Safety of testosterone therapy
It is important that prescribing clinicians and patients are aware of the side effects associated with testosterone therapy to make informed choices on their care.
Side effects of topical
gel therapy
Common adverse reactions include the following and are mild-to-moderate in severity: [1]
Reduced sperm count and fertility
Headaches
Application site reactions which are mild-moderate in severity
Headaches
Treatment using topical gels have been shown to reduce incidence of application site reactions ten-fold compared to transdermal patches.[1] However, a concern on their use is person-to-person transfer, particularly to a female or a prepubescent individual. While research indicates such transfer is unlikely, [2] caution must be exercised and patients should be educated on the risk as transfer on a repeated basis can cause hyperandrogenism, sexual precocity and virilisation.[3]
Risk can be minimised by taking the appropriate precautions such as washing hands after use and covering the application area with clothes.
Prostate Cancer Concerns
A common notion is that testosterone initiates and promotes the development of prostate cancer and has been assumed from this that testosterone replacement therapy would increase the risk of malignant development.
Studies have shown that low testosterone levels are not protective against prostate cancer development and high levels do not results in a high risk of prostate cancer development.[4]
It has also been demonstrated that men treated with TRT following a diagnosed of localised prostate cancer do not have worse outcomes or higher rates of recurrence [4] [5] and that men treated with TRT during active surveillance for prostate cancer do not have higher rates of progression. [6,7]
Evidence now strongly contests the link between prostate cancer and the androgen, building a strong use-case for TRT in hypogonadal men. [6]
However, TRT is contraindicated for those who have untreated prostate cancer. [8] Please see Contraindications for the full list
Cardiovascular concerns
With men having an increased risk of cardiovascular disease, any association between cardiovascular risk and testosterone has been of considerable interest.
The data on both the use of TRT and of androgen deprivation therapy on the increased or decreased risk of cardiovascular events remains inconclusive. [7] The latest guidelines from the European Association of Urology (EAU, 2020) conclude that on review of the interventional studies to date, there is no evidence that TRT increases risk of major adverse cardiovascular events.[4] For any product, it is advisable to review the Summary of Product Characteristics for adverse events.
Contraindications for TRT and risk of transference
The main contraindications of TRT include: [8]
Untreated prostate cancer*
An active desire to have children
Hematocrit higher than 54%
Severe chronic heart failure
Due to insufficient information on long-term effects of therapy, those acute cardiovascular events or uncontrolled congestive heart failure and those with severe lower urinary tract symptoms may also not be suitable for treatment and these conditions should be considered relative contraindications. [9] Individuals with elevated PSA levels may require further consultation with a urology specialist before beginning treatment and severe sleep apnea may also be contraindicated. [8]Transdermal gels should be used with caution so as to minimise risk to other individuals. It has been reported that secondary transfer has caused hyperandrogenism in women and precocious puberty in children.[3]
* TRT is not indicated for treatment of women. TRT is contraindicated for treatment of males with diagnosed breast cancer
TRT = testosterone replacement therapy.
Prostate cancer concerns
A common notion is that testosterone initiates and promotes the development of prostate cancer and has been assumed from this that testosterone replacement therapy would increase the risk of malignant development.
Evidence now strongly contests the link between prostate cancer and the androgen, building a strong use-case for TRT in hypogonadal men. [6]
Studies have shown that low testosterone levels are not protective against prostate cancer development and high levels do not results in a high risk of prostate cancer development.[4]
It has also been demonstrated that men treated with TRT following a diagnosed of localised prostate cancer do not have worse outcomes or higher rates of recurrence [4] [5] and that men treated with TRT during active surveillance for prostate cancer do not have higher rates of progression. [6]
However, TRT is contraindicated for those who have untreated prostate cancer. [8] Please see Contraindications for the full list
Cardiovascular concerns
With men having an increased risk of cardiovascular disease, any association between cardiovascular risk and testosterone has been of considerable interest.
The data on both the use of TRT and of androgen deprivation therapy on the increased or decreased risk of cardiovascular events remains inconclusive. [7] The latest guidelines from the European Association of Urology (EAU, 2020) conclude that on review of the interventional studies to date, there are no evidence that TRT increases risk of major adverse cardiovascular events.[4]
For any product, it is advisable to review the Summary of Product Characteristics for adverse events.
Contraindications for TRT and risk of transferenc
The main contraindications of TRT include: [8]
Untreated prostate cancer
Untreated breast cancer*
An active desire to have children
Hematocrit higher than 54%
Severe chronic heart failure
Due to insufficient information on long-term effects of therapy, those acute cardiovascular events or uncontrolled congestive heart failure and those with severe lower urinary tract symptoms may also not be suitable for treatment and these conditions should be considered relative contraindications. [9]
Individuals with elevated PSA levels may require further consultation with a urology specialist before beginning treatment and severe sleep apnea may also be contraindicated. [8]
Transdermal gels should be used with caution so as to minimise risk to other individuals. It has been reported that secondary transfer has caused hyperandrogenism in women and precocious puberty in children. [3]
References
1. Kumar et al. J Adv Pharm Technol Res. 2010; 1(3): 297–301.
2. Rolf et al. Clin Endocrinol (Oxf). 2002; 56(5):637-41.
3. Michael G. Miller, Alan D. Rogol & Troy L. ZumBrunnen. Current Medical Research and Opinion. 2012. 28:2, 267-269
4 Khera et al. Eur Urol. 2014;65(1):115-23. doi: 10.1016/j.eururo.2013.08.015
5. Kaplan et al. J Sex Med. 2014;11(4):1063-1070.
6. Khera et al. Eur Urol. 2014;65(1):115-23. doi: 10.1016/j.eururo.2013.08.015
7. Kaur & Werstuck. CJC Open. 2021.3(10). 1238-1248
8. Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. The journal of sexual medicine. 2017;14(12):1504-1523
9. Salonia A, Bettocchi C, Carvalho J. EAU Guidelines on Sexual and Reproductive Health. 2020