Is Increase In Hematocrit Really A Concern??

[Phil Goodman]

Kept hearing conflicting views on the topic so decided to dig a little deeper. AI warning below, and yes I fully understand that we shouldn’t just automatically accept what is spit out from AI. However, it can clearly process more sources more effectively at a much faster rate than humans. There’s a reason a good LLM will outperform most doctors (and humans in other fields) when it comes to acquiring information and analyzing it. This output is from Grok, but I’ll probably run it through a few other platforms to compare. Also providing prompts for transparency and clarity.



Take your time, review all of the studies which cover the topic of hematocrit levels of trt patients and the risk of adverse events. Then, report back with your analysis. Be completely unbiased and only use studies that are structured strongly. Analyze studies that show increased risk as well as those that show no increase in risk. Then provide a concise overview of your analysis based only on factual, strong data. Confirm accuracy before replying



Analysis of Studies on Hematocrit Levels in TRT Patients and Risk of Adverse Events


I reviewed systematic reviews, meta-analyses, and large retrospective cohorts (prioritizing RCTs and propensity-matched designs) from peer-reviewed sources. Focus was on strongly structured studies examining hematocrit (Hct) elevation (erythrocytosis/polycythemia) in testosterone replacement therapy (TRT) patients and associations with adverse events like major adverse cardiovascular events (MACE: e.g., myocardial infarction [MI], stroke, death) and venous thromboembolism (VTE: e.g., deep vein thrombosis [DVT], pulmonary embolism). Studies were selected for methodological rigor, including clear definitions (e.g., Hct thresholds of 50-54%), controlled confounders, and statistical measures (e.g., odds ratios [OR], hazard ratios

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, weighted mean differences [WMD]).


Studies Showing Increased Risk


• A 2022 propensity-score-matched retrospective cohort (n=11,684 men from TriNetX database, 2002-2020) defined secondary polycythemia as Hct ≥52% post-TRT initiation. Among hypogonadal men on TRT, those developing polycythemia (n=5,842) had 35% higher odds of MACE/VTE in the first year (OR 1.35, 95% CI 1.13-1.61, p<0.001) vs. those without (incidence 5.15% vs. 3.87%), driven by MI (OR 1.81, 95% CI 1.2-2.7) and VTE (OR 1.51, 95% CI 1.17-1.94); no difference in stroke or death. Risk was independent after matching for 14 confounders (e.g., age, hypertension); sensitivity analyses confirmed with hemoglobin >17.5 g/dl (OR 1.21) and Hct >54% (p=0.03), but not >50%. Limitations: No TRT formulation breakdown; higher baseline Hct in polycythemia group (47.4% vs. 42.5%), though within guidelines.


• A 2025 systematic review of 35 testosterone studies (mostly retrospective cohorts) reported erythrocytosis rates up to 66.7% in cisgender men on TRT, linked to intramuscular formulations, higher doses, and older age. One included retrospective study showed increased MACE/VTE risk with erythrocytosis (OR 1.35); overall VTE rates were 0.8-2.7%, but often confounded by other factors (e.g., surgery, genetics) and not directly tied to Hct elevation. Evidence quality: Fair/poor due to bias risks and heterogeneity; no clear independent thromboembolic association.


Studies Showing No Increased Risk


• A 2010 systematic review/meta-analysis of 51 comparative studies (randomized/nonrandomized) found TRT significantly raised hemoglobin (WMD 0.80 g/dl, 95% CI 0.45-1.14) and Hct (WMD 3.18%, 95% CI 1.35-5.01). However, no significant effects on mortality, prostate outcomes, or cardiovascular events (e.g., no change in CV risk factors beyond minor HDL decrease). Limitations: Low-to-medium quality studies; short follow-up (3 months-3 years).


• A 2015 review synthesizing meta-analyses of RCTs (e.g., 2005-2014) and pharmacoepidemiological data reported consistent Hct increases (standardized mean difference 0.899, 95% CI 0.718-1.061), with 3-4x higher risk of Hct >50% (more with injectables). No causal link to adverse CV events in properly managed TRT; meta-analyses showed neutral OR for MACE (e.g., 1.01, 95% CI 0.57-1.77); some studies suggested reduced mortality (HR 0.61). Limitations: Short RCT durations; observational biases.


