He was born in 74.
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Wise to be cautious here seeing as you had previous cardiovascular issues/surgery and you have AFib.
As I stated in one of your older threads your baseline hematocrit 48% was already sitting near the top-end.
You need to stay on top of your diet, blood pressure, lipids, inflammatory markers, endothelial/vascular health, CBC, visceral adipose.
* Most current guidelines, including those from the American Urological Association and the Endocrine Society, flag hematocrit above 54% as a threshold requiring intervention. Some clinicians use 52% as a softer “watch and manage” threshold, particularly for men with additional cardiovascular risk factors.
Dropped some big ones in 2025!
Professor Michael Zitzmann
We also know hematocrit can be increased by testosterone preparations. It depends on the preparation, and we think that there is data that shows that the threshold of 52-54% should not be surpassed, and men should be controlled for the hematocrit especially in the first year of treatment every 3 months
Hematocrit & Thromboembolic Risk
* TTh increase Hematocrit - clinically relevant at >52-54%
* Recommended: Control Hematocrit every 3 months in the 1st year
Professor Michael Zitzmann
We also know hematocrit can be increased by testosterone preparations. It depends on the preparation, and we think that there is data that shows that the threshold of 52-54% should not be surpassed, and men should be controlled for the hematocrit especially in the first year of treatment every 3 months
Hematocrit & Thromboembolic Risk
* TTh increase Hematocrit - clinically relevant at >52-54%
* Recommended: Control Hematocrit every 3 months in the 1st year
...
7 FUTURE RESEARCH DIRECTIONS
While substantial progress has been made in understanding the CV safety of TTh, key areas for future research remain to further refine its application and optimize patient outcomes.
1. Long-term CV outcomes
The TRAVERSE trial and similar studies have reassured us of TTh’s short-to-medium-term CV safety, yet long-term effects, especially across diverse populations, require further investigation. Extended follow-up studies are needed to assess the potential for long-term CV safety in men undergoing decades-long TTh.
2. Personalized medicine and genetic factors
Genetic factors, like the CAG repeat polymorphism in the androgen receptor (AR) gene, which affects receptor sensitivity to T, merit deeper study. Future research should explore how genetic polymorphisms influence TTh’s efficacy and safety, aiming for a personalized approach that considers not only clinical symptoms and T levels but also genetic profiles.15,47,48
3. Hct and thromboembolic risks
Although current evidence indicates that Hct increases with TTh can be managed safely, refining thresholds for Hct monitoring and intervention remains a priority. Future studies should aim to develop guidelines tailored to patients at higher thromboembolic risk.
4. Broader health implications of TTh
Expanding research to assess TTh’s impact on cognitive function, bone health, and mortality will deepen understanding of its overall health effects. Such insights would allow for a more comprehensive balancing of TTh’s risks and benefits for varied patient populations.
5. Comparative effectiveness of TTh formulations
Comparative studies on different TTh formulations (e.g., gels, injections, patches) are needed to identify the safest and most effective options for patients with specific comorbidities. This can guide formulation choice in tailored clinical contexts.
By focusing on these research areas, the TTh evidence base can be enhanced, leading to safer, more effective treatment approaches for men with hypogonadism. Integrating genetic factors, broader health outcomes, and real-world data from registries will also support optimized, long-term TTh use, particularly as RCT trials become increasingly challenging due to ethical and financial considerations.
* our meta-analysis stands as the most up to date analysis restricted to RCTs directed to men aged 40 or older.
* The main fndings were as follows: (1) there were no significant diferences between groups in all-cause mortality, cardiovascular mortality, MI, and stroke; (2) TRT signifcantly increased the incidence of cardiac arrhythmias; (3) TRT was associated with decreased levels of HDL-c; and (4) there was a marginal increase in SBP levels in the TRT group.
* our meta-analysis stands as the most up to date analysis restricted to RCTs directed to men aged 40 or older.
* The main fndings were as follows: (1) there were no significant diferences between groups in all-cause mortality, cardiovascular mortality, MI, and stroke; (2) TRT signifcantly increased the incidence of cardiac arrhythmias; (3) TRT was associated with decreased levels of HDL-c; and (4) there was a marginal increase in SBP levels in the TRT group.
Long‑Term Cardiovascular Safety of Testosterone‑Replacement Therapy in Middle‑Aged and Older...
Elevated haematocrit is common with TTh, typically occurring within 3–12 mo. Levels up to 54% appear safe, but higher values may increase CV risk [15].
* Treatment adjustments are required for haematocrit >54% (requiring withdrawal and phlebotomy in high-risk cases)
* Elevated haematocrit is common with TTh, typically occurring within 3–12 mo. Levels up to 54% appear safe, but higher values may increase CV risk [15].
* Treatment adjustments are required for haematocrit >54% (requiring withdrawal and phlebotomy in high-risk cases)
Fig. 1 – Diagnostic evaluation of late-onset hypogonadism. cFT = calculated free testosterone; LH = luteinising hormone; MRI = magnetic resonance imaging; PRL = prolactin; SHBG = sex hormone–binding globulin; T =...
@Melody68
Throwing in Zitzmann's paper that dropped earlier this year and the updated 2026 EAU Guidelines.
* Aside from TRAVERSE, meta-analyses have now concluded that TTh, in doses restoring physiological levels, is not associated with elevated cardiovascular risk. A 2024 systematic review and meta-analysis encompassing nearly 40 studies found no increase in heart attack, stroke, or mortality with TTh [23].
