Speaker 1: All right, so let's talk about polycystic overy 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 p COS as
I like to call it, So polycystic overy 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
overies 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 PCOS is one of the
most common endochronopothies in women of reproductive age. It effects
between six point five and ten percent 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 piacos. So
starting with your LH levels. So PACOS patients have altered
LH levels with relatively higher serum lutinizing hormone concentrations relative
to FSH concentrations. This is just a small component of
the whole picture, but I think is important to understand.
So let's do a quick review of a normal functioning
hypothalamic pituitary ovariant axis. In a normal HPO axis, the
hypothalamus releases GnRH in a pulsatile manner, stimulating the anterior
pituitary to secrete LH and FSH. LH goes down and
acts on the thika cells in the ovary, promoting androgen
production primarily androstendon, while FSH stimulates granulosa cells to produce aromatase.
Romatase is an enzyme that converts these androgens into estrogen,
specifically estradil. So as this process goes on, a dominant
follicle develops. F SH 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
lutium provides negative feedback, slowing down GnRH pulses, reducing LH
and FSH secretion to complete the cycle. It's a lot,
but here's the part that you need to know and
p cosse. This balance is disrupted due in part two,
a higher pulsatile frequency of g n rh which LH
is more responsive to, leaving us with excessive amounts of
LH relative to f SH levels. So it means those
thikas cells which are stimulated by LH are now producing
too many androgens and FSH can't keep up to convert them.
These elevated androgen levels, along with the relatively lower f
SH levels, which normally stimulate follicular development, impair normal follicle maturation,
resulting in anovulation and in 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 to FSH ratio. One other part of the
pathway I feel is important to understand is how insulin
resistance plays a role. So fifty to seventy percent of
females with p costs demonstrate clinically measurable insulin resistance, So
we have insulin resistance which leads to compensatory hyper insulinemia.
So high levels of insulin in the body. But what
do high levels of insulin have to do with androgen
excess and ovulatory to spunction. 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 THECA 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 hyper androgenic effects.
High insulin levels even seem to override the ovara's natural
resistance to LH, making them hyperresponsive, 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.
May take away. Excess LH relative to FSH, 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, hersutism, 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 oligomenareea amenareea. So
women with PA costs 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 pea costs
will seek medical attention. So remember oligomenarea or amenarea and
the potential for infertil Next, hyper androgenism, hersaitism, acne, female
pattern hair loss. So these are the repercussions of those
excess androgens like testosterone we mentioned earlier. So hersaitism 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 perieriolar 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 a menorrhea, and hyper androgenism.
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 hyper androgenic features. Let's talk
about diagnosis next. So when we're talking about the diagnosis
of PECOS, there is no no single lab or imaging
study you can do to definitively diagnose this 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 does the criteria entail?
So to make the diagnosis of PA costs, you need
to have two out of the three based on the
Rotterdam criteria. The first is oligoovulation or anovulation, 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 hyper androgenism. So this means
either the patient has clinical signs of hyperandrogenism so hersitism,
actne et cetera. Or they have biochemical signs of hyper
androgenism 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 defindings. So the
last criteria is polycystic ovaries by ultrasound. So let's talk
about the ultra findings. Like I mentioned before, the fluid
filled structures in the ovary that we see in some
women with PA costs are not cists, but rather these
immature follicles that never developed during those failed ovulation events.
So an 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 p COS ultrasound findings. So the Rotterdam criteria
states a positive finding on ultrasound is twelve or more
of these small follicles and either ovary measuring two to
nine millimeters in diameter and or increased ovarian volume over
ten mL. Now, there are some groups that suggest revising
this increasing to twenty or more follicles per ovary because
of the improvements and resolution of pelvic ultrasound and the
fact that a percentage of normal cycling women met the
threshold without having PA costs. 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 pea cos all right.
So that's the Rotterdam criteria. That's what you need to know.
Irregular ovulation, hyper androgenism, and polycystic ovaries on ultrasound you
need two out of a three, meaning if you have
a patient with irregular mensis and hyper androgenic 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 pea costs, 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 rule out your
very important 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.
