Risk of Parkinson's disease after tamoxifen treatment

Abstract

BackgroundWomen have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.MethodsA cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.ResultsIn total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.ConclusionsThese results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.

Gender differences in Wilson's disease

“…We presented the similar, like in PD, clinical gender related observations in WD about the age of symptom onset and neurological signs. In PD (and maybe in WD) the differences in age of onset and symptoms are explained by probably higher (dependent on estrogens) initial striatal dopamine levels in women, what can delay the neurological symptom onset in neurodegenerative disorders [20][21][22][23][24]. It is possible that in women with WD, estrogens can also protect neurons against copper accumulation and the oxidative stress that occurs secondary to this accumulation, leading to less frequent neurological symptoms and forms of disease.…”

“…After oophorectomy, a 36% reduction in dopaminergic neurons was observed in women [11], which can be avoided by supplementation with hormones before the procedure [9]. There are data that women who underwent oophorectomy before the menopause or were treated with tamoxifen (selective estrogen receptor modulator) had an increase risk of parkinsonism [23,24]. The "estrogen hypothesis" about gender influence on PD was confirmed by the Parkinson's Disease on Estrogen Therapy Replacement in the Menopause Years study, which showed women on estrogen replacement therapy (ERT) had an 8 point improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) compared to placebo patients [11].…”

The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson's disease

“…On the other hand, other studies have shown that raloxifene prevents MPTPinduced striatal depletion of dopamine (Grandbois et al, 2000). Thus, the neuro-protective properties of estrogen against PD may be disrupted by tamoxifen therapy and treatment may be associated with an increased rate of PD as has been reported by Latourelle et al (2010).…”

Parkinson's Disease Genes Do Not Segregate with Breast Cancer Genes' Loci

“…Women have a reduced Parkinson's disease risk compared with age-matched men, a phenomenon attributed by some researchers to the neuroprotective properties of estrogen in Parkinson's disease relevant neurons (11). Tamoxifen, a selective estrogen receptor (ER) modulator given to patients with ER-positive breast cancer, has been reported to increase Parkinson's disease rates (12). Thus, in postmenopausal women, markedly reduced estrogen synthesis may both increase the risk of Parkinson's disease and promote the expression of ER genes in breast tissue to enhance breast cancer risk.…”