Long-Term Testosterone Undecanoate Replacement Therapy

Impact of Ethnicity

Punith Kempegowda; Lauren M. Quinn; Joht Singh Chandan; Lisa Shepherd; Samina Kauser; Asad Rahim; Andrew Bates


Clin Endocrinol. 2020;92(5):428-433. 

In This Article

Abstract and Introduction


Background: Testosterone replacement therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety and efficacy profiles across different ethnicities for long-term TRT remain unclear.

Objective: To measure the impact of ethnicity on various biochemical parameters following testosterone undecanoate (TU) replacement.

Method: A retrospective analysis of 50 male patients treated with TU from 2006 to 2017 in a large secondary care centre was performed. Changes in total testosterone, PSA, haematocrit, haemoglobin, total cholesterol and low-density lipoprotein (LDL) over eight years of treatment were analysed. Wilcoxon rank sum test was used to assess differences in these parameters between Caucasians and South Asians.

Results: Thirty-one Caucasians (age: median (IQR) 55.0 years (49.0–68.0); total duration of follow-up 6.1 years (2.9–9.3)) and 19 South Asians (age: median (IQR) 52.0 years (38.0–69.0); duration of follow-up 6.5 years (1.3–8.4)) were treated with TU during the study period. There was no significant difference in total testosterone levels between the two ethnicities. We noted a higher free and bioavailable testosterone in South Asians than Caucasians, albeit within their reference range. PSA was higher in Caucasians than South Asians at two and eight years of TU therapy. After one year of TRT, haematocrit was higher in South Asians than Caucasians at one year, whereas LDL and total cholesterol were significantly higher in Caucasians than South Asians.

Conclusions: Caucasians have a tendency towards increased PSA, total cholesterol and LDL compared with South Asians with TU replacement therapy. There is a higher increment of haematocrit in South Asians following one year of TU replacement therapy. All biochemical changes following TRT were within the respective reference ranges suggesting no apparent risk of prostate cancer and venous thromboembolism.


Hypogonadism is a condition when serum testosterone levels fall below lower limits of normal range, and associated symptoms and signs of low testosterone are present, principally sexual symptoms.[1–3] Primary hypogonadism arises from testicular failure, and the most common causes include Klinefelter's syndrome, undescended testicles, mumps orchitis, haemochromatosis, testicular trauma or chemotherapy,[4] whereas secondary hypogonadism is commonly due to pituitary adenoma, obesity and chronic opiate use. Hypogonadism results in a clinical and biochemical syndrome detrimentally affecting multiple organ systems and quality of life.[5] The mainstay of treatment for male hypogonadism involves testosterone replacement therapy (TRT). Benefits of TRT include improved libido, mood and bone mineral density, increased muscle mass and decreased fat mass.[1,2,4,6]

Testosterone replacement therapy can be delivered in multiple ways: subdermal, transdermal, buccal and intramuscular (IM). The efficacy and safety of testosterone undecanoate (TU) is well reported in the literature, with minimal side effects.[7–9] A long-term retrospective analysis performed by Conaglen et al[10] showed that serum trough levels of testosterone were in normal range in 77% of patients receiving IM TU therapy. However, data regarding changes in other biochemical parameters following TU therapy are sparse.[11]

Despite the multitude of benefits with TRT, there are two main concerns that regularly recur: impact on prostate cancers and risk for thrombosis due to raised haematocrit. Evidence to date has demonstrated no increased risk for prostate cancer, albeit these are from studies with limited follow-up.[12] Conaglen et al[10] showed that PSA and haematocrit significantly increased with TU at some point during treatment in 13% and 14% of patients, respectively, but ethnicity was not accounted for. Similarly, Tan et al[13] assessed safety and efficacy of TU in Malaysian men and showed that PSA and haematocrit both significantly increased, but both were within clinically safe limits.

Given the potential risk, TRT is contraindicated in men with previous prostate or breast cancer and biochemical monitoring is indicated prior to initiation and during TRT. Also, it is recommended to measure prostate-specific antigen (PSA) in all men aged >40 years prior to initiation and following 3–6 months of treatment.[2,12,14] It is recommended to measure haematocrit and haemoglobin before and at regular intervals during TRT, to monitor for erythrocytosis and secondary polycythaemia. How patient's ethnicity affect various biochemical levels in response to long-term TRT is yet to be determined.