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    Default PCOS and Genetics - Audio link and Interview Transcript

    PCOS and Genetics

    By Ron Feinberg, MD, Chairman, PCOS Pavilion Editorial Advisory Board with Dr. Richard Legro | September 20, 2006

    HEAR the interview here>>

    Dr. Richard Legro: "I think women who reproduce later in life are probably going to raise a higher quality child. That is a philosophical issue more than anything else but if you’re asking why has PCOS been around for a long time and nobody’s figured out it’s genetic, I think that PCOS causes you to be fertile in times of stress and famine when other people lose weight and die, women with PCOS lost weight, ovulated, got pregnant, and kind of carried on the human species.”

    Dr. Ron Feinberg: “So these are times that we may not see a lot, at least in American society but perhaps around the world. What have your notions been about the incidence of PCOS and underdeveloped countries as an example?”

    Dr. Richard Legro: “What’s interesting is that you can find PCOS in all underdeveloped countries, and I’ll give you one example right now. When the Aborigines in Australia live in a westernized Australian society with surplus and relative inactivity, they gain weight in a centripetal pattern, the women become hirsute and anovulatory much like PCOS so I think that’s a good example of how environment or specifically plenty can bring out the PCOS phenotype.”

    Dr. Ron Feinberg: “Dr. Legro, let’s change topics a little bit. Do you think that some of the changes that are seen in the ovary as a result of the development of PCOS, specifically those changes that promote hyperandrogenism, do you think they’re reversible?”

    Dr. Richard Legro: “Yes, we have good evidence of that from Stein-Levanthal who did a wedge resection. Clearly, there are a lot of vicious circles in PCOS and once you start with high androgen levels you can feedback at the hypothalamic pituitary access and get further abnormalities and get gonadotropin secretion, which perpetuate the circle. So one way of breaking the circle was to wedge out part of the ovary producing high androgens in these women which has been shown in many different surgical methods be it a wedge resection, ovarian cautery, or ovarian drilling with a laser. All these can result in spontaneous ovulation and normal androgen levels. Certainly the future will probably be developing medical therapies that can achieve the same androgen lowering effects that the surgical therapies of the past did.”

    Dr. Ron Feinberg: “Many women who have conceived and ultimately delivered daughters are concerned about PCOS and their daughters. I guess I’m referring specifically to women who were diagnosed with PCOS and have been treated for that. What advice can you give those women with regards to taking care of their daughters as their daughters grow up and reach puberty?”

    Dr. Richard Legro: “One thing is I would urge them to participate in our study in which we’re studying the children of women with PCOS. We have a study in which we want to study children from one year of age and older perspectively to see if they manifest insulin abnormalities and androgen abnormalities in both male and females and get an idea of what is the earliest form of PCOS because clearly something is going on and affecting girls before their first period.”

    Dr. Ron Feinberg: “Do you think there are certain red flags that some of these women may want to look for in their daughters?”

    Dr. Richard Legro: “Yes, I think the red flags that I would look for is - one, obesity developing early on and specifically obesity that appears to be right around the middle section. Two, I would look for the premature development of hair and for girls that is probably less than age eight and for boys less than age nine.”

    Dr. Ron Feinberg: “Do you think there are certain lifestyle changes that moms may want to try to intervene as far as their daughters are concerned to try to lessen some of these early characteristics of risks of PCOS?”

    Dr. Richard Legro: “I’m not quite sure, I hate always putting the burden for abnormalities of the disease back on the afflicted and say - it’s all in your diet or your life and reform, heal thyself. So I think we really need to do the studies to see what exactly happens and when it happens, and once we understand that process better, we might be able to make “treatment recommendations.”

    Dr. Ron Feinberg: “It is interesting, just to interject one point, I’ve seen patients in my practice who developed PCOS not necessarily in their teenage years but maybe in their twenties. A common theme that I’ve seen is women tell me – I used to be very active in sports when I was in junior high and high school and maybe less so in college, and I’ve clearly been less active and I’ve noted that I’ve gained a lot of weight. What are your thoughts about that as far as activity levels and how that might impact on development of PCOS even a little bit later in life?”

    Dr. Richard Legro: “I think that most girls who do sports and exercise a lot are often placed on birth control pills because they don’t have periods due to another mechanism which is probably excess activity, too little body fat, etc., and that history often isn’t reliable when you ask if they had regular periods, and they say yes but they were on the birth control pill. It’s clear that exercise can improve insulin sensitivity but whether it improves it to the degree that PCOS disappears, I don’t think so. So I think that what we tend to see is that they probably had irregular periods from the beginning independent of exercise and that it was masked with the birth control pill, and when they gained a little weight and stopped the birth control pills, suddenly they report for the first time irregular periods.”

    Dr. Ron Feinberg: “Some of these women actually had fairly regular periods and maybe even conceived early in their lives without too much difficulty. I’m wondering if they had maintained the same level of activity into their older years whether they would have avoided some of the PCOS type symptoms.”

    Dr. Richard Legro: “As far as this category, we’re talking about acquired PCOS, and to me our family studies may be useful for a model of what’s going on. We certainly see sisters that have high androgen levels but regular periods and they tend to weigh a little less than affected sisters who have irregular periods and high androgen levels. So it’s possible they have that predisposition to PCOS I talked about in the beginning and that there’s a critical weight threshold that brings on the irregular periods, and certainly losing weight would help to improve many aspects of it.”

    Dr. Ron Feinberg: “It’s already been raised as a controversy here at the meeting or an issue, but what is your opinion about the long-term use of insulin sensitizing agents particularly where fertility is not an issue?”

    Dr. Richard Legro: “I have no opinion because I have no data on which to base an opinion, and I think we have to wait for a study. There is a diabetes prevention trial going on which has one “insulin sensitizer,” metformin(Drug information on metformin) is one of the treatment arms and I think we should wait and see what that shows. Right now it’s just someone’s hunch or opinion, and I don’t that’s a basis for long-term treatment with insulin sensitizers.”

    Dr. Ron Feinberg: “So perhaps a little circumspection is in order. One last question, did PCOS affect 5%-10% of women a hundred years ago?”

    Dr. Richard Legro: “This is what Dr. Paul McDonough would call a thought experiment because no one will really be able to answer that. Believe me I’ve searched the literature as well as I can and my guess is most likely not, and I think there’s a couple of reasons for that. Most likely our lifestyle wasn’t the same prevalence of obesity a hundred years ago that there is right now.”

    Dr. Ron Feinberg: “And we didn’t have the Internet a hundred years ago either but we won’t touch that.”

    Dr. Richard Legro: “One more thing, we need also to be victims of our scrutiny in our technology and we didn’t have androgen assays and transvaginal ultrasounds, I’m not even sure we had pelvic exams a hundred years ago. Certainly the body was well enough covered that it probably would have been pretty hard to pick up hirsutism.”

    Dr. Ron Feinberg: “Perhaps there was more silent suffering a hundred years ago then we might have even thought about.”

    Dr. Richard Legro: “Yes, I think so. I think they were still probably more concerned with rectovaginal fistulas and things like that from multiparity then they were with the disorders of menstruation.”

    Dr. Ron Feinberg: : “I want to give my sincere thanks to Dr. Rick Legro. Dr. Legro is an Associate Professor in Obstetrics and Gynecology and Reproductive Endocrinology and Infertility at the Hershey Penn State Medical Center. He’s one of the world’s leading authorities on polycystic ovary syndrome and maintains a center and a vast collaborative network of investigators who are studying PCOS. He has also graciously agreed to be part of the PCOS Advisory Board of”


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