Doctors tell me I had a TIA . . .

[Melody68]

I'm 68 and starting taking T enanthate about 9 months ago; I'm a good responder and do well on 77mg/wk, putting me at the high end of the T reference range. I very much like the effects; I've lost weight and gained some good muscle.

Yesterday, while talking to my wife, I suddenly couldn't enunciate my words, slurring them instead. It stopped after 2 minutes, but left both my wife and I kind of startled.

I went to emergency, where they took blood and did a head CT scan, which was negative for a stroke. The feeling is that it was a TIA (transient ischemic attack). They prescribed daily Plavix and aspirin for me, and set me up for a clinic next week where I'll see some high powered specialists.

Some studies show that there may be a relationship between TRT in older men and a slight increase in coronary events. Other studies show no relationship. What to believe?

I definitely could have some arteriosclerotic plaque in my brain arteries; I had a successful heart bypass 12 years ago after many years of neglecting my blood profile. But will the doctors see it that way, or will they just blame the TRT and ask me to stop the injections? What if they refuse to prescribe the T for me?

I know that I'd certainly get good results even cutting the dose down to 70mg/wk, which I would do, but I sure don't want to stop taking T. Thoughts? Many thanks for your input . . .

 

[Systemlord]

You have to be very careful which doctors you listen to because the majority of them are clueless and have knee jerk reactions to when people have problems on therapy that usually always involve stopping treatment.

There was a patient of a doctor that I know it had been on TRT for eight years. He moved up to Boulder, Colorado, which is 13,500 feet elevation and his face started tingling and he had problems breathing.

The doctors immediately blamed the TRT because of the elevation in hematocrit, which he had been on successfully without problems for eight years.

All his doctors were clueless, which is why they blame the TRT. His private doctor took control of the situation. He already knew where to look. The guy had a 75% blockage in the heart.

Had this man not moved to high elevation. He would not have found out about the blockage until much later and the outcome would’ve likely been much worse.

 

[excelnelg]

Not saying it wasn't a TIA...BUT I've seen TIA used as a diagnosis when they missed the real problem. So, that is to say, keep an open mind to other possibilities.

 

[Melody68]

Systemlord and Excelnelg; your points are well taken - there are many possibilities as to what happened and I'll try to see to it that the doctors keep an open mind.

For the 5 year period before TRT my hematocrit ran .46-.49 and my hemoglobin was in the higher 160's. My last blood test about a month ago (and while on T) showed a hematocrit of .51 (not bad) and a hemoglobin of 181 (should be a bit lower, not great). But, the night before the suspected TIA, I had the stomach flu and spent almost the entire night awake throwing up and with episodes of diarrhea. I might have slept 1-2 hours in the morning. I didn't have breakfast. My wife gave me some Gatoraid, but I only drank a bit because I didn't feel right (should have drank the whole thing.) We went out at noon and shortly after I had the two minute episode with the slurred speech. I suspect I was quite dehydrated because of the flu; that together with the higher hemoglobin of 181, and perhaps some compromised brain arteries from my early days when I had heart disease, might have caused the TIA. Is that plausible?

 

[madman]

I'm 68 and starting taking T enanthate about 9 months ago; I'm a good responder and do well on 77mg/wk, putting me at the high end of the T reference range. I very much like the effects; I've lost weight and gained some good muscle.

Yesterday, while talking to my wife, I suddenly couldn't enunciate my words, slurring them instead. It stopped after 2 minutes, but left both my wife and I kind of startled.

I went to emergency, where they took blood and did a head CT scan, which was negative for a stroke. The feeling is that it was a TIA (transient ischemic attack). They prescribed daily Plavix and aspirin for me, and set me up for a clinic next week where I'll see some high powered specialists.

Some studies show that there may be a relationship between TRT in older men and a slight increase in coronary events. Other studies show no relationship. What to believe?

I definitely could have some arteriosclerotic plaque in my brain arteries; I had a successful heart bypass 12 years ago after many years of neglecting my blood profile. But will the doctors see it that way, or will they just blame the TRT and ask me to stop the injections? What if they refuse to prescribe the T for me?

