How to Manage Increased Hematocrit Caused by Testosterone Replacement Therapy

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Testosterone Replacement Therapy and Polycythemia
By Nelson Vergel, B.S.Ch.E., M.B.A.

Polycythemia is an excessive production of red blood cells. With polycythemia, the blood becomes very viscous or "sticky," making it harder for the heart to pump. High blood pressure, strokes and heart attacks can occur.

The association between testosterone replacement therapy and polycythemia has been reported for the past few years as this therapy has become more mainstream. In addition to increasing muscle and sex drive, testosterone can increase the body's production of red blood cells. This hematopoietic (blood-building) effect could be a good thing for those with mild anemia.

Although all testosterone replacement products can increase the number of red blood cells, the study showed a higher incidence of polycythemia in those using intramuscular testosterone than topical administration (testosterone patch was the main option used -- no gels). Smoking has also been associated with polycythemia and may contribute to the effects of other risk factors.


Below is an excerpt from my book, Testosterone: A Man's Guide, further detailing the prevention and management of polycythemia.

Preventing and Managing Polycythemia

It's important to check patients' hemoglobin and hematocrit blood levels while on testosterone replacement therapy. As we all know, hemoglobin is the substance that makes blood red and helps transport oxygen in the blood. Hematocrit reflects the proportion of red cells to total blood volume. A hematocrit of over 52 percent should be evaluated. Decreasing testosterone dose or stopping it are options that may not be the best for assuring patients' best quality of life, however. Switching from injectable to transdermal testosterone may decrease hematocrit, but in many cases not to the degree needed.

The following table shows the different guideline groups that recommend monitoring for testosterone replacement therapy. They all agree about measuring hematocrit at month 3, and then annually, with some also recommending measurements at month 6 after starting testosterone (it is good to remember that there is a ban on gay blood donors in the United States).


Many patients on testosterone replacement who experience polycythemia do not want to stop the therapy due to fears of re-experiencing the depression, fatigue and low sex-drive they had before starting treatment. For those patients, therapeutic phlebotomy may be the answer. Therapeutic phlebotomy is very similar to what happens when donating blood, but this procedure is prescribed by physicians as a way to bring down blood hematocrit and viscosity.

A phlebotomy of one pint of blood will generally lower hematocrit by about 3 percent. I have seen phlebotomy given weekly for several weeks bring hematocrit from 56 percent to a healthy 46 percent. I know physicians who prescribe phlebotomy once every 8-12 weeks because of an unusual response to testosterone replacement therapy. This simple procedure is done in a hospital blood draw or a blood bank facility and can reduce hematocrit, hemoglobin, and blood iron easily and in less than one hour.

Unfortunately, therapeutic phlebotomy can be a difficult option to get reimbursed or covered by insurance companies. The reimbursement codes for therapeutic phlebotomy are CPT 39107, icd9 code 289.0.

Unless a local blood bank is willing to help, some physicians may need to write a letter of medical necessity for phlebotomy if requested by insurance companies. If the patient is healthy and without HIV, hepatitis B, C, or other infections, they could donate blood at a blood bank.

TRT Caused High Hematocrit: Where Can I Go for a Therapeutic Phlebotomy?

One unit of whole blood is around 350 to 450 cc; approximately 4 units of blood need to be withdrawn to decrease this man's hemoglobin from 20 mg/mL to 14 mg/mL. However, taking this much blood out in one phlebotomy session may deplete ferritin and iron levels which can cause extreme fatigue. So, be conservative give 1-2 units max even if you have to go more frequently. Donations more frequently than every 3 months run the risk to lower your ferritin and iron too much (which can cause fatigue), so make sure that you measure these two variables to determine if you should take an iron supplement.

You can order a CBC test (includes hematocrit) and ferritin (after you donate blood) here: Blood tests

The frequency of the phlebotomy depends on individual factors, but most men can do one every two to three months to manage their hemoglobin this way. Sometimes red blood cell production normalizes without any specific reason. It is impossible to predict exactly who is more prone to developing polycythemia, but men who use higher doses, men with sleep apnea, and older men may have a higher incidence. It is important not to draw too much blood at once due to dramatic decreases in iron levels and ferritin that could cause fatigue.

