A study from this time last year found evidence that the common and debilitating reproductive condition, polycystic ovary syndrome, could start in the brain, not the ovaries, as researchers had long assumed.
If verified, the research could change the way we think about the painful and severely misunderstood condition, which affects at least one in 10 women worldwide.
Anyone who has polycystic ovary syndrome (PCOS) - or knows someone with the condition - will be aware of how incredibly frustrating it can be.
Thanks to the variety of symptoms it can cause - from weight gain, large ovarian cysts, difficulty ovulating, acne, facial hair, depression, and agonising and heavy periods - it can take women years to get diagnosed.
Even then, there's very little in the way of treatment options. Most women are simply told to go on the pill or take other hormonal medications to manage their individual symptoms, but not the underlying cause.
In the long-term, PCOS can lead to metabolic disorders, such as type 2 diabetes, cardiovascular disease, and hormonal dysfunction, including infertility. In fact, PCOS is the cause of more than 75 percent of anovulatory infertility, which is infertility caused by a woman not ovulating.
And yet, despite the severity of the condition, researchers still don't understand how PCOS arises and how we can treat it.
Research led by the University of New South Wales in Australia showed that mice without receptors for androgens - a group of steroid hormones commonly associated with males, such as testosterone - in their brains can't develop PCOS. But if the androgen receptors in the ovaries are removed, the condition can still arise.
Seeing as mouse and human reproductive systems share many similarities, it's compelling evidence that doctors and scientists might have been focussing on the wrong piece of the puzzle all along.
"For the first time we have a new direction of where we should be looking to try and develop treatments that will treat the cause of PCOS, the androgen excess in the ovary but also in the brain," said lead researcher Kirsty Walters in an emailed press release.
Before this, researchers knew that an increase in androgens, known as hyperandrogenism, was linked to the onset of PCOS. But exactly how and where these androgens act in the body was poorly understood.
"Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS," the researchers wrote in their paper.
To get a better idea, the researchers took four groups of mice:
- a control group of normal mice
- a group of mice genetically engineered to have no androgen receptors (ARs) anywhere in their bodies
- a group that had been engineered to have no ARs in just their brains
- a final group that only had ARs missing from their ovaries.
The team then used a high dose of androgen to attempt to trigger PCOS in all four groups of mice.
While the control group developed PCOS as they expected, the mice missing ARs entirely, or just missing them from their brains, didn't get the condition.
Interestingly, the mice that were only missing ARs from their ovaries still went on to develop PCOS, although at a lower rate than the control group. That meant androgens acting on the mice's ovaries couldn't have been the sole cause of PCOS.
The result suggests two important things: researchers were right about an excess of androgens triggering the condition; and the action of androgens on the brain is important to the development of PCOS.
That means if we can find a way to stop those excess androgens in the brain, it could signal a new way to treat PCOS.
"These data highlight the previously overlooked importance of extraovarian [outside the ovary] neuroendocrine androgen action in the origins of PCOS," the researchers explained.
To be clear, this study only looked at mice and the results still need to be replicated in humans before we can get an idea of whether the same thing is happening in our own reproductive systems.
But this is still a big deal because, until this study, the focus when looking for effective treatments and preventions has been on the ovaries - and we haven't had much luck there.
The study gave researchers a new target to look into; hopefully it's inspiring inspiring new studies that will eventually produce more effective treatments for people with the condition.
The research has been published in PNAS.
A version of this story was originally published in 2017.