That’s just one of many impacts that reduced oestrogen levels can have on the brain, says Brinton. She and her collaborators have found that declining sex-hormone levels have enormous effects on the metabolism and immune status of the brain in both rodents9 and humans10. Key to this is oestrogen’s role in regulating the uptake of glucose, the brain’s principal food source. Brinton and her colleagues have found that when oestrogen levels decline, metabolic activity in the brain initially plummets, says Brinton. “That starvation response is sending out an SOS — ‘I’m starving out here; I need another fuel.’”

In response, Brinton says, the brain starts to shift its metabolism from glucose to lipids. This transition, she thinks, can trigger inflammation, which in turn could contribute to the brain fog experienced during menopause and the increased risk of Alzheimer’s disease and Parkinson’s disease women face after menopause. “Perimenopause is a very important part of this transition,” she says. “It really depends on how that perimenopausal transition goes, whether you come out with a heightened risk generated by inflammation, or whether you come out and you’re OK.” Brinton and her collaborators are conducting brain-imaging studies in perimenopausal women to extend their findings beyond animal models. Results so far suggest that after a period of neurobiological unrest, glucose use in the brain settles into a post-menopausal ‘new normal’, and people’s performance on memory and cognitive tests improves10.

Ongoing epidemiological studies might also firm up the relationship between perimenopause and brain health. The US Study of Women’s Health Across the Nation, for example, is tracking women aged 42 to 52 using clinical visits, blood tests and bone-density imaging, and so could capture some aspects of the perimenopausal transition.

As for Rance, she retired and closed her lab last year, leaving a field that was a bit more populated than when she started, she says. “But not as much as you might think,” she adds. “There’s still a lot of room for people to do basic research.”