APGO OBJECTIVES

• • Define Amenorrhea and Oligomenorrhea
  • Explain the pathophysiology and identify etiologies of amenorrhea and oligomenorrhea, including possible nutritional causes
  • Describe associated symptoms and PE findings of amenorrhea
  • Discuss the steps in the evaluation and initial management of amenorrhea and oligomenorrhea
  • Describe the consequences of untreated amenorrhea and oligomenorrhea

Definitions

Amenorrhea means the absence of menstrual flows. It may be “Primary” or “Secondary.”

• • Primary amenorrhea means the patient has never had a menstrual flow.
  • Secondary amenorrhea means that she used to have menstrual flows, but they have stopped.

Normally, in the United States, menstruation will have begun by age 15, and if it hasn’t, that’s defined as primary amenorrhea.

But there are a couple of important additions to that general rule:

• • If a 13 year old has never had a menstrual flow, and has no secondary sexual characteristics, such as breasts and pubic hair, then we would consider her to have primary amenorrhea.
  • If a girl of any age hasn’t had a menstrual flow within 5 years of developing secondary sexual characteristics, she is considered to have primary amenorrhea.

Oligomenorrhea means infrequent menstrual flows. If a woman has fewer than 9 cycles per year, she is said to have oligomenorrhea.

Secondary amenorrhea means the absence of menses for at least 3 previous cycles or 6 months.² Pregnancy is the single most common cause of secondary amenorrhea.

Pathophysiology and Etiologies of Amenorrhea

For normal menstrual function to occur, a succession of properly communicated signals and functional end organs must be present.

• • The hypothalamus must be intact and able to send GnRH signals to the anterior pituitary.
  • After receipt of this signal, the anterior pituitary must be able to produce and deliver the follicle stimulating hormone and luteinizing hormone messages to the ovary.
  • The ovary must be normal with an adequate number of follicles, and a uterus must be present with a lining that is capable of responding to the sex hormones created by the ovary.
  • Finally there should be an unobstructed path for the uterine menstrual blood to be delivered to and through the vagina.

So when investigating the cause for either primary or secondary amenorrhea, we must consider the possibility of an abnormality in any of these areas critical for normal menstrual function:

• • The Hypothalamus and Central Nervous System
  • The Anterior Pituitary
  • The Ovary and
  • The uterus and genital outflow tract.

Disorders of the Hypothalamus

Functional Hypothalamic Amenorrhea

There are two clinically important disorders of the hypothalamus:

• • Functional Hypothalamic Amenorrhea, and
  • Kallman Syndrome

If energy demand is high (with excessive exercise) or supply is low (eating disorder), the body will favor shifting its resources away from reproduction and towards other critical processes. This is what happens with Functional Hypothalamic Amenorrhea, or FHA.

Extremes of weight, stress, and physical activity are thought to cause reproductive restraint through abnormal secretion of GnRH, as well as increases in CRH and cortisol, which can also inhibit gonadotropin secretion.

Functional hypothalamic amenorrhea (FHA) is a diagnosis of exclusion, but one that should be considered in the setting of a hypogonadal state, normal to low gonadotropin levels, and in the absence of any sellar mass on brain imaging.

The majority of women who suffer from FHA either report frequent or strenuous exercise, rapid weight loss, or are themselves ≥10% below their ideal body weight. If an eating disorder, such as anorexia nervosa or bulimia, is suspected, a multi-disciplinary approach involving a mental health specialist, physician, and nutritionist should be taken.

Not all exercise is the same. Exercise regimens that lead to low body weight, such as running, ballet, ice-skating and gymnastics, are linked to a greater chance for amenorrhea.

The most serious complication of hypothalamic amenorrhea is bone loss, thus a baseline DEXA scan should be considered following diagnosis.

For women with eating disorders, weight gain is critical as hormone therapy alone is not sufficient in restoring bone density.

Women with exercise-induced amenorrhea should be counseled about reducing the intensity, frequency or duration of their exercise regimen to reduce their risk for bone loss and fracture. Hormone therapy can be considered for this group, along with supplemental vitamin D and calcium.

Kallman Syndrome

A rare cause of hypothalamic amenorrhea is congenital GnRH deficiency.

Although a number of genetic aberrations have been linked to this disorder, the classic X linked type, which is associated with a mutation in the KAL gene, is associated with a loss of one’s sense of smell.

The KAL gene is responsible for transcribing the anosmin protein, a molecule responsible for the migration of olfactory neurons and GnRH neurons from the olfactory placode to the hypothalamus during embryogenesis.

Patients with this condition generally present with delayed puberty and have a family history of the syndrome.

