Testosterone Increases Erythropoietin

Can our mild anemia be alleviated by increasing testosterone?

I found several studies that show that testposterone can increase erythropoietin. Erythropoietin will increase hemoglobin. This is a quite indicative study:

Testosterone regulates erythropoiesis in numerous mammalian species, including humans of both sexes (1). Excessive erythrocytosis is the most common serious adverse event associated with testosterone therapy in older men (2). However, the mechanisms by which testosterone stimulates erythropoiesis remain poorly understood.

It has been suggested that testosterone stimulates erythropoietin secretion and directly stimulates erythroid progenitor cells (3, 4). We showed previously, however, that testosterone dose-dependently increases hemoglobin and hematocrit, but without an associated increase in erythropoietin (5). In addition, testosterone has minimal proliferative effect on purified (CD34_) erythroid progenitors ex vivo (6).

We considered the hypothesis that testosterone increases hematocrit by suppressing the master iron regulatory peptide hepcidin, thus resulting in increased bioavailable iron. Hepcidin is a liver-derived peptide that binds to and degrades the iron channel ferroportin (7, 8). Increased hepcidin, in response to infection and inflammation restricts systemic iron bioavailability and results in mild anemia in chronic disease (9). Low hepcidin, conversely, is associated with increased iron absorption, increased systemic iron transport, and erythropoiesis.

To test the hypothesis that testosterone suppresses serum hepcidin, we measured serum hepcidin levels in a testosterone dose response study, in which healthy younger (19–35 yr old) and older (59–75 yr) men were administered a long-acting GnRH agonist to suppress endogenous testosterone production, along with varying doses of testosterone enanthate for 20 wk (10, 11). This design produced cohorts of subjects with graded, stable levels of testosterone within 4wkthat were maintained for 20 wk. This intervention resulted in dose-dependent increases in hematocrit and hemoglobin that were greater in older than younger men (5).

We measured serum hepcidin in serum samples from these men, and tested the hypothesis that age-related differences in erythropoietic response are related to the magnitude of hepcidin suppression. We also assessed whether early changes in hepcidin levels predict subsequent changes in hematocrit and hemoglobin.


Bachman E, Feng R, Travison T, et al. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis. J Clin Endocrinol Metab:jc.2010-0864.

Context: The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown.

Objective: The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin.

Participants: Healthy younger men (ages 19-35 yr; n = 53) and older men (ages 59-75 yr; n = 56) were studied.

Methods: Weekly doses of testosterone enanthate (25, 50, 125, 300, and 600 mg) were administered over 20 wk, whereas endogenous testosterone was suppressed by monthly GnRH agonist administration. Blood and serum parameters from each individual were measured at wk 0, 1, 2, 4, 8, and 20. Longitudinal analyses were performed to examine the relationship between hepcidin, hemoglobin, hematocrit, and testosterone while controlling for potential confounders.

Results: High levels of testosterone markedly suppressed serum hepcidin within 1 wk. Hepcidin suppression in response to testosterone administration was dose-dependent in older men and more pronounced than in young men, and this corresponded to a greater rise in hemoglobin in older men. Serum hepcidin levels at 4 and 8 wk were predictive of change in hematocrit from baseline to peak levels.

Conclusion: Testosterone administration is associated with suppression of serum hepcidin. Greater increases in hematocrit in older men during testosterone therapy are related to greater suppression of hepcidin.

Also this one:
http://bloodjournal.hematologylibrary.org/cgi/reprint/31/4/453.pdf

And this one:
http://bloodjournal.hematologylibrary.org/cgi/reprint/33/4/564.pdf

In thal patients, the erythropoietin are muted so what is the benefit of increasing there number with no use. Actually increasing erythropoietin means that the bone marrow is exta active and therefore there will be more chances of getting bone deformity

The above study was done on NON thal patients and that is why the results may vary

manal

I think what you say is trued for majors and intermedia thalassemics. But in beta minor I think increasing testosterone and erythropoietin would be beneficial.
I remember reading about an athlete that had thalassemia minor and has trouble performing. Then after administration of erythropoietin his performance improved as well as his hemoglobin. I ll try and find that article.

