PCOS and Teens

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Dr. Mark Perloe:  “This is Dr. Mark Perloe, and I’m here with Professor Jeffrey Chang who is Head of the Division of Reproductive Endocrinology at the University of California, in San Diego.  Thank you so much for joining us.  We’re at the PCOS Support Association’s meeting, and I was very interested in your talk this morning; you had talked about some of the changes that occur during sleep at the time of puberty with LH secretion.  I wonder if you might review some of that information.”

Professor Jeffrey Chang:  “What we tried to show was that in normal puberty there’s an emergence of LH secretion that is affected a little bit during sleep, and early in puberty there’s not much of an effect by sleep.  But as a child moves through the different stages, usually by mid-puberty when she goes to sleep, there are increases in LH secretion.  Subsequently, as they move into late puberty, this nighttime rise of LH or sleep associated rise of LH is then lost or disappears, and the entire level of LH is raised to that of the adult.”

Dr. Mark Perloe:  “Now many patients symptoms onset may occur later in life.  They report that menarche may have been early, their periods were regular until sixteen or eighteen, with some people it was regular until a pregnancy or pregnancy loss, and then they note dramatic weight gain and increase in these symptoms.  Has the issue of LH pulsatility been evaluated in that sort of scenario?”

Professor Jeffrey Chang:  “I’m not sure it’s been carefully analyzed with regard to outside events such as weight gain and the emergence of the symptoms of polycystic ovary syndrome.  I think it’s clear that some young girls who present with excessive male hormone production or with excessive hair growth already have the changes that we characterize for polycystic ovary, in particular, having increased pulses.  In other words, there are more pulses per unit time than in a normal individual.  How that plays into these other events that are associated with the development of the disease is not really clear.”

Dr. Mark Perloe:  “Do you think that PCOS is a disorder of ovarian abnormalities, LH pulsatility, or insulin secretion - can you separate them into specific abnormalities that may result in this condition?”

Professor Jeffrey Chang:  “You know, Mark, that’s a tough one and that’s something we’ve been working on for a long time, as have others in the field.  Clearly, they all are inner related to some degree.  What comes first has really never been established and obviously if we knew the sequence of events, then potentially, we could target a particular area and start to investigate that with more intensity than we have before.  Unfortunately, that doesn’t exist right now so when we try to construct the concept for this condition, we try to include everything that we see is abnormal, and that would include abnormalities of the hypothalamus and pituitary as well as the ovary and now to include the metabolic consequences of abnormal insulin secretion.”

Dr. Mark Perloe:  “A lot of recent researchers have been looking at how leptin plays a role in this and leptin resistance as a potential factor that ties in LH secretion and dietary stimulus.  What is your understanding of that literature on leptin and LH, and do you feel that that holds promise for us to gain better understanding of PCOS?”

Professor Jeffrey Chang:  “I think originally we were all excited by some of the early reports that there may have been abnormalities in leptin that could be associated with polycystic ovary syndrome but, subsequently, papers came out that really couldn’t support that possibility.   To date, to be quite honest with you, I am not aware of data that would really suggest a correlation between the two other than the fact that they’re obese.”

Dr. Mark Perloe:  “You showed a group of pictures of women with different manifestations of PCOS, as did Dr. Futterweit earlier.  Some of the patients may present primarily with acne, some with hirsutism, and some with hair loss.  Why would one patient be seen primarily with acne and another with hirsutism; is it different types of androgens, or is it a genetic basis?  Why do you think we see that difference in phenotype?”

Professor Jeffrey Chang:  “First of all, I think patients will come to physicians for a variety of problems, and with regard to androgen excess, it could be either with acne, hair growth, or with some temporal balding or male pattern balding.  The specific characteristics may depend largely on the genetic makeup of the individual.  This is obviously the one area that we are really lacking knowledge in but there are certain ethnic populations that will demonstrate either greater or lesser severity of symptomatology, and I would have to attribute the diversity to some of that.  Why one develops one disorder or one symptom versus the other, I can’t really tell you that.”

Dr. Mark Perloe:  “At each of these conferences, the definition of PCOS is presented and discussed and we will find that one group defines PCOS based on ultrasound findings, one on androgen, and one on menstrual abnormalities.  I think you addressed that in terms of clinically approaching our patient, is the criteria of the diagnosis helpful in pinpointing the approach to management?”

Professor Jeffrey Chang:  “Yes, and kind of no.  It’s clearly the women who brandish the classical symptoms or features of polycystic ovary syndrome - excess androgen and chronic anovulation.  I think that on a cost effective level this is probably very appropriate.  Other investigations to lead us to different therapies really haven’t panned out as necessarily impacting on how we manage the patients.”

