INTRODUCTION: PD is more common with increasing age and shows male predominance, which is more obvious in Western studies. The reasons of this remain obscure. However, it has been suggested that exposure to endogenous and exogenous oestrogen contributes to these sex differences and that oestrogen prevents dopaminergic neuron depletion induced by neurotoxins in and therefore is neuroprotective. OBJECTIVES: we wanted to investigate if the exogenous administration of testosterone in males, and oestrogen with or without progesterone in females, had any protective effect towards to PD. METHODS: clinical records of 99929 residents in North West England were scrutinised in primary care setting for diagnosis of PD, HRT, and timing of onset in those cases were the adverse event had been identified.RESULTS: PD overall prevalence was of 0.55% in males and 0.36% in females (M/F=3:2). The NNT for HRT with testosterone was 1.016 (harm) significance level P<0.0001, and NNT for HRT oestrogen+/-progesterone was 17.092 (harm) significance level P<0.0001.CONCLUSIONS: HRT for males or females have not demonstrated any beneficial effects in terms of PD onset prevention or procrastination. On the contrary HRT, particularly with testosterone, is more likely to have a detrimental effect. Our results need to be interpreted cautiously as the treatment with HRT was not randomized and it cannot be excluded that stopping HRT may cause a sudden hormonal drop which in turn may have a negative effect.