Polycythemia high red blood

Hepcidin for controlling polycythemia?

The biggest challenge in TRT for me has been keeping my HCT down.

I've donated blood (and platelets) to the point of iron deficiency and hit the FDA red-cell loss limit.
I've tried to limit my donations to platelets only, but when my HCT hit 55 recently I caved and added a whole blood donation.

I've been thinking about other ways to help address this.

Since hepcidin suppression seems to be the mechanism by which androgens raise hematocrit, it seems like supplementing hepcidin could be of help.

I won't post a link, but there is at least one company offering hepcidin peptide for research use. I'm not about to jump into this, but I'm wondering if anyone else has done any research along these lines?

One problem is that there does not seem to be an FDA approved assay for hepcidin.

I could see hepcidin being compounded with testosterone for TRT and possibly reducing or eliminating one of the main undesirable side effects. Thoughts?



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Introduction Testosterone replacement therapy (TRT) is a common treatment for hypogonadism in aging males. Men with low to low-normal levels of testosterone have documented benefit from hormone replacement.

Recent meta-analyses have revealed that increases in hemoglobin (Hb) and hematocrit (Hct) are the variants most commonly encountered. Clinically, this response is described as erythrocytosis or polycythemia secondary to TRT. However, the recent Food and Drug Administration warning regarding the risk for venothromboembolism (VTE) has made the increases in Hb and Hct of more pertinent concern. The risks associated with androgen replacement need further examination.

Aim To review the available literature on erythrocytosis and polycythemia secondary to TRT. To discuss potential etiologies for this response, the role it plays in risk for VTE, and recommendations for considering treatment in at-risk populations.

Methods A literature review was performed through PubMed regarding TRT and erythrocytosis and polycythemia.

Main Outcome Measures To assess the mechanisms of TRT-induced erythrocytosis and polycythemia with regard to basic science, pharmacologic preparation, and route of delivery. To review Hct and risk for thrombotic events. To offer clinical suggestions for therapy in patients at risk for veno-thrombotic events.

Results Men undergoing TRT have a 315% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control. Mechanisms involving iron bioavailability, erythropoietin production, and bone marrow stimulation have been postulated to explain the erythrogenic effect of TRT. The association between TRT-induced erythrocytosis and subsequent risk for VTE remains inconclusive.

Conclusions All TRT formulations cause increases in Hb and Hct, but injectables tend to produce the greatest effect. The evidence regarding the risk for VTE with increased Hct is inconclusive. For patients with risk factors for veno-thrombotic events, formulations that provide the smallest effect on blood parameters hypothetically provide the safest option. Further trials are needed to fully evaluate the hematological side effects associated with TRT.

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Since the syndrome of hypogonadotropic hypogonadism (HH) is associated with anemia and the administration of testosterone restores hematocrit to normal, we investigated the potential mechanisms which may contribute to it.

We measured serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. 44 men had HH (defined as free testosterone <5ng/dl along with low or normal LH concentrations) while 50 were eugonadal.

Hematocrit concentrations were lower in hypogonadal men (41.2±3.8% vs. 43.8±3.2%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin, iron or transferrin saturation or in ferroportin expression in MNC among hypogonadal and eugonadal men.

Men with HH were randomized to testosterone treatment (200 mg i.m., every two weeks) or placebo (saline 1ml every 2 weeks) for 24 weeks. 20 men in testosterone group and 14 men in placebo group completed the study.

Free testosterone concentrations increased from 4.5±1.3 to 13.8±4.1ng/dl (p<0.001) after testosterone therapy but did not change in placebo group.
The hematocrit increased from 42.0±2.7% to 45.4±4.6% (p<0.001) but did not change after placebo (40.7±2.9% to 41.6±3.1%, p=0.22).

There was a 30±7% decrease in plasma hepcidin (p<0.01) and 29±8% increase in erythropoietin concentrations (p<0.05) after testosterone therapy.

There was no significant change in iron or ferritin concentrations but transferrin concentration increased by 21±7% and transferrin saturation decreased by 30±10% (p<0.01). Ferroportin mRNA expression in MNC increased by 70±13% (p<0.01) at 4 weeks and 15 weeks but came back to baseline at 24 weeks after testosterone therapy when the hematocrit normalized. There was no change in any of these parameters after placebo.

We conclude that the administration of testosterone to restore normal testosterone concentration led to a significant increase in plasma erythropoietin concentrations, reduction in plasma hepcidin concentration, marked increase in ferroportin expression which was transient, a smaller but significant increase in transferrin and a small reduction in plasma iron concentrations.

Clearly, therefore, the increase in hematocrit is supported by an increase in erythropoietin and an increase in iron transport through an increase in ferroportin. This increase is probably through the known suppression of hepcidin which suppresses ferroportin expression.

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Hematocrit concentrations were lower in hypogonadal men (41.2±3.8% vs. 43.8±3.2%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin, iron or transferrin saturation or in ferroportin expression in MNC among hypogonadal and eugonadal men.

Men with HH were randomized to testosterone treatment (200 mg i.m., every two weeks) or placebo (saline 1ml every 2 weeks) for 24 weeks. 20 men in testosterone group and 14 men in placebo group completed the study.