Dr. Mark Perloe:  “The original trials on the use of metformin and troglitazone did not use insulin resistance as a criteria to determine entry into the study.  Clinically, many physicians are then saying that patients are not insulin resistant based on a fasting blood sugar or a fasting insulin value.  What is your approach to looking at insulin as a factor in a patient who may not fit a definition but you know when you see them that they have PCOS?  What is your approach to looking at insulin abnormalities and treating outside of a protocol?”

Professor Jeffrey Chang:  “I think that’s one of the toughest questions to answer today.  Clearly, I’ve looked at all the fasting measures that one can do and on an epidemiologic basis they’re very effective but on an individual basis they’re not.  I know many people have taken up the charge of doing oral glucose tolerance tests, which are very easy, they’re acceptable, and they can give you quite a bit of information with respect to glucose levels.  They tend not to give you a lot of information about insulin secretion.  So until a time when we can find a cost effective way of screening these patients, I think that it’s going to be pretty much up to the individual physician how they approach it.  Some have used the fasting glucose insulin ratio but that hasn’t been born out by all investigators in terms of it being effective and highly sensitive for insulin resistance.”

Dr. Mark Perloe:  “On a population basis, it appears that a significant number of patients will demonstrate impaired glucose tolerance and/or type 2 diabetes.  Is there a benefit in making that diagnosis of impaired glucose tolerance in a patient who comes in with symptoms that you’re going to treat with dietary management and weight loss exercise programs?  Is it important to make the diagnosis of impaired glucose tolerance?”

Professor Jeffrey Chang:  “I think definitely one should try to do that and if you suspect that there is, then an oral glucose tolerance test in my mind would be an appropriate way to go.  That has not been embraced by the ADA, as you may know because of the cost implications of it, but I think that if one has a glucose intolerance, my goodness, where do we put the cutoff and to what degree and what implications does it have long term?  I think that data needs to be obtained before we can substantiate but certainly if you or your daughter had impaired glucose tolerance, it would seem like you might want to at least pay some consideration to treatment.”

Dr. Mark Perloe:  “I think we certainly need to see the results from the Diabetes Prevention trial to know whether a medical treatment will actually prevent type 2 diabetes and the complications later in life.  In that case, then certainly treating at an earlier stage would be beneficial, and I think the other issue about making the diagnosis and looking at the fasting, as you said on the ADA, maybe they need to learn from the obstetricians who screen the pregnant women with the 2-hour post-prandial rather than a fasting blood value.”

Professor Jeffrey Chang:  “One of the problems is that not everybody with impaired glucose tolerance will develop type 2 diabetes, and not everybody with polycystic ovary syndrome has type 2 diabetes.  So again, that’s kind of a gray area if you have impaired glucose tolerance and you have insulin resistance, to what degree will that impact subsequent health?  That’s the crucial question.”

Dr. Mark Perloe:  “I want to change tracks here a little bit.  There are a number of studies looking at ovarian drilling, and I think there are some interesting questions that are still not answered.  Why doesn’t it work?  It appears not to work in smokers and when it does work, is it working because we’re draining the follicles, doing superficial work, or do we need to get deep into the stroma and destroy stromal tissue?”

Professor Jeffrey Chang:  “I think if you go back and talk to individuals who have done wedge resections in the past and similar interventions that violate the capsule of the ovary including just stripping away a little bit of the capsule, I think the experience has been that these patients have sustained subsequent ovulation, perhaps not permanently but for a reasonable period of time such that any violation of the capsule seems to be associated with the resumption of ovulation to a certain degree.  How that comes about - the studies that have been done to try and investigate this have not been able to show a particular mechanism by which this works.  I’m intrigued with it because I do think it’s a reasonable option when all other options fail but how that happens, I don’t have a clue.”

Dr. Mark Perloe:  “I think it is in an area of interest and I would certainly hope that we can see some more research on that.  I want to thank so much for joining us today, and I look forward to coming back to San Diego.  Any words for visitors who are coming here this fall?”

Professor Jeffrey Chang:  “I think we have a wonderful program.  It’s really quite fortunate, I believe, that the ASRM is going to have its Annual meeting in the city where I’ll be the host so to speak, and I think my wife has provided a wonderful program for the people that attend the meeting.”

Dr. Mark Perloe:  “Both as President of ASRM and having the host city here, you must be overwhelmed.”

Professor Jeffrey Chang:  “Yes, it’s been a big year so far but, again, it’s also been a pleasure.”

Dr. Mark Perloe:  “Thank you so much for joining us.”