EDIT: Found it:

A 22-Year Old Division I Male Football
Player Diagnosed With Beta-Thalassemia
Minor Blood Disorder: A Case Study
O’Brien MS, Ransone JW, Smith KB:
College of Education, Oklahoma State
University, Stillwater, OK
Personal data
A 22-year-old division one collegiate football
player with no remarkable medical history complains
of fatigue and inability to recover from bouts
of exercise.
Physical signs and symptoms
The athlete presented symptoms of cardiovascular
(CV) deficiency (shortness of breath, irregular
CV endurance) for which, the team physician ordered
a blood work up including baseline levels of
comprehensive metabolic profile (CMP) and complete
blood count (CBC).
Differential diagnosis
Differential diagnosis of signs and symptoms include
iron deficiency anemia, sickle cell anemia,
beta thalassemia minor, hereditary leptocytosis,
minor heterozygous beta thalassemia intermedius
Results of diagnostic imaging/laboratory tests
After a baseline CMP and CBC were completed
revealing depressed levels of hemoglobin, further
tests were ordered by the team physician. Results
of these tests coincided with hypochromic
microcytic anemia. A sickle-dex was conducted
and was found to be positive. Results of the
hemoglobin electrophoresis conducted thereafter
indicated a depressed amount of hemoglobin A
(90%, reference 93.5%- 98.3%) revealing the betathalassemia
minor disorder. Additionally, initial
blood work presented low levels of blood erythropoietin
levels (4.7 mu/mL, reference 7.3- 27.7),
hemoglobin (11.8 g/dL, reference 14.0-18.0 g/dL),
and hematocrit (37.4%, reference 42.0- 52.0%).
Blood work conducted one week post Procrit®
injections exhibited elevated hemoglobin (16.1 g/
dL) and hematocrit (48.7%). Follow up measures
obtained one month post injections revealed
a marked decrease in blood erythropoietin levels
(3.8 mu/mL) and normal levels of hemoglobin
(14.9 g/dL), and hematocrit (45.6%)
Clinical course
To treat the beta thalassemia minor anemia, the
team physician prescribed the administration of
10,000 units of Procrit® (erythropoietin supplement)
according to the athletes body weight, three
times per week for one month to restore normal
levels of hemoglobin production, 325 mg of
Ferosul® (ferrous sulfate) and 500 mg of ascorbic
acid daily.
Deviation from expected
Thalassemia minor is a blood anemia characterized
by a genetic anomaly that affects the number of
hemoglobin proteins of a single red blood cell and
their ability to carry oxygen. Thalassemia minor
is not typically seen in the athletic population
and treatment for the disorder has not been
thoroughly addressed. In this particular case, the
prescription of Procrit erythropoietin was decided
upon to elevate hemoglobin levels and re- establish
the athlete’s oxygen carrying capacity to that of
normal levels required for athletic competition.
The athlete responded well to this treatment and
continued full participation in football activity.

Thal minors could decrease or eliminate their symptoms through a good program  of nutrition and supplementation. Taking Procrit could cause other serious side effects, so risks must be weighed in thal minors.

WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE

Chronic Renal Failure:

In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:

ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1).
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense PROCRIT® to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance.
Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

(See WARNINGS: Increased Mortality, Serious Cardiovascular Events, Thromboembolic Events, and Stroke, WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION.)

http://www.rxlist.com/procrit-drug.htm

Procrit is usually used to correct the anemia in cancer patients after the course of chemotherapy.

Some doctors advise their patients to have these injections but no real benefits were confirmed

manal


manal

Hi Karoloydi,

I am 31 years beta thal carrier. I also have elevated testosterone level which I found out recently. To be honest with you this is not helping me much.

I think because of testosterone elevation I start having irregular period, hair loss and hair growth in unusual places. My hemoglobin is 11.3. High testosterone level may give more energy but my irregular period is truly bothersome. It might be beneficial to male but I am suffering badly here.

Just wanted to share this info with you.

WOW... MY FIRST POST.  SO EXCITED!!!!!!  THANKS TO EVERYONE ON THIS SITE... YOU'RE A GODSEND!!!!

