Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations

Objective: To test the efficacy, tolerance, and safety of low-dose oral est rogen in postmenopausal women with PD associated with motor fluctuations. B ackground: Motor fluctuations in PD may be predictable or unpredictable, an d eventually affect most patients after long-term levodopa therapy. Althoug h estrogen can modulate nigrostriatal dopamine levels, its effects on PD ar e unclear. Methods: Patients were randomized to receive conjugated estrogen (oral Premarin 0.625 mg daily; n = 20) or placebo (n = 20) in a double-bli nd, parallel-group, prospective study over 8 weeks. Existing antiparkinsoni an drug regimes were kept unchanged. Changes in "on" and "off" periods usin g patient diaries, Unified Parkinson's Disease Rating Scale (UPDRS) score, timed tapping score, and Hamilton Depression Scale score were determined by one rater. Subgroup analyses were also performed on patients with only pre dictable motor fluctuations. Results: Both treatment groups were similar in age, duration of disease and menopause, antiparkinsonian medication, and c ompliance with test medication and diary assessments. "On" and "off" times, and motor score (UPDRS subscale III) improved with estrogen, using the Man n-Whitney U test (p < 0.05 after Bonferroni adjustment). Mean "on" time imp roved by 7% (9 hours/week of awake time) in estrogen-treated patients versu s a deterioration of 0.5% (1.4 hours) in placebo-treated patients (95% conf idence interval, [CI] of mean difference, 5.73 to 14.9). Mean "off" time im proved by 4% (4.4 hours/week of awake time) in estrogen-treated patients ve rsus no change in placebo-treated patients (95% CI, 1.54 to 7.16). Mean sub scale III score improved by 3.5 points in estrogen-treated patients versus 0.4 in placebo-treated patients (95% CI, 1.02 to 5.18). No other significan t changes were observed (p > 0.05). Subgroup analyses in patients with only predictable motor fluctuations showed similar results, except improvement in mean subscale III score was marginally not significant (p = 0.07; 95% CI , 1.06 to 6.24). Five patients on estrogen had facial flushing, three had l ower abdominal discomfort, and two had mild withdrawal vaginal bleeding. Th e adverse events were mild and resolved without sequelae. Conclusion: Low-d ose estrogen is a safe and effective adjunct therapy to existing antiparkin sonian treatment in reducing motor disability in postmenopausal women with PD associated with motor fluctuations.