Cram The Pance - S1E55 Polycystic Ovary Syndrome (PCOS)

Episode Date: July 9, 2025

High Yield Polycystic Ovary Syndrome (PCOS) ReviewReview for your PANCE, PANRE, Eor's, Physician Assistant exams, Medical, USMLE, Nursing Exams.Merchandise Link: https://cram-the-pance.creator-spring.com/►Paypal Donation Link: https://bit.ly/3dxmTql (Thank you!)Included in review: Pathophysiology, PCOS symptoms ,PCOS diagnosis, PCOS treatment, PCOS infertility, Rotterdam criteria, LH/FSH imbalance, Hyperandrogenism, Anovulation, Insulin resistance in PCOS, Letrozole, Clomiphene, PCOS vs NCCAH, PCOS ultrasound findings, 17-hydroxyprogesterone, PCOS and endometrial hyperplasia, Combined estrogen-progestin oral contraceptives, Medical mnemonics for examsBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right, so let's talk about polycystic ovary syndrome before we get started. As always, thank you so much for the support. Thank you, thank you so much. All right, let's talk about polycystic ovary syndrome or picos, as I like to call it. So polycystic ovary syndrome, the name quite literally means a syndrome of many cysts of the ovaries. So you might think that that's all this is, but in actuality, you don't even need to have polycystic ovaries to be diagnosed. And the fluid-filled structures in the ovaries, they're not even true cysts.

But we'll talk more about that later. So Picos is one of the most common endocrinopathies in women of reproductive age. It affects between 6.5 and 10% of all women of reproductive age. Let's go ahead and get started with the patho first. So the patho is pretty complex, multifactorial. There's a lot going on. So we'll keep it focused on what you need to know, some key concepts or trends that we typically see in patients with PECOS. So starting with your LH levels. So PECOS patients have altered LH levels with relatively higher serum lutinizing hormone concentrations relative to FSAH concentrations. This is just a small component of the whole picture, but a part I think is important to understand. So let's do a quick review of a normal

functioning hypothalamic pituitary ovarian access. In a normal HPO access, the hypothalamus releases GNRH in a pulsatile manner, stimulating the anterior pituitary to secrete LH and FSAH. LH goes down and acts on the Thika cells in the ovary, promoting androgen production, primarily androstin Dion, while FSA stimulates granulosis cells to produce aromatase. Romatase is an enzyme that converts these androgens into estrogen, specifically estradiol. So as this process goes on, a dominant follicle develops. FSA-h stimulates the follicle to develop, rising estrogen levels, trigger positive feedback on the pituitary, leading to a surge in LH, which induces ovulation. Most of this you probably already know. After ovulation, progesterone from the corpus luteum provides negative

feedback, slowing down GNRH pulses, reducing LH and FSAH secretion to complete the cycle. It's a lot, but here's the part that you need to know. In PECOS, this balance is disrupted. Do in part to a higher pulsatile frequency of GNRH, which LH is more responsive to, leaving us with excessive amounts of LH relative to FSAH levels. So it means those Thika cells, which are stimulated by LH, are now producing too many and FSAH can't keep up to convert them. These elevated androgen levels, along with the relatively lower FSAH levels, which normally stimulate follicular development, impair normal follicle maturation, resulting in an ovulation and an accumulation of these immature follicles in the ovary, which lead to the classic appearance we'll see on ultrasound in some

patients. Okay, so remember the increased LH-2-FSA ratio. One other part of the path, who I feel is important to understand, is how insulin resistance plays a role. So 50 to 70% of females with PCOS demonstrate clinically measurable insulin resistance. So we have insulin resistance, which leads to compensatory hyperinsulinemia. So high levels of insulin in the body. But what do high levels of insulin have to do with androgen excess and ovulatory dysfunction?

Well, more than you'd think. So besides the obvious regulation of glucose that comes to mind when thinking of insulin, it does something else when in high levels. And that is to stimulate the thika cells of the ovaries to produce more androgens. So kind of like what we were talking about before with the effect of LH on the ovaries, insulin can stimulate steroidogenesis, causing those thika cells to crank out more androgens. and these increased levels of insulin also inhibit production of something known as SHBG, sex hormone-binding globulin.

