Melanie Cole, MS (Host): Today, we're talking about a condition that's often misunderstood that affects women and it can go years undiagnosed or really giving women the clear answers that they need regarding their health and fertility. It's PCOS. Welcome to Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey.

I'm Melanie Cole, and joining me, as always is Dr. William Ziegler. He's a specialist in Reproductive Endocrinology and Infertility, and he's the Medical Director of the Reproductive Science Center of New Jersey, Dr. Ziegler, always a pleasure. So what is PCOS? We've heard that term before, but not everybody really knows what it is or how common it is.

William Ziegler, DO, FACOG: Well, a lot of times patients are given the diagnosis of polycystic ovarian syndrome just because of their symptoms. Just a little history, polycystic ovarian syndrome was actually coined back in 1935, and there were two gynecologists by the name of Irving Stein and Charles Leventhal. So sometimes this is called Stein Leventhal Syndrome.

And at that time they realized that these ovaries had many, which is the word poly and fluid-filled cysts, or fluid-filled sacs, and that's where the cyst came from, but they're not cysts. Over time we realized that they're actually follicles, that each one contains an egg, and it was an anatomical disease at that time.

And in 1960s, we realized the hormones were not in the right proportions. Two hormones that come from the pituitary gland, luteinizing hormone, and follicle stimulating hormone are not in the right proportions. So therefore, these patients who have PCOS recruit 10 or 15 follicles like they're supposed to, but they don't go on to ovulate.

So therefore, it then became an endocrine disease. And in the 1970s and eighties, we realized these patients were at a higher risk for diabetes, for stroke, for heart attack, arterial sclerosis. So now, at that time, the National Institutes of Health wanted to study these patients and they wanted to, put funding to it, but they needed a definition.

So in 1990, in Bethesda, Maryland, the PCOS conference took place and that's where they defined what PCOS is. Because we realized that close to 15% of the reproductive age women have or have been diagnosed with PCOS. However, there's probably 70% that are not diagnosed. So now we need to diagnose these patients because it does have some health risks.

And that's where they came up with the definition of having irregular cycles, laboratory or clinical evidence of hirsutism, which is cystic acne, facial hair, hair falling out. And you rule out other causes, thyroid issues, adrenal causes, and that was the definition in 1990. Things then progressed and in 2003, they came up with what's called the Rotterdam criteria, which basically you need two of three variables.

One, it's either irregular cycles, laboratory or clinical evidence of high androgens, PCOS looking ovaries, which is on ultrasound, that's an ovary that has a bunch of follicles in it. It kind of looks like a pearl necklace around the outside of black pearls. And you rule out everything else.

You need two of the three to make the diagnosis of PCOS. That's kind of the etiology of polycystic ovarian syndrome. And we now know that it does have clinical implications where for infertility a problem with getting pregnant. Also if they don't have regular cycles, it does predispose them to abnormal cells in the uterine lining that could actually progress to cancer.

Host: Dr. Ziegler, that is the best explanation of PCOS that I have ever heard. You explained that so well. So it's really an endocrine disorder. It's not really gynecologic in nature. Is that what we consider it now? Yes.

William Ziegler, DO, FACOG: Yeah, basically is an endocrine disorder, and then it comes down to why are those hormones not in the right proportions. And the etiology behind PCOS, there's basically two. If you ever Google a PCOS patient and what they look like; they're usually overweight, they're hairy, they're oily.

And a lot of times we believe that there's two types of PCOS. There's obese PCOS patients, and there's lean PCOS patients. Those that are overweight, we believe it's because of insulin resistance, which is not part of the definition of PCOS, but it can add to the symptomatology. And in those patients, a lot of times we screen them for insulin resistance or pre-diabetes.

And we treat them with a medication called metformin and that helps lower the insulin levels. Because insulin will stimulate the ovary to make more of those male hormones. So if we lower insulin, we lower the effects of the high androgens that are causing facial hair and acne, but also high insulin stimulates growth hormone from the pituitary gland. So if we lower insulin, we lower growth hormone, we lower growth hormone, they lose weight. So that's obese, PCOS.

Then we have the lean PCOS patients. Those that don't have insulin resistance. So why do they have PCOS? Well now we find there is a genetic issue, and depending on which, what are called alleles, depending on which ones mesh up, will determine whether they just have irregular cycles or whether they have what's called metabolic X or HAIR-AN syndrome, which is where they have, where they're shaving like two or three times a week.

 So in those situations, again, depending on what their symptomatology is, and the etiology will determine the treatment.

Host: This is really interesting. So as we think of the common signs and symptoms, and you mentioned criteria for diagnosis; but what would a woman notice, and generally at what age? Dr. Ziegler is this something that women sometimes notice in their teen years and then maybe it goes undiagnosed or written up as something else, and then as they get into their reproductive years, that's when we start to look a little bit closer to determine what the cause is?

