Mood, mental performance, menopause: Hormone-related?

LOS ANGELES – For many women, the end of fertility – and the sharp drop in circulating estrogen and progesterone that comes with it – is a time of forgotten keys, tip-of-the-tongue moments with names and words, and a malaise that can morph into all-out depression. Naturally enough, many believe there is a causal link here, and wonder whether hormone replacement therapy might hold at bay the mood and cognitive changes that commonly occur at midlife.

Scientists, too, have been debating the relationship between sex hormones, mood and cognition, and whether there exists a “critical window” following menopause when propped-up levels of sex hormones might change a woman’s mood or mental performance as she ages. A new study adds to a mounting pile of evidence that after menopause, mood and mental performance do not seem to rise and fall in sync with naturally circulating levels of sex hormones, whether a woman is fewer than six years past her last menstrual period or 10 years into menopause.

So, it would seem to follow, it makes little sense to take hormone replacement medication, or to stay on it, in hopes of propping up mood and cognition. Not now, and not later.

The study, conducted by researchers at Stanford University and USC, was published Tuesday in the Online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS).

This is just the first – and smallest – of three studies that will begin to bring clarity to a question of interest to millions of aging women: In the balance of risks and benefits of hormone replacement therapy, might there be some improvement in mood and mental agility for healthy women who do take it?

Two large clinical trials are expected soon to publish results – one called the Kronos Early Estrogen Preventions Study (KEEPS), and the Early-Versus-Late Intervention with Estradiol (ELITE) trial (from which the subjects in this study come). Those will demonstrate more definitively whether there is value – and when – in taking hormone replacement therapy to prevent conditions associated with aging, including heart disease and cognitive decline.

What none of these studies addresses is another mystery: whether those slips in memory and attention, and the common appearance of depression in women around menopause (when nearly one in four women takes an antidepressant – are hormone-related. While research evidence is contradictory, there’s some reason to believe that fluctuating hormones at midlife – not their decline – may contribute to a slight rise in mood-related problems and changes in memory and attention. But that, too, awaits further and better research.

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