I know that I'd certainly get good results even cutting the dose down to 70mg/wk, which I would do, but I sure don't want to stop taking T. Thoughts? Many thanks for your input . . .

Sorry to hear this brother!

Definitely do not want to be running around in a hypogonadal state.

https://www.nejm.org/doi/full/10.1056/NEJMoa2215025

BACKGROUND

The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined.


METHODS

In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial,we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo.


RESULTS

The mean (±SD) duration of treatment was 21.7± 14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in thetwo groups. A higher incidence of atrial fibrillation, of acute kidney injury, and ofpulmonary embolism was observed in the testosterone group.


CONCLUSIONS

In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others;TRAVERSE ClinicalTrials.gov number, NCT03518034.)

Adverse Events​

Event
Transient ischemic attack

Testosterone Group (N=2596)
15 (0.6)

Placebo Group (N=2602)
17 (0.7)

P Value†
0.73


Table 3. Investigator-Reported Adverse Events.*

Dr. Giovanni Corona is one of the top in the field when it comes to testosterone/TTh.

He would be considered top tier when it comes to (research/clinical experience) in the field!

Been at this for decades.


12:56-22:36

Is testosterone therapy dangerous for the heart

The EAU Guidelines Office will provide a state-of-the-art update on male hypogonadism and testosterone replacement therapy. This recording will be of great educational value for urologists as internationally-known experts will focus on the controversial and challenging areas of this rapidly...

www.excelmale.com

Androgen Society Position Paper on CV Risk With Testosterone Therapy

Abraham Morgentaler, MD, Blavatnik Faculty Fellow in Health and Longevity at Beth Israel Deaconess Medical Center and Harvard University in Boston, MA, shares results of his article appearing in the November 2024 issue of Mayo Clinic Proceedings, where he and his colleagues found definitive...

www.excelmale.com

Androgen Society Position Paper on Cardiovascular Risk With Testosterone Therapy

* It is the position of the Androgen Society that it has been conclusively determined that TTh is not associated with increased risk of heart attacks, stroke, or CV deaths. Abstract The Androgen Society is an international, multidisciplinary medical organization committed to advancing...

www.excelmale.com

* It is the position of the Androgen Society that it has been conclusively determined that TTh is not associated with increased risk of heart attacks, stroke, or CV deaths.




CONCLUSION

The TRAVERSE trial, supported by an extensive prior literature, has found beyond any reasonable doubt that TTh in testosterone deficient individuals is not associated with increased risk of MACE. This has been studied in multiple populations, all with the same result, including in men 65 years and older who were relatively healthy, in a diabetic and prediabetic population, and in men at high risk for MACE. We believe this is now “settled science” and see no reason to expend valuable resources to investigate this issue further.








Before jumping the gun something that need to be kept in mind here!


post #21

TRAVERSE Trial Video Series: Cardiovascular Risk

https://live.arealive.org/webinars/public/index.html#home

www.excelmale.com

TRT and cardiovascular risk: TRAVERSE with caution

The relationship between testosterone replacement therapy (TRT) and cardiovascular(CV) disease (CVD) risk in older, hypogonadal men has been debated for years. Observational studies have variably linked low endogenous testosterone levels with adverse cardio metabolic effects and increased CVD...

www.excelmale.com

*We bring attention to the limitations of the TRAVERSE trial due to the potential for misleading reassurance of the safety of TRT at physiologic or supraphysiologic levels. The long term CV effects and the safety of such regimens have yet to be studied. We certainly advocate for further research to explore the long-term CV impact of TRT, especially at these higher dosing levels.

*The debate surrounding TRT and CVD risk thus far can be summarized as follows: current evidence suggests TRT does not increase CVD risk in older, hypogonadal men when administered over a short duration and at low-normal levels of replacement. The question remains open when considering the effects of TRT at physiologic or supraphysiologic levels.

https://www.ahajournals.org/doi/10.1161/STR.0000000000000475

2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association​

AIM

The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke.


