Testosterone Induced Polycythemia/Erythrocytosis (Elevated Hematocrit/Hemoglobin)

Discussion in 'Men's Health Forum' started by Michael Scally MD, Jul 21, 2010.

  1. Dr JIM

    Dr JIM Member

    For those with SYMPTOMS and RISK FACTORS which don't improve after 3 months (because the Hct declines thereafter in 95% of effected pts on TRT) of watchful waiting phlebotomy is typically recommended somewhere between Crit of > 58-60%

    Jim
     
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  2. Dr JIM

    Dr JIM Member

    It may be suggested at even lower HCT depending upon a patients particular set of circumstances, signs, symptoms and/or risk factors.

    Jim
     
  3. bruiser

    bruiser Junior Member

    A a note to getting blood drawn for donation purposes. They always throw it away....!!
    Who would give bad to a health person. Its bad blood.
    I've been there and done it.
    My Hemotologist now watches over me but when drawen at the hospital it still goes into the biohazard bin for disposal.
    This is just what I've found in North Dakota anyway.
    Bruce/BSRT(R)
     
  4. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Ruchala P, Nemeth E. The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. Trends in Pharmacological Sciences - The pathophysiology and pharmacology of hepcidin

    Inappropriate production of the iron-regulatory hormone hepcidin contributes to the pathogenesis of common iron disorders. Absolute or relative deficiency of hepcidin causes iron overload in hereditary hemochromatosis and iron-loading anemias. Elevated hepcidin causes iron restriction in inflammatory conditions including autoimmune disease, critical illness, some cancers, and chronic kidney disease.

    Multiple agents targeting hepcidin and its regulators are under development as novel therapeutics for iron disorders. This review summarizes hepcidin biology and discusses the current landscape for hepcidin-targeting therapeutic strategies.

    The Role of Hepcidin in Iron Metabolism

    Hepcidin–ferroportin interaction determines the flow of iron into plasma. Hepcidin concentrations are in turn regulated by iron, erythropoietic activity, and inflammation.

    [​IMG]
     

    Attached Files:

    Last edited: Dec 16, 2014
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  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Beggs LA, et al. testosterone alters Iron metabolism and Stimulates Red Cell Production Independently of Dihydrotestosterone. American Journal of Physiology - Endocrinology and Metabolism. http://ajpendo.physiology.org/content/early/2014/07/24/ajpendo.00184.2014.abstract

    Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues.

    Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men.

    Sixty men aged ≥60 years with serum T <300ng/dL or bioavailable T <70ng/dL received treatment with TE (125mg/week) vs. vehicle, paired with finasteride (5mg/day) vs. placebo using a 2x2 factorial design.

    Over the course of 12 months, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8%, while suppressing serum hepcidin 57% (p<0.001 for all measures). Most of the aforementioned changes occurred in the first 3 months of treatment and finasteride co-administration did not significantly alter any of these effects.

    TE also reduced serum ferritin 32% (p=0.002) within 3 months of treatment initiation, without altering iron, transferrin or transferrin saturation.

    We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.
     
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  6. polygirl

    polygirl Junior Member

    Question please, For anyone who was on TRT long term and then stopped, how long before your H & H returned to normal levels naturally ?
     
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    It will depend upon the H/H. Red blood cells have a life of about 90 days so it could take some time. Also, the reason for the level is another factor. Search - "hepcidin and estradiol".

    Here is a start:
    A Novel Direct Pathway for Estrogen Control of Iron Homeostasis
    http://michaelscally.blogspot.com/2012/12/a-novel-direct-pathway-for-estrogen.html
     
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  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Estradiol [E2] & Hemoglobin/Hematocrit - Random Thoughts

    There is an increase of E2 production (saturable) with graded testosterone administration. [Lakshman KM, Kaplan B, Travison TG, et al. The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men. Journal of Clinical Endocrinology & Metabolism 2010;95(8):3955-64. http://jcem.endojournals.org/content/95/8/3955.long ]

    There is an increase of Erythropoiesis with graded Testosterone administration. [Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men. J Clin Endocrinol Metab 2008;93(3):914-9. http://jcem.endojournals.org/content/93/3/914.long ]

    Non-aromatizable androgens do NOT increase Erythropoiesis. [Jockenhovel F, Vogel E, Reinhardt W, Reinwein D. Effects of various modes of androgen substitution therapy on erythropoiesis. Eur J Med Res 1997;2(7):293-8. http://www.ncbi.nlm.nih.gov/pubmed/9233903 ]

    Testosterone Suppresses Hepcidin. [Bachman E, Feng R, Travison T, et al. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis. Journal of Clinical Endocrinology & Metabolism 2010;95(10):4743-7. http://jcem.endojournals.org/content/95/10/4743.long ]

    E2 inhibits Hepcidin. [Yang Q, Jian J, Katz S, Abramson SB, Huang X. 17Beta-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site. Endocrinology 2012;153(7):3170-8. http://endo.endojournals.org/content/153/7/3170.abstract ; Dacks PA. Estrogens Iron Out the Details: A Novel Direct Pathway for Estrogen Control of Iron Homeostasis. Endocrinology 2012;153(7):2942-4. http://endo.endojournals.org/content/153/7/2942.extract ]
     
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  9. Avies48

    Avies48 Member

    ok so question (s)

    since hep is lowered or all together blocked and causes high hemo and hct, would it be possible to add something in that allows ur hep to re activate? or is there something suck as IP-6 that may help along with cardio etc? im also on narginin, in hopes it will help curtail the hct amount...

    ive been off trt since sept-oct and my hmematologist says i still need phlems? mine is right around 50-52 constantly...


    is there something else she should be investigating perhaps to find out why my hematocrit still has not come back down to below 50? she said polycythemia vera but from my understanding it could be a few different things?
     