Since adrenarche occurs independent of the maturation of the hypothalamic-pituitary-ovarian access, pubic hair is generally present, while breast development and menstrual flows are absent.

The main laboratory findings are very low or undetectable levels of LH and FSH, low estrogen, a normal karyotype and absence of other causes of amenorrhea.

Although sequencing of the KAL gene may lead to definitive diagnosis, but as there are likely many unknown genetic etiologies for Kallman, a negative result cannot exclude the diagnosis.

Treatment involves hormone therapy for both pubertal initiation and bone protection.

Disorders of the Pituitary

Elevated Prolactin Levels or Hyperprolactinemia

The important pituitary disorder related to amenorrhea is hyperprolactinemia.

Because prolactin inhibits the GnRH pulse generator, elevations in prolactin can also cause a hypothalamic state.

Patients may present with shortened luteal phase, oligomenorrhea, or amenorrhea, galactorrhea, and occasionally headache or visual changes.

Prior to testing, the patient should be advised to fast, to abstain from intercourse, and to avoid exercise, as these activities can lead to a false positive result.

If persistently elevated prolactin levels are found, the next step is to determine the etiology.  Typically, hyperprolactinemia is caused by primary thyroid dysfunction, medications (more often dopamine inhibitors), or prolactin producing pituitary adenomas.  Thus, evaluation includes thyroid function testing, review of medications, and a brain MRI.

Correction of the thyroid disorder will lead to restoration of normal prolactin levels and resolution of hyperprolactinemic symptoms.  If an anti-psychotic medication is the cause, it is best to coordinate the patient’s care with her primary mental health professional.  Strategies may include transitioning the patient to an alternative medication.

Dopamine agonists are the primary treatment for lactotroph adenomas of all sizes, however special attention should be given to women with

• • macroadenomas (greater than 10 millimeters),
  • tumors that do not reduce in size following normalization of prolactin levels (which may suggest a nonfunctioning adenoma), or
  • those that rapidly grow and cause significant neurologic deficit (suggesting a malignancy).

Women should be followed closely with serial prolactin measurements and repeat brain imaging to assure resolution.

Disorders of the Ovary

Polycystic Ovary Syndrome

Let’s consider some problems with the ovaries that can lead to amenorrhea.

Although listed as a disorder of the ovary, the polycystic ovary syndrome is a complex disorder stemming from abnormal GnRH secretion and leading to intra-ovarian hyperandrogenism and abnormal folliculogenesis.

Cyclical release of LH and FSH from the anterior pituitary stimulates the granulose and thecal cells of the ovary to produce estrogens, androgens and progesterone in varying amounts, leading to ovulation, all in support of the monthly opportunity for a pregnancy.

In PCOS, the normal rise and fall of the gonadotropins doesn’t occur. Because abnormal GnRH pulsatility favors LH release over FSH release, increased thecal androgen production occurs.

Insulin resistance can also contribute to increased ovarian androgen production and hyperandrogenemia as insulin acts synergistically with LH and suppresses hepatic sex hormone binding globulin production.

Elevated local androgen prevents normal folliculogenesis and the result is the appearance of polycystic ovaries on ultrasound.

For the diagnosis of PCOS, the patient should meet two of three of the following conditions, known as the Rotterdam Criteria:

1. 1. Oligo- or anovulation
   2. Clinical and or biochemical evidence of hyperandrogenism and
   3. Ultrasound evidence of polycystic ovaries.

The sonographic definition of polycystic ovaries includes the presence on one ovary of at least 12 antral follicles or a total ovarian volume of at least 10 cc.  As many as 20% of normal women have this ultrasound finding without having the syndrome.

Patients with PCOS are at risk for insulin resistance, diabetes mellitus, metabolic syndrome, endometrial hyperplasia and cancer, obstructive sleep apnea, and depression.

Because about half of women with PCOS are obese, and because obesity is associated with the long-term cardio-metabolic risks of PCOS, the most important initial and maintenance treatment are the lifestyle changes of a healthy diet and exercise.  A 2-5% reduction in weight can reduce metabolic risk and improve reproductive potential.

If fertility is not desired, the progestins found in oral contraceptives, cyclic provera, or the mirena IUD can be used to protect the endometrium from hyperplasia.

In women seeking fertility, ovulation induction agents, such as clomiphene citrate, can be used.

In women complaining of androgen excess (hair and acne) and not currently seeking a pregnancy, oral contraceptive pills can effectively reduce androgens. Anti-androgens can also be used.

Gonadal dysgenesis

Structural or numerical sex chromosome abnormalities can cause gonadal dysgenesis, ultimately leading to abnormal gonadal formation and the appearance of “streak gonads.”