Donating Blood: Red Cross List of Exclusions

Some doctors recommend the use of baby aspirin (81 mg) a day and 2,000 to 4,000 mg a day of omega-3 fatty acids (fish oil capsules) to help lower blood viscosity and prevent heart attacks. These can be an important part of most people's health regimen but they are not alternatives for therapeutic phlebotomy if the patient has polycythemia and does not want to stop testosterone therapy. It is concerning that many people assume that they are completely free of stroke/heart attack risks by taking aspirin and omega-3 supplements when they have a high hematocrit.

Although some people may have more headaches induced by high blood pressure or get extremely red when they exercise, most do not feel any different when they have polycythemia. This does not make it any less dangerous.

WARNING:

Donating more than 1 unit every 2-3 months may lower your iron and ferritin levels and cause fatigue. That is why it is good to start donating when you are in the 51-52 hematocrit range. Also, the Red Cross and other organizations will reject donors with high hematocrit over 52. Those who get rejected can ask for a written order from their doctors and may have to pay to get phlebotomies.

Increasing testosterone enanthate versus hemoglobin, PSA and cholesterol:

testosterone dose versus psa hemoglobin cholesterol.jpg


Reference



More information:

Testosterone-Induced High Red Blood Cell Volume (Hematocrit) | Discounted Labs

balancing low ferritin levels and frequent donation.

Warning about frequent blood donations used to decrease hematocrit.

Donating Blood Prevents Heart Disease

Previous discussions on ways to manage hematocrit: grapefruit hematocrit excelmale.com site:www.excelmale.com - Google Search


iron loss donation.jpg
TRT guidelines.jpg
 
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Nelson Vergel

Founder, ExcelMale.com
#2
Before you try grapefruit talk to your doctor since this fruit can cause unwanted interactions with medications.
t J Vitam Nutr Res.1988;58(4):414-7.
Ingestion of grapefruit lowers elevated hematocrits in human subjects.
Source: Food Science and Human Nutrition Department, IFAS, University of Florida, Gainesville.

Abstract
This study was based on in vitro observations that naringin isolated from grapefruit induced red cell aggregation and evidence that clumped red cells are removed from the circulation by phagocytosis. The effect on hematocrits of adding grapefruit to the daily diet was determined using 36 human subjects (12 F, 24 M) over a 42-day study. The hematocrits ranged from 36.5 to 55.8% at the start and 38.8% to 49.2% at the end of the study. There was a differential effect on the hematocrit. The largest decreases occurred at the highest hematocrits and the effect decreased on the intermediate hematocrits; however, the low hematocrits increased. There was no significant difference between ingesting 1/2 or 1 grapefruit per day but a decrease in hematocrit due to ingestion of grapefruit was statistically significant at the p less than 0.01 level.
 

Nelson Vergel

Founder, ExcelMale.com
#6
Hematocrit may stabilize after long term testosterone replacement

Although this study was done in mice, it may explain why hematocrit may eventually decrease and stabilize in men on TRT. I am one of those men who only went for therapeutic phlebotomy twice. There seems to be an adaptive mechanism that makes red blood cells get change form while hematocrit stabilizes.

Guo W, Bachman E, Vogel J, Li M, Peng L, et al. The Effects of Short-Term and Long-Term Testosterone Supplementation on Blood Viscosity and Erythrocyte Deformability in Healthy Adult Mice. Endocrinology. http://press.endocrine.org/doi/abs/10.1210/en.2014-1784


Testosterone treatment induces erythrocytosis that could potentially affect blood viscosity and cardiovascular risk. We thus investigated the effects of testosterone administration on blood viscosity and erythrocyte deformability using mouse models.


Blood viscosity, erythrocyte deformability, and hematocrits were measured in normal male and female mice, as well as in females and castrated males after short-term (2-weeks) and long-term (5-7 months) testosterone intervention (50 mg/kg, weekly).


Castrated males for long-term intervention were studied in parallel with the normal males to assess the effect of long-term testosterone deprivation. An additional short-term intervention study was conducted in females with a lower testosterone dose (5 mg/kg).


Our results indicate no rheological difference among normal males, females, and castrated males at steady-state.


Short-term high dose testosterone increased hematocrit and whole blood viscosity in both females and castrated males. This effect diminished after long-term treatment, in association with increased erythrocyte deformability in the testosterone-treated mice, suggesting the presence of adaptive mechanism.


