Updated: Jul 6, 2018
Kyan Lynch, MD, MA
What lab tests are typically done before initiating hormone replacement therapy?
Step 1: Which Lab Tests Are Used?
Here are the lab tests recommended by the most commonly-used protocols for adults seeking hormone therapy. Some of these tests are primarily done at baseline, some are just done during follow-up after starting hormones, and some are done at both the beginning of HRT, and throughout treatment. Let's start off by listing them, and then we can go into more detail:
Labs for Masculinizing Hormones: CBC, Urine HCG, Testosterone
Labs for Feminizing Hormones: Prolactin, Estradiol, Testosterone
Trans Folks with HIV: Vitamin D Levels
Trans Folks at Risk for STIs: RPR, GC/CT
All Trans Folks: (the above, plus): CMP, HIV, Hep A,B,C, HgbA1c, DEXA (maybe)
Please note: every person is different, and these tests are just covering the basics. Some people might need additional tests based on family history, medical history, or physical exam.
Step 2: What the F Do All Those Letters Mean?
Let's get into it.
Let's start with the first group: lab tests for trans masculine folks.
CBC: A CBC stands for complete blood count. As the name implies, it tells us quite a bit about what's going on in your blood. As you may know, there are a few different types of cells in your blood. You've got your white cells, which are mostly responsible for taking care of infections, red blood cells, responsible for feeding your organs oxygen, platelets (and a few other floating components called factors) which clot your blood when you're injured, and the plasma, the fluid in which all the cells swim.
While all of those cells are super important in keeping you healthy and intact, the most relevant cells here are the red blood cells. That's because one of the possible side effects of testosterone is called erythrocytosis. Basically, that's a condition where your blood is overly crowded with red blood cells.
If red blood cells are good for you, what's the problem? Well, a study (called the Framingham study) found that blood crowded with red blood cells (demonstrated through an abnormally high hematocrit level) is more likely to lead to chest pain, heart attacks, and strokes. How? The theory is that thick blood running through your veins is more likely to get stuck than thinner blood; just like how thicker fluid is more likely to cause a pipe clog in your house than plain water.
When blood is stuck, it's not delivering oxygen. When organs lack oxygen, bad stuff happens. When your heart lacks oxygen, you have a heart attack. When your brain lacks oxygen, you have a stroke.
To keep an eye out for erythrocystosis, it's recommended that folks getting supplemental (exogenous) testosterone for hormone therapy get regular CBCs. For example, the Endocrine Society recommends that folks seeking testosterone therapy get a CBC at baseline, then every 3 months in their first year on T, then once or twice a year thereafter.
Urine hCG: The first part is pretty straightforward; you're gonna have to pee in a cup.
The second part, hCG, stands for Beta-Human Chorionic Gonadotropin. This is a hormone that placentas make like hotcakes when they are trying to convince embryos to stick around. Since I've used the words embryo and placentas, you've probably guessed where this is going. An hCG test will determine if a person is pregnant or not.
While many trans men would prefer not to think about being pregnant, it is an important thing to rule out prior to testosterone therapy. Why? Because testosterone can interfere with a fetus' development.
In addition to getting a pregnancy test prior to starting on testosterone, depending on the person, their sexual activities,and method(s) of birth control, pregnancy tests might be appropriate while a person is on testosterone as well.
Generally speaking, after some time (typically 1-6 months) testosterone will shut down menstruation, thereby shutting down the pregnancy apparatus and kissing shark week goodbye. However, as many trans men on youtube can attest, shark week can sometimes make an unscheduled appearance. While it is unlikely to get pregnant while on testosterone, it's not impossible. Hence, sometimes a pregnancy test might be appropriate. For more information on shark week see our article entitled, "What's the Deal with Shark Week?"
Testosterone level: I don't think I need to translate this too much. It's exactly as it sounds. So, instead, I'll just point out a couple of things:
1) The goal is to get your testosterone into the normal range for men assigned male at birth. Not too high, not too low, but just right. That range would be 400ng/dL - 700ng/dL. According to the Endocrinology Society, it's best to check this level every 3 months until it's where it's supposed to be.