Often this occurs in utero or in the first few years of life, and is the most common cause of primary amenorrhea.

Affected girls usually present with primary amenorrhea or pubertal delay as well as elevated FSH levels and low estradiol levels.  As adrenarche is driven by the adrenal gland, which is unaffected, pubic hair may still be present.

The key initial step to determining the cause for ovarian failure in the setting of primary amenorrhea is by obtaining a karyotype.  Although 25% of patients will have a normal 46 XX karyotype, Turner syndrome must also be ruled out.

Turner Syndrome

Turner syndrome, the most common form of gonadal dysgenesis, is associated with a 45, X karyotype.  Physical examination may reveal the classic Turner phenotype, which includes a webbed neck, shield chest, and cubitus valgus.

Because patients with Turner syndrome are at increased risk for coarctation of the aorta, hearing loss, thyroid dysfunction, metabolic syndrome and celiac disease, they should undergo routine surveillance for these conditions.

Treatment is aimed at improving final adult height with growth hormone, as well as initiating puberty and maintaining bone protection with hormone therapy.

Premature Ovarian Insufficiency

Cessation of menstrual function, or menopause, normally occurs around age 51, but with premature ovarian insufficiency, it may occur at a much younger age.

The diagnosis of premature ovarian insufficiency involves amenorrhea or menstrual irregularity as well as menopausal levels of follicle stimulating hormone on two different occasions 4-6 weeks apart.

Patients may present with menopausal symptoms, such as hot flushes, vaginal dryness, and menstrual irregularity.  Carrier status for fragile X permutation and assessment of thyroid and adrenal autoimmunity should be obtained in addition to a karyotype; a baseline DEXA scan can also be considered.

Similar to young girls with gonadal dysgenesis, treatment is centered around hormone therapy for bone protection.

Ovarian Surgery, Chemotherapy, Radiation therapy

Other causes of late gonadal failure include gonadal surgery, or a history of chemotherapy and radiation.

Multiple excision procedures which reduce ovarian stroma, or a prior history of bilateral salpingo-oophorectomy, can lead to amenorrhea and the diagnostic picture appears similar to gonadal failure.

Chemotherapy and pelvic radiation can also lead to a reduction in the number of eggs and subsequently lead to amenorrhea.  The effect is largely dependent on the type of agent used, the dose, and duration of treatment.

Although fertility preservation procedures, such as in vitro fetrtilization or oocyte cryopreservation, prior to gonadotoxic therapy can help future fertility, hormone therapy is still required if gonadal failure is encountered.

Importantly, all patients with gonadal failure should be offered emotional support and the option for counseling.

Disorders of the Genital Outflow tract

Now, let’s consider disorders of the genital outflow tract.

Imperforate Hymen

Girls with imperforate hymen generally present with primary amenorrhea, normal secondary sexual characteristics, and cryptomenorrhea, or cyclic abdominal pain without menses.  On examination, a thin, bulging, blue membrane just proximal to the introitus can be seen.  Treatment involves surgical correction:  generally, a cruciate incision is made in the redundant tissue, which is then excised and the hymeneal ring restored.

Transverse Vaginal Septum

A transverse vaginal septum can form if the mullerian ducts improperly fuse during embryogenesis.

This condition is far more rare than imperforate hymen, occurring in 1/20000-1/80000 women.

Girls with a transverse vaginal septum typically present with primary amenorrhea, normal secondary sexual characteristics, and cryptomenorrhea.  The main difference between this and an imperforate hymen is the physical exam.

Unlike imperforate hymen, girls with transverse vaginal septum have a normal introitus and ruptured hymen, and what appears to be a blind ending vaginal pouch and no visible cervix.  A Valsalva maneuver can be helpful in also distinguishing the two, as the introitus distends in those with imperforate hymen but not in those with transverse vaginal septum.  Pelvic MRI confirms the diagnosis.

Surgical resection is best done by a surgeon with expertise in mullerian anomalies.

Mullerian Agenesis (Mayer Rokitansky Juster Hauser Syndrome, MRKH Syndrome)

The most common cause of primary amenorrhea in the presence of normal secondary sexual characteristics is mullerian agenesis, also known as Mayer Rokitansky Kuster Hauser or MRKH syndrome.

In this disorder, all or part of the uterus and vagina are absent and girls present with primary amenorrhea, normal female secondary sexual characteristics, and findings of a blind ending vaginal pouch.

Unlike transverse vaginal septum, these patients do not present with cryptomenorrhea, but like the former a pelvic MRI will make the diagnosis.

A higher risk for urogenital malformation is also associated with the syndrome and should be evaluated once the diagnosis is confirmed.  Treatment involves counseling and emotional support along with the creation of a neovagina through successive vaginal dilation or surgical construction.