Your apartment as an 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
NCCAH can present with almost identical signs and symptoms as
those with PECOS hyperindrogenism, olligo, manaia, polycystic overies, So you
don't want to miss this. So to screen for this,
you obtain a serum seventeen hydroxy progesterone, which is also
super high heal to know, I sometimes remember the as
apartment seventeen 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 tumor, so a patient with an adrenal
androgen secreting tumor or an adrenal cortical carcinoma. These patients
can have clinical and biochemical manifestations of hyper androgenism like
pa COS, but generally more severe. These patients usually have
significant elevation of testosterone and or DHVAS levels way higher
than PECOS patients, and usually will exhibit more severe signs
of hersitism and even signs of virilization things like cliteromegaly,
increased muscle mass, and deepening of the voice, which we
typically don't see in pea COS. Okay, so that's the
a for apartment. Adrenal main takeaway, don't forget NCCAH screened
with the seventeen hydroxy progesterone. Remember your apartment seventeen. Next
letter in the apartment is P which stands for pituitary. Specifically,
we're talking about hyper prolactinemia. So hyperperlactinemia, which is an
elevation of prolactin levels from the pituitary, can lead to infertility,
oligomenarea or a menareea, so this needs to be in
your workup. And then finally, the T stands for thyroid,
so both hypo and hyperthiroidism can also lead to oligomenarea,
so check a TSH as well. There are, of course
other differentials Cushing syndrome, primary ovarian insufficiency, ovarian hyperthiicosis, pregnancy
of course a very important cause of a menarea. 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 screen for
with a seventeen hydroxy progesterone. 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 oligomanarea, hyperindrogenism and fertilities, obesity,
insulin resistance, dyslibidemia. 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 peacos, and that is
lifestyle changes diet exercise, weight reduction. Specifically in our overweight
or obese patients with p costs, Diet, exercise and weight
loss are very effective for improving insulin resistance, decreasing the
hyperandrogenic symptoms, and some studies have found that modest weight
loss five to ten percent 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 two diabetes, etc. So
this should be the first step for all overweight and
obese women with PA costs. The next step for treatment
we're going to talk about. Our medications are 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 the coeocs have a
number of benefit for women with PCOS. First, they suppress
ovarian androgens, decreasing the hyper androgenic features. Obviously, provide contraception
because even women with oligomenarrhea may still ovulate intermittently lead
to unwanted pregnancy. And then finally, something that we may
not be thinking about, but patients with chronic annovulation like
in PECOS. These patients are at higher risk for endometril
hyperplasia and even endometrial cancer. And that's because we have
this chronic anovulatory 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 hersitism. Binding these in a CEOC
helps you manage both hyper androgenism 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 COEC 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 spirinolactone.
Spiralactone is a minerali cordiicoid receptor antagonist, and it is
an effective treatment option for androgen excess as it blocks
androgen receptors and also decreases testosterone production. And spirinalactone falls
under the women not pursuing 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 finess, dride fluta, mind, but spirinalactone 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 peacos who are overweight oral beats should attempt to
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 navulatory women who are overweight oral beese
weight loss is recommended first. If lifestyle changes and weight
loss are not effective and medication is needed, the one
you should know is in romatase inhibitor by the name
of lectrisol. Lectrosols should be first line treatment for ovulation
induction in infertile analvieslory women with peacos. Now this has
shifted over the years, as clomaphene used to be first
line by per up to date and the twenty eighteen
International evidence based guidelines, lectrosol is now the first line
treatment option for ovulation induction in women with peacos, Like
a number of pea cost treatments. It's still not FDA
approved for the syndication, so your patients need to be
aware of that, And there are some alternatives clomaphene met foreman,
although both of those are less effective for live birth
rates compared to lectrozol, so I would just focus on
lectrosol after weight loss in women pursuing pregnancy. So how
does letrozol work for ovulation induction? While letrozol is in
aromatase inhibitor. Romatase, as we briefly discussed earlier during the
path or review, is an enzyme that converts androgens into estrogen.
So if we inhibit aromatase, less endrogens 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 sense 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 FSH we have improved follicular development and improved
ovulatory rates. Those are the mens 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 p COS.
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 pa cos. In no way do I intend
for this to be offensive to anyone with PCUS. It's
just a simple little visualization that helped me remember. So
PCUS or pa COS I used to remember in Seat
of Peacos as pea clause. Piacos is pea clause as
in Santa Claus, and Santa Claus contains all of the
high old things you need to know about peacos, including
a Rotterdam criteria and the most important meds. So again,
PACs is now pea clause as in Santa Claus. So
when we visualize our Pea cos 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 twenty fifth circle,
and of course has 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 Peacas. First,
that ball of lettuce in his right hand, That lettuce
ball helps remember the first line pharmacologic therapy for patients
pursuing pregnancy letrasol lettuce ball letrasol. And his left hand
holds the clue for first line treatment for women not
pursuing pregnancy, COC's or combined oral contraceptives with the first
three letyers of Coca Cola highlighted coc What about the
big pimple on his forehead being popped by a spear.
