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The real side effects of testosterone replacement therapy for men

Catherine Jeans
Article written by Catherine Jeans

Date published 14 August 2019

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As men go through male menopause, or 'andropause', they can experience physical and emotional changes that vary dramatically in severity between men. Here we examine the potential side effects of testosterone replacement therapy and dispel the myths.

What is testosterone replacement therapy?

Testosterone replacement therapy is designed to raise testosterone levels, to help prevent symptoms associated with its deficiency. It is available in a variety of formats, including gels which are rubbed onto the skin, oral tablets, injections, and patches. A number of studies have been done to assess which is most effective, however it has not yet been proven which type of preparation raises testosterone levels most efficiently.

The benefits found in research from taking testosterone replacement therapy include a minor to moderate improvement in lean body mass and muscle strength, increased bone mineral density, a modest enhancement in sexual function, a reduction in body fat, and a reduction in depressive symptoms.1

Who requires testosterone replacement therapy?

It is difficult to assess which men should be given testosterone replacement therapy, because there are a lack of established reference ranges for 'normal' testosterone. Testosterone levels vary greatly between individuals, and if a man has always had fairly high testosterone levels and these drop to normal ranges, he may experience the same symptoms as a man whose levels have dropped from normal to low. Generally, the prescription of testosterone is assessed based on hormone levels, as well as symptom analysis.

Are all the symptoms of male menopause due to low testosterone?

Another issue with the therapy is that it is not entirely clear whether the symptoms associated with male menopause are purely down to a reduction in testosterone levels. Research studies have failed to clearly attribute this link. The symptoms experienced around this time could also be due to other health problems that tend to develop with age, such as cardiovascular disease, and side effects from the medication used. However some studies show that a low level of testosterone may actually increase the risk of heart disease and brittle bones, suggesting that testosterone indeed has a role to play.

What are the potential side effects of testosterone replacement therapy?

There have been limited studies looking at the potential benefits and health risks of testosterone replacement therapy, and it is difficult to make a clear conclusion on these risks. This is because studies vary widely in terms of the type of testosterone replacement therapy used, dose, duration of treatment, and age group or health status of men analysed.

Findings are inconsistent, and what is required are a number of placebo-controlled research trials on a large group of men. The results of these trials also need to be compared to the health risks of having low testosterone, which can include an increased risk of heart disease and osteoporosis.

There are three key areas of concern when it comes to the use of testosterone replacement therapy, based on a number of studies, notably, those by Calof OM et al. (2005),2 Fernandez-Balsells et al. (2010),3 and Haddad RM et al. (2007).4

Raised red blood cell count (polycythaemia)

This could potentially increase the risk of thrombosis or a stroke, due to alterations in the thickness of the blood. However, research has not clearly proven an increased risk of these events from taking testosterone.

An increased risk of cardiovascular disease

Research into testosterone replacement therapy and cardiovascular risk has produced many conflicting results. Despite research suggesting a link between an increased risk of cardiovascular problems in those with low testosterone, some research has suggested that testosterone replacement therapy may increase the risk of heart attack and stroke. A large review of the data in over 55,000 patients showed twice the risk of heart attack in those who received testosterone replacement therapy, including in younger men with a pre-existing heart condition.5

However this review did not analyse the effect of different types of testosterone prescription. In 2014, a different study found that oral testosterone replacement therapy produces a significant increase in the risk of cardiovascular disease, but this was not seen when given via injections, or through the skin.6 Furthermore, a more recent review of the data revealed that no link was established between a higher risk of cardiovascular problems and the therapy.7

Prostate problems

The area of greatest concern is the data suggesting an increased risk of prostate cancer or non-cancerous enlargement of the prostate. This was first analysed in research which showed that testosterone replacement therapy increases the levels of prostate-specific antigen, a marker used in the detection of prostate cancer.8 However, not a single study has yet shown a clear correlation between testosterone replacement therapy and actual prostate cancer diagnosis. It is not fully clear the role testosterone plays in prostate cancer risk, especially given that most men are diagnosed as they age, when testosterone levels are naturally declining.

What is clear from the data is that more research is required. For those considering testosterone replacement therapy, it's vital that you are properly screened for prostate cancer, both with a digital rectal examination and blood test. Alongside this, cardiovascular health should be assessed before making a decision as to whether the therapy is appropriate.

It has been recommended that anyone who has pre-existing prostate problems or prostate cancer should avoid taking the therapy, and those who are deemed appropriate for starting testosterone replacement therapy should be regularly reviewed, re-examined and have their blood analysed to ensure their risk of developing health problems has not increased.9 There are of course many natural agents which may help to support testosterone levels without the need for hormone replacement therapy, including zinc, vitamin E and various herbal preparations.

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Catherine Jeans

About Catherine Jeans

Catherine Jeans DipION mBANT CNHC is a nutritional therapist and founder of The Family Nutrition Expert. She has a special interest in women’s health, supporting hormonal balance and optimal wellbeing in women of all ages, through the use of food, nutrition and functional health.


1Huanguang Jia et al. (2015). Review of health risks of low testosterone and testosterone administration, World Journal of Clinical Cases
2Calof O (2005). Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials, The journals of Gerontology
3Fernández-Balsells M (2010). Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis, Journal of Clinical Endocrinology & Metabolism
4Haddad R (2007). Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials, Mayo Clinic Proceedings
5Finkle W et al. (2014). Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men, PLOS ONE
6Borst S (2014). Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis, BMC Medicine
7Corona G et al. (2014). Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis, Expert Opinion on Drug Safety
8Kang D et al. (2015). The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis, Medicine (Baltimore)
9Isidori A (2015). Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology, Journal of Endocrinological Investigation