Considering that cardiovascular events in human trials are seen early after intervention, rheological changes as potential mediator of vascular events warrant further investigation.
 

Nelson Vergel

Founder, ExcelMale.com
#9
Testosterone Replacement Therapy and Blood Donations

"While on TRT patients need to be monitored very closely due to the increased the risk of thrombosis and stroke. Increased testosterone has also been shown to cause polycythemia, an increase in red blood cells, resulting in an increase in blood viscosity. If this occurs patients on the therapy need to lower their dosage or discontinue treatment. However, another option is to donate blood on a regular basis. This donation would be categorized as a therapeutic phlebotomy and is a special donation that requires physician approval.

A variance is listed under FDA Exceptions and Alternative Procedures Approved Under 21 CFR 640.120 to “Allow individuals on prescription testosterone to donate blood and blood components more frequently than every eight weeks without examination or certification of health by physician at time of donation, provided the donor is referred with a prescription by a physician containing instructions regarding frequency of phlebotomy and hematocrit/hemoglobin limits and to be exempt from placing special labeling about the donor's disorder on the blood components. This approval is granted under the condition that only the Red Blood Cells collected from these individuals may be distributed; the plasma and platelet components from these individuals should not be distributed for transfusion.”

In these therapeutic phlebotomies in which a variance is obtained by the blood center, the red blood cells are used and the plasma or platelets are discarded. Have blood centers seen an increase in therapeutic donors due to TRT therapy? Obtaining a variance for TRT donors may be an opportunity for a blood center looking to increase their available donors. Is this something your blood center has considered or implemented? Should TRT donors be handled any differently in comparison to other therapeutic phlebotomies?"

Source
 

Nelson Vergel

Founder, ExcelMale.com
#15
Blood Donation Intervals Should Be Extended to 180 Days To Avoid Iron Deficiency

Most blood collection agencies require a 56-day minimum interval between donations of whole blood to allow hemoglobin levels to return to normal. However, new insight from recent studies, including research published in Blood, suggest that the deferral should be lengthened to prevent iron deficiency. Researchers compared hemoglobin levels and iron parameters over 180 days in 24 new male donors and compared them to 25 regular male donors who have donated more than 10 times. Over the 180 day observation period, regular donors had lower levels of hemoglobin, ferritin and hepcidin, while erythropoietin and soluble transferrin receptor were higher compared to new donors. Although hemoglobin indices returned to normal by day 57, both groups of donors had low levels of ferritin at day 57 compared to pre-donation levels. Only 25% of new and 32% of regular donors had returned to baseline levels. After 180 days, all regular donors and 82% of new donors had reached baseline ferritin levels. The study authors suggest ferritin levels may be used to determine personalized donation intervals, or the donation interval should be increased to 180 days to avoid iron deficiency in all donors. More research is needed to confirm these results and investigate trends in female donors.

Reference:

Schotten N, Pasker-de Jong PC, Moretti D, Zimmermann MB, Geurts-Moespot AJ, Swinkels DW, van Kraaij MG. The donation interval of 56 days requires extension to 180 days for whole blood donors to recover from changes in iron metabolism. Blood 2016;128: 2185-8.
 

Nelson Vergel

Founder, ExcelMale.com
#16

https://www.ncbi.nlm.nih.gov/m/pubmed/28150363/


Blood donation and testosterone replacement therapy.
Abstract
BACKGROUND: Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT.

STUDY DESIGN AND METHODS: We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors.

RESULTS: We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations.

CONCLUSION: Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia.
 

Nelson Vergel

Founder, ExcelMale.com
#17
Warning: Some doctors and patient advocates are recommending not to get therapeutic phlebotomies since they say there is no data proving that high hematocrit can cause blood clots or other issues.

Here is an article you can show them:

High hematocrit as a risk factor for venous thrombosis. Cause or innocent bystander?


In conclusion, Brækkan and colleagues have performed an interesting, large-scale study into the relation between high levels of hematocrit and the risk of venous thrombosis. They convincingly demonstrated a dose-response relation between level of hematocrit and risk of venous thrombosis. However, questions remain on the causal interpretation and the clinical consequences of their results.
 
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