Review Article

Hormone Replacement Therapy and Risk for Neurodegenerative Diseases

Table 3

Case-control and epidemiological studies of HRT and Parkinson’s disease.

Study (reference)Sample descriptionOverall findings

Marder et al. [25]87 women with Parkinson’s disease without dementia (PDND), 80 women with Parkinson’s disease with dementia (PDD), and 989 nondemented healthy women.ERT reduced risk of dementia among the PD-only sample (OR = 0.22, 95% CI: 0.05–1.0), and also when PDD patients were compared to healthy controls (OR = 0.24, 95% CI: 0.07–0.78). ERT did not affect the risk of PD.
Fernandez and Lapane [26]Data from 10,145 elderly women with PD available via the Systematic Assessment in Geriatric drug use via Epidemiology (SAGE) database. Included 195 women with PD who received estrogen and 9950 who did not receive estrogen.Independent of age, estrogen users had better cognitive functioning and were more independent with regards to activities of daily living. More estrogen users were depressed and likely to be taking antidepressant medications.
Benedetti et al. [27]72 women with PD and 72 healthy women.The PD group had undergone hysterectomy (with or without unilateral oophorectomy) more than the control group (OR = 3.36; 95% CI: 1.05–10.77). The PD group had more frequent occurrence of early menopause (< or = 46 years) (OR = 2.18; 95% CI: 0.88–5.39). The PD group used ERT for at least 6 months after menopause less frequently than the control group (14%; OR = 0.47; 95% CI = 0.12–1.85). The PD group did not have earlier menopause than the control group.
Martignoni et al. [28]150 women with idiopathic PD and 300 healthy women, all postmenopausal.Duration of reproductive life was similar between women with PD and those without PD. Women with PD reported less access to HRT. The PD group also reported more premenstrual symptoms, fewer deliveries and abortions, and less use of contraception, indicating a relationship between PD and reproductive events.
Currie et al. [29]68 women with PD and 72 healthy women, all postmenopausal.50% of women in the control group took ERT, as compared to 25% of women in the PD group. Women who had taken postmenopausal ERT were less likely to develop PD than those who had not (odds ratio, 0.40; 95% CI: 0.19–0.84). Among women with PD, postmenopausal ERT was not associated with age of onset.
Ragonese et al. [30]131 women with idiopathic PD and 131 healthy women.PD was significantly associated with a fertile life length of less than 36 years (OR 2.07; 95% CI: 1.00 to 4.30). PD was also associated with a cumulative pregnancy length of longer than 30 months (OR 2.19; 95% CI: 1.22 to 3.91). There was an inverse association between PD and surgical menopause (OR 0.30; 95% CI: 0.13 to 0.77).
Popat et al. [31]178 women with PD and 189 healthy women.Among women with history of hysterectomy (with or without an oopherectomy), ERT use was associated with a 2.6-fold increased risk for PD, and a trend for additional risk was noted for increasing duration of estrogen use. Among women with natural menopause, no increased risk of PD was observed with HRT (ERT alone or in conjunction with progestin). Earlier age of menopause was associated with reduced risk of PD.
Ragonese et al. [32]145 women with PD.A significant correlation was found between age at PD onset and age at menopause, and also between age at PD onset and fertile life duration.
Rocca et al. [16, 17]1,252 women with unilateral and 1,075 women with bilateral ophorectomy, and 2,368 referent women.Women who underwent either unilateral or bilateral oophorectomy had an increased risk of parkinsonism compared to referent women (HR 1.68; 95% CI: 1.06–2.67). This risk increased with younger age at oophorectomy.
Simon et al. [33]22-year prospective study of 244 women with PD enrolled in the Nurses’ Health Study.Risk of PD was not significantly associated with reproductive factors or HRT. The association of smoking and caffeine with PD risk was modified by HRT, however. Based on a very small sample (4), women using progestin only hormones had increased risk for PD.