Research suggests that both excessively high and excessively low levels of the male hormone testosterone increase the risk of depression.

It has long been believed that low levels of testosterone , a male hormone, are associated with a higher risk of developing depression. However, a study of 133,733 men registered in the UK Biobank, a large health database in the UK, showed that not only men with lower-than-average testosterone levels for their age group, but also men with higher-than-average levels, were at higher risk of developing depression.

The complex relationship between testosterone imbalance and the risk of depression and anxiety in men - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/S016503272600666X

The complex relationship between testosterone imbalance and the risk of depression and anxiety in men - UK Biobank
https://www.ukbiobank.ac.uk/publications/the-complex-relationship-between-testosterone-imbalance-and-the-risk-of-depression-and-anxiety-in-men/

Men with atypical testosterone levels face a higher risk of depression
https://www.psypost.org/men-with-atypical-testosterone-levels-face-a-higher-risk-of-depression/

Testosterone in the blood consists of both protein-bound and protein-free testosterone, which is more readily available in the body. The total amount of both is called 'total testosterone,' while the protein-free testosterone is called 'free testosterone.' Many previous studies on testosterone levels and mental health have analyzed data at a single point in time, and it has not been sufficiently understood how differences in testosterone levels relate to the future onset of depression.

Therefore, a research team led by He Dan of Xi'an Jiaotong University in China measured 'total testosterone' and calculated 'free testosterone' from blood samples taken at the start of the study for men aged 40 to 70 registered in the UK Biobank. Subsequently, they tracked the participants' medical records for an average of approximately 11 years.

Individuals who had been diagnosed with depression or anxiety disorder at the start of the study, or who were taking antidepressants or medications that affect testosterone levels, were excluded from the analysis.

He Dan and his colleagues divided the study participants into six age groups in 5-year increments, and within each age group, classified their testosterone levels into three groups—low, normal, and high—based on 'how far they deviated from the average.' Then, considering factors such as obesity, lifestyle, and pre-existing conditions, they analyzed the relationship between testosterone levels at the start of the study and subsequent diagnoses of depression.

During the follow-up period, 3,701 of the study participants were diagnosed with depression. According to He Dan et al.'s analysis, compared to men with normal total testosterone levels, men with low total testosterone levels had a 1.48 times higher risk of developing depression, while men with high total testosterone levels had a 1.27 times higher risk.

Furthermore, the risk of developing depression in men with low free testosterone levels was 1.99 times higher than in men with normal free testosterone levels. In addition, when analyzing the relationship between high and low free testosterone levels and the risk of developing depression without dividing free testosterone levels into three groups (low, normal, and high), Dr. He Dan and colleagues explained that there was a tendency for the risk of developing depression to be higher whether free testosterone levels were too low or too high compared to the average for their age group.

According to the science media outlet PsyPost, 'An analysis by age group showed that men aged 55-59 with low free testosterone levels had more than three times the risk of developing depression compared to men of the same age with normal free testosterone levels.'

PsyPost points out that this study is an observational study that tracks the relationship between actual testosterone measurements and subsequent diagnoses, rather than manipulating testosterone levels, and therefore does not demonstrate a causal relationship that 'abnormal testosterone levels cause depression.'

He Dan and colleagues state that because testosterone levels were measured only once at the start of the study, future research should involve repeatedly measuring testosterone levels to investigate the relationship between long-term hormonal changes and mental health.