Introduction
Parkinson's is one of the major neurodegenerative diseases of our century and is characterized by progressive neuronal degeneration. This degeneration occurs in the substantia nigra, where the production of dopamine decreases consistently. Accumulations of α-synuclein begin to appear spreading the disease throughout the brain. (K Taguchi)
Although pathogenic mechanisms are not yet known, it seems that there are several factors at play, among which the most relevant are genetic mutations, toxic environmental factors that inhibit the activity of the mitochondrial complex, microglial activation and inflammation, impaired autophagy, and the neural damage associated with aging more in general.
Epidemiological studies have revealed a high male prevalence in Parkinson. A study in which 297 patients (181 males and 116 women) were evaluated using the Unified Parkinson Disease Rating Scale (UPDRS) showed that even the clinical progression of the disease can be significantly faster in men than in women (H Sawada).
Although the reason for this gender difference is not yet known, it would seem that oestrogens can play an important protective role against dopaminergic neuronal degeneration.
A series of studies that have investigated the neuroprotective mechanisms of oestrogens, have revealed complex mechanisms that include the antioxidant properties of oestrogens and their ability to adjust adaptively the genes associated with apoptosis
(Petrovska S).
Clinical and the experimental evidence indicate a modulatory role of oestrogens on the activity of the nigrostriatal dopaminergic neurons. However, conflicting data make the precise effect of oestrogen on the nigrostriatal dopaminergic neurons unclear suggesting either a facilitator, or inhibitory role.
Use of HRT is widespread in general practice and, more recently, also testosterone replacement therapy is becoming more frequent among the male population.
We wanted to investigate, retrospectively, if the exogenous administration of testosterone in males, and oestrogen with or without progesterone in females, for reasons other than PD, had protective, neutral, or negative effect, towards to developing PD later in life.
Methods
This is a large retrospective cohort study.
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
Of the base population, 47164 were males and 54901 were females. Of them, respectively 47068 and 52861 never received male or female HRT. HRT treatment was therefore significantly more frequent in women.
Parkinson disease was diagnosed in 261 males and 196 females.
Of them, 1 man had received TRT and 13 women HRT.
To summarise, 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.