Most women with polycystic ovary syndrome often struggle to maintain a steady weight. A nasal spray of insulin might help such women burn calories, according to preliminary research in sheep, which can show many of the same symptoms of PCOS. A trial in women with PCOS is now being planned.
Around 7 to 8 per cent of women have polycystic ovary syndrome, which affects the way ovaries work. Women with PCOS often have irregular periods and can find it difficult to get pregnant. But PCOS also appears to put women at risk of obesity and diabetes. In the US, around three-quarters of women with PCOS are also obese.
at the University of Edinburgh says that most of his patients can have restored ovulation with the right treatment, but treating obesity is much harder. That’s because women with PCOS find it more difficult to lose weight.
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A study published in the 1990s suggests that this is because . After most people eat a meal, their fat tissue starts to burn through calories, releasing heat, but this is reduced by around 25 per cent in women with PCOS.
This means that women with PCOS would have to eat around 4 per cent less, or exercise around 20 per cent more, than another woman of a similar height and weight who doesn’t have the disorder, just to maintain a steady weight, says Duncan.
To find out why this might be, Duncan and his colleagues turned to sheep. When Scottish greyface ewes are injected with male levels of testosterone, their female offspring show the symptoms of PCOS – they stop ovulating, develop polycystic ovaries and gain weight, says Duncan.
His team then implanted thermometers in the fat tissue of the sheep with PCOS symptoms, to record minute-by-minute changes in temperature. In sheep that didn’t receive testosterone injections, the temperature reading soared after a meal, before settling back down. The same pattern was seen in overfed obese sheep.
But the temperature rise was significantly less in the sheep that received testosterone injections, suggesting these animals aren’t burning calories as well. “It pretty much looks exactly like what you’d expect to see in women [with PCOS],” says Duncan.
In other experiments, the team found that nerves supplying fat tissue were less active in the sheep with PCOS. This suggests that some signal in the brain is essentially telling the fat to burn fewer calories, says Duncan. He thinks that this signal is insulin, partly because the degree of temperature rise in the sheep’s fat correlated with their resistance to insulin.
If a lack of insulin means that fat tissue isn’t getting the signal to burn calories, boosting insulin levels in the brain might help, says Duncan. Previous studies have already experimented with nasal sprays to get insulin in the brain – the practice seems safe, and doesn’t appear to affect blood sugar levels, he says.
When Duncan’s team sprayed insulin up the noses of 12 sheep with PCOS, the sheep’s fat tissue appeared to burn more calories. The group hasn’t yet studied the animals for long enough to see whether they lose weight. “This was a short-term proof-of-concept study,” says Duncan, who presented the findings at the Society for Endocrinology BES annual meeting in Brighton on 12 November.
Duncan is currently applying for funding to trial the same approach in women with PCOS. Because insulin has been associated with satiety, Duncan hopes the women that try it will benefit from both effects. “Maybe squirting insulin up your nose gets you two benefits: it burns off calories and makes you not want to eat anymore,” he says.
Hormone production in sheep isn’t the same as that of humans, cautions Lina Schiffer at the University of Birmingham, UK, who chaired the session at which Duncan presented his results. “[Duncan’s] work has established the rationale and applicability of this in sheep with great success,” she says. “We now need to translate this into the human setting.”
Article amended on 20 November 2019
We have corrected how sheep were given symptoms of polycystic ovary syndrome.