Free testosterone concentrations increased from 4.5±1.3 to 13.8±4.1ng/dl (p<0.001) after testosterone therapy but did not change in placebo group.
The hematocrit increased from 42.0±2.7% to 45.4±4.6% (p<0.001) but did not change after placebo (40.7±2.9% to 41.6±3.1%, p=0.22).

There was a 30±7% decrease in plasma hepcidin (p<0.01) and 29±8% increase in erythropoietin concentrations (p<0.05) after testosterone therapy.

There was no significant change in iron or ferritin concentrations but transferrin concentration increased by 21±7% and transferrin saturation decreased by 30±10% (p<0.01). Ferroportin mRNA expression in MNC increased by 70±13% (p<0.01) at 4 weeks and 15 weeks but came back to baseline at 24 weeks after testosterone therapy when the hematocrit normalized. There was no change in any of these parameters after placebo.

We conclude that the administration of testosterone to restore normal testosterone concentration led to a significant increase in plasma erythropoietin concentrations, reduction in plasma hepcidin concentration, marked increase in ferroportin expression which was transient, a smaller but significant increase in transferrin and a small reduction in plasma iron concentrations.

Clearly, therefore, the increase in hematocrit is supported by an increase in erythropoietin and an increase in iron transport through an increase in ferroportin. This increase is probably through the known suppression of hepcidin which suppresses ferroportin expression.

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Since the syndrome of hypogonadotropic hypogonadism (HH) is associated with anemia and the administration of testosterone restores hematocrit to normal, we investigated the potential mechanisms which may contribute to it.

We measured serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. 44 men had HH (defined as free testosterone <5ng/dl along with low or normal LH concentrations) while 50 were eugonadal.

Hematocrit concentrations were lower in hypogonadal men (41.2±3.8% vs. 43.8±3.2%, p=0.001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin, iron or transferrin saturation or in ferroportin expression in MNC among hypogonadal and eugonadal men.

Men with HH were randomized to testosterone treatment (200 mg i.m., every two weeks) or placebo (saline 1ml every 2 weeks) for 24 weeks. 20 men in testosterone group and 14 men in placebo group completed the study.

Free testosterone concentrations increased from 4.5±1.3 to 13.8±4.1ng/dl (p<0.001) after testosterone therapy but did not change in placebo group.
The hematocrit increased from 42.0±2.7% to 45.4±4.6% (p<0.001) but did not change after placebo (40.7±2.9% to 41.6±3.1%, p=0.22).

There was a 30±7% decrease in plasma hepcidin (p<0.01) and 29±8% increase in erythropoietin concentrations (p<0.05) after testosterone therapy.

There was no significant change in iron or ferritin concentrations but transferrin concentration increased by 21±7% and transferrin saturation decreased by 30±10% (p<0.01). Ferroportin mRNA expression in MNC increased by 70±13% (p<0.01) at 4 weeks and 15 weeks but came back to baseline at 24 weeks after testosterone therapy when the hematocrit normalized. There was no change in any of these parameters after placebo.

We conclude that the administration of testosterone to restore normal testosterone concentration led to a significant increase in plasma erythropoietin concentrations, reduction in plasma hepcidin concentration, marked increase in ferroportin expression which was transient, a smaller but significant increase in transferrin and a small reduction in plasma iron concentrations.

Clearly, therefore, the increase in hematocrit is supported by an increase in erythropoietin and an increase in iron transport through an increase in ferroportin. This increase is probably through the known suppression of hepcidin which suppresses ferroportin expression.

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Iron is required for many biological processes but is also toxic in excess; thus, body iron balance is maintained through sophisticated regulatory mechanisms. The lack of a regulated iron excretory mechanism means that body iron balance is controlled at the level of absorption from the diet.

Iron absorption is regulated by the hepatic peptide hormone hepcidin. Hepcidin also controls iron release from cells that recycle or store iron, thus regulating plasma iron concentrations. Hepcidin exerts its effects through its receptor, the cellular iron exporter ferroportin.

Important regulators of hepcidin, and therefore of systemic iron homeostasis, include plasma iron concentrations, body iron stores, infection and inflammation, and erythropoiesis.

Disturbances in the regulation of hepcidin contribute to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and nontransfused beta-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic kidney disease, chronic inflammatory diseases, some cancers, and inherited iron-refractory iron deficiency anemia.

This review summarizes our current understanding of the molecular mechanisms and signaling pathways involved in the control of hepcidin synthesis in the liver, a principal determinant of plasma hepcidin concentrations.

Bump.
I messed up and repeated post so, sorry but good info in here it's a few posts on same topic I put together I found here and there

I tried to rep you but said I need to spread the love

Bump

Forms needed if on TRT to donate more than 8 weeks....
Those are old ones I have in photo gallery. Will take new ones this week I am currently as needed. The every 3 don't cut lowering 19 hemo or more. Only way is to go 3x in 4 weeks for me then I can lower 19 hemo to 14 hemo and don't have to go but every 4 weeks check and it often not need to be done but every 6 weeks to 8 after that...

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