Gender differences in Parkinson's disease

There are several indications of gender differences in Parkinson's disease (PD). Epidemiological studies have shown that both incidence and prevalence of PD are 1.5-2 times higher in men than in women. ^{1- 6} Furthermore, in 6 out of 8 incidence studies mentioning gender specified age at onset, onset in women was slightly later than in men (by a mean of 2.2 years (range 1-4)). ⁷ After progression into the clinical phase of the disease, women had better Unified Parkinson's Disease Rating Scale (UPDRS) motor scores ⁸ but a greater prevalence of dyskinesias ^{8, 9} compared with men (at a disease duration of more than 5 years). Furthermore, men reported several parkinsonian symptoms more frequently than women when asked at a disease duration of 9 years. ¹⁰ Gender differences in the earlier stage of PD, before initiation of dopamine agonists or levodopa, have not been investigated.

The reported gender differences reflecting distinct time periods-before and after symptom onset-could be related to the different levels of circulating oestrogens in men and women. Several findings indicate that oestrogens may play a role in PD. In animal models of PD, oestrogens had a neuroprotective effect when administered prior to or coinciding with a toxic insult. ^{11- 13} Secondly, the dopaminergic neurons in the substantia nigra and the striatal dopamine content were more vulnerable to chemical lesioning at dioestrus (low oestrogen) than at pro-oestrus (high oestrogen). ¹⁴ However, the possibly beneficial effects of oestrogens suggested by these reports could not be confirmed in humans. Postmenopausal oestrogen use in women was associated with both higher, lower and equal risks of PD. ^{15- 17} Furthermore, trials of postmenopausal oestrogen supplementation, which started after symptom onset, did not affect parkinsonian symptoms. ^{18, 19} However, women who had undergone ovariectomy or hysterectomy had an increased risk of PD. ^{20, 21} Thus the precise nature and extent of gender differences and the role of oestrogens in PD remain unclear.

Here we investigated whether and how gender affects both the preclinical and clinical disease stages, reflected by (1) the age of PD onset, (2) the presenting symptom, (3) the severity and progression of motor symptoms assessed with UPDRS derived variables and (4) the amount and progression of nigrostriatal degeneration assessed using [¹²³ I]FP-CIT single...