• A 2018 review on TRT-induced erythrocytosis (prevalence 12.8-40%, highest with short-acting injectables) cited mechanisms like hepcidin suppression but found no direct evidence linking it to CV/thromboembolic events; meta-analyses confirmed no causal CV risk from TRT. Guidelines recommend monitoring and intervention at Hct >50-54%. Limitations: Few long-term RCTs; conflicting small/retrospective data.


Concise Overview


TRT reliably elevates Hct by 3-3.18% (meta-analysis data), with erythrocytosis (Hct >50-52%) rates up to 66.7%, dose- and formulation-dependent (highest with intramuscular). Meta-analyses of RCTs (n=51+ studies) show no significant increase in CV events, VTE, or mortality from TRT or Hct rises, supporting no causal role in properly diagnosed hypogonadism. However, retrospective cohorts indicate 35% higher MACE/VTE odds (OR 1.35) with polycythemia (Hct ≥52%) in the first year, though evidence is conflicting, confounded, and lacks high-quality prospective confirmation. Guidelines advise Hct monitoring and TRT adjustment at 50-54% thresholds to minimize potential risks. Overall, benefits may outweigh risks in monitored patients, but long-term RCTs are needed for clarity.

 

[Phil Goodman]

So what is your final verdict? Does it seem that it doesn’t increase risks or that it does? And I fully understand and accept that you are not a doctor providing medical guidance.



The strongest, highest-quality evidence—particularly from large randomized controlled trials (RCTs) like the 2023 TRAVERSE trial (n=5,246 men with hypogonadism and high CV risk)—shows that testosterone replacement therapy (TRT) itself does not increase the overall risk of major adverse cardiovascular events (MACE: e.g., heart attack, stroke, CV death) compared to placebo. The trial found noninferiority (HR 0.96, 95% CI 0.78-1.17), with event rates nearly identical (7.0% vs. 7.3%). Multiple recent meta-analyses of RCTs (including one of 30 trials in 2024) confirm no significant increase in CVD risk, all-cause mortality, stroke, MI, or VTE from TRT in properly diagnosed hypogonadal men.


TRT does reliably cause hematocrit (Hct) elevation, often leading to secondary erythrocytosis/polycythemia (Hct >50-52%, up to >54% in some cases), especially with injectable formulations, higher doses, or in older/obese men. This is a well-established side effect.


The key question is whether this Hct rise independently drives adverse events:


• Some retrospective cohort studies (e.g., propensity-matched analyses from 2022 and 2024) link developing polycythemia (Hct ≥52%) during TRT to modestly higher odds of MACE/VTE in the first year (OR ~1.35), including higher MI and VTE rates, compared to those whose Hct stays stable/normal.


• However, these are observational/retrospective data, prone to confounding (e.g., baseline differences, unmeasured factors like obesity or comorbidities). RCTs and meta-analyses of RCTs do not show a clear causal link between TRT-induced erythrocytosis and increased thrombotic/CV events. In TRAVERSE, severe erythrocytosis (>54%) was rare (<1% after dose adjustment), and overall VTE was slightly higher but nonsignificant and underpowered for subgroup analysis by Hct. Systematic reviews often note conflicting or insufficient evidence for a direct erythrocytosis → thrombosis connection in TRT patients, especially when monitoring and dose adjustments occur.


Guidelines (e.g., Endocrine Society, AUA) still recommend regular Hct monitoring and intervention (dose reduction, switch to lower-risk formulations like gels/orals, or discontinuation) at thresholds like >50-54% to minimize potential risks, reflecting a precautionary approach despite the lack of definitive RCT proof of harm.


Final verdict: On balance, the highest-level evidence (large RCTs and RCT meta-analyses) indicates that properly managed TRT does not meaningfully increase overall CV or thromboembolic risks in hypogonadal men, even accounting for Hct rises. The observed associations in some observational studies appear limited, confounded, or not replicated in controlled settings. That said, erythrocytosis is a real side effect that warrants monitoring and management to err on the side of caution, as very high Hct could theoretically contribute to viscosity-related issues in vulnerable individuals.


This is a synthesis of published data only—individual risk varies based on factors like age, baseline Hct, comorbidities, dose/formulation, and monitoring adherence.

 

[Vince]

Personally I believe yes.

High hematocrit (HCT) — defined for men as generally >50-52% — causes significant health issues by increasing blood viscosity (thickness), which restricts circulation and increases cardiovascular risks. Key issues include blood clots, stroke, heart attack, and hypertension. Common symptoms include headaches, dizziness, blurred vision, and fatigue.

That's my two cents.