What is hypogonadism?
The hormone testosterone is predominantly known for its role in the development of male primary sexual tissues and secondary sexual characteristics such as increased body and muscle mass, body hair, as well as deepened voice. It’s also a core hormone in the maintenance of overall health, from the maintenance of bone and muscle mass to stabilising moods and emotions.1
Normally, testosterone levels begin to decline in men after the age of 40. However, in some men, testosterone levels can significantly decline beyond a certain threshold (<8 nmol/L)*, with the effect that symptoms such as decreased sexual function, emotional changes and reduced muscle and bone mass arise.1 This is also known as hypogonadism and is predominantly managed with testosterone replacement therapy (TRT).2
Understanding risk factors
Testosterone is produced in the testes and is regulated by the hypothalamic-pituitary-gonadal axis. There are many conditions which influence this regulatory process, and in turn, cause less testosterone to be produced. These conditions may impact testosterone at the level of the testes, known as primary hypogonadism, or may impact at the level of the hypothalamus and the pituitary, known as secondary hypogonadism.3
Conditions which are associated with hypogonadism or act as a cause can serve as a useful clinical marker for healthcare professionals to identify and diagnose hypogonadism. Collectively, these are referred to as risk factors.
Common co-morbidities and risk factors in hypogonadism
Obesity & type 2 diabetes
The relationship between obesity and hypogonadism is a complicated one and appears to be bidirectional.4 There are plausible mechanisms to explain why obese men are more likely to develop hypogonadism, such as the elevated insulin in obese men impairing the signalling of key hormones from the hypothalamus (responsible for initiating the production of testosterone in the testes).5 This is also thought to explain why type 2 diabetes, a condition caused by excess body fat, also increases hypogonadism risk. There are however reasons to suggest that lower levels of testosterone in the body could increase obesity risk too.4
It's estimated that the prevalence of obesity-related hypogonadism could be as high as 45% in obese men.6 In adolescent males with obesity, a separate study found that 33% of 14–35 year old males with obesity had hypogonadism as measured by free testosterone concentrations.7 As obesity and type 2 diabetes are both modifiable conditions through weight loss this can, in turn, reverse hypogonadism and cause levels of testosterone in the body to return to normal.6
The exact percentage of male cancer patients with hypogonadism is unclear, although the prevalence could be as high as 40-90%; considerably higher than the prevalence in the general population. The potential reasons include damage from chemotherapy or from localised development of the cancer. Systemic inflammation from cancer can also impair testosterone production.7 Importantly, it is cancer that seems to increase hypogonadism risk with no evidence to suggest that low levels of testosterone increase cancer risk.
Hypogonadism is commonly found in HIV-positive men, including those who are treated and those who are untreated.8 The underlying mechanism is most often due to damage to the pituitary gland, sitting at the base of the brain and responsible for producing hormones to signal testosterone production in the testes. Another potential reason is the compromised immune system induced by HIV, which can increase the risk of viral and bacterial infections; affecting the signals from the pituitary gland to the testes.8
Injury or trauma to the testes
Another common cause is a significant injury to the testes which hampers their ability to produce testosterone.8
Like in the case of cancer, the presence of systemic inflammation such as through infection from tuberculosis or from diseases such as sarcoidosis can lead to the development of this syndrome.8
Some medications, particularly those which are opioid-based can cause hypogonadism, by impairing the function of the hypothalamus.9
- This is a genetic condition characterised by abnormal development of the hypothalamus, responsible for signalling to the pituitary gland to produce luteinizing hormone (LH), which in turn signals to the testes to produce testosterone. With an underdeveloped hypothalamus, this stimulation does not occur leading to low testosterone levels.8
- This inherited abnormality is characterised by the male being born with XXY sex chromosomes, as opposed to the regular XY. The extra X chromosome causes the abnormal development of the testes which can lead to the development of hypogonadism.8
Understanding which conditions are associated with hypogonadism can be helpful for doctors to identify whether or not hypogonadism could be present to inform future diagnostic testing. If you are concerned about your health, or feel you are showing symptoms of hypogonadism, speak to your healthcare professional to receive a professional diagnosis.
Take home points
- Hypogonadism is associated with many different co-morbidities that can increase the risk of low testosterone levels
- An understanding of these co-morbidities is important for healthcare professionals to be able to identify at-risk individuals to provide tailored treatment
1. Goodale, et al. Methodist Debakey Cardiovasc J 2017;13(2):68-72.
2. Jayasena CN, et al. Clinical Endocrinology 2022;96:200–219.
3. Carnegie C, et al. Rev Urol 2004;6(6):S3–S8.
4. Alukal JP. Hypogonadism 2016;43(2).
5. Fernandez CJ, et al. Eur Endocrinol 2019;15(2):83–90.
6. Calderon B, et al. Andrology 2016;4:62–67.
7. Burney J. Cachexia Sarcopenia Muscle 2012 Sep;3(3): 149–155.
8. Kumar et al. J Adv Pharm Technol Res 2010;1(3):297–301.
9. Daniel HW. J Pain 2002;3(5):377-84.