Testosterone, Progesterone and Allopregnanolone—Critical and Timely Neurosteroid Interventions in the Risk Reduction of Alzheimer’s Disease.

In women, how important of a role does progesterone play in cognitive function?

While a number of studies have shown that estrogen replacement therapy in women is protective against the risk for late-onset Alzheimer's disease (LOAD), only a few studies have demonstrated that progesterone also benefits cognitive function.

Indeed, progesterone could be important in preserving cognitive function in women as they age—particularly in the menopausal transition when there is a precipitous drop in progesterone.

Studies that investigated the protective role of hormone replacement therapy (HRT) in the potential prevention of LOAD have theorized that there is a "critical window" of opportunity for HRT in women.

Research has demonstrated that early in menopause estrogen replacement therapy (ERT) may have a brain protective benefit, whereas ERT after 60 may increase the risk for LOAD.

The same may hold true for progesterone replacement therapy.

In 2021, a "University of Arizona Health Sciences study found women on hormone therapy were up to 58% less likely to develop neurodegenerative diseases including Alzheimer’s disease, and reduction of risk varied by type and route of hormone therapy and duration of use."

The study included estrogens and progestins and combination therapies on neurodegenerative diseases. Note that progestins are synthetically derived forms of progesterone.

In fact, the study "found that using the natural steroids estradiol or progesterone resulted in greater risk reduction than the use of synthetic hormones."

Not often included in the studies centered around the potential role of HRT in the risk reduction of LOAD, is the role of estrogen and progesterone metabolites.

A key progesterone metabolite—allopregnanolone, is linked to the generation of new brain cells—neurogenesis.

In a study published in 2020, allopregnanolone was determined to be  "a first in class regenerative therapeutic for early AD that targets endogenous neural stem cells and disease-modifying mechanisms."

In adult neurogenesis, neural stem cells and progenitor cells are the neural precursor cells that give rise to new brain cells, including astrocytes, microglia, oligodendrocytes and neurons.

The phenomenon of adult neurogenesis is a critical component to a healthy aging brain and the potential prevention of cognitive decline and impairment that marks the development of LOAD.

Please listen in to today’s episode and the continuing story on the role of hormones that are potentially a vital therapeutic intervention in both women and men at midlife.