This is a transport protein that binds to hormones like testosterone as well as others, and it regulates their access to certain tissues. When hormones like testosterone are bound to SHBG, though, and this is the important part, these hormones are rendered inactive, meaning they can't do anything. So the fact that these high insulin levels inhibit production of SHBG means we have more of those androgens hanging out free in the bloodstream, in their active state able to unleash their hyperandrogenic effects. High insulin levels even seem to override the ovary's natural resistance to LH, making them hyper-responsive driving even more androgen production, all of which lead to some of the clinical manifestations will go over. All right, so that's a lot of info.

Main takeaway, excess LH relative to FSA, excess insulin from insulin resistance. Remember those, and let's move on to the clinical manifestations next. So this is a syndrome. So the clinical presentation can vary from person to person, and there's many potential clinical manifestations. Irregular menstrual cycles, hercetism, acne, obesity, mood disorders, metabolic issues, cardiovascular issues, diabetes. But the two, the two I want you to remember that are also part of the diagnostic criteria will go over shortly is as follows.

The first is menstrual dysfunction, oligomenorrhea, amenorrhea. So women with Peacos will have infrequent or absent menstrual cycles, which is caused by infrequent or absent ovulation. As a result, infertility is a common consequence of these menstrual regularities and is frequently one of the reasons women with picos will seek medical attention. So remember, oligomanorrhea or amenorrhea and the potential for infertility. Next, hyperandrogenism, hercetism, acne, female pattern hair loss. So these are the repercussions of those excess androgens like testosterone we mentioned earlier. So hercetism, which is a thick or pigmented body hair, also known as terminal hair, and a male distribution pattern. So we can see dark hair growth on the upper lip, the chin, around the nipples, the periareolar surface,

as well as the lower abdomen, the linear alba. Acne is common as well. This can be on the face, back, chest, as well as other areas of the body. And then finally, female pattern hair loss. So these women may start to have thinning of the hair on their head, this diffuse alopecia. Okay, so menstrual dysfunction, oligo or amenorrhea, and hyperandrogenism. Now, these are the two I want you to focus on, but of course, be aware there are other potential clinical manifestations. metabolic issues like obesity, insulin resistance, but focus on the menstrual dysfunction, infertility, and hyperangiogenic features. Let's talk about diagnosis next. So when we're talking about the diagnosis of PECOS, there is no single lab or imaging study you can do to definitively

diagnose the syndrome. So what we do to make the diagnosis is by using something known as the Rotterdam criteria. There are a few different criteria out there, but the Rotterdam criteria is the one most expert groups use, and therefore it's the one you need to know. So what is the criteria entail. So to make the diagnosis of Pecos, you need to have two out of the three based on the Rotterdam criteria. The first is oligo ovulation or an ovulation, which will generally manifest with menstrual regularity, like we talked about before, so infrequent or absent menstrual cycles. The next is clinical and or biochemical signs of hyperandrogenism. So this means either the patient has clinical signs of hyperandrogenism, so hercetism, acne, etc.

or they have biochemical signs of hyperandrogenism. So you obtain labs and they have elevated testosterone levels. And then finally, the last criteria, which we haven't talked too much about yet, is the ultrasound findings. So the last criteria is polycystic ovaries by ultrasound. So let's talk about the ultrasound findings. Like I mentioned before, the fluid-filled structures in the ovary that we see in some women with picos are not cis, but rather these immature follicles that never developed during

those failed ovulation events. So on ultrasound will see abnormally high numbers of small follicles within these enlarged sclerotic ovaries. The small follicles are often located on the periphery of the ovary, and sometimes they'll resemble a string of pearls. And you'll sometimes hear them being referred to as that string of pearl sign when describing Picos ultrasound findings. So the Rotterdam criteria states a positive finding on ultrasound is 12 or more of these small follicles in either ovary measuring 2 to 9 millimeter in diameter and or increased ovarian volume. over 10 ML. Now, there are some groups that suggest revising this, increasing to 20 or more follicles per ovary because of the improvements in resolution of pelvic ultrasound and the fact that a percentage of normal cycling women met the threshold without having PCOS. What that means to you is don't memorize