William Ziegler, DO, FACOG: Polycystic ovarian syndrome really cannot be diagnosed before the age of 18 because cycles are so irregular and for a woman to undergo what, what's called a growth spurt, they have to gain weight. To gain weight, they have to become insulin resistant. That's a normal physiologic response.

So over the age of 18, if they're having irregular cycles and facial hair, acne, then that's in reason to look into, okay, what else is going on? Is the etiology coming from the ovary? And we have to also keep in mind that the increased facial hair and acne, they can have a psychological sequelae that women don't want to go out because, okay, I, you know, I didn't shave today, or my acne is flaring up or in school, they can get picked on.

I'm not saying that the symptoms that somebody would have in the teenage years, we can't treat. We can definitely do it the same way as we do in those women that are diagnosed with PCOS over the age of 18. So yes, we do use birth control pills to help regulate those hormones. We may even use another medication to block the androgen receptor so they don't have those symptomatology even in the adolescent years.

But to have the diagnosis of PCOS, really you cannot give that until after the age of 18, till after the hypothalamic pituitary ovarian axis is fully mature.

Host: What about fertility? So how does it directly affect their ability to conceive as they get into those reproductive years?

William Ziegler, DO, FACOG: Part of it is these women are not ovulating. So if you're not ovulating, you're not going to get pregnant. If the androgen levels are elevated, it can actually thin the uterine lining, and that can also impede implantation. So when we look at a patient and they want to get pregnant, we do focus on body mass index.

And the first thing to do is to focus on getting the weight down to an ideal body weight based on their height. And we try getting it down to around a body mass index of around 30, okay. Or less than 30. At that time, if it's because of the weight is the reason why they're not getting their period, then

they should start having regular menstrual cycles. If they don't, that is when we need to intervene with medication. And if they have insulin resistance in which we screen for, we do give metformin to help lower those androgen levels. And we may try that as first line and if they are still not getting their regular cycles, and then we talk about oral medications, and there's two types out there. One is called Clomid or clomophine citrate. The other one is called letrozole. In PCOS patients, because they have a high androgen level, male hormone, that is converted to estrogen, and that suppresses follicle stimulating hormone that stimulates the follicles to grow.

Well, we want to lower that. So we can lower it by stopping the conversion. And we use letrozole for that. And that is called an aromatase inhibitor. So we actually block that conversion and therefore we lower the concentration of estrogen and that increases FSH and helps the woman ovulate. So that's one way which we can help.

Another way is that if they are resistant to the oral medications, we can move over to the injectable fertility drugs, which basically are follicle stimulating hormone, and that directly stimulates the ovary. That's usually not the first line. We usually use the oral medications first.

Host: So, Dr. Ziegler, we've got lifestyle and you mentioned diet and exercise, weight management, getting down to that acceptable BMI and weight so that you know you can work with them. And you've mentioned all the medications. So you've talked about all of the things that we try. What do you see as far as outcomes for these women when they have done all of these things, and if they don't have to go to injectables, but all of the other things seem to fall into place, what have you seen as far as fertility outcomes?

William Ziegler, DO, FACOG: We have a good ovulation rate with letrozole because these patients that come to us, we just need to make them ovulate. We can make them ovulate in around 80% of cases with the oral medications, and around 60 to 70% of them will conceive within three cycles. So it does have a good outcome for these patients.

We don't need to run to the injectable fertility drugs unless there's some other etiology in which we need to do that; blocked fallopian tubes or maybe a male factor issue, but in most cases, the oral medications work very well.

Host: Dr. Ziegler, as we get ready to wrap up, and I mean, you have just outdone yourself today, really given us so much information that even I haven't heard before. So this was such a learning experience and so informative. What's your message of hope for someone who is feeling a little bit discouraged about their fertility, they've been diagnosed with PCOS, what would you like them to know from the incredible expert that you are?

William Ziegler, DO, FACOG: I think what patients need to realize is, okay I'm having irregular cycles. They're probably online and they've done their own Google research and they find that they, in which they may have polycystic ovarian syndrome. Well, I think at that point they need to see their OB GYN because it does have some medical

sequelae to it as well as fertility. And if they are not looking to get pregnant, then they need to look at regulating their cycles and possibly decreasing the androgens through birth control pills or another medication called spironolactone. There's other ones out there also. However, if they want to get pregnant, that's when they come to see us.

If they're having irregular cycles, make an appointment, come in, get the information, and from there they can make a decision of whether or not they want to proceed down the fertility path or whether they're not ready yet. And they just need the information because they're getting it from all different sides and they need somebody who's going to organize it for them, make it understandable, and understand that it is treatable. We can't cure it, but we can treat the symptoms.

Host: Thank you so much Dr. Ziegler. What a great guest you always are. Thank you again for joining us, and you can always visit fertilitynj.com to schedule an appointment to speak to one of our fertility specialists. That concludes this episode of Fertility Talk with RSCNJ, the Reproductive Science Center of New Jersey. I'm Melanie Cole.