Thursday, 21 August 2003
This presentation is part of : Thursday Poster Sessions

PD-025 A Pilot Study on the Effect of Estrogen-Progestin Replacement Therapy on Brain Dopamine Transporter Activity in Healthy, Postmenopausal Women

Sara Anne Gardiner1, Mary Frances Morrison1, P. David Mozley2, Lyn Harper Mozley3, Colleen Brensinger4, Michelle Battistini5, and Warren Bilker4. (1) Clinical Neuroscience Department, Merck & Co., Inc., Blue Bell, PA, USA, (2) Eli Lilly & Co., Inc., Indianapolis, IN, USA, (3) Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA, (4) Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, (5) Department of Obstetrics & Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Background: Considerable interest surrounds the health benefits and risks associated with menopausal hormone replacement therapy (HRT). In aging women, estrogen appears to modulate dopaminergic function based upon findings from preclinical and clinical research on schizophrenia and Parkinsonís disease. Neuroimaging studies have documented age-related declines in dopamine markers, including the dopamine transporter (DAT), the primary measure of dopaminergic tone. These changes might be related to menopause.

Objective: This study sought to clarify the relationship between 1 standard cycle of HRT and striatal DAT availability in postmenopausal women.

Design: In this pilot study, subjects were seen for 3 neuroimaging visits across 6 weeks. At each visit, single-photon emission computed tomography (SPECT) was used to assess striatal DAT availability. Visit 1 occurred before hormone intervention. Visit 2 occurred after 4 weeks of treatment with 0.625 mg of conjugated estrogens. Visit 3 occurred at week 6, following 2 additional weeks of treatment with 0.625 mg conjugated estrogens plus 10 mg of medroxyprogesterone acetate.

Materials and Methods: Subjects were 13 cognitively intact, medically stable, postmenopausal women aged 50 and above. SPECT was performed using [99mTc]TRODAT-1, a radiolabeled analog of cocaine that binds DAT. The primary efficacy measure included specific uptake values (SUVs) of TRODAT-1 calculated for subregions of the caudate, putamen and entire supratentorium. An intergroup analysis compared SUVs measured before and after hormone intervention with SUVs from a comparable female control group. An intragroup analysis compared SUVs within study subjects across imaging visits. Neuropsychological testing occurred at each visit.

Results: Intergroup analysis revealed no differences in DAT availability between study subjects at Visit 1 and female controls. However, following 4 weeks of treatment with conjugated estrogens, study subjects demonstrated higher SUVs in regions of the left posterior putamen (p<0.021) and posterior putamen (p<0.007) as compared with controls. Intragroup analysis revealed that, following both 4 and 6 weeks of HRT, SUVs significantly increased in regions of the putamen, but not the caudate.

Conclusion: In aging women, 1 standard cycle of HRT increases striatal DAT availability and, presumably, dopaminergic tone. These findings may help elucidate the role of hormones in the observed sex differences in occurrence rates of schizophrenia and Parkinsonís disease. Future research should investigate the possible therapeutic affect of estrogen in the treatment of diseases involving dopaminergic function.

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