JU INSIGHT Hematocrit Rises and Increased Risk of Major Cardiovascular Events in Men Starting Testosterone Therapy

By: Taylor P. Kohn, MD, MPhil, Johns Hopkins University School of Medicine, Baltimore, Maryland; Pranjal Agrawal, BS, Johns Hopkins University School of Medicine, Baltimore, Maryland; Jesse Ory, MD, Dalhousie University, Halifax, Nova Scotia, Canada; Joshua M. Hare, MD, University of Miami Miller School of Medicine, Florida; Ranjith Ramasamy, MD, University of Miami Miller School of Medicine, Florida | Posted on: 21 Feb 2024

Kohn TP, Agrawal P, Ory J, Hare JM, Ramasamy R. Rises in hematocrit are associated with an increased risk of major adverse cardiovascular events in men starting testosterone therapy: a retrospective cohort claims database analysis. J Urol. 2024;211(2):285-293.

Study Need and Importance

Elevated hematocrit (Hct) can result in an increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). While a previous study demonstrated that a rise in Hct to over 52% was associated with a higher risk for MACE for men starting TTh, no study has looked at the impact of the magnitude of the change in Hct from baseline after starting TTh.

What We Found

In a cohort analysis of over 29,000 men, we found that any increase in Hct from baseline was associated with an increased risk of MACE for men prescribed testosterone when compared to men who were prescribed testosterone who had no increase in Hct (Table). Thus, an increase in Hct for men starting TTh may be a risk factor for men who are started on TTh.

Table. Proportion of Major Adverse Cardiovascular Events by Change in Hematocrit After Starting Testosterone Therapy

		Hematocrit after starting testosterone
		36%-39%	40%-43%	44%-47%	48%-51%	≥52%	Relative risk of MACE	Matched men in each group^a
Hematocrit before testosterone	36%-39%	6.1%-6.7%^b	10.7%				1.62 (1.12-2.34)	n = 631
				10.3%			1.52 (1.05-2.21)	n = 621
					11.3%		1.68 (1.14-2.47)	n = 551
						14.3%	2.29 (1.33-3.95)	n = 274
	40%-43%			3.4%			1.66 (1.13-2.43)	n = 1985
			2.1%-2.7%^b		4.3%		2.09 (1.27-3.45)	n = 1059
						5.6%	2.06 (1.15-3.71)	n = 589
	44%-47%			1.0%-1.6%^b	2.2%		2.07 (1.34-3.19)	n = 2700
	44%-47%			1.0%-1.6%^b		4.3%	2.67 (1.56-4.56)	n = 1102
	48%-51%				1.4%	3.3%	2.35 (1.27-4.38)	n = 1004
	≥52%					——	——	Too infrequent
Abbreviations: MACE, major adverse cardiac events. Bold indicates significance. ^aSample size changes between comparisons due to propensity score matching based on age, race/ethnicity, smoking status, baseline hematocrit level, history of myocardial infarction, history of cerebral infarction, hyperlipidemia, sleep apnea, type 2 diabetes mellitus, current age, and frequency of outpatient services, emergency department services, and inpatient hospital services. ^bEach group with an increase in hematocrit after testosterone was matched to the men with same baseline hematocrit but with no change after starting testosterone. Range reported for MACE inidence for each matched group without change in hematocrit. Since hematocrit before testosterone of 48% to 51% is only compared to 1 group, no range is given.

Limitations

This was a retrospective claims database analysis extracted from electronic medical records, and as such we lack important granularity from the data. We were not able to assess pre- and post-TTh levels, or confirm that men used the prescriptions for testosterone that were given or the type of testosterone prescribed. This hypothesis will need to be further tested in a clinical-based setting.

Interpretation for Patient Care

Clinicians should monitor Hct after initiating TTh, as large increase from baseline may be a risk factor for future MACE. Physicians and patients should have ongoing conversations regarding the risk of MACE when Hct increases are observed.