Last updated July 16, 2018 at 5:19 pm
Scientists have made a major breakthrough in understanding what causes polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) affects 10 to 18% of women worldwide. The occurrence is even higher for Indigenous women. Despite how common PCOS is among women there is currently no standardised treatment, let alone a cure.
Scientists have suspected for some time that there may be more than a heritable or genetic component to the disease. Environmental factors such as hormone exposure may affect the PCOS trait being shared within families.
A French research group have now potentially found a hormone that plays a major role in PCOS in women. By injecting increased levels of anti-Müllerian hormone (AMH) they were successfully able to replicate PCOS-like symptoms in a mouse model.
Polycystic ovary syndrome symptoms include irregular ovulation, fertility problems, excessive hair, severe acne, insulin resistance and weight gain. There are co-morbidities with PCOS such as type II diabetes and cardiovascular disease; obesity is also known to exacerbate the disease. Due to the wide range of PCOS symptoms, treatment options vary for individuals.
A story of hormones
Previous research has shown there are links between PCOS, the brain and hormones. Many individuals with PCOS have high levels of luteinizing hormone (LH) which influences higher secretions of gonadotropin-releasing hormone (GnRH) and AMH compared to healthy women. These hormones, in turn, have impacts on the brain in signalling production of other hormones like testosterone, and further stimulate LH.
AHM is intrinsically tied with pregnancy. In women without PCOS, it is normal for their AMH levels to drop during pregnancy. However, in this study they were able to show that AMH concentrations during pregnancy are higher in lean women with PCOS than those who don’t have PCOS.
They found that mice exposed to high levels of AMH prenatally while in the womb were more likely to develop PCOS-like symptoms during adulthood. The offspring from the AMH group displayed a variety of PCOS-like symptoms such as delayed puberty, disrupted menstruation cycles, altered ovary structures and impaired fertility such as delayed first litter and fewer pups per litter.
They also showed how exposure to excess AMH could activate brain cells via GnRH mechanisms which can lead to increase testosterone and LH, and induce the PCOS-like symptoms.
Drug treatment success in mice
Realising the role of GnRH the researchers then trialed an existing IVF drug called cetrorelix which impacts on GnRH receptors and essentially controls hormone production. By treating the pregnant mice the researchers were able to prevent the PCOS-like symptoms of the mice offspring.
Furthermore, they showed that postnatal treatment with centrorelix in their PCOS mouse model could reverse their symptoms. Normal cycles were restored, as well as levels of LH and testosterone, and even restoring the ovary follicles to a healthier state.
The weight of it all
It is worth noting that many of the differences of AMH levels in women, regardless of whether or not they had PCOS, are not seen in obese women. As they represent a small, but nevertheless existing population of women with PCOS, this is an unexplored gap. In determining the AMH levels in pregnant women, they also only classified women in the extremes of lean (BMI ≤ 25) and obese (BMI ≥30), leaving a gap for those between BMI of 26 to 29.
The authors also note that their mouse model did not present any weight differences compared to their control mice so their findings represent those with a lean PCOS condition. They highlight that despite the lack of effect on weight in their mouse model, it would still be worthwhile for further research into metabolic symptoms also associated with PCOS; such as glucose tolerance, insulin resistance or abdominal fat storage.
Hope for sufferers of PCOS
This ground-breaking study provides hope for the millions of women suffering from PCOS. It has made a huge leap in understanding PCOS as well as created a new PCOS mouse model with clinical relevance for future PCOS research.
Perhaps most exciting is that cetrorelix is already frequently used clinically. “It could be an attractive strategy to restore ovulation and eventually increase the pregnancy rate in these women,” as Paolo Giacobini, who lead the team, told New Scientist.
The researchers plan to carry out a clinical trial of centrorelix in women with PCOS.
The research was published in Nature Medicine.
