Estrogen Therapy

Summary:

Scientists believe that estrogen may be neuroprotective, which would explain why pre-menopausal women have a lower incidence of Parkinson’s disease than do post-menopausal women who are not on estrogen replacement therapy,  and why  men have a higher incidence than women.

While there is no proven mechanism for estrogen’s neuroprotection , one theory is that it may inhibit mitochondrial failure and oxidative stress thought to play a part in Parkinson’s disease. Scientists believe estrogen prevents cell death in large measure by ensuring that mitochondrial membranes remain functionally intact. Cells that are protected from sudden mitochondrial failure are also protected from the gradual mitochondrial dysfunction associated with Parkinson’s disease.^[1]

Because estrogen’s anti-oxidative abilities protect the brain, estrogen deprivation is likely to initiate or enhance degenerative changes caused by oxidative stress. Oxidative stress reduces the brain's ability to maintain synaptic connectivity, leading to the cognitive decline seen in individuals who are  elderly and disease-afflicted.^[2]

Potential benefits:

• Neuroprotection

• Slower disease progression

• Anti-oxidative abilities

• Improved cognitive function

Risks:^[3]

• Estrogen combined with levodopa is sometimes associated with dyskinesias

• Higher incidence of  uterine cancer

• Blood clots

• Nausea

• Edema

• Weight gain

Obstacles:

• Oral treatments in men may produce unwanted feminizing side effects

Current research:

• MIGENIX:   MX-4509

MIGENIX’s 17a-estradiol sodium sulfate (“17a-estradiol”), designated MX-4509, is being considered for the treatment of neurodegenerative diseases associated with mitochondrial failure, including Alzheimer’s disease, Parkinson’s disease, and Friedreich’s ataxia. This estrogen compound should be suitable for chronic treatment of degenerative diseases in both men and women because it has minimal feminizing consequences.^[4]

• POETRY study

The Parkinson Study Group (PSG) is conducting a study in postmenopausal women with Parkinson’s Disease to measure the safety and tolerability of estrogen replacement therapy (ERT). The study includes how ERT affects daily activities, thinking and behavior, and motor fluctuations and dyskinesias. Thirty participants will be enrolled at six US sites. Enrollment began in 2003.^[5]

Source

[1] Mitochondria Play a Central Role in Estrogen-Induced Neuroprotection, James W. Simpkins, Jian Wang, Xiaofei Wang, Evelyn Perez, Laszlo Prokai and James A. Dykens, Current Drug Targets - CNS & Neurological Disorders, Volume 4, No. 1, 2005