METHODS

A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed.


STRUCTURE

Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the lifespan. These recommendations align with the American Heart Association’s Life’s Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.

Synopsis

The potential increased risk of stroke in men with confirmed hypogonadism using exogenous testosterone has been debated for several years. Observational studies and small randomized clinical trials showed conflicting results, leading the US Food and Drug Administration to issue a warning about the potential for increased risk of stroke and heart attacks in 2015.707 Recent data suggest that initiation or continuation of transdermal testosterone therapy in individuals with appropriate indications is reasonable and does not increase the risk of stroke.




Recommendation-Specific Supporting Text

1. Two systematic reviews of randomized clinical trials and observational studies published before 2017 found no evidence for an increased risk of stroke in men using exogenous testosterone therapy.However, they noted that the low level of evidence limited definitive conclusions.705,706 The 2023 TRAVERSE study (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men) sought to provide higher-quality evidence through a multicenter, randomized, double-blind,placebo-controlled noninferiority trial.704 The study enrolled 5246 men 45 to 80 years of age with confirmed hypogonadism (defined as reporting associated symptoms and having 2 fasting testosterone levels <300 ng/dL) to receive daily transdermal 1.62% testosterone gel with dose adjustments to target levels between 350 and 750 ng/dL or placebo gel for a mean of 21.7± 14.1 months. The participants either had preexisting CVD (defined as coronary artery disease, cerebrovascular disease, or peripheral arterial disease) or had high risk of CVD (defined as ≥3 risk factors, including hypertension, dyslipidemia, current smoking, stage 3 chronic kidney disease, diabetes, elevated C-reactive protein level, age ≥65 years, or Agatston coronary calcium score >75th percentile for age and race). Investigators found no significant difference in the incidence of the primary composite end point of major adverse cardiac events or in the component end point of nonfatal stroke.




Knowledge Gaps and Future Research

• The 2023 TRAVERSE study provides reassurance that testosterone gel does not increase the risk of stroke in men with risks for stroke and who have confirmed hypogonadism. The risks of stroke for other populations of men who use testosterone off label are not known.

• The effects of other testosterone formulations and routes of administration on the risk of stroke are not well studied.

• Future research may include investigation into other populations who may use testosterone, testosterone preparations and routes of administration, and longer durations of testosterone use

 

[Melody68]

Madman, thanks for the research and excellent reading selections.

The Traverse trial is reassuring, but one thing I hadn't noticed before, is the following statement . . .

"*The debate surrounding TRT and CVD risk thus far can be summarized as follows: current evidence suggests TRT does not increase CVD risk in older, hypogonadal men when administered over a short duration and at low-normal levels of replacement. The question remains open when considering the effects of TRT at physiologic or supraphysiologic levels."

The statement seems to limit their safety findings to lower levels of T replacement and not "physiologic or supraphysiologic levels". The article seems to imply that those T levels are limited to 350-750ng/dl; my TT levels have been higher than that, at trough being over 800 ng/dl. Do I interpret that statement correctly? A downward dose adjustment could be warranted.

Madman, sometimes the research is difficult to understand for the layperson. Yes, they argue that TRT on the whole is safe, but what about, in my case, the high hemoglobin caused by the TRT? I suppose that my best argument would be to reduce the T dose and take advantage of blood donation to make up the rest if needed. What a kicker that would be if the hemoglobin wasn't even the issue . . . but, somebodies going to find something to point at.

 

[madman]

Madman, thanks for the research and excellent reading selections.

The Traverse trial is reassuring, but one thing I hadn't noticed before, is the following statement . . .

"*The debate surrounding TRT and CVD risk thus far can be summarized as follows: current evidence suggests TRT does not increase CVD risk in older, hypogonadal men when administered over a short duration and at low-normal levels of replacement. The question remains open when considering the effects of TRT at physiologic or supraphysiologic levels."