these numbers. If they can't agree on the criteria for the specifics here, they can't expect you to remember them or memorize that for an exam. So don't worry so much about the specific number, but keep in mind if the question is describing numerous small follicles and a big old plump ovary, they're probably describing Peacos. All right, so that's the Rotterdam criteria. That's what you need to know, irregular ovulation, hyperandrogenism, and polycystic ovaries on ultrasound. You need two out of a three, meaning if you have a patient with irregular mencies and hyperandrogenic symptoms, you don't even need an ultrasound to diagnose. But there is one last part we're missing, one very important component before you make the

diagnosis based on the Rotterdam criteria. You absolutely have to rule out your differentials. Rotterdam criteria also require exclusion of other conditions that mimic Pecos. So Peacos has some very sneaky impostors, conditions that have many of the same or in some cases exactly the same clinical findings. So once you establish a patient fits the Rotterdam criteria, the next step is to roll out your very important different differentials. Now, there are a number of differentials. I'm not going to cover every single one, but the ones you need to know and the ones that will

likely be tested on can all be found in your apartment. Yep, your apartment as an individual. APT. What does that mean? Apartment. APT stands for three important areas, and those are adrenal, pituitary, and thyroid. So these are the differentials to roll out before making your diagnosis, and they can all be found in your apartment. So starting with adrenal, the letter A. What I'm going to cover right now is the most important differential you need to know. And if they're going to give you a differential on an exam, it will very likely be this one. This is known as NCCAH, non-classic congenital adrenal hyperplasia. If you want to forget all of the

other differentials I'm going to go over and just remember one this is it a patient with ncca can present with almost identical signs and symptoms as those with picos hyperandrogenism oligomanorrhea polycystic ovaries so you don't want to miss this so to screen for this you obtain a serum 17 hydroxyprogesterone which is also super high yield to know i sometimes remember the demonic as apartment 17 just to help me remember this screening test because it's just so popular to be tested on and i definitely got a question on this in school So please remember this one. And then the other adrenal differential is an adrenal adrenal tumor.

So a patient with an adrenal androgen secreting tumor or an adrenal cortical carcinoma, these patients can have clinical and biochemical manifestations of hyperandrogenism like Pecos, but generally more severe. These patients usually have significant elevation of testosterone and or DHEAS levels, way higher than Pecos patients, and usually will exhibit more severe signs of hercetism and even signs of virulization, things like clitoromagely, increased muscle mass and deepening of the voice, which we typically don't see in Pcos. Okay, so that's the A4 apartment, adrenal, main takeaway, don't forget NCCAH, screen with the 17 hydroxyprogesterone.

Remember your apartment 17. Next letter in the apartment is P, which stands for pituitary. Specifically, we're talking about hyperprolactinemia. So hyperprolactinemia, which is an elevation of prolactin levels from the pituitary, can lead to infertility, oligomenorrhea or amenorrhea. So this needs to be in your workup. And then finally, the T stands for thyroid. So both hypo and hyperthyroidism can also lead to oligomanorrhea.

So check a TSA as well. There are, of course, other differentials, Cushing Syndrome, primary ovarian insufficiency, ovarian hyperthecosis, pregnancy, of course, a very important cause of a manorea. But the ones I highlighted in your apartment, those are the ones to remember as those will likely be tested on, again, highlighting non-classic congenital adrenal hyperplasia, which you screened for with a 17 hydroxyprogesterone. All right, next let's talk about treatment. So treatment for PCOS is targeted at a number of different areas because of all of the complications

associated with this condition. Remember, we have oligomanorrhea, hyperandrogenism, and fertility, obesity, insulin resistance, dyslipidemia. So I'm breaking this down to highlight the essentials. Let's start with what is considered the first line intervention for many women with PCOS. And that is lifestyle changes, diet, exercise, weight reduction. So specifically in our overweight or obese patients with PCOS, diet exercise and weight loss are very effective for improving insulin resistance.

