TRT Side Effects: High Hematocrit and Hemoglobin
So I'm scanning the results of my latest blood draw and all the values are lining up in the "normal" column like good little blood soldiers. Yep, nailed it. A testament to clean livin'. I'd pat myself on the back if my rotators weren't so tight.
But wait, what's this? Two turncoats have deigned to slip into the "high" column.
Yep, hematocrit and hemoglobin.
I should have known. Those two are thick as thieves, and where one goes, the other usually follows. Hematocrit is simply a measurement that indicates what percentage of your blood is taken up by red blood cells. The hemoglobin test simply measures the amount of hemoglobin in your blood. (Hemoglobin is an iron-based protein that transports oxygen throughout the body.)
If hematocrit goes up, so too, almost always, will hemoglobin.
While a lot of things can cause elevated levels of those two blood values, I've got one giant, red-light-flashing risk factor working against me: Testosterone replacement therapy or TRT.
As terrific as it is, TRT carries with it a few possible negative side effects, and elevated hematocrit is perhaps the most serious of them.
It's simple physics. And simple plumbing. If you have too many red blood cells (high hematocrit), your blood gets thicker. Imagine replacing the motor oil in your car with maple syrup. The pickup pipe to the oil pump would slow or clog, and engine failure would be imminent.
That's almost identical to what thickened blood could do to your heart. The risk of heart attack or stroke escalate considerably. Engine failure becomes imminent. Little Bobby cries, "Why is Daddy's face in the bowl of oatmeal???"
Other possible dangers include an elevated risk of dementia and the general oxidative damage to the system that can occur when iron levels are high (you actually rust, in a biological sort of way).
While no one knows for sure why TRT raises hematocrit levels, there are a couple of decent theories. One is that testosterone stimulates red blood cell production by kicking up the production of a kidney hormone named erythropoietin (EPO) and recalibrating EPO's set point in relation to hemoglobin.
Another theory is that testosterone reduces hepcidin, a liver hormone that's involved with the absorption of iron (the backbone of hemoglobin). When hepcidin levels go down, production of red blood cells goes up, thus thickening the blood.
(Of course, there are various reasons why people can present with high levels of hematocrit even when they're not using TRT. I'll address those reasons later in the article.)
It seems contradictory, but symptoms of high hematocrit include fatigue, weakness, low energy, dizziness, and headaches. You'd think that having all those extra oxygen-carrying red blood cells would energize you, but it doesn't work that way. Increased viscosity makes the accessibility of all that extra iron/oxygen problematic.
However, most men on TRT with elevated hematocrit levels likely wouldn't feel any of those symptoms above. Either their hematocrit levels are only slightly higher than desired (which is still a risk factor for cardiovascular problems), or the TRT itself is energizing and overrides any feelings of fatigue that might otherwise manifest themselves.
- Normal hematocrit for men: 41% to 50%
- Normal hematocrit for women: 36% to 48%
- Normal hemoglobin for men: 13.2 to 16.6 grams per deciliter
- Normal hemoglobin for women: 11.6 to 15 grams per deciliter.
There's a little leeway in the men's values, however. A man, using what doctors call "strict criteria," isn't considered to be suffering from erythrocytosis until hematocrit is higher than 52% and hemoglobin is higher than 18.5 g/dl.
For some reason, women aren't granted that same leeway. Using those same strict criteria, a woman is considered to be suffering erythrocytosis when hematocrit is at least 48% and hemoglobin is 16.5 g/dl or higher.
You don't have to be on TRT to develop erythrocytosis. Before I list other potential causes, we need to differentiate between primary and secondary erythrocytosis. The former is usually a result of a neoplasm that causes the bone marrow to create too many red (and white) blood cells. It's a doubly serious condition that requires doctoring.
The second type of erythrocytosis is referred to as "secondary erythrocytosis," and it's the type associated with TRT. It's caused either by an increase in EPO production or a decrease in hepcidin levels.
Several things can cause secondary erythrocytosis. First up are conditions that cause oxygen deprivation, which in turn simulate the production of EPO:
- Severe lung disease, such as COPD (chronic obstructive pulmonary disease)
- Birth defects of the heart
- Carbon monoxide poisoning
- High altitude
And then there's secondary erythrocytosis that isn't caused by oxygen deprivation. The causes include:
- Kidney tumors, cysts, or narrowing of nephrotic arteries.
- Tumors of the liver, brain, or adrenal gland
- Genetic disorders
- And, of course, TRT
Obviously, most of the causes of erythrocytosis require medical attention. There are, however, several ways to reduce erythrocytosis, TRT-induced or otherwise, and not all of them require visiting a doctor.
Your elevated hematocrit/hemoglobin might well be directly related to your TRT. If so, there are ways to address that. However, your TRT might only be partly to blame as there are other conditions that can either contribute to high hematocrit/hemoglobin or even give false readings.