The statement seems to limit their safety findings to lower levels of T replacement and not "physiologic or supraphysiologic levels". The article seems to imply that those T levels are limited to 350-750ng/dl; my TT levels have been higher than that, at trough being over 800 ng/dl. Do I interpret that statement correctly? A downward dose adjustment could be warranted.

Madman, sometimes the research is difficult to understand for the layperson. Yes, they argue that TRT on the whole is safe, but what about, in my case, the high hemoglobin caused by the TRT? I suppose that my best argument would be to reduce the T dose and take advantage of blood donation to make up the rest if needed. What a kicker that would be if the hemoglobin wasn't even the issue . . . but, somebodies going to find something to point at.

You need to do what you feel is best for you.

Due to your previous cardiovascular issues you need to stay on top of your diet, blood pressure, lipids, inflammatory markers, endothelial/vascular health, CBC, visceral adipose.




That statement was taken from this paper.

TRT and cardiovascular risk: TRAVERSE with caution

The relationship between testosterone replacement therapy (TRT) and cardiovascular(CV) disease (CVD) risk in older, hypogonadal men has been debated for years. Observational studies have variably linked low endogenous testosterone levels with adverse cardio metabolic effects and increased CVD...

www.excelmale.com

Testosterone replacement therapy and cardiovascular risk:TRAVERSE with caution
Srikanth Krishnan, Jairo Aldana-Bitar, Ilana Golub, Sina Kianoush, Travis Benzing, Keishi Ichikawa, Matthew J. Budoff


* However, interpreting these results within the context of real-world clinical practice raises unresolved questions. The TRAVERSE trial, which significantly contributes to this meta-analysis and serves as its foundational study, has notable limitations. These include a high discontinuation rate (> 60%) during follow-up, a mean treatment duration of less than two years, and an 18% loss to follow-up rate6. Most significantly, the trial achieved a median testosterone level of 350 ng/dL, which is at the lower end of the normal range and may not reflect the effects of physiologic and supraphysiologic dosing levels that are often targeted in clinical practice for symptom relief and quality of life improvement.


* We bring attention to the limitations of the TRAVERSE trial due to the potential for misleading reassurance of the safety of TRT at physiologic or supraphysiologic levels. The long term CV effects and the safety of such regimens have yet to be studied. We certainly advocate for further research to explore the long-term CV impact of TRT, especially at these higher dosing levels.


* The debate surrounding TRT and CVD risk thus far can be summarized as follows: current evidence suggests TRT does not increase CVD risk in older, hypogonadal men when administered over a short duration and at low-normal levels of replacement. The question remains open when considering the effects of TRT at physiologic or supraphysiologic levels.

Transformative Insights from the Landmark Traverse Trial: A new era in testosterone therapy

Nelson's house is where it's at!

www.excelmale.com

Some key takeaways here:

Cardiovascular Disease (CVD)

*Current available data from interventional studies suggest that there is no increased risk up to three years of testosterone therapy [167-171]. The currently published evidence has reported that testosterone therapy in men with diagnosed hypogonadism has neutral or beneficial actions on MACE in patients with normalised testosterone levels. The findings could be considered sufficiently reliable for at least a three year course of testosterone therapy, after which no available study can exclude further or long-term CV events [172,173]




Erythrocytosis

*There is no evidence that an increase of haematocrit up to and including 54% causes any adverse effects. If the haematocrit exceeds 54% there is a testosterone independent, but weak associated rise in CV events and mortality [79, 177-179]. Any relationship is complex as these studies were based on patients with any cause of secondary polycythaemia, which included smoking and respiratory diseases. There have been no specific studies in men with only testosterone-induced erythrocytosis.








Look over my reply from this thread.

High Testosterone on only 80mg/week

Also please enlighten us on where you attended medical school and where you got your degree in endocrinology? Your argument is small-minded and weak. If I told you, the moon revolves around the earth and the earth revolves around the sun, so by your logic, I don’t know what I’m talking about...

www.excelmale.com

Some critical points here!

* In men with pre-existing CVD extra caution is advised with a definitive diagnosis of hypogonadism before initiating testosterone therapy and monitoring of testosterone as well as haematocrit during treatment.


