Polycystic ovarian syndrome (PCOS) has baffled doctors from the moment they gave the disease its name.
In people with ovaries, PCOS has historically been defined by abnormally high levels of androgens – hormones that typically regulate male sexual development – which lead to irregular menstrual periods, abnormal ovulation and often infertility, as well as other symptoms such as acne or excessive facial or body hair. But in recent decades, a better understanding of the root causes of PCOS has led to a strange connection. Many male relatives of people with PCOS appear to share many of the same symptoms that arise from what researchers believe causes PCOS: a genetic susceptibility that leads to metabolic dysfunctionwhich in turn causes insulin resistance which disrupts hormone signaling.
This awareness has led the medical community to advocate for a name change that more closely matches the root causes of the syndrome, STATUS reported earlier this month. (Slate reported on this previously.) If that happens, researchers hope this change could open the door to more treatments and better diagnosis of the disease in everyone who suffers from it.
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There was never any question of cysts
In the 1930s, doctors Irving Stein and Michael Leventhal identified a pattern of symptoms in some women, including enlargement the ovariesirregular or absent periods and infertility. To treat the disease, doctors would cut out or resect a wedge-shaped part of the ovary. For reasons that are not yet fully understood, the treatment sometimes worked; many people have started ovulating again.
When Stein and Leventhal examined the resected ovarian tissue, they saw numerous small, fluid-filled sacs lining the edges, which looked like cysts. These “cysts” became the defining feature of the disease that was quickly named polycystic ovary syndrome.
There was just one problem: Because imaging technology for this disease didn’t exist at the time, these surgeons didn’t realize that they were actually looking at follicles (not cysts), which contained underdeveloped eggs that had failed to mature and release. Today, on ultrasound, they look like a string of pearls. Unlike cysts, they do not grow or rupture.
Yet the name stuck – and with it, misunderstandings about the disease also reared their head. However, over the past few decades, researchers have gradually determined what drives the syndrome and who it affects.
“Polycystic ovarian syndrome is the most common hormonal disorder among women” of reproductive age, says Ricardo Azziz, professor of reproductive endocrinology and gynecology at the University of Alabama at Birmingham, who has spent much of his career studying the syndrome. “It’s a global disease, and [it] affects between 10 and 15 percent of all women worldwide,” says Azziz.
But among those affected, he said, studies suggest only about half are correctly diagnosed. PCOS appears to have multiple causes And several presentations. “It’s not a single disorder,” says Azziz. “It’s a set of signs and characteristics.”
Doctors now recognize four distinct PCOS phenotypesmany of which do not require the signing of excess follicles. Azziz and endocrinologist Andrea Dunaif say one area researchers have zeroed in on is that a person’s genetics strongly influence whether or not they develop PCOS.
In their research, Azziz and Dunaif found that the disease runs in families. From there, “we were able to show that if you were the sister of a woman with PCOS, you had about a 40 to 50 percent increased risk of having PCOS, which also led us to ask the question, ‘Well, what if it’s hereditary and it’s not sex-related?’ [or passed on the X chromosome]which does not seem to be the case, are men affected? says Dunaif, professor of molecular medicine at the Icahn School of Medicine at Mount Sinai in New York.
In a form of PCOS that occurs in people with ovaries, genetic susceptibility increases the risk of insulin resistance. Insulin is a hormone produced by the pancreas that helps move sugar from the blood to other cells in the body. But if a person’s body doesn’t respond properly to insulin, the pancreas ends up producing even more insulin to compensate, leading to high amounts of glucose and insulin in the blood. The high insulin levels then stimulate the ovaries to produce excess androgens, including testosterone, which can disrupt normal follicle development and ovulation, leading to irregular menstrual cycles and other PCOS symptoms.
Researchers are now discovering that this underlying genetic susceptibility to insulin resistance and high androgen levels can also appear in men.
“Almost 20 years ago, we did studies where we looked at brothers and fathers [of women with PCOS] “We found that men had an increased risk of being overweight, of metabolic syndrome – and that younger men also had higher levels of a male hormone produced by the adrenal glands,” she says. “This suggests that these were genetic characteristics.”
The problem is that although men clearly face these problems, “the medical community is largely unaware of these problems,” especially in general internal medicine, Dunaif says. “The tragedy of PCOS is that the specialties who should care don’t know about it.”
What’s in a name?
This new understanding of PCOS has led many experts to call for a name change, to one related to the genetic and metabolic underpinnings of the syndrome instead of mistakenly focusing on the cysts.
Researchers around the world recently reached unofficial agreement on a new name for PCOS, although it is being kept secret for now. Dunaif, who is aware of the proposed new name but cannot disclose it, says she is not sure it will even make it through the renaming process. Researchers have gone through this process once before, in 2012, when a group of researchers and doctors coordinated efforts to rename PCOS as “metabolic and reproductive syndrome.” But it would have been abbreviated to “MRS,” which could have perpetuated the female nature of the syndrome, Dunaif says.
A change in lexicon could increase awareness not only among doctors and patients, but also among researchers who study the disease. There is precedent for this. For example, the condition now known as metabolic syndrome was once called syndrome X, simply because the exact mechanism was not yet understood. This change helped unify research and improve diagnosis because it made the underlying mechanism clearer to doctors and patients. Dunaif says medical research databases show how, once the name changed, there was suddenly an explosion of research into metabolic syndrome.
Azziz agrees that a name change could help the many people with PCOS. “This is a huge population. Ten to 15 percent of all women have PCOS and maybe 10 to 15 percent of men have PCOS, and we don’t have a single, not a single drug that’s actually effective. [Food and Drug Administration] approved directly for PCOS,” he says. “If more funding was available…then we would be able to have much better treatments and targeted treatments for PCOS than we currently have.”