rubber. Just a quirk of working with natural products.

   2. Your pharmacy won’t give you any problems about replacing the vial, and it shouldn’t cost you anything. Like I said, it’s just a thing that happens from time to time.

3. Never, ever use a needle for more than one injection. If you go to jab yourself and don’t get deep enough, either push it the rest of the way into its proper depth (ouch!), or remove it, change the needle, and try again.

   1. You might not expect it, but every single time a needle goes into anything, it gets damaged. It only takes a couple of pokes to make it really dull and jagged, which means it’ll hurt you a lot more.