* Elevated haematocrit in the absence of comorbidity or acute CV or venous thromboembolism can be managed by a reduction in testosterone dose, change in formulation or if the elevated haematocrit is very high by venesection (500 mL), even repeated if necessary, with usually no need to stop the testosterone therapy.


* The knowledge that men with hypogonadism and/or ED may have underlying CVD should prompt individual assessment of their CV risk profile. Individual risk factors (e.g., lifestyle, diet, exercise, smoking, hypertension, diabetes and dyslipidaemia) should be assessed and treated in men with pre-existing CVD and in patients receiving androgen deprivation therapy. Cardiovascular risk reduction can be managed by primary care clinicians, but patients should be appropriately counselled by clinicians active in prescribing testosterone therapy [83]. If appropriate, patients should be referred to cardiologists for risk stratification and treatment of comorbidity.


* There is no evidence that an increase of haematocrit up to and including 54% causes any adverse effects. If the haematocrit exceeds 54% there is a testosterone independent, but weak associated rise in CV events and mortality [79, 177-179]. Any relationship is complex as these studies were based on patients with any cause of secondary polycythaemia, which included smoking and respiratory diseases. There have been no specific studies in men with only testosterone-induced erythrocytosis.


* In conclusion, current available data from interventional studies suggest that there is no increased risk up to three years of testosterone therapy [167-171]. The currently published evidence has reported that testosterone therapy in men with diagnosed hypogonadism has neutral or beneficial actions on MACE in patients with normalised testosterone levels. The findings could be considered sufficiently reliable for at least a three year course of testosterone therapy, after which no available study can exclude further or long-term CV events [172,173].








EAU GUIDELINES ON SEXUAL AND REPRODUCTIVE HEALTH - LIMITED UPDATE APRIL 2024


3.5 Safety and follow-up in hypogonadism management


3.5.5 Cardiovascular Disease

Evidence suggests that hypogonadal men have an increased risk of CVD [146, 147]. Whether or not LOH is a cause or a consequence of atherosclerosis has not been clearly determined. Late-onset hypogonadism is associated with CV risk factors, including central obesity, insulin resistance and hyperglycaemia, dyslipidaemia, pro-thrombotic tendency and chronic inflammatory state [147]. Atherosclerosis is a chronic inflammatory disease, that releases pro-inflammatory cytokines into the circulation, which are known to suppress testosterone release from the HPG axis. Evidence from RCTs of testosterone therapy in men with MetS and/or T2DM demonstrates some benefit in CV risk, including reduced central adiposity, insulin resistance, total cholesterol and LDL-cholesterol and suppression of circulating cytokines [28-30, 35, 147, 148]. However, due to the equivocal nature of these studies, testosterone therapy cannot be recommended for use outside of treatment of specific symptoms.

Published data show that LOH is associated with an increase in all-cause and CVD-related mortality [7, 149-152]. These studies are supported by a meta-analysis that concluded that hypogonadism is a risk factor for cardiovascular morbidity [136] and mortality [153]. Importantly, men with low testosterone when compared to eugonadal men with angiographically proven coronary disease have twice the risk of earlier death [147]. Longitudinal population studies have reported that men with testosterone in the upper quartile of the normal range have a reduced number of CV events compared to men with testosterone in the lower three quartiles[149]. Androgen deprivation therapy for PCa is linked to an increased risk of CVD and sudden death [154].Conversely, two long-term epidemiological studies have reported reduced CV events in men with high normal serum testosterone levels [155, 156]. Erectile dysfunction is independently associated with CVD and may be the first clinical presentation in men with atherosclerosis.

The knowledge that men with hypogonadism and/or ED may have underlying CVD should prompt individual assessment of their CV risk profile. Individual risk factors (e.g., lifestyle, diet, exercise, smoking, hypertension, diabetes and dyslipidaemia) should be assessed and treated in men with pre-existing CVD and in patients receiving androgen deprivation therapy. Cardiovascular risk reduction can be managed by primary care clinicians, but patients should be appropriately counselled by clinicians active in prescribing testosterone therapy [83]. If appropriate, patients should be referred to cardiologists for risk stratification and treatment of comorbidity.