2) The timing of when to draw your blood to check your testosterone level depends on the type of testosterone and the way in which you receive it. For some types of testosterone injections, it'll be best to measure testosterone levels midway between injections, for others, it should be measured right before the next injection. When using testosterone creams or patches, on the other hand, it's important to allow at least one week of daily application prior to drawing the lab.
Next, let's talk about labs drawn for folks on feminizing regimens.
First, it's important to remember that feminizing regimens can be a bit more complicated than masculinizing regimens. Whereas trans men typically just stick to testosterone to achieve masculinization, folks seeking feminization often start with estrogen and an androgen blocker (which blocks the masculinizing effects of testosterone and it's biological relatives still being pumped out by testes), and in some cases, progesterone, although the use of progesterone has been discouraged by many medical providers in recent years.
Now that we've got that covered, here are the lab tests that we'll talk about in this section: prolactin, estradiol, testosterone level, and BMP.
Prolactin: Prolactin is a hormone produced in all bodies by the pituitary gland. The pituitary gland is a very cute little bean-shaped gland the size of a pea that hangs down from the brain at the end of a stalk.
Prolactin is a very aptly named hormone. Pro = good, encouraging, more, and lacti- = milk. So, prolactin is a hormone that encourages milk production.
When, physiologically, does the body want to start encouraging milk production? During pregnancy, of course! The body is preparing for a baby, which includes food for the baby's first months on the planet. What's the hormone secreted like crazy during pregnancy to make the body more comfortable for a baby? Estrogen.
So, more estrogen = more prolactin.
Hopefully, it makes sense now that we would want to monitor prolactin levels in a person who is getting extra estrogen.
But why? What's wrong with more prolactin?
Well, picture a muscle. What happens when you ask the muscle to do more reps and work harder? It grows!
An analogous process can occur within that pesky pituitary. If estrogen therapy is causing the pituitary to work harder to produce a bunch of prolactin, the pituitary can grow, leading to a prolactinoma (also known as a pituitary adenoma).
As you can tell from this picture, when the pituitary is pea-sized, it just sort of hangs out and doesn't bother anybody. But when it grows, it starts encroaching on some sensitive territory. For example, a big pituitary (macroprolactinoma) can push on the optic nerve, causing people to lose their peripheral vision.
So, to keep tabs on this hormone and the cute little gland that produces it, it's recommended that folks on feminizing regimens get their prolactin measured at baseline, then yearly for a few years, then every 2 years. When prolactin levels are in the normal range (~5ng/mL - 25ng/mL), there's no reason to worry about the pituitary size.
Estradiol: Estradiol is the form of estrogen in the blood that we measure via lab test. Why measure estradiol? Well, one reason is pretty obvious: we want to see it go up!
However, another very important reason to check up on that estradiol level is to make sure it doesn't get too high.
The goal of all types of hormone replacement therapy is to get the hormone level into the normal range for a person who makes that hormone naturally. This is because we want to get the benefit of that hormone without dealing with the side effects. Another way of saying this: we want the lowest level of estradiol at which a person achieves the desired feminizing outcomes.
Why are we being so cautious? What's the problem with a little extra estrogen?
Well, estrogen is no joke. It's a very potent drug. And like all other potent drugs, it can do some damage if it's left unchecked.
The most worrisome side effect of estrogen is blood clotting. When blood estrogen levels go up, so does the blood's ability to clot. In some situations, this can be a really good thing. For example, during pregnancy, the excess estrogen produced leads to something called a hypercoagulable state, where hyper = extra and coagulable = blood clotting. While this can sometimes complicate pregnancies, it also makes a lot of sense, because as anyone who has seen a live birth can tell you - birth is a bloody affair. It's good to have a little extra clotting power.
Now, for folks taking estrogen for the feminizing effects, the clotting effects of estrogen are generally seen as unhelpful and potentially harmful. Blood clots can form inside the body, not just at the surface when a person is bleeding from a wound or birth. When clots form in blood vessels, they prevent blood from flowing to your organs. This can lead to bad things, like heart attacks, difficulty breathing, and strokes.
In addition to blood clotting, estrogen can also cause problems with the liver and high blood pressure.
