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A New Understanding of PCOS

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A New Understanding of PCOS

Sep 08, 2015

Polycystic ovary syndrome (PCOS) is the leading cause of infertility in reproductive age women. A new reveals genetic changes that lead to PCOS, findings that are helping to explain why the disorder occurs. Endocrinologist , a clinician at the Utah Diabetes Center, describes what the study shows and what it might mean for women with the condition.

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    PCOS and Infertility

    Interviewer: Research that's giving us a new understanding of PCOS, the most common cause of infertility in women, up next on The Scope. I'm talking with Dr. Corinne Welt, Professor of Reproductive Endocrinology and a clinician at the Utah Diabetes Center at the 人妻中出视频 of Utah.

    Dr. Welt, I have to admit I had not heard of PCOS or polycystic ovary syndrome before I started looking into your work, and it turns out that it's actually the leading cause of infertility among reproductive age women. Is that correct?

    Dr. Welt: Yes, it's a very common disorder found in one in ten reproductive age women. It's very underdiagnosed and typically is found by women who have irregular menstrual cycles, and any sign of excessive androgen levels, so high testosterone levels or signs such as increased hair growth on the face or abdomen, belly or too much adrenal androgen hormone.

    Challenges in Diagnosing PCOS

    Interviewer: And from what I understand, the diagnosis of PCOS is actually somewhat controversial, that different women present differently and so it's difficult to tell who really has and who doesn't. Do I have that right?

    Dr. Welt: I think rather than controversial, I think it's under-recognized. There's definitely a component that patients who will see a reproductive endocrinologist who have infertility because of their irregular menstrual cycles. The polycystic ovary syndrome is associated with a high risk of diabetes, so some patients will present to endocrinology. There is an under-recognition of the irregular menstrual cycles in general in medicine, because it's not often asked about. So I think a lot of women go undiagnosed.

    Genetics of PCOS

    Interviewer: And so you worked with a research team to look at the genetics behind PCOS, what are some of the underlying genetic causes of this disorder. Why did you decide to take that approach?

    Dr. Welt: Well, polycystic ovary syndrome has been known since the 1930s, but we really don't understand the cause of polycystic ovary syndrome, and we and others have spent many, many decades looking at the physiology, trying to figure out what is the starting point for PCOS. So we decided to take a genetics approach about 15 years ago, and we have been working on this for quite some time.

    What we found is that there are several different risk genes that are associated with polycystic ovary syndrome. Some of these appear to have a relationship to the pituitary gland, which is something that we've known for a long time but put on the side. It didn't seem to be the most important thing, but I think now this comes up as one of the more important causes of polycystic ovary syndrome. There are some genes that appear to be related to the ability to make androgen hormones so the testosterone levels may be related to some of the genes, and then there are definitely some that overlap with diabetes so they probably control insulin resistance PCOS.

    So as far as we know, these three big categories are probably separate, and there are other genes, actually, that have been found in these studies that may even have other etiologies or other causes for PCOS that we can't yet identify. They're not totally clear so we do have things in the three big pathways, the androgens, the pituitary gland and the insulin resistance, but there are definitely others in the group that we have found that are not totally clear and may have some other cause for PCOS. We hope that in the end, patients may fall into one of the different subcategories and that it may be easier to break them out into different groups so that we know what the cause of their PCOS was, and what treatment would work best for them.

    Impact of Weight and Environmental Factors

    Interviewer: In this particular study did most women fall into one of these categories or was it pretty evenly divided between who had differences in those three genes?

    Dr. Welt: Each of these gene regions control the risk in about, I would say, 10% to 30% of patients. So some patients will have more than one, and some patients will have just one, and some patients won't have any. And it's not a hard and fast that if you have the gene variant that you will definitely have PCOS. There may be other things that contribute such as something in the environment or a weight gain that might also be required to cause the PCOS.

    Interviewer: Okay, and so that might help explain why PCOS might look differently in different women?

    Dr. Welt: Absolutely, and we even know that women who have PCOS and gain weight actually get much worse. They can get much worse menstrual cycle irregularities. They tend to get more metabolic syndrome problems and more risk for diabetes. So we definitely know that weight gain exacerbates the problems and makes them worse, as one example.

    Pituitary Hormone-Related Gene Insights

    Interviewer: So maybe we could focus in on one of those genes, the one that's involved in the pituitary hormone. Is that right?

    Dr. Welt: That's right.

    Interviewer: Hormones. Now that you have that information, what can you do with it? How does it help you to think about how to treat these women or what might you do down the road?

    Dr. Welt: What's interesting about this one gene change that is related to the pituitary gland is that we've actually been able to look at this gene change, and look at big studies that have given women a medication called Letrozole or Clomiphene for treatment of infertility, and we actually can show that in small studies that this base pair change actually determines or predicts who might respond to Clomiphene in these studies. So you might be able to take some of these gene changes and suggest that one treatment versus another might work better for these women.

    It also brings us back quite a long way. I think 20 years ago we were studying these same hormones without having any genetic basis for it, and we have been able to show that there are a group of women that have these very high pituitary hormone levels, and they always seemed somewhat different than other women with PCOS. So they probably have this very robust pituitary gland that seems to shoot out more hormone than other women might have, and so we can probably work with low-dose medications like maybe estrogen or lower dose contraception to try to suppress some of those hormones early on so that women don't have so much difficulty with the side effects of PCOS, like excessive hair growth or acne that might come along with the high pituitary hormone levels.

    Personalized Treatment Approaches

    Interviewer: So it gives you a direction of different treatment approaches that you can try, you think?

    Dr. Welt: Exactly, and I think we've always had this sense that PCOS might have different causes and that it might be more than one syndrome, and so this might help us just break patients out to use things that we already have, or to develop new medications that are targeted directly at the hormone abnormalities that are caused by the gene changes.

    Integrating Endocrinology with OB/GYN Care

    Interviewer: And so really you think these women would be well-served if they saw an endocrinologist maybe in addition to their OB/GYN or something like that?

    Dr. Welt: Yeah, I think the OB/GYNs certainly are very aware of the condition, and I think they are absolutely doing the right things with their patients. I think when they are finished with fertility-related procedures, sometimes the overweight or the diabetes aren't necessarily taken care of by the OB/GYNs and so they may be better served to go an endocrinologist at that point.

    But I also think that the internists may not be as aware of the condition, and if they are aware of taking a menstrual cycle history, aware of the diagnosis, and then either if they don't feel comfortable taking care of the patients to refer them to an endocrinologist or a gynecologist, I think that is an important first step. I think a lot of women are unrecognized and don't have someone who actually has made the diagnosis or is aware of the treatment for the diagnosis.