Pimple represents your hyper androgenic symptoms like acne and the
spear popping it helps you remember how you treat it
speir in a lactone, spear rhonolacton, speierronolactone. The anti androgen
we used for patients with persistent hyperandrogenic symptoms despite coc monotherapy,
is why beard helps you remember the hersaitism we can
see in patients with peacos. 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 twenty fifth circled, symbolizing infrequent
or aps in periods like Sanna 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 Sanna and Apartment seventeen 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 twenty
nine 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 five
feet five inches tall, weighs one hundred and thirty two pounds,
and has a BMI of twenty two. On physical examination,
there is terminal hair noted on the face and along
the line 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 and the absence
of contraindications. Which of the following would be the most
appropriate next step in management for the likely diagnosis A
letrazol B spirriinalactone C met foreman 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 twenty nine
year old female presenting with hersaitism or regular metro cycles
based on the Rotterdam criteria. She has pics. Of course,
to definitively say that full work up 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 her hyper
androgenic symptoms? So we know the medication we're going to
prescribe as a coc or combined oral contraceptive. Remember that
bottle of Coca Cola and Santa's left hand. Now, what
about the other options? While letrozol would not be appropriate,
this medication is used for ovulation induction in women pursuing pregnancy.
Spirinalactone could be used as an adjunct therapy for persistent
hyperandrogenic symptoms, but it's generally not first line met foreman
which at one time was used pretty frequently for peacs,
is no longer recommended for hersaitism per the twenty eighteen
Endercin 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 as a normal BMI of twenty two. Question two.
A twenty six 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 hersatism on the
upper lip and lower abdomen. Her height is five foot four,
weight is two hundred pounds BMI thirty four point three.
A transvaginal ultrasound reveals enlarged ovaries with multiple small follicles
arranged peripherally. Differentials will rule DOWNT and the patient was
diagnosed with PCOS. Which of the following is the most
appropriate first step in managing her infertility? A clomiphene citrate,
B letrasol, C met foreman D spirrinalactone E lifestyle change
weight loss, So that is going to be E weight loss.
So this patient has a BMI of thirty four point three,
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 letrasol. Question three. A twenty five 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 the 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 galactoria, headaches, visual changes, heater, cold intolerance, or fatigue.
Physical examination confirms hersaitism and reveals no other abnormalities. BMI
is twenty seven. Which of the following is the most
appropriate next step in management of this patient. A initiate
treatment with combined oral contraceptives. B prescribes sphere and lactone
for hersuitism, C refer for laser hair removal. D conduct
a diagnostic workup to exclude other causes of hyper androgenism
and oligomenerrhea. Or E suggests lifestyle changes diet and exercise.
So the correct answer is D conduct a diagnostic workup
to exclude other causes of hyper androgenism and oligomenarhea. While
all of these are decent answers and may all be
adequate treatment options at some point in the future for
this patient. The first step before initiating any form of
treatment for a patient with the expected PACs is the
first ensured that they have piacos. 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 PACs 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
twenty nine year old woman with PCUS wishes to conceive.
Over the past six months, she has attempted lifestyle modification,
including dietary changes, increase physical activity, and has achieved modest
weight loss. Despite these efforts, he continues to experience and
ovulatory cycles. According to current evidence, which is the most
appropriate first line treatment option for ovulation induction for this
patient A chlomiphene citrate, b letrazol, C met foreman D,
gonadotropins E laparoscopic ovarian drilling. So the correct answer is
going to be b letrozol. So remember, let's tresol your
lettuce ball in Santa's right hand is the first line
ovulation induction agent over klomaphene citrate Answer A and met
format Answer C, which are both less effective for live
birth rates than electrosol 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 diathermy or electrocoagulation. This is a surgical option, meaning
more invasive, and would generally only be utilize after the
patient has tried and failed pharmacotherapy. All right, So that
was picos. I hope that was helpful. Thank you so
much for the support of the and best of luck
in school.