Testosterone Therapy: An Assessment of the Clinical Consequences of Changes in Hematocrit and Blood Flow Characteristics

Abstract

Introduction. Clinical guidelines indicate that haematocrit should be monitored during testosterone replacement therapy (TTh) with action taken if a level of 0.54 is exceeded. Aim. To consider the extent of changes in haematocrit and putative effects on viscosity, blood flow and mortality following TTh. Methods. We focused on literature describing benefits and possible pitfalls of TTh including increased haematocrit. We used data from the BLAST RCT to determine change in haematocrit after 30 weeks of TTh and describe a clinical case showing the need for monitoring. We consider the validity of the current haematocrit cutoff value at which TTh may be modified. Ways in which haematocrit alters blood flow in the micro-and macro-vasculature are also considered. Main Outcome Measures. (1) change in haematocrit, (2) corresponding actions taken in clinical practice and (3) possible blood flow changes following change in haematocrit. Results. Analysis of data from the BLAST RCT showed a significant increase in mean haematocrit of 0.01, the increase greater in men with lower baseline values. While, none of 61 men given TTh breached the suggested cutoff of 0.54 after 30 weeks, a clinical case demonstrates the need to monitor haematocrit. An association between haematocrit and morbidity and mortality appears likely but not proven and , may be evident only in patient subgroups. The consequences of an increased haematocrit may be mediated by alterations in blood viscosity, oxygen delivery and flow. Their relative impact may vary in different vascular beds. Conclusions. TTh can effect an increased haematocrit via poorly understood mechanisms and may have harmful effects on blood flow that differ in patient

Testosterone Therapy in Adult-Onset Testosterone Deficiency: Hematocrit and Hemoglobin Changes

“…An increase in viscosity associated with higher HCT is likely to affect blood flow and perfusion. 16 This effect would be dependent on many factors such as erythrocyte age, deformability, and morphological changes associated with glycemic status. 16 Thus, the optimal HCT may vary for the various conditions leading to increased HCT, as they may have differing effects on the condition of the erythrocyte.…”

“…52 It is essential that the effects of the TTh-associated changes in HCT, Hb, and HCT/Hb ratio on outcomes such as erythrocyte life span, blood flow characteristics such as peak systolic velocity, CVD, and mortality be evaluated via prospective studies. 16,54…”

“…15 An elevated hematocrit (HCT) appears the most frequent adverse effect of TTh. 16,17 The relationship between HCT, atherogenesis, and mortality is not well understood, with many conflicting studies. [18][19][20][21][22][23] Interestingly, one of these showed a U-shaped association between HCT and mortality, suggesting a complex nonlinear relationship.…”

Testosterone Treatment (TTh) Improves Anemia and Hematocrit Increase Reduced Death in Hypogonadal Men: Paradigm Shift of a Risk Factor of TTh

“…No evidences in the literature confirm the assumption that there is a link between cardiovascular disease (especially venous thromboembolism) and elevated level of hematocrit [4,7]. While some population studies suggest that high hematocrit is associated with increased risk of venous thromboembolism [8], cardiovascular diseases and all-cause mortality [9] this was assumed based on explained by the presence of other medical conditions that cause both a high hematocrit and venous thrombosis or cardiovascular disease [7].…”

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Real-life 12 years data show that long-term treatment with testosterone treatment has significant reduction in mortality [1-3] and increase of hematocrit, which theoretically could increase risk of fatal cardiovascular events, could not be proven [4]. Summarizing results of research results that aimed to throw the light on the relationship between hematocrit and all-cause mortality in men receiving TTh in long-term setting [5,6].

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