resistance, decreasing the hyperangiogenic symptoms, and some studies have found that modest weight loss, 5 to 10% reduction in body weight, may restore normal ovulatory cycles and improve pregnancy rates. Of course, this is also beneficial for managing the underlying metabolic abnormalities we talked about, cardiovascular disease, type 2 diabetes, et cetera. So this should be the first step for all overweight and obese women with PCOS. The next step for treatment, we're going to talk about our medications, our pharmacologic therapy. We're going to break this down into two categories, women pursuing pregnancy and those who are not pursuing pregnancy. So starting first with women not pursuing pregnancy, a patient who does not want to get pregnant, who has menstrual dysfunction and or androgen excess,

which medication can we use? So the first line pharmacotherapy for most women will be with a combined oral contraceptive or a COC, which is a combination of estrogen and progestin. So these COCs have a number of benefit for women with PCOS. First, they suppress ovarian androgens, decreasing the hyperandrogenic features. They obviously provide contraception because even women with oligomanorrhea may still ovulate intermittently, leading to unwanted pregnancy. And then finally, something that we may not be thinking about, but patients with chronic anovulation, like in Pecos, these patients are at higher risk for endometrial hyperplasia and even endometrial cancer, and that's because we have this chronic and ovulatory state causing the endometrium to be exposed to estrogen without the balancing effect of progesterone.

We call this unopposed estrogen. And combined oral contraceptives help prevent this by providing daily progestin, which is a synthetic form of progesterone, which counteracts the proliferative effects of estrogen on the endometrium. And the second part of the combined oral contraceptive, the estrogen component reduces serum androgen concentrations by increasing SHBG concentration. Remember SHBG, the guy who gives testosterone a big hug and doesn't let go, so this in turn reduces the symptoms of acne or hercitism. So combining these in a COC helps you manage both hyperandrogenism and menstrual dysfunction. And that's why these are generally considered first-line pharmacologic treatment.

Now, what about a patient with hyperandrogenic symptoms who's been on a COC for many months with no improvement? What other medication do we have in our arsenal specifically for these persistent hyperandrogenic symptoms? Well, the one you should know is spirinalactone. Spirnalactone is a mineralicordicoid receptor antagonist, and it is an effective treatment option for androgen excess as it blocks androgen receptors and also decreases testosterone production. And spiroinolactone falls under the women not pursuing preternetone. pregnancy category because you do not want to get pregnant while taking this medication, as it can actually feminize male fetuses preventing development of their genitalia. So the patient needs to also be on a contraceptive while taking this medication. There are some other options out there such as

venestride, flutamine, but spyrinolectone is the preferred agent compared to the other available options due to its efficacy. All right, next let's talk about women who are pursuing pregnancy, who are experiencing infertility and require treatment. So before we go over our meds and ovulatory women with picos who are overweight or obese should attempt weight loss prior to initiating ovulation induction therapy in most cases. Some older women or women whose testing shows diminished ovarian reserve, sometimes they'll go straight to meds, but in general, weight loss for in ovulatory women who are overweight or obese, weight loss is recommended first. If lifestyle changes and weight loss are not effective and medication is needed, the one you should know is an aromatase

inhibitor by the name of lettrosol. Lettrizo should be first-line treatment for ovulation induction in infertile an ovus glory women with picos. Now, this has shifted over the years as clomophine used to be first line, but per up to date and the 2018 international evidence-based guidelines, letharzol is now the first-line treatment option for ovulation induction in women with pcos. Like a number of p-cost treatments, it's still not FDA approved for this indication, so your patients need to be aware of that. And there are some alternatives, clomaphene, metformin,

