A new class of synthetic estrogens could offer women most of the benefit and less of the risk of standard hormone replacement therapy, a study in animals suggests.

The study, appearing online Jan. 31 in the journal Endocrinology, reports that mice with induced Alzheimer’s-like symptoms got better when given the synthetic hormone propylpyrazole triol (PPT).

“It improved behavior much the way that estrogen does,” said study leader Christian Pike, associate professor at the USC Davis School of Gerontology.

But unlike estrogen, which enlarges the uterus and is a known risk factor for endometrial and breast cancer, PPT caused no obvious changes to the animals’ reproductive tract.

Pike called the study a first step in the search for safer compounds that mimic estrogen’s positive effects on mental function and bone density.

“If hormone therapy as it is now is a problem, what are the alternatives?” he asked.

PPT is one in a class of alternatives known as selective estrogen receptor modulators, or SERMs. These are tissue-specific compounds, acting only on certain parts of the body.

Some already are commercially available. The cancer drug tamoxifen blocks estrogen in breast tissue. Another drug, raloxifene, is an estrogen-like compound that promotes bone density but inhibits estrogen action in breast and uterus.

Raloxifene has been shown to reduce the risk of cognitive impairment in postmenopausal women, Pike said. The Endocrinology study should encourage further animal and human research on the potential benefits of SERMs, he added.

Another SERM in Pike’s study, diarylpropionitrile (DPN), showed limited benefits for mice with Alzheimer’s symptoms. PPT and DPN act on different parts of the estrogen system, Pike said.

The finding of differential effects among SERMs suggests it may be possible to design an optimal compound with the best possible risk-to-reward profile.

The study was funded by the National Institute on Aging under a large grant to USC researcher Roberta Diaz Brinton, who is leading a university-wide effort to study the effects of hormone therapy on women’s health.

Doctors prescribe hormone therapy to counter some of the harmful consequences of menopause, such as losses in bone density. But other large studies have shown that hormone therapy also increases the risk of breast cancer.

USC graduate student Jenna Carroll was the other author of the study.