Androgen Insensitivity Syndrome

Complete androgen insensitivity syndrome (or AIS) presents similarly to MRKH syndrome, with normal female secondary sexual characteristics, primary amenorrhea and a blind ending vaginal pouch.  However, it is more rare.

In this disorder, genetic males have abnormal androgen receptors, which ultimately leads to an absence of virilization and a female phenotype coupled with scant pubic hair.

Inguinal masses may also be present, representing the underdeveloped testes.  Serum androgen levels and a karyotype are key to distinguishing these two diagnoses.

As in the case of MRKH Syndrome, those with AIS will benefit from counseling, social support and consideration of creation of a neovagina.

Unlike MRKH, gonadectomy should be performed following puberty in those with a diagnosis of AIS to avoid the formation of gonadoblastoma.

Asherman Syndrome  and Cervical Stenosis

Anatomic defects associated with secondary amenorrhea include cervical stenosis and Asherman syndrome, in which the endometrial cavity is scarred.

Historical clues include a prior history of cervical dysplasia requiring multiple excision procedures or postpartum dilation and curettage in the setting of postpartum hemorrhage.

Generally, a diagnosis can be made using physical exam for the former and saline infusion sonohysterogram for the latter.  Treatment usually involves cervical dilation or hysteroscopic lysis of adhesions.

Evaluation

In cases of primary amenorrhea, it is important to assess if and at what age other pubertal milestones have been reached, such as breast and pubic hair development.  A typical exam should also include Tanner staging of breast development and pubertal hair distribution as well as a pelvic exam.

The most important initial step is to determine if there is any clinical or biochemical evidence of estrogen. This can be done through Tanner staging on physical exam (is there breast development?) or response following a progestin challenge test (does the patient bleed after a short course of progestin therapy?).

We can narrow the differential diagnosis further based on the results of 3 additional blood tests: Follicle Stimulating Hormone (FSH), Leutinizing hormone (LH) and Estradiol, which are helpful in determining the causes for both primary and secondary amenorrhea.  The exception to this rule is polycystic ovary syndrome, in which isolated elevations in LH can be seen or a eugonadotropic state can be seen.

The key diagnostic components of an amenorrhea evaluation should include a thorough physical exam along with

• • Serum Pregnancy Test
  • Pelvic ultrasound or MRI
  • Serum FSH, LH, and estradiol
  • Serum fasting prolactin
  • Serum TSH and FT4
  • Brain MRI (to rule out hypothalamic or pituitary space occupying lesion, and to rule in functional hypothalamic amenorrhea)
  • Karyotype (If hypergonadotropic hypogonadism is encountered, or to distinguish between MRKH and AIS)
  • Total Testosterone levels (To rule in PCOS or AIS)

---

References

¹Current evaluation of amenorrhea.  The Practice Committeee of the American Society for Reproductive Medicine.  Fertility and Sterility. 2008. 90(3):S219-S225.

²Fritz M.  Clinical Gynecologic Endocrinology and Infertility.  Philadelphia: Lippincott Williams & Wilkins, 2011.  Print.

³Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.  Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome.  Fertil Steril 2004; 1:19-25.