although both of those are less effective for live birth rates compared to lettrizo. So I would just focus on lettrizo after weight loss in women pursuant. doing pregnancy. So how does letharazole work for ovulation induction? Well, letrozole is an aromatase inhibitor. Aromatase, as we briefly discussed earlier during the patho review, is an enzyme that converts androgens into estrogen. So if we inhibit aromatase, less androgens are converted to estrogen and we have much less estrogen in the body. When we have less estrogen in the body, the hypothalamus and pituitary sensed this, say, oh crap, we need to help out, and they produce more fsh. That hormone we have been lacking

because LH took over the show. And with more FSAH, we have improved follicular development and improved ovulatory rates. But those are the men's I think you should know. There's plenty of others, but the ones I went over are the most commonly used and the ones you'll likely get tested on. All right, so that is PECOS. It's a lot, so you probably need a mnemonic. Now, before I tell you what the mnemonic is, I first want to be clear. This is just a memory tool. It's just a way to remember what you need to know about PECOS. In no way do I intend for this to be offensive to anyone with PCOS. It's just a simple little visualization that helped me to remember.

So PCOS or Peacos, I used to remember instead of Peacoss as P-Claas. P-Claas, as in Santa Claus. And Santa Claus contains all of the high-old things you need to know about Peacos, including your Rotterdam criteria and the most important meds. So again, Peacos is now P-Claas, as in Santa Claus. So when we visualize our P-Coss, Santa Claus, you'll notice a few things about this version of him. First, in his right hand, he's holding a ball of lettuce, a lettuce ball.

His left hand, he's holding a bottle of Coca-Cola. On his forehead is a big old pimple being popped with a spear. He's wearing a pearl necklace on the wall as a calendar with December 25th circled. And of course, as expected, he has a big white beard as we've all come to know him for. Now, what do all these things represent when it comes to Pecos? First, that ball of lettuce in his right hand, that lettuce ball helps to remember the first-line pharmacologic therapy for patients pursuing pregnancy, letharzol. Lettrizole.

And his left hand holds the clue for first-line treatment for women not pursuing pregnancy, COCs or combined oral contraceptives, with the first three letters of Coca-Cola highlighted COC. What about the big pimple on his forehead being popped by a spear? Well, that pimple represents your hyperandrogenic symptoms like acne, and the spear popping it helps you remember how you treat it. Spearinalactone. Spear ronolactone. Spear ronalactone, the anti-adrogen we used for patients with persistent hyperandrogenic symptoms

despite COC monotherapy. His white beard helps you remember the hercetism we can see in patients with picos. The pearl necklace helps you remember the string of pearl sign. Remember those numerous follicles on the periphery of the ovary. And then the calendar on the wall shows December 25th circled, symbolizing infrequent or absent periods, like Santa who only shows up once a year in his red suit. So there's a lot to remember in Peacos, but I feel like if you can just remember Santa in Apartment 17, cement this crazy image in your brain. You should be just fine. Now that we have our mnemonic, let's do a few quick questions to test your knowledge.

Question one. A 29-year-old woman presents to the office complaining of excessive hair growth on her upper lip, chin, lower abdomen, as well as irregular menstrual cycles. The patient is 5 feet 5 inches tall, weighs 132 pounds, and has a BMI of 22. On a physical examination, there is terminal hair noted on the face and along the lini alba of the lower abdomen. She's not currently taking any medications, denies any known medical conditions, and is not planning on pregnancy at any point in the near future. She's interested in starting a medication to address the persistent hair growth on her

face and abdomen. In the absence of contraindications, which of the following would be the most appropriate next step in management for the likely diagnosis? A, letharazole. B, spirnalactone, C, metformin, D, combined oral contraceptive, or E, lifestyle changes, diet, exercise, weight reduction. So the correct answer is D, combined oral contraceptive. So why is that the correct answer? So we have a 29-year-old female presenting with hercetism irregular menstrual cycles based on the Rotterdam criteria she has PICOS.

Of course, to definitively say that full workup to roll out your differentials would be needed, but that's not what this question is asking. It's asking based on the likely diagnosis, which treatment are you going to recommend to improve her hyperandrogenic symptoms? So we know the medication we're going to prescribe is a COC or a combined oral contraceptive. Remember that bottle of Coca-Cola and Santa's left hand. Now, what about the other options? Well, letharzole would not be appropriate. This medication is used for ovulation induction in women pursuing pregnancy.