* One safety consideration that does remain is erythrocytosis. As noted, testosterone often raises hematocrit. In T4DM, for example, about 20% of men on testosterone developed hematocrit >54%, versus 1% on placebo [16]. Similar results were observed in the HEAT-registry [19]. While an increased red cell mass can be beneficial up to a point (alleviating anemia), excessive erythrocytosis can increase blood viscosity and theoretically the risk of thrombosis. Therefore, managing hematocrit is crucial: therapy should be adjusted or briefly halted if hematocrit exceeds the upper limit, and secondary causes (smoking, OSA) addressed. Phlebotomy is an effective measure to quickly reduce hematocrit if needed.
* Notably, in the aggregate of studies, testosterone therapy has not been shown to raise the incidence of venous thromboembolism significantly; still, caution is warranted in men with prior thrombotic events.
* Notably, in the TRAVERSE Trial, TTh increased neutrophil and monocyte counts while decreasing lymphocytes and platelets compared with placebo. Higher neutrophil and monocyte counts, both at baseline and during treatment, were independently associated with increased risk of major adverse cardiovascular events, and treatment-related increases in these cell types correlated with higher venous thromboembolism risk. These findings suggest that monitoring neutrophil and monocyte counts may be important when evaluating thromboembolic risk in hypogonadal men receiving TTh [44]
GANGSTARR
* Aside from TRAVERSE, meta-analyses have now concluded that TTh, in doses restoring physiological levels, is not associated with elevated cardiovascular risk.
* One safety consideration that does remain is erythrocytosis. As noted, testosterone often raises hematocrit. In T4DM, for example, about 20% of men on testosterone developed hematocrit >54%, versus 1% on placebo [16]. Similar results were observed in the HEAT-registry [19]. While an increased red cell mass can be beneficial up to a point (alleviating anemia), excessive erythrocytosis...
Regarding the TRAVERSE study and CVD looking at the current EAU Sexual and Reproductive Health Guidelines limited update March 2026 the conclusion sums it up here!
In conclusion, current available data from interventional studies suggest that there is no increased risk up to three years of testosterone therapy [179-183]. 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 [184, 185].
3.5.5 Cardiovascular disease
No RCTs have provided a clear answer on whether testosterone therapy affects CV outcomes. The TTrial (n = 790) in older men [169], the TIMES2 (n = 220) [30] and, the BLAST studies in men with MetS and T2DM, and the pre-frail and frail study in elderly men, all of one year duration, and the T4DM two-year study, did not reveal any increase in Major Adverse Cardiovascular Events (MACE) [30, 33, 34, 169, 170]. Randomised controlled trials between three and 12 months in men with known heart disease treated with testosterone therapy have not found an increase in MACE, but have reported improvement in cardiac ischaemia, angina and functional exercise capacity [171-173]. A large cohort study (n=20,4857 men) found that neither transdermal gel or intramuscular testosterone was associated with an increased risk of composite CV outcome in men with or without prevalent CVD (mean follow up 4.3 years) [174]. 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 therapy 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 medicines" [175].
Data released from the TRAVERSE study confirm the findings of the EMA [85]. The latter is the first double-blind, placebo-controlled, noninferiority 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.
A mild higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism was observed in the testosterone group [85]. The latter observations need to be confirmed, as previous available data do not support an increased risk of venous thromboembolism [86, 176] or major arrhythmias [177] 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 [178].
In conclusion, current available data from interventional studies suggest that there is no increased risk up to three years of testosterone therapy [179-183]. 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 [184, 185].
3.5.6 Erythrocytosis
An elevated haematocrit is the most common adverse effect of testosterone therapy. Stimulation of erythropoiesis is a normal biological action that enhances 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 12 months after testosterone therapy initiation. However, polycythaemia can also occur after any subsequent increase in testosterone dose, switching from topical to parenteral administration, or the development of comorbidity that are linked to an increase in haematocrit (e.g. respiratory or haematological diseases).
There is no evidence that an increase in haematocrit up to and including 54% causes any adverse effects. If haematocrit exceeds 54%, there is a testosterone-independent but weak associated rise in CV events and mortality [88, 189-191]. 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 that included symptomatic men with hypogonadism, aged 45-80 years, who had pre-existing or 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%) [85].
However, three previous large studies did not show any evidence that testosterone therapy is associated with an increased risk of venous thromboembolism [192, 193]. Of those, one study showed that an increased risk peaked at six months after initiation of testosterone therapy, then declined over the subsequent period [194]. In one study, venous thromboembolism was reported in 42 cases, and 40 of these had a diagnosed underlying thrombophilia (including factor V Leiden deficiency, prothrombin mutations and homocysteinuria) [195].
A meta-analysis of RCTs of testosterone therapy reported that venous thromboembolism was frequently related to underlying undiagnosed thrombophilia-hypofibrinolysis disorders [86]. 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 [196]. Similarly, another meta-analysis and systematic review of RCTs found that testosterone therapy was not associated with an increased risk of venous thromboembolism [176].
With testosterone therapy, elevated haematocrit is more likely when baseline levels are near the upper limit of normal prior to initiation. Additional risk factors for increased haematocrit during therapy include smoking and pre-existing respiratory conditions. Elevated haematocrit occurs more frequently with parenteral formulations compared to topical preparations. In line with this, a large retrospective two-arm open registry comparing long- acting testosterone undecanoate with testosterone gels found that the injectable formulation was associated with a higher risk of haematocrit levels exceeding 50%, compared to gel therapy [197].
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.
In cases of elevated haematocrit without comorbidities, acute CV or venous thromboembolism events, management can include reducing the testosterone dose, switching to a different formulation, or - if haematocrit is markedly high - performing venesection (500mL), repeated if necessary. In most cases, discontinuation of testosterone therapy is not required.