No RCTs have provided a clear answer on whether testosterone therapy affects CV outcomes. The TTrial (n=790) conducted in older men [157], the TIMES2 study (n=220) [29], along with the BLAST studies involving men with Metabolic Syndrome (MetS) and Type 2 Diabetes Mellitus (T2DM), as well as the study involving pre-frail and frail elderly men - all of which lasted for one year, and the T4DM study spanning two years - did not show any increase in Major Adverse Cardiovascular Events (MACE) increase in Major Adverse Cardiovascular Events (MACE) [29,32, 33, 157, 158]. Randomised controlled trials, between three and twelve months, in men with known heart disease treated with testosterone have not found an increase in MACE, but have reported improvement in cardiac ischaemia, angina and functional exercise capacity [159-161]. A large cohort study (n=20,4857 men) found that neither transdermal gel or intramuscular testosterone was associated with an increased risk of composite cardiovascular outcome in men with or without prevalent CVD (mean follow-up 4.3 years) [162]. The European Medicines Agency (EMA) has stated that ‘The Co-ordination Group for Mutual recognition and Decentralisation Procedures-Human (CMDh), a regulatory body representing EU Member States, has agreed by consensus that there is no consistent evidence of an increased risk of heart problems with testosterone in men. However, the product information is to be updated in line with the most current available evidence on safety, and with warnings that the lack of testosterone should be confirmed by signs and symptoms and laboratory tests before treating men with these drugs [163].

Data recently released from the TRAVERSE study confirm the findings of the EMA [77]. The latter is the first double-blind, placebo-controlled, non-inferiority RCT with primary CV safety as an end point. The results showed that testosterone therapy was noninferior to placebo with respect to the incidence of MACE. However, a mild higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism was observed in the testosterone group [77]. The latter observations, however, need to be confirmed since previous available data do not support an increased risk of venous thromboembolism [78, 164] or major arrhythmias [165] after testosterone therapy. Similarly, the long-term follow-up (median of 5.1 years since last injection) of the T4DM study showed no differences in self-reported rates of new diagnosis of CVD [166].

In conclusion, current available data from interventional studies suggest that there is no increased risk up to three years of testosterone therapy [167-171]. The currently published evidence has reported that testosterone therapy in men with diagnosed hypogonadism has neutral or beneficial actions on MACE in patients with normalised testosterone levels. The findings could be considered sufficiently reliable for at least a three year course of testosterone therapy, after which no available study can exclude further or long-term CV events [172,173].








3.5.6 Erythrocytosis

An elevated haematocrit level is the most common adverse effect of testosterone therapy. Stimulation of erythropoiesis is a normal biological action that enhances the delivery of oxygen to testosterone-sensitive tissues (e.g., striated, smooth and cardiac muscle). Any elevation above the normal range for haematocrit usually becomes evident between three and twelve months after testosterone therapy initiation. However,polycythaemia can also occur after any subsequent increase in testosterone dose, switching from topical to parenteral administration and, development of comorbidity, which can be linked to an increase in haematocrit (e.g., respiratory or haematological diseases).

There is no evidence that an increase of haematocrit up to and including 54% causes any adverse effects. If the haematocrit exceeds 54% there is a testosterone independent, but weak associated rise in CV events and mortality [79, 177-179]. Any relationship is complex as these studies were based on patients with any cause of secondary polycythaemia, which included smoking and respiratory diseases. There have been no specific studies in men with only testosterone-induced erythrocytosis.

