Multiple clinically relevant hormone therapy regimens fail to improve cognitive function in aged ovariectomized...

Area of Science:

• Neuroscience
• Endocrinology
• Primatology

Background:

• Preclinical studies suggest intermittent estrogen benefits working memory and prefrontal cortex in aged monkeys.
• Clinical studies report inconsistent effects of hormone therapy (HT) on cognitive function in women.
• Discrepancies may arise from varied HT formulations and administration sequences impacting neurobiological outcomes.

Purpose of the Study:

• To evaluate the cognitive effects of four HT regimens in aging, surgically menopausal rhesus monkeys.
• To compare the efficacy of HT protocols modeled on human clinical practice.
• To investigate potential neurobiological mechanisms underlying cognitive changes.

Main Methods:

• Aging, surgically menopausal rhesus monkeys were administered four distinct HT regimens.
• Regimens were designed to mimic common human clinical practices, including continuous estrogen with progesterone.
• Cognitive function, specifically prefrontal cortex-dependent working memory, was assessed.
• Physiological hormone levels were monitored to ensure regimen efficacy.

Main Results:

• None of the tested HT regimens demonstrated any significant cognitive benefits.
• This lack of effect was observed despite achieving physiologically relevant serum hormone levels.
• No improvements in prefrontal cortex-dependent working memory were detected.

Conclusions:

• Commonly used hormone therapy (HT) protocols may not confer cognitive benefits for healthy aging.
• The specific formulation and sequence of HT regimens significantly influence neurobiological and cognitive outcomes.
• Future research should focus on designing HT regimens that optimize cognitive benefits, potentially through targeted delivery or novel formulations.