A new study on mice has shown that progesterone, when taken with estrogen has no clear preventive benefits against Alzheimer's disease.
Progesterone is given with estrogen in hormone replacement therapy. Previous studies have suggested that estrogen offers women some protection against Alzheimer's disease.
The study's authors, led by gerontologist Christian Pike of the University of Southern California, report that progesterone has only limited benefit for mice with Alzheimer's symptoms when taken alone.
They also found that when taken with estrogen, progesterone actually inhibits some of the other hormone's beneficial effects.
The problem is not necessarily progesterone itself, Pike said. It could be the constant daily dosage, which fails to replicate the pre-menopausal body's natural cycles of hormone production.
"This is probably not the best way to be delivering progesterone. Giving a constant dose of progesterone appears to antagonize a lot of the beneficial effects of estrogen," Pike said.
Pike's group tested progesterone on female mice whose hormone production had been blocked to simulate menopause. The mice, which were genetically predisposed to develop an Alzheimer's-like disease, showed symptoms within months.
Treatment with estrogen reversed the symptoms, while treatment with progesterone did not, Pike's group reported.
When the two hormones were given together, progesterone appeared to hamper estrogen's main beneficial function: preventing the build-up of beta amyloid protein, the key risk factor in Alzheimer's.
"Estrogen no longer decreases the amount of beta amyloid" when progesterone is present, Pike said.
Progesterone's effects were not all bad, Pike added. The hormone appeared to inhibit tau hyperphosphorylation, another chemical process implicated in Alzheimer's.
Progesterone also is known to counteract the increased risk of endometrial cancer from estrogen therapy, which is one reason most women receive both hormones.
Pike said his group's study should provide guidance for the design of human trials studying hormone therapy and Alzheimer's. He added that future studies might need to focus both on the dosage and the formulation of progestins -- the synthetic versions of progesterone given to humans -- as well on the starting age for hormone therapy.
The study is published in the Journal of Neuroscience.