As detailed, the TRAVERSE study, which had included symptomatic hypogonadal men aged 45-80 years who had pre-existing or a high risk of CVD, showed a mild higher incidence of pulmonary embolism, a component of the adjudicated tertiary end point of venous thromboembolic events, in the testosterone therapy than in the placebo group (0.9% vs. 0.5%) [77]. However, three previous large studies have not shown any evidence that testosterone therapy is associated with an increased risk of venous thromboembolism [180, 181]. Of those, one study showed that an increased risk peaked at six months after initiation of testosterone therapy, and then declined over the subsequent period [182]. In one study venous thromboembolism was reported in 42 cases and 40 of these had a diagnosis of an underlying congenital thrombophilia (including factor V Leiden deficiency, prothrombin mutations and homocysteinuria) [183]. A meta-analysis of RCTs of testosterone therapy reported that venous thromboembolism was frequently related to underlying undiagnosed thrombophilia-hypofibrinolysis disorders [78]. In an RCT of testosterone therapy in men with chronic stable angina there were no adverse effects on coagulation, by assessment of tissue plasminogen activator or plasminogen activator inhibitor-1 enzyme activity or fibrinogen levels [184]. Similarly, another meta-analysis and systematic review of RCTs found that testosterone therapy was not associated with an increased risk of venous thromboembolism [164]. With testosterone therapy elevated haematocrit levels are more likely to occur if the baseline level is toward the upper limit of normal prior to initiation. Added risks for raised haematocrit on testosterone therapy include smoking or respiratory conditions at baseline. Higher haematocrit is more common with parenteral rather than topical formulations. Accordingly, a large retrospective two-arm open registry, comparing the effects of long-acting testosterone undecanoate and testosterone gels showed that the former preparation was associated with a higher risk of haematocrit levels > 50%, when compared to testosterone gels [185]. In men with pre-existing CVD extra caution is advised with a definitive diagnosis of hypogonadism before initiating testosterone therapy and monitoring of testosterone as well as haematocrit during treatment.

Elevated haematocrit in the absence of comorbidity or acute CV or venous thromboembolism can be managed by a reduction in testosterone dose, change in formulation or if the elevated haematocrit is very high by venesection (500 mL), even repeated if necessary, with usually no need to stop the testosterone therapy.

 

[Melody68]

Thanks Madman.

What can be said, I guess the ball is in their court. They'll probably have me reduce my T dosage, which I'll do. Hopefully they won't ask me to discontinue use . . . I'm not going back to where I was pre TRT. I've also been using Niacin for 20+ years for cholesterol control (works VERY well) and they'll probably start hassling me about getting on a statin, which I won't want to do, but my wife will be all nervous about it. What a pain . . .

 

[Ribeye]

I'm 68 and starting taking T enanthate about 9 months ago; I'm a good responder and do well on 77mg/wk, putting me at the high end of the T reference range. I very much like the effects; I've lost weight and gained some good muscle.

Yesterday, while talking to my wife, I suddenly couldn't enunciate my words, slurring them instead. It stopped after 2 minutes, but left both my wife and I kind of startled.

I went to emergency, where they took blood and did a head CT scan, which was negative for a stroke. The feeling is that it was a TIA (transient ischemic attack). They prescribed daily Plavix and aspirin for me, and set me up for a clinic next week where I'll see some high powered specialists.

Some studies show that there may be a relationship between TRT in older men and a slight increase in coronary events. Other studies show no relationship. What to believe?

I definitely could have some arteriosclerotic plaque in my brain arteries; I had a successful heart bypass 12 years ago after many years of neglecting my blood profile. But will the doctors see it that way, or will they just blame the TRT and ask me to stop the injections? What if they refuse to prescribe the T for me?

I know that I'd certainly get good results even cutting the dose down to 70mg/wk, which I would do, but I sure don't want to stop taking T. Thoughts? Many thanks for your input . . .

Watch your HCT and HBG closely. If they start to climb, you will need to make changes. If you have any other symptoms, follow up with your Doc. Assuming your Docs will do a cardiac workup on you as well, to be sure something else is not going on with your heart you should be fine. When I say cardiac workup they probably did a 12 lead EKG on you when you went to the ER, and probably ran a test for increased cardiac enzymes to be sure you were not also having a heart attack too. This wasn't likely caused by the T.