My name is Jason Yeh
00:02
and I’m in my last year
00:03
of an OBGYN residency
00:04
at Duke University.
00:06
This talk is an overview
00:07
of PCOS.
00:07
00:11
Our objectives are to understand
00:13
the history of PCOS.
00:14
Also, we will talk about how
00:16
the mechanisms of how PCOS
00:17
develops.
00:18
It will also
00:19
be important to discuss how
00:20
to work up and treat PCOS
00:22
and its related co-morbidities.
00:23
00:27
PCOS was first characterized
00:29
in 1935 by Dr. Stein
00:30
and Leventhal.
00:32
They collected a series
00:33
of patients that had
00:33
demonstrated signs and symptoms
00:35
of hirsutism, obesity,
00:37
amenorrhea, and oligomenorrhea.
00:39
They also had polycystic ovaries
00:41
and because of this it was felt
00:42
that this was probably the cause
00:44
of their problems.
00:45
It was later found
00:46
that these women had
00:47
menstrual cycles restored
00:48
with partial ovarian resections,
00:50
and therefore, PCOS really stuck
00:52
as the name and likely cause
00:53
of the disease.
00:54
However, since then we’ve
00:55
realized that having
00:56
polycystic ovaries
00:58
is not necessary.
00:59
And some patients don’t have
01:00
the ovarian findings
01:01
but have everything else.
01:03
Therefore, lots of meetings
01:04
have been made to secure
01:05
a good definition of PCOS.
01:08
In 1990 the NIH decided that you
01:10
need all three to diagnose PCOS
01:12
which include,
01:13
oligoovulation, signs
01:15
and symptoms of androgen excess,
01:18
and you need to exclude
01:19
other things that could cause
01:20
PCOS.
01:21
In 2003 a meeting in Rotterdam
01:23
suggests that you need two
01:24
of three things
01:25
to diagnose PCOS.
01:26
Those are,
01:27
oligoovulation/anovulation
01:30
excess androgen activity,
01:32
or polycystic ovaries
01:33
by ultrasound.
01:35
Of no polycystic ovaries can be
01:36
diagnosed with 12 or more
01:38
follicles in one ovary, with
01:39
follicles ranging anywhere from
01:41
2 to 9 millimeters, and/or
01:43
an increase of total ovarian
01:44
volume greater than 10 cc’s.
01:46
01:49
First it’s important to say
01:50
that no one is entirely
01:51
clear what starts the PCOS
01:53
process.
01:54
But in order to understand how
01:55
PCOS may come about we
01:57
need to talk about the two cell
01:58
and two gonadotropin theory.
02:00
The key players are
02:01
follicle stimulating hormone,
02:02
FSH, and luteinizing hormone,
02:04
LH, which are released
02:05
from the gonadotropes
02:06
in the anterior pituitary
02:08
of the brain.
02:09
Imagine a sphere shaped follicle
02:11
with an outside cell layer
02:12
and an inside cell layer.
02:14
There is also a basement
02:15
membrane in between.
02:16
The cells on the outside
02:18
are the theca cells, which have
02:20
LH receptors.
02:21
There’s also another layer
02:22
of cells on the inside
02:23
of the membrane called granulosa
02:24
cells, which have FSH receptors.
02:27
So the key to understanding this
02:29
is that the two cells work
02:30
together to convert cholesterol
02:31
to estrogen. First,
02:33
LH stimulates the theca
02:35
cells, which responds by taking
02:36
cholesterol
02:37
and converts it to androgens,
02:39
specifically
02:40
testosterone and
02:40
androstenedione.
02:42
There is no significant amount
02:43
of aromatase in the theca cells
02:45
so the process of conversion
02:46
stops at the androgen level.
02:49
Then the antigens are then
02:50
small enough to cross
02:52
the membrane
02:52
and get into the granulosa
02:53
cells.
02:54
These granulosa cells respond
02:56
to FSH and have lots
02:58
of aromatase, which then allows
03:00
the conversion of androgen
03:01
to estrogen. So ultimately,
03:03
the process of converting
03:04
cholesterol to estrogen
03:05
requires two cells and two
03:07
separate hormones.
03:08
If you have a defect
03:09
in either cell, you don’t have
03:11
a balanced process.
03:13
So now that we’ve established
03:14
how the synthesis of androgens
03:16
and estrogens happens
03:17
we can talk about how PCOS
03:18
starts.
03:19
No one really knows what starts
03:20
the process but it’s believed
03:22
that it’s caused
03:23
by a poor balance of FSH to LH.
03:26
On one hand, if you have too
03:27
much LH secretion
03:29
you have ovarian theca cells
03:30
stimulated to make androgens.
03:32
Lots of LH, therefore, makes
03:34
lots of androgens, and overloads
03:35
the capacity of the granulosa
03:37
cells
03:37
to aromatize into estrogens.
03:40
On the other hand, it may also
03:41
be possible that there is not
03:42
enough FSH and therefore
03:44
your conversion to estrogen
03:45
is too slow
03:46
and you get a back-up
03:47
and build-up of androgens.
03:48
When you don’t have
03:49
enough estrogen a woman
03:50
may progress to anovulation,
03:52
which
03:52