Spirnalactone could be used as an adjunct therapy for persistent hyperendrogenic symptoms, but it's generally not first line. Metformin, which at one time was used pretty frequently for Pecos, is no longer recognized. recommended for hercetism per the 2018 Endocrine Society guidelines, as it has been found to provide little or no benefit. And then finally, lifestyle would have been appropriate if this patient was overweight or obese, but this patient has a normal BMI of 22. Question two, a 26-year-old woman presents to the clinic with concerns about difficulty becoming pregnant. She and her partner have been trying to conceive for several months without success. She reports only one to two menstrual cycles over the past year. It's not on any medications and has no significant past medical history.

Physical examination reveals hercetism on the upper lip and lower abdomen. Her height is 5 foot 4, weight is 200 pounds, BMI 34.3. A transvaginal ultrasound reveals enlarged ovaries with multiple small follicles arranged peripherally. Differentials will roll down and the patient was diagnosed with PCOS. Which of the following is the most appropriate first step in managing her infertility. A. Chlomophine citrate. B.

Lettrosol. C. Metformin. D. Spirinalactone. E. lifestyle change, weight loss. So that is going to be E weight loss. So this patient has a BMI of 34.3, so she is classified as obese. And for younger women with PCOS and inovulatory infertility,

attempts at weight loss should be attempted first in those with obesity. If this does not restore ovulatory cycles, ovulation induction is attempted next, usually with letharzol. Question three, a 25-year-old woman presents to the clinic after noticing increasing facial hair growth, acne in irregular menstrual cycles over the past year. She reports that her periods now occur every two to three months. After researching a line, she believes she has polycystic ovary syndrome and requests treatment to help regulate her cycles and reduce the hair growth. She's otherwise healthy, not taking any medication, denies galactorea, headaches, visual changes, heat or cold intolerance or fatigue. Physical examination confirms hercetism and reveals no other abnormalities.

BMI is 27. Which of the following is the most appropriate next step in management of this patient. A, initiate treatment with combined oral contraceptives, B, prescribed spiroinolactone for hercetism, C, refer for laser hair removal, D, conduct a diagnostic workup to exclude other causes of hyperandrogenism and oligomanorrhea, or E, suggest lifestyle changes, diet and exercise. So the correct answer is D, conduct a diagnostic workup to exclude other causes of hyperandrogenism and oligomania. While all of these are decent answers and may all be adequate treatment options at some point the future for this patient, the first step before initiating any form of treatment for a patient

with suspected Pecos is the first insurer that they have Peacos. And while she has some convincing symptoms based on the Rotterdam criteria, we can't forget that Rotterdam criteria also requires exclusion of other conditions that mimic Peacos before making the diagnosis. So we need to roll out our differentials to ensure we are treating the right thing. So start in the apartment for those differentials, APT, adrenal pituitary, thyroid, among others. Question four. A 29-year-old woman with PCOS, wishes to conceive. Over the past six months, she has attempted lifestyle modification, including dietary changes, increased physical activity, and has achieved modest weight loss. Despite these efforts, she continues to experience in ovulatory cycles. According to current

evidence, which is the most appropriate first-line treatment option for ovulation induction for this patient. A, clomophine citrate, B, letrozole, C, metformin, D, gonadotropins, E, laparoscopic ovarian drilling. So the correct answer is going to be B. Letrazole. So remember, lettrosol, your lettuce ball in Santa's right hand, is the first-line ovulation induction agent over-clomaphine citrate, answer A, and metformin answer C, which are both less effective for live birth rates than letharazole. And the other two options, gonadotropins, exogenous gonadotropin regimens are complex and expensive and considered second line, and of course laparoscopic ovarian drilling, also referred to as ovarian diatheromy or

electrocoagulation. This is a surgical option, meaning more invasive and would generally only be utilized after the patient has tried and failed pharmacotherapy. All right, so that was Pcos. I hope that was helpful. Thank you so much for the support of and best of luck in school.