OK, SO I AM A THAL MINOR W HEMOGLOBIN ABOUT 10.6-11.2.  I AM AN AVID RACQUETBALL PLAYER, RUNNER, SURFER, ETC... BUT FOR OBVIOUS GENETIC REASONS I SUCK AT ALL OF THESE!!!!  I NEED HELP... I HAVE TRIED EVERY SUPPLIMENT IN THE WORLD TO CORRECT THIS PROBLEM, SO PLEASE NO SNAKE OIL, AS WE'RE TALKING GENETICS HERE.  THAT MEANS U CAN TAKE 5,000 MG OF FOLIC ACID TILL UR BLUE IN THE FACE... IT DOESNT WORK!!!!!!!!!!!!!!!!!!!!!!!  I HAVE GONE AS FAR AS INJECTABLE EPO IN BIOLOGIC DOSES ENOUGH TO KILL A DUTCH CYCLING TEAM!!!!  (YES, THAT ACTUALLY HAPPENED ONCE UPON A TIME).  IT DIDN'T RAISE MY CRIT EVEN A LITTLE!!    I'VE EVEN EXPERIMENTED WITH HU, A DRUG DESIGNED TO INCREASE FETAL HEMOGLOBIN, BUT IS A CHEMOTHERAPEUTIC AGENT (LONG TERM EFFECTS?).  ANYWAY, I'M 47, AND NOT REALLY READY TO SIT ON THE COUCH N WATCH OPRAH.  I'M INTRIGUED BY TESTOSTERONE.  ANYONE TRY THIS YET?  I HAPPEN TO KNOW THAT IM A LITTLE LOW ANYWAY, SO IM SURE I COULD GET A SCRIPT FOR THE GEL.  BTW, I EAT VERY CLEAN, TAKE SUPPS, AND EXERCISE MORE THAN ANY NORMAL PERSON, SO I'M LOOKING FOR SOMETHING OUT OF THE USUAL.  ANY INPUT APPRECIATED.  I'VE ASKED GOD A MILLION TIMES A DAY WHY HE WOULD GIVE ME THIS CRAPPY DISEASE, BUT THEN I THANK HIM I DONT HAVE COOLEYS...

BLESSINGS,

PHIL  

I am no expert by any means, but after reading your post I did wonder if the real problem may be linked, quite simply, to your over-active lifestyle. I have read several posts on this site that describe how oxygen in the body is effected in people with Thalassemia. Could it be that you are exerting yourself to a point that your body simply cannot keep up in regards to oxygen delivery and production of healthy cells?

I know this is quite a different case and we still have not determined the exact type of Thalassemia that our toddler has, but when he is rested and wants to play he goes full force, no one would think anything is wrong (and he has severe iron deficiency in combination with the Thalassemia). It is the next day that we see the effects of his exertion, his body simply cannot keep up with the demands. I hope that this changes, and I really commend you for leading such a healthy and active lifestyle, just make sure all those efforts are really in your best interest...might be a case where you just need to scale it back a bit.

Best wishes,
Sarah

I think what you say is trued for majors and intermedia thalassemics. But in beta minor I think increasing testosterone and erythropoietin would be beneficial.
I remember reading about an athlete that had thalassemia minor and has trouble performing. Then after administration of erythropoietin his performance improved as well as his hemoglobin. I ll try and find that article.

EDIT: Found it:

• Is there a source for the quoted abstract? I could only find a link to thalpal via Google search.
• Why did they give an iron supplement to a thal minor? Does that have anything to do with the epo supplement? I'm confused. [Seems they probably wanted to make sure there was enough iron to produce RBCs after the administration of the epo supplement.]

Thal minors could decrease or eliminate their symptoms through a good program  of nutrition and supplementation. Taking Procrit could cause other serious side effects, so risks must be weighed in thal minors.
http://www.rxlist.com/procrit-drug.htm

In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

The reason for this seems to be that the hemoglobin levels caused by a treatment with an epo supplement tend to not be stable and can go up and down quite a bit. I read an article in a German magazin which stated that the levels take a 'zig-zag' course. Imagine a +/- amplitude around a certain desired level. Other than that, I probably think the increased stroke risk is also caused by the increasing hematocrit which usually follows the higher Hb levels in a patient. But I think this would always be the case if you increase the Hb levels, so it's not an 'isolated' epo risk. It's also there for testosterone users, for example.

Edit: The article also mentions that there are other types of epo supplements with a half-life period of 130 hours (Epoetin Alfa = 7 hours) that are able to provide more stable Hb levels.

Edit 2: If you see what the team physician of the football player did, I'm pretty sure that the often-mentioned examples like Pete Sampras Zinédine Zidane both had their minor symptoms treated with all kinds of supplements. And they would never be able to talk about that anyways, because that would probably mean they'd also have to admit to doping.

For what it's worth, I've boosted my testosterone by injections to high normal - and it made no difference. Gave me energy and clarity, libido etc.
But the easy fatigue and lack of endurance and cardiovascular function, along with out of range low haemoglobin tests remain. And I mean remain untouched. They are literally identical to when my testosterone was tanked.

