Intramuscular Testosterone Therapy Tied With Rise in Hematocrit

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The risk of hematocrit elevation may depend on testosterone therapy's route of administration, according to investigators.

A rise in hematocrit levels occurs with 4 months of treatment with intramuscular testosterone therapy but not with intranasal testosterone gel, investigators reported at the American Urological Association’s 2023 Annual Scientific Meeting in Chicago, Illinois and in The Journal of Urology.1

Previous research has linked polycythemia, abnormally high hematocrit levels exceeding 52% during testosterone therapy, to a higher probability of major adverse cardiovascular events such as stroke and venous thromboembolism.2

The current finding is based on a randomized trial examining hematocrit change in men aged 18-75 years with hypogonadism. Investigators randomly assigned 31 men to receive intranasal testosterone gel (5.5 mg per nostril thrice daily) and 23 men to receive intramuscular testosterone cypionate (200 mg intramuscularly once every 2 weeks). At baseline, mean serum testosterone levels were 244.6 vs 240.7 ng/dL and mean hematocrit levels were 44.4% vs 42.7% in the intranasal vs intramuscular testosterone groups, respectively.

Serum testosterone levels significantly increased over 4 months in both groups, but more so in the testosterone cypionate group (mean change 511 vs 283 ng/mL). In the injection group, mean hematocrit significantly increased from 42.7% at baseline to 46.6% at 4 months, Marco-Jose Rivero, BA, of Desai Sethi Urology Institute, University of Miami Miller School of Medicine in Florida, reported on behalf of his team. The testosterone cypionate group also experienced significant increases in estradiol (mean change 22.9) and decreases in 17-hydroxyprogesterone (mean change -39.8). Elevated estradiol can increase risks for gynecomastia and fluid retention. Decreases in 17-hydroxyprogesterone possibly increases the risk for infertility.

The nasal testosterone group had no significant change in mean hematocrit, estradiol, 17-hydroxyprogesterone, or IIEF-6 over 4 months, according to Rivero.

PSA levels stayed stable in both groups. The 6-item International Index of Erectile Function score significantly increased in the injection group (IIEF-6, mean change 4.8 over months). Treatment dissatisfaction was higher in the nasal testosterone group (15% vs 2.4%).

“Patients who are at increased risk of developing polycythemia or those who wish to avoid changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as [intranasal testosterone gel],” Rivero and colleagues concluded in their study abstract.

Disclosure: This research was supported by Acerus Pharmaceuticals. Please see the original reference for a full list of disclosures.


Rivero MJ, Ory J, Diaz P, et al. Comparison of hematocrit change in testosterone-deficient men treated with intranasal testosterone gel versus intramuscular testosterone cypionate: A single-center randomized clinical trial. Presented at: AUA 2023, Chicago, Illinois, April 28-May 1. Abstract MP79-03.

Rivero MJ, Ory J, Diaz P, et al. Comparison of hematocrit change in testosterone-deficient men treated with intranasal testosterone gel vs intramuscular testosterone cypionate: A randomized clinical trial. J Urol. Published online May 1, 2023.doi:10.1097/JU.0000000000003487

This article originally appeared on Renal and Urology News