Depending on your situation, here are several ways to address high levels of hematocrit/hemoglobin:
1. Use a lower dose of testosterone
This is the most obvious solution to elevated hematocrit, but it's probably also the least popular. Hardly any man wants to use less testosterone and give up any of the increased energy, sexuality, and muscularity that the hormone has gifted him. But truth be told, a lot of men are probably taking more than they need. The standard TRT clinic dosage is 200 mg. a week, which is, frankly, equivalent to a mild steroid cycle.
2. Switch to subcutaneous injections
A study conducted by the Department of Urology at University of California found that subcutaneous (subQ) injections (under the skin rather than into the muscle) led to higher levels of free T, along with evidence of subQ being physiologically superior to IM shots in several other important ways.
Men who received subQ injections of testosterone exhibited the following:
- 14% greater total testosterone levels than those receiving IM injections.
- 41% lower hematocrit than those receiving IM injections.
- 26.5% lower estradiol than those receiving IM injections.
- No rise in PSA (the IM method didn't raise PSA either).
The second result is the kicker. Since subQ injections led to a 41% reduction in hematocrit levels, you could theoretically use the same dosage you use for intramuscular injections. Of course, given that subQ injections led to a 14% increase in total T, you might just use a lesser dosage anyhow and further reduce hematocrit while retaining all the positive effects of your TRT.
3. Consider another mode of TRT
Studies have shown that testosterone creams and gels raise hematocrit less than intramuscular testosterone injections.
4. Donate blood
This is the standard go-to treatment for high hematocrit. Every pint donated has been shown to decrease hematocrit by about 3 points. Unfortunately, you'd likely have to continue to periodically donate blood if you hadn't adopted any other hematocrit-lowering strategies.
That being said, there's some evidence that hematocrit levels stabilize after donating blood five times. Whether that's universally true is unlikely.
You can donate blood to places like the Red Cross or have your doctor perform what's known as a "therapeutic blood draw." Be careful not to donate too often, though. Giving a pint of blood more than every two and a half months or so may lead to long stints of fatigue.
High hematocrit readings sometimes occur because the patient was simply dehydrated, making it appear that the concentration of red blood cells was higher than it really was.
Of course, one simple way to determine whether your high hematocrit was caused by dehydration is to do a little simple math: hematocrit must always be three times the value of hemoglobin. If it's lower (Hct<3 x Hb), you're over-hydrated. If it's higher (Hct>3 x Hb), you're dehydrated. Either way, you're getting a false value because of your hydration status.
6. Avoid or reduce red meat consumption
Red meats are high in heme iron (the type of iron found only in animal tissues), which is more efficiently absorbed than non-heme iron (the type found in whole grains, nuts, seeds, legumes, and leafy greens), and ingesting it can raise hemoglobin and, subsequently, hematocrit.
7. Address sleep apnea
Sleep apnea is a medical condition where patients suffer from fragmented sleep. They literally stop breathing from 10 to 50 seconds multiple times throughout the night.
As a result of this interrupted breathing/sleep, patients experience poor oxygen saturation, which forces the body to produce more red blood cells and more hemoglobin.
8. Take curcumin
Evidence suggests that curcumin binds to ferric acid in the digestive system, thus reducing hemoglobin levels. Be sure to use micellar curcumin which is 95 times more bioavailable than regular curcumin with piperine.
9. Use Losartan to treat high blood pressure
If you've got high hematocrit/hemoglobin AND have high blood pressure, ask your doctor to consider switching your high blood pressure medicine to Losartan. It's been used by physicians since the early 2000s to bring down hematocrit in kidney transplant patients and patients with chronic obstructive pulmonary disease (COPD).
The only way to determine whether you have high hematocrit/hemoglobin is to have your doc order a standard blood chemistry panel. If you're a do-it-yourself kind of guy, plenty of online organizations will order the test for you without having to pester your doctor.
For instance, you can buy a Complete Blood Count/Chemistry/Lipid Panel Blood Test from Life Extension for $26.95. They'll email you the lab order, and then you can take it to your nearest LabCorp or equivalent to have your blood drawn. A few days later, they send you the results in an email.
You may balk at this, but it's a smart thing to do. There's too much irony (and tragedy) in getting your muscularity, libido, and overall joie de vivre up to snuff only to die from molasses-thick blood.
- Bachman E et al. Testosterone Induces Erythrocytosis via Increased Erythropoietin and Suppressed Hepcidin: Evidence for a New Erythropoietin/Hemoglobin Set Point. J Gerontol A Biol Sci Med Sci. 2014 Jun;69(6):725-35. PubMed.
- Choi EJ et al. Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate. J Urol. 2022 Mar;207(3):677-683. PubMed.
- Hanneke JC et al. Erythrocytosis in the general population: clinical characteristics and association with clonal hematopoiesis. Blood Adv. 2020 Dec 22;4(24):6353-6363. PubMed.
- Luoma TC. Luoma's Big Damn Book of Knowledge. Harper Collins, Moose Jaw, Saskatchewan, 12th Edition, 2019.
- Wang AYM et al. Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis. Am J Kidney Dis. 2002 Mar;39(3):600-8. PubMed.
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