Why testosterone boosts hematocrit

[Jerry Brainum]

http://biomedgerontology.oxfordjournals.org/content/early/2013/10/24/gerona.glt154.abstract

Testosterone Induces Erythrocytosis via Increased Erythropoietin and Suppressed Hepcidin: Evidence for a New Erythropoietin/Hemoglobin Set Point
Eric Bachman Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Boston Medical Center, Massachusetts.


Background. The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear.

Methods. We assessed the hormonal and hematologic responses to testosterone administration in a clinical trial in which older men with mobility limitation were randomized to either placebo or testosterone gel daily for 6 months.

Results. The 7%–10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. Consistent with increased iron utilization, soluble transferrin receptor (sTR) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men. Hormonal and hematologic responses were similar in anemic participants. The majority of testosterone-treated anemic participants increased their hemoglobin into normal range.

Conclusions. Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis.

 

[Gene Devine]

Nice find Jerry!

 

[Brooksy Chuck]

does anyone have time to break this down in "laymans" terms?

 

[Austinite]

does anyone have time to break this down in "laymans" terms?

Hepcidin is a peptide that your liver produces. It exists to regulate iron metabolism. We're gonna come right back to hepcidin in a second...

You see, there's this protein called Ferroportin. It's job is to find cells that are holding/storing iron, and it dives inside and pulls the iron out of that cell. Now that iron is free and ready to be metabolized.

Hepcidin is released whenever your Ferroportin pulls too much iron from the cells. Hepcidin is the boss here. It's the 'master iron regulator' and wants to manage the iron so that you have a balance. So Hepcidin swims over to Ferroportin and puts handcuffs on it. Now Ferroportin is in jail and can't free anymore iron.

So what would happen if Hepcidin wasn't around to police Ferroportin? Well, Ferroportin would go nuts and start yanking all the iron out of every cell it can find. And you would end up with a whole bunch of iron in your body that's ready to be metabolized, even though it's supposed to be stored for emergencies. But wait... How is all this iron supposed to get around? It can't swim on it's own. They needs a vehicles. Are you thinking what I'm thinking? Oxygen!

Hemoglobin is the protein that lives inside of the red blood cells. It holds the oxygen that RBC's are transporting. That oxygen is like a magnet for iron. So when the red cells come around... iron hops inside the cell and binds to oxygen. Now we have oxygen, iron and hemoglobin all nice and cozy inside papa red cell.

There's a problem with this scenario, though. If Ferroportin is out of control and releasing a ton of iron, what happens when there's too much iron and not enough red cells (vehicles)? A phone call is made. "Hello? Houston! We have a problem!" (Houston is the red bone marrow that produces red cells). So this phone call is causing red bone marrow to produce a whole bunch of red cells so we can have enough vehicles to carry all this iron around. Non stop production. Millions by the second I tell ya, millions!

So now we have a ton of red cells. But hold on a minute... I know that my body didn't generate more veins to make room for all these cells. So what's going on? There must be a RIDICULOUS traffic jam in my blood. That's exactly what happened. Tons of red cells are swimming in the blood, only a lot slower than they should because of traffic. Man! My blood is jammed up and moving very slowly. Not cool!

Hmm. I remember that red cells also carry oxygen, does that mean my body is not getting oxygen fast enough? Yup! And I'm also going to have trouble breathing, causing even more problems. Oxygen deprivation also increases red cell production and inevitably, hematocrit (blood thickness) rises.

Any oxygen deprivation scenario will increase hematocrit. Sleep apnea, smoking, living in elevated areas, etc..

Hope that helps.

 

[Brooksy Chuck]

Wow! this is great! thank you Austinite! that helps to understand why taking iron isn't good while on TRT. nice visualizations!

 

[GettingAnswers]

So why does supplemental testosterone cause this but natural production does not? Is it due to the constant non-pulsatile nature of TRT, the larger less frequent doses, or what? And has anyone found a way to combat it beyond donating blood? i.e. more frequent injections, a supplement (I read grapefruit on here) or anything else.

 

[Nelson Vergel]

GettingAnswers:

You are right. You have basically said what is a fact. Besides donating blood or taking a drug that can cause anemia (in HIV the drug AZT is known to decrease hematocrit. In cancer, chemo decreases hematocrit also), there is no other way to manage the problem. More frequent injections with lower spread out doses may help. Also, the use of testosterone gels daily may present less of a problem with hematocrit than injections.

The effect on hematocrit is larger in older men than younger men. Here is a study: Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men
Here is a section of my book that talks about high hematocrit caused by testosterone:
How to Manage Increased Hematocrit Caused by Testosterone Replacement Therapy

 

[Carlos]

Austinite, good explication on the theme. Very clear now.

 

[Nelson Vergel]

Hepcidin is not essential for mediating testosterone's effects on erythropoiesis - PubMed

Although hepcidin suppression by testosterone increases iron availability and erythropoiesis, hepcidin suppression is not essential for mediating testosterone's effects on erythropoiesis in healthy mice.

pubmed.ncbi.nlm.nih.gov