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

Abstract

Introduction: Clinical guidelines indicate that hematocrit 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 hematocrit and putative effects on viscosity, blood flow, and mortality rates after TTh.

Methods: We focused on literature describing benefits and possible pitfalls of TTh, including increased hematocrit. We used data from the BLAST RCT to determine change in hematocrit after 30 weeks of TTh and describe a clinical case showing the need for monitoring. We consider the validity of the current hematocrit cutoff value at which TTh may be modified. Ways in which hematocrit alters blood flow in the micro- and macro-vasculature are also considered.

Main outcome measures: The following measures were assessed: (i) change in hematocrit, (ii) corresponding actions taken in clinical practice, and (iii) possible blood flow changes following change in hematocrit.

Results: Analysis of data from the BLAST RCT showed a significant increase in mean hematocrit of 0.01, the increase greater in men with lower baseline values. Although 0 of 61 men given TTh breached the suggested cutoff of 0.54 after 30 weeks, a clinical case demonstrates the need to monitor hematocrit. An association between hematocrit and morbidity and mortality appears likely but not proven and may be evident only in patient subgroups. The consequences of an increased hematocrit 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 hematocrit via poorly understood mechanisms and may have harmful effects on blood flow that differ in patient subgroups. At present, there appears no scientific basis for using a hematocrit of 0.54 to modify TTh; other values may be more appropriate in particular patient groups. König CS, Balabani S, Hackett GI, et al. Testosterone Therapy: An Assessment of the Clinical Consequences of Changes in Hematocrit and Blood Flow Characteristics. Sex Med Rev 2019;7:650-660.

Keywords: Adult-Onset Testosterone Deficiency; Blood Viscosity; Hematocrit; Microvascular Flow; Testosterone Therapy; Type 2 Diabetes.