is an important characteristic
03:54
of PCOS.
03:54
03:58
PCOS is one of the most
03:59
common disorders
04:00
in endocrinology.
04:02
In the USA it affects anywhere
04:03
from 4% to 12% of people.
04:05
In Europe is probably closer
04:06
to 6% to 8%.
04:08
If you remember the way you
04:09
diagnose it
04:10
from the first slide,
04:11
there are not a lot
04:12
of specific clinical features.
04:14
This is meant to provide lots
04:15
of flexibility in the diagnosis,
04:17
therefore,
04:17
the physical presentation
04:18
is very varied.
04:20
For example, if an Asian
04:22
and Caucasian have the same
04:23
hyper androgen levels, the Asian
04:25
will, overall, have much less
04:27
hair.
04:28
Also, people think that PCOS
04:29
patients need to be obese
04:31
but there is also
04:31
a non-obese type
04:33
of presentation.
04:34
Also, the inheritance for PCOS
04:36
is unclear
04:37
but a few familial studies
04:38
suggest that it may actually
04:40
be autosomal dominant.
04:41
Unfortunately, there are
04:42
no specific genes that have been
04:43
identified that definitely
04:44
caused PCOS.
04:45
04:49
Although people can present
04:50
with varied symptoms, there’s
04:51
a typical presentation
04:52
for the average PCOS patient.
04:54
Most patients are obese,
04:56
they typically have
04:56
oligomenorrhea, which means
04:58
bleeding less
04:58
frequent than the normal woman
05:00
with a cycle length between 35
05:01
days and six months.
05:03
They could also have
05:03
secondary amenorrhea, which
05:05
is no bleeding for six months.
05:06
They also have symptoms
05:08
of hyperandrogenism,
05:09
such as deepening voice,
05:11
clitoromegaly, acne, and
05:12
abnormal or excessive hair
05:14
growth.
05:14
05:17
Once you’ve suspected PCOS
05:19
you need to rule out
05:20
all other diseases that could be
05:21
confusing and confounding
05:22
the clinical picture.
05:24
Congenital adrenal hyperplasia
05:25
is a disease where there is
05:27
a defective 21-hydroxylase
05:29
enzyme.
05:30
This deficiency is a defect
05:31
in the steroid hormone pathway.
05:33
Some cases are so severe that it
05:35
presents as a newborn,
05:36
but when the enzyme is not
05:37
entirely defective,
05:38
and it partially works,
05:39
the disease can actually present
05:40
later in life
05:41
in the early reproductive years.
05:43
When the enzyme is defective
05:45
steroid precursors build up.
05:46
So if you look
05:47
at your steroid hormone pathway,
05:49
the precursors that build up
05:50
are progesterone,
05:51
17-hydroxypregnenolone,
05:54
17-hydroxyprogesterone.
05:56
Blood levels of 17-OHP
05:58
can reach up to 10 to 1,000
06:00
times the normal concentration.
06:01
These excess precursors actually
06:03
overload the entire system
06:05
and result
06:05
in excessive synthesis
06:06
of androgens.
06:07
When it presents later in life
06:09
the elevated precursor levels
06:10
are sometimes not
06:11
detectable until, or unless, you
06:13
run a cosyntropin or ACTH
06:15
stimulation test.
06:17
Cushing syndrome can also result
06:19
in suspected PCOS.
06:21
A common way to test for this
06:23
is to run
06:23
a urine-free cortisol level.
06:26
There are many ways of testing
06:27
for this but this happens to be
06:28
one of the easiest ways.
06:30
Hyperprolactinemia needs to be
06:31
ruled out as well.
06:32
This can be accomplished
06:33
with a fasting prolactin level,
06:35
and if elevated,
06:36
you’ll need to look for causes,
06:37
which include prolactinomas
06:38
in the brain.
06:39
Androgen levels also need to be
06:41
checked to make sure there isn’t
06:42
a tremendous elevation that
06:43
would suggest
06:44
an androgen secreting tumor.
06:46
Next, the LH and FSH levels
06:48
could also be checked to rule
06:49
out the possibility
06:50
of premature ovarian failure.
06:52
In PCOS LH is typically elevated
06:54
because most people think
06:55
that is, again, what causes
06:57
the excessive theca cell
06:58
stimulation and androgen excess.
07:01
A glucose tolerance test should
07:02
also be done to look
07:03
for undiagnosed diabetes,
07:05
because a hallmark of PCOS
07:06
is actually insulin resistance.
07:08
And levels become very, very
07:10
high.
07:10
Women with PCOS
07:11
often have diabetes as well as
07:14
the need to be treated
07:15
to prevent all the bad outcomes
07:16
associated with diabetes,
07:17
such as renal disease,
07:19
cardiovascular disease, eye
07:21
disease, et cetera.
07:22
Also, imaging studies can also
07:24
be helpful if there is something
07:25
you suspect
07:26
or if there is a need to image
07:27
the uterus
07:28
or ovaries to identify
07:29
any tumors or cysts.
07:30
07:33
So although there is no cure
07:34
for PCOS, there are a few very
07:37
important goals for treatment.
07:38
We will talk about how to do
07:40