  10. toolman

    toolman Member

    If you stopped in Oct then you are looking at another few weeks before you have no depot left. Have you had a donation after that? If not, your crit would still be high as your RBC's have a life of 90 days so you would still be showing high but it should start normalize within 4 months of your last injection. Sounds like time to get another opinion. Not sure you needed phlebs at 50-52 as that is still in the upper part of normal range. Sounds like she wants a client to stay around.
     
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  11. Avies48

    Avies48 Member

    well whats odd is that i was taken off my test cyp in june or july and by september my hct had already returned to 49.....then i was told to start back up till i saw the endo, and stopped again in october.... and now its constantly between 50-52, so i was wondering if perhaps polycythemia vera might be something else entirely? such as perhaps capillary leak syndrome? bp has been good, tho so it was just a wondering?

    Capillary leak syndrome (also known as systemic capillary leak syndrome, SCLS, or Clarkson’s disease) is an extremely rare medical condition characterized by self-reversing episodes during which the endothelialcells which line the capillaries are thought to separate for a few days, allowing for a leakage of fluid from the circulatory system to the interstitial space, resulting in a dangerous hypotension (low blood pressure), hemoconcentration, and hypoalbuminemia. It is a life-threatening illness because each episode has the potential to cause damage to, or the failure of, vital organs due to limited perfusion. It is often misdiagnosed as polycythemia, polycythemia vera, or sepsis.
     
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Bachman E, Travison TG, Basaria S, 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;69(6):725-35. http://biomedgerontology.oxfordjournals.org/content/69/6/725.abstract

    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.
     
  13. Avies48

    Avies48 Member

    Thanks doc i believe i read this above, but it leaves some to wonder IF any of this can be counteracted? Can u alter any of this? Even while on test can u say take an iron chelator and see results perhaps?
     
  14. toolman

    toolman Member

    Averies what I do not understand is why are they so concerned with a hematocrit of 50-52? Do you have other CVD risk factors such as HBP or high cholesterol and triglycerides?
     
    21p likes this.
  15. Avies48

    Avies48 Member


    Well ive had high cholesterol since i got out of the service.... Even before trt.... And no matter what i do i cant get my ldl below 170....and my vit d has been low ever since i got on trt....

    Weird as my vit d has risen a bit since being taken off trt...

    Got taken off trt due to passing out when i gave my only phlem ive ever had to do (this past july) since being put on trt almost 7 years ago.... And was on 200 e7d for the first few years then dropped down to 100 mlg per week....

    No other issues as far as me and my hematologist are aware of? Or any of my other docs ive been to....
     
  16. toolman

    toolman Member

    The statin lobby focuses on high, but I have learned from reading and many docs there is far more too it. How are your triglycerides? I stand by my layman's understanding from a lot of reading and some pretty solid docs...why is your phlebotomist so concerned about a crit level of 50-52. Sounds a bit alarmist to me.
     
  17. jonkobeck

    jonkobeck Member

    For those of us with elevated HcT, are there any benefits to a daily baby aspirin?
     
  18. Avies48

    Avies48 Member

    She believes i may have polycythemia vera, so ahe wants my hct below 50....

    Triglycerides are always normal....
     
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Gammella E, Diaz V, Recalcati S, et al. Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly. Am J Physiol Regul Integr Comp Physiol. http://ajpregu.physiology.org/content/early/2014/12/12/ajpregu.00410.2014

    Under conditions of accelerated erythropoiesis, elevated erythropoietin (Epo) levels are associated to inhibition of hepcidin synthesis, a response that ultimately increases iron availability to meet the enhanced iron needs of erythropoietic cells.

    In the search for erythroid regulators of hepcidin many candidates have been proposed, including Epo itself. We aimed to test whether direct interaction between Epo and the liver is required to regulate hepcidin.

    We found that prolonged administration of high doses of Epo in mice leads to great inhibition of liver hepcidin mRNA levels, and concomitant induction of the hepcidin inhibitor erythroferrone (ERFE).

    Epo treatment also resulted in liver iron mobilization, mediated by increased ferroportin activity and accompanied by reduced ferritin levels and increased TfR1 expression. The same inhibitory effect was observed in mice that do not express the homodimeric Epo receptor (EpoR) in liver cells because EpoR expression is restricted to erythroid cells. Similarly, liver signaling pathways involved in hepcidin regulation were not influenced by the presence or absence of hepatic EpoR.

    Moreover, Epo analogues possibly interacting with the postulated heterodimeric beta common EpoR, did not affect hepcidin expression. These findings were supported by the lack of inhibition on hepcidin found in hepatoma cells exposed to various concentrations of Epo for different periods of times.

    Our results demonstrate that hepcidin suppression does not require the direct binding of Epo to its liver receptors, and rather suggest that the role of Epo is to stimulate the synthesis of the erythroid regulator ERFE in erythroblasts, that ultimately downregulates hepcidin.
     
  20. Avies48

    Avies48 Member

    Soo IS there any way at all to take hepcidin or something that will allow it to become up suppressed while on trt???