Abstract
The case described by Dhillon and colleagues [1] underlines the importance of noting significant clinical events in single case studies as well as providing very important information about the impact of gonadal hormone administration on the central nervous system.
In this case, the transgender patient had nine years of administration of testosterone 250 mg intramuscular injection (IMI) three weekly. It was only when the patient had declining levels of circulating estradiol due to perimenopausal changes at age 47, that he developed a psychotic illness which required treatment with 30 mg olanzapine. The assumption is that the neuroprotection provided by higher levels of estradiol when the patient was younger decreased over time and then the continued administration of testosterone precipitated psychosis.
Oestrogens provide neuroprotection via many complex physiological mechanisms including both genomic and non-genomic mechanisms. Oestrogen has direct effects on the serotonin, dopamine, and cholinergic and other neurotransmitter systems. Also, oestrogen influences axonal sprouting and has other neurocircuitry impact. Hence, with loss of estradiol in the menopause, the CNS effect is marked in a number of areas. In this case, the addition of testosterone would have the opposite effects in the CNS.
The role of the hormones of the hypothalamo-pituitary-gonadal axis in the development or protection against the onset of psychosis are grossly underestimated and poorly understood. Far more research into this area is needed since the potential use of estradiol, as a treatment is now feasible, as we have shown in our clinical trials.
The lesson learned from this case is that without the tempering effect of oestrogen, testosterone can be a psychosis-inducing hormone. Tongue in cheek; is this a metaphor for the roles that women and men play in society?