 

[Melody68]

Ribeye, you've either been there before, or you're a doctor; I remember at emerg that they did an EKG and a while later they did another one "with 12 leads". My last blood test in November showed higher hemoglobin of 181 and hematocrit at 51.0. Normally, perhaps, that wouldn't cause a blood clot, but recall that I was quite dehydrated before the incident. Also of interest, I found a blood test done in October of 2023, several months BEFORE I started TRT, and my Hemoglobin was 178 and hematocrit was 50.0; there's a note beside it that says "eating a lot of red meat at the time". I don't think, in my case, that the hemo and hemato are (much) affected by TRT. I think it's dependent on what I'm eating at the time, and lately I've been eating a lot of red meat to get my daily protein intake up.

I'm in the process of reducing my TRT, perhaps mistakenly thinking that will help the situation. I'm curious Ribeye, why do you think it wasn't caused directly by T?

 

[Melody68]

I just came from the clinic. They never even mentioned my T use or anything about hemoglobin or hematocrit. They do think it was a TIA caused by a blood clot, but they can't tell me whether it was a newly formed clot, or if it was an existing piece of plaque that broke off and migrated to the brain. They seem to be focused on my heart, which had some problems and plaque in the past. I'm wearing a holter monitor for two weeks (over Christmas!) and they prescribed something called ezetimibe (a cholesterol reducer) that I'll take for a time. Otherwise, I continue on the Plavix for 21 days and then the baby aspirin for the rest of my life. All in all, not bad so far . . .

 

[Ribeye]

Ribeye, you've either been there before, or you're a doctor; I remember at emerg that they did an EKG and a while later they did another one "with 12 leads". My last blood test in November showed higher hemoglobin of 181 and hematocrit at 51.0. Normally, perhaps, that wouldn't cause a blood clot, but recall that I was quite dehydrated before the incident. Also of interest, I found a blood test done in October of 2023, several months BEFORE I started TRT, and my Hemoglobin was 178 and hematocrit was 50.0; there's a note beside it that says "eating a lot of red meat at the time". I don't think, in my case, that the hemo and hemato are (much) affected by TRT. I think it's dependent on what I'm eating at the time, and lately I've been eating a lot of red meat to get my daily protein intake up.

I'm in the process of reducing my TRT, perhaps mistakenly thinking that will help the situation. I'm curious Ribeye, why do you think it wasn't caused directly by T?

Your HCT and HBG are at the high end of normal but it sounds like you were at the high end of normal prior to starting HRT too. They usually give folks at clot risk anti thrombotics, regardless of the source. Your cardiac issues put you at a higher risk of a clot. Stay hydrated, take the meds and talk to your docs about if you should reduce the T at least temporarily. I am not a doc, nor have I been there, but I have worked in the medical field for a long time. Be careful, you really need to get this sorted out and taken care of properly.

 

[Melody68]

Thank you Ribeye, I very much appreciate your input and will be vigilant in all my actions.

 

[fun2drive]

You have to be very careful which doctors you listen to because the majority of them are clueless and have knee jerk reactions to when people have problems on therapy that usually always involve stopping treatment.

There was a patient of a doctor that I know it had been on TRT for eight years. He moved up to Boulder, Colorado, which is 13,500 feet elevation and his face started tingling and he had problems breathing.

The doctors immediately blamed the TRT because of the elevation in hematocrit, which he had been on successfully without problems for eight years.

All his doctors were clueless, which is why they blame the TRT. His private doctor took control of the situation. He already knew where to look. The guy had a 75% blockage in the heart.

Had this man not moved to high elevation. He would not have found out about the blockage until much later and the outcome would’ve likely been much worse.

Boulder is 5,400 feet not 13,500 feet which is vastly different.

 

[Johnny08910]

@madman all the studies you listed say that no CV risk increase for low normal replacement level and one was even at 350? Are there risks at 800-900 levels? The powerpoint above from the doc also states that no CV risk in hypogonadal men but what if my levels are 500 and I start trt to 800-900 will my risks be higher given that Im technically not hypogonadal by lab values?