this specifically
07:40
in the next slide.
07:41
In general, though, the goals
07:43
are as follows.
07:44
The first goal is to prevent
07:45
endometrial cancer.
07:47
Next, a clinician should also
07:48
try to lower insulin levels
07:49
and either to diagnose
07:51
or prevent diabetes.
07:53
Also, it is important to give
07:54
these patients a chance
07:55
for fertility restoration
07:56
when they are ready to start
07:57
a family, since infertility is
07:59
very common among PCOS patients.
08:01
Lastly, treatment of hirsutism
08:03
and acne
08:04
is often one of the most
08:05
frequent complaints that brings
08:06
patients to the clinic to begin
08:07
with,
08:08
so it’s important to address
08:09
this.
08:10
08:13
Treatment of PCOS
08:14
is a multimodal process
08:15
and requires an attack on all
08:17
the different symptoms
08:18
and disease processes.
08:20
First, lifestyle modifications
08:22
is one thing we would recommend
08:23
to many patients.
08:25
Patients are often anovulatory
08:26
because of complex interactions
08:28
of insulin and imbalanced
08:29
gonadotropins.
08:31
What is interesting
08:31
is that diet and exercise that
08:33
leads to,
08:34
even a modest 5% weight loss,
08:36
is usually enough to resume
08:37
normal menstrual function.
08:39
The second
08:40
is endometrial protection.
08:42
This is very important
08:43
because patients who don’t have
08:44
regular cycles
08:45
are at very high risk
08:46
of developing
08:46
endometrial cancer.
08:48
The goal is, therefore,
08:49
to resume
08:49
normal menstrual cycles,
08:51
or at least give
08:52
medications enough to stabilize
08:54
the endometrium.
08:55
PCOS is a state
08:56
of excess of estrogen and not
08:57
enough progestins.
08:59
The endometrium doesn’t have
09:01
a chance to shed monthly,
09:02
therefore, these patients
09:04
require medications to prevent
09:05
endometrial hyperplasia that can
09:07
turn into endometrial cancer.
09:09
This can be accomplished
09:10
with oral contraceptives,
09:11
or OCP’s, progestin only pills,
09:13
a progestin secreting IUD,
09:15
progesterone injections,
09:16
et cetera.
09:19
Number three,
09:19
another common intervention
09:20
is to give OCP’s, or
09:21
oral contraceptives, for PCOS.
09:23
This is done because, number
09:24
one, it has enough progestin
09:26
to protect the endometrium
09:28
against cancer in the future.
09:29
And two, OCP’s increase a sex
09:31
hormone binding globulin which
09:33
then binds to androgens,
09:34
and overall will decrease
09:35
the free testosterone levels
09:37
to improve acne and hirsutism.
09:41
Next, when PCOS patients need
09:42
to get pregnant they usually
09:43
require help.
09:45
The most common way of inducing
09:46
ovulation
09:46
is the use of clomiphene citrate
09:48
and metformin, together.
09:50
The way this works
09:50
is a bit beyond the scope
09:51
of this talk
09:52
but if you’re interested, please
09:53
look into it
09:53
and see how the medication
09:54
works.
09:56
Hirsutism and acne is treated
09:58
in a variety of ways, none
09:59
of which are permanent.
10:01
We already talked about how
10:02
OCP’s work, other treatments
10:03
include lasers and electrolysis,
10:06
also, creams and Retin-A
10:07
are used for acne treatment.
10:10
Diabetes is often
10:11
a co-morbid diagnosis with PCOS.
10:13
And if you treat it like you
10:15
treat non-PCOS patients
10:16
that usually works out pretty
10:17
well.
10:18
Because insulin resistance is
10:20
a part of the PCOS
10:21
pathophysiology, metformin
10:23
is usually first line since it
10:25
increases insulin sensitivity.
10:27
Insulin regimens are added
10:28
if oral medications are not
10:29
sufficiently effective.
10:31
Lastly, an interesting treatment
10:32
is something called ovarian
10:33
drilling, where you do
10:35
laparoscopy to poke holes
10:37
in the ovary
10:37
with electrocautery instruments.
10:40
It’s not completely understood
10:41
why this works but it’s done
10:42
when PCOS was diagnosed,
10:45
and wedge resections
10:45
of the ovary
10:46
were done
10:47
for histologic analysis.
10:48
It was noted at that time
10:49
that these women, oftentimes,
10:51
started having normal cycles.
10:52
So ovarian drilling is just
10:54
a less morbid, and technically
10:55
easier, version of wedge
10:56
resection.
10:57
11:00
I will conclude this talk
11:01
with a list of all
11:02
the associated risks of PCOS
11:04
and why it’s so important
11:05
that you need to treat
11:05
the different aspects of such
11:07
a multimodal disease.
11:08
This slide is pretty
11:09
self-explanatory so there’s
11:10
no need to talk
11:11
through each one.
11:12
But just know that if PCOS is
11:13
left untreated
11:14
it can lead to very significant
11:16
multiorgan system disease.
11:17
11:54
Thank you for your attention.