For these reasons, it's very important for a person to get the safest types of estrogen (not all estrogen is made equally) from a licensed medical provider, and to get their estradiol level checked every 3 months, to ensure that it's in the normal range (100-200 pg/mL).
Testosterone: This is a repeat, I know. But there are a few things to mention about testosterone levels in persons on a feminizing hormone regimen.
First, as you might imagine, a person on a feminizing regimen wants more estrogen and less testosterone. Therefore, in addition to measuring estradiol every 3 months, we recommend that folks on feminizing regimens get their testosterone level checked at that interval as well. The goal is <50 ng/dL.
But, unfortunately, adding estrogen is usually not enough to suppress that testosterone level. There are two ways to get rid of testosterone: medicine and surgery. Surgery gets rid of testosterone by striking at the source; removing the testes and scrotum through a procedure called an orchiectomy will stop the body from producing testosterone, and estrogen therapy will take care of the rest.
For folks who don't want surgery, or aren't ready for surgery, another option is to use a medication called an anti-androgen. An androgen is a hormone that produces male/masculine development like body/facial hair. Therefore, an anti-androgen is a medication that blocks these masculinizing effects. Testosterone levels, therefore, might tell you more about how the anti-androgen is working, while the estradiol level tells you how well the estrogen dose is working.
BMP: A BMP is a basic metabolic panel. What makes it basic? Well, it's less informative than its big brother, the CMP, or complete metabolic panel. We'll talk about the CMP in a minute.
For now, let's talk about the BMP.
Even though it's "basic," the BMP actually contains some important information. A BMP will tell you about your glucose (sugar) level, calcium level, electrolytes (yep, the stuff in gatorade) like sodium, potassium, and chloride, and how well your kidneys are doing.
Why am I bringing it up now? Well, because of those anti-androgens I mentioned.
One of the most commonly prescribed anti-androgens is called Spironolactone. Interestingly, Sprinolactone wasn't developed to be an anti-androgen. It was developed and is most often used as a diuretic. A diuretic is a medication that makes you lose water by peeing a lot.
How does Spironolactone work? Basically, Spironolactone convinces the kidneys to throw out a bunch more salt (sodium) than usual. When the kidneys decide to pee out more sodium, they have to allow you to pee out more water than usual too, to balance it out. In the end, you pee a bunch, have less sodium, and less water in the body, which can lead to lower blood pressure.
What does this have to do with being trans? I'm getting there.
When folks start taking Spironolactone to block the masculinizing effects of androgens like testosterone, they are also going to experience the diuretic effects of Spironolactone. In addition to peeing more, it means that they can be in danger of losing too much sodium. Also concerning, Spironolactone is known as a "potassium sparing" diuretic because, unlike other diuretics, it stockpiles potassium in the body. This can lead to an excess of potassium, also known as hyperkalemia.
Electrolytes like sodium and potassium are really important. They are pretty much necessary for every cell in your body to complete it's daily tasks. So, yah, good to keep an eye on those levels. Namely, we don't want your sodium too low, or potassium too high.
Also, interestingly, this loss of sodium can lead trans women to start craving salt when they begin their hormone replacement therapy. Science is actually pretty cool, right?
Let's finish up with the most important lab tests for everyone.
CMP: As mentioned earlier, CMP stands for complete metabolic panel. It's more complete than the basic metabolic panel because it also offers liver function tests (LFTs). Hormones like testosterone and estrogen are metabolized, or broken down, in the liver.
Therefore, it's a good idea to make sure that your liver is healthy before you start HRT, and that it's handling everything OK once you start.
HgbA1c: Yes, that's a ridiculous combination of letters and numbers. It stands for hemoglobin A1c. Hemoglobin A1c is a kind of hemoglobin (the molecule responsible for transporting oxygen in your blood) that has been altered by the presence of glucose (aka sugar). When you've got a lot of sugar/glucose floating around in your bloodstream, the amount of hemoglobin A1c you have goes up. Therefore, it's a good way of knowing if you've been exposed to more sugar than is healthy over the course of the last few months. If so, you might be diagnosed with diabetes. According to the latest guidelines, a hemoglobin A1c level of 5.7 or higher is indicative of diabetes.
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