Polycystic ovary syndrome (PCOS) is a disease characterized by excess hormone production from the ovaries, resulting in irregular menstrual cycles and fertility issues. PCOS affects around one in ten women, making it one of the most common endocrine disorders among women of reproductive age. Beyond its relationship to menstruation and fertility, PCOS is also associated with significant long-term cardiometabolic consequences, such as hypertension, type 2 diabetes, and obesity.
Hyperglycemia—elevated blood sugar levels—is a key culprit in PCOS-related cardiometabolic complications. High blood sugar can result in endothelial dysfunction, in which the thin layer of cells lining blood vessels cannot circulate blood and maintain a balanced cardiovascular system. Endothelial dysfunction is particularly common among women with PCOS.
These complications led Danielle Berbrier, a recent PhD graduate of McGill’s Department of Kinesiology and Physical Education and current first-year medical student in McGill’s School of Medicine, to search for a potential intervention.
In her recent study, published in the American Journal of Physiology, Endocrinology and Metabolism, Berbrier investigated the role of ketone monoester (KME) as a therapeutic for mitigating high blood sugar and endothelial impairments in women with PCOS. Berbrier employed a double-blind randomized control design, comparing 10 females with PCOS and 10 matched controls.
Berbrier’s desire to study PCOS stemmed from the lack of attention the syndrome has received in scientific research thus far.
“You put 10 women in a room, and the stats say one out of 10 should have it,” Berbrier said in an interview with The Tribune. “The other part that drove me was how understudied it was and how there’s no real universal treatment for [PCOS]. The more [I] worked with women and heard their stories of what they’ve been through, it felt like the least I could do was do research in this area.”
Berbrier’s study found that women with PCOS had higher blood glucose levels when administered the oral glucose tolerance test—a drink containing 75 grams of sugar—compared to their controls, which could be a marker of pre-diabetes or metabolic impairment. Researchers then administered KME and placebo supplementation to determine whether the treatment altered blood sugar levels.
“We found that [women with PCOS] had higher glucose levels and that their blood vessel health was impaired following that glucose [ingestion], but with a quick shot of KME, both their glucose levels and vascular health improved,” Berbier said.
The findings also demonstrated that KME’s ability to reduce hyperglycemia improved endothelial function, which is critical for preventing cardiovascular disease.
“Endothelial dysfunction is one of the earliest indicators of cardiovascular disease risk, and it’s a key role in the development of hypertension and atherosclerosis [….] It could also occur way before cardiovascular disease even happens,” Berbrier explained.
Other studies have found that ketogenic diets may improve hormone levels in women with PCOS. So, could KME supplementation through dietary sources achieve similar benefits for women with PCOS who have hyperglycemia and endothelial dysfunction?
“The dose of KME that the participants took was really high and so acute, […] ketone diets would take longer to see those types of benefits,” Berbier said. “It would be a hard comparison just because of dosing differences, but both [avenues] are promising.”
Berbier emphasized how meticulous her recruitment of participants was, noting that it represents both a strength and a limitation to the study’s findings.
“Anyone on Metformin or Ozempic were excluded, [which] ended up excluding a lot of females who were in the obese category,” Berbrier explained. “So, not by design, but by my rigorous inclusion criteria, I studied a non-obese cohort, which allowed me to look at the syndrome through its intrinsic symptoms with no confounding variables.”
However, up to 80 per cent of women with PCOS are obese. Berbrier noted that her findings are therefore not fully generalizable and suggested further investigation with more diverse cohorts of participants.
Given the increased prevalence of cardiometabolic diseases among females with PCOS, early intervention strategies are critical to preserving long-term health. PCOS must be addressed as being related not just to reproductive issues, but as having further significant cardiometabolic implications. Berbrier’s study helps address those implications through KME treatment, a promising avenue.