There are steroids besides testosterone, like boldenone, that are VERY well known for raising hematocrit and many athletes use, but that's a bit foolish and not a long term solution. Even if it was an improvement, that's more strain on your heart, which would cause you to have to donate blood to lower the hematocrit, which would bring you back to square one anyway.

out of range low haemoglobin

The blood test you posted showed a pretty high hemoglobin value. Do you know how much that value fluctuates for you?

The blood test you posted showed a pretty high hemoglobin value. Do you know how much that value fluctuates for you?

Oh to clarify I mean cell hemo sorry, not outward hemo. But in any case:

Yep I do know how much it fluctuates - not at all. Literally hasn't changed. In fact on my new test it's all even LOWER but by such a minuscule amount as to be of no significance.

I have a blood test from when my Testosterone was low, and a blood test as of last week showing just over high normal Testosterone (out of range, even) and the haematology on both from top to bottom is literally what I'd call identical. Not even my red cell count improved, which Testosterone is notoriously known to do.

EDIT: In fact here they are. First number is during low Testosterone blood test. Second number is 6 months on Testosterone - with it being JUST high out of normal range.

Hb: 159  /  155
Hct: 0.50   /   0.49
RBC: 6.2   /   6.2
MCV: 80   /   79   Both out of range low
MCH: 26   /   25   Both out of range low
MCHC 319   /   317  Both out of range low
RDW: 14.3  /  14.4

You mean the MCV? Do you know why this could cause a pale skin? I had my hemoglobin at 14.3, but my MCV was only 69 and I'm also very pale.  Could this be a problem with releasing oxygen into the tissue? All the explanations don't mention the exact factor/mechanism that causes the pale skin...

You mean the MCV? Do you know why this could cause a pale skin? I had my hemoglobin at 14.3, but my MCV was only 69 and I'm also very pale.  Could this be a problem with releasing oxygen into the tissue? All the explanations don't mention the exact factor/mechanism that causes the pale skin...

The MCH and MCHC particularly but also the volume. Yes, I believe it is primarily oxygen-related. And secondarily nutrient related.

You have to keep in mind that, this is why a specific hemo blood test is ordered, as there are more than 400 types of anemia, and countless types of hemoblogin which could be causing the issue.

For example - you could have an abundance of hemoglobin - but it is a type that is very poor at carrying oxygen.

You could have plenty of RBC's - but they could be poorly shaped and formed.

You could have a great type of hemoglobin - but very low levels of it in blood cells.

At the end of the day, it all results in starved oxygen in the blood which causes the breathlessness, fatigue and the pale skin (instead of the healthy pink/red of oxygenated cells).

And also the fact that cells are constantly destroyed with the spleen turnover mentioned elsewhere, stressing the body and causing it not to absorb the nutrients and minerals it needs elsewhere, also needed for the production of things like healthy melanin, vitamin D etc which also negatively affect skin tone.

I don't think there are so many different types of hemoglobin that it would play a big role; afaik, mostly those that show up in a hemoglobin electrophoresis. I think I'm going to do this test soon and include a few other blood values in my next blood test, e.g. hemolysis parameters , thyroid glans (TSH is at 3; I should probably check FT/T 3/4) and hormones.

• Are there any specific hormones one could check that could cause the fatigue? Only testosterone?
• Is there only the hemoglobin electrophoresis or 'real' genetic tests that could show me the exact deletions etc.?

I don't think there are so many different types of hemoglobin that it would play a big role; afaik, mostly those that show up in a hemoglobin electrophoresis. I think I'm going to do this test soon and include a few other blood values in my next blood test, e.g. hemolysis parameters , thyroid glans (TSH is at 3; I should probably check FT/T 3/4) and hormones.

• Are there any specific hormones one could check that could cause the fatigue? Only testosterone?
• Is there only the hemoglobin electrophoresis or 'real' genetic tests that could show me the exact deletions etc.?

From WebMD:
There are more than 350 types of abnormal hemoglobin.1 The most common are:
Hemoglobin S. This type of hemoglobin is present in sickle cell disease.
Hemoglobin C. This type of hemoglobin does not carry oxygen well.
Hemoglobin E. This type of hemoglobin is found in people of Southeast Asian descent.
Hemoglobin D. This type of hemoglobin is present in some sickle cell disorders.

Yep not hormones but things worth checking.
Vitamin D
Potassium
Iodine
Vitamin B12
Zinc
Vitamin C
Vitamin E
Thyroid
Testosterone (free and total)
LH/FSH
Estradiol
Prolactin
DHT
Growth Hormone
Adrenals/Cortisol
DHEA

I'm not sure on a complete DNA test. I would think that would be quite expensive.