hey guys so today I wanted to share my
00:06
PCOS story I believe I started to
00:09
showing signs of PCOS when I was as
00:13
young as seven years old because at that
00:15
time I had developed body hair armpit
00:18
hair and pubic hair and I noticed that
00:22
my peers didn’t so I felt really really
00:24
self-conscious and when I say I had hair
00:26
I don’t mean like it was just coming in
00:28
I mean like it was full-on bushy but I
00:31
was so ashamed that I didn’t tell anyone
00:33
and my mom didn’t find out until about a
00:35
year and a half to two years later when
00:37
another family member saw and it
00:40
eventually made its way to my mom and so
00:43
she decided that she didn’t want me
00:45
shaving instead she purchased Mayer and
00:47
that’s what I used at the age of 10 I
00:50
got my first period and I don’t think
00:52
anybody could have prepared me for that
00:55
moment that was so excruciating and it
00:57
was so heavy but at the time I didn’t
00:59
know it because it was my first period
01:02
and I I didn’t know how periods were
01:06
supposed to be or how they were supposed
01:08
to feel after I got my first period it
01:10
wasn’t showing up every month and when
01:13
it would show up it would last for about
01:15
15 days and it was excruciating I was in
01:19
so much pain I was vomiting I would be
01:24
sent home from school I would stay home
01:26
from school I would leave school all the
01:29
time because of my periods and it really
01:32
interferes with my life and it made me
01:34
really self-conscious and then when I
01:38
was 12 I started developing body hair in
01:43
places that women are not supposed to be
01:45
particularly on my face and I did tell
01:49
my mom about that but she gonna just
01:51
brush me off and got me some hair bleach
01:53
and that’s what I used until I turned 15
01:57
because as the years went on the hair
02:01
got darker and denser and bleaching that
02:05
hair was not gonna hide it from anyone
02:07
in fact I remember being in high school
02:10
and some jerk
02:12
blurted it out in front of everyone and
02:15
at that moment I thought I was hiding it
02:17
so looking back I know I wasn’t I know
02:20
that more people saw and I’m grateful
02:22
that they didn’t say anything but it
02:25
really made me feel bad but I was never
02:29
taken to the doctor uh when I was
02:31
younger my periods weren’t coming every
02:33
month I did tell my mom and for some
02:36
reason she thought I was and so she kind
02:37
of again she brushed me off and so I was
02:40
kind of alone in this when I was 15 I
02:43
decided to get a job and I got my first
02:47
job and with my money I chose to buy wax
02:51
and so I started waxing my face and I
02:54
hated having to do it but I I felt like
02:58
there was no getting around it because
03:00
you know nobody’s gonna take me to the
03:01
doctor I just have to put up with the
03:04
symptoms my skin was really bad
03:07
Mike’s again is still back to this day
03:10
and I still have to baby it but I kind
03:14
of thought you know puberty acne and all
03:17
those hand-in-hand but I was getting
03:18
cystic acne and that was my normal and
03:21
so I just continued using the wax and
03:26
the acne cream until I could get myself
03:28
into a doctor and so when I was 18 maybe
03:34
I was 19 I made an appointment and I
03:39
told the doctor everything and it took
03:42
so much in me to come out and admit and
03:45
to even acknowledge that there’s
03:47
something wrong this is not normal it
03:50
took everything in me to make that
03:52
appointment because I felt so incredibly
03:55
ashamed and growing up I was always told
03:58
oh it’s because you’re polish you know
04:00
your dad sided their hairy people and
04:02
but I never felt like that was the right
04:05
answer so I went to the doctor and I
04:08
told her that I was getting really bad
04:10
acne that I was getting cystic acne all
04:12
over my face I told her that I was
04:16
growing hair in abnormal places but I
04:18
was getting my periods every month at
04:21
that time so she sent me off to go get
04:24
some blood work done and not my fault of
04:25
appointment
04:26
she told me that my hormone levels are
04:30
normal and then it must be because I am
04:32
polish
04:33
I cannot even express how disappointing
04:37
it was to hear that because there are
04:40
people who are the same ethnicity as me
04:43
and nowhere near as hairy as I am but I
04:47
let it get to me and I let it go I I
04:49
felt like well there’s nothing I can do
04:53
and it wasn’t until earlier this year
04:56
that my periods once again stopped
04:58
coming every month and when they were
05:00
coming it was awful
05:03
once again I scheduled an appointment
05:05
and I went to my OB office and I saw
05:10
nurse practitioner and she decided to
05:13
put me on birth control to at least get
05:16
a period coming hopefully to kind of
05:19
help with the hair growth but she
05:22
instructed me to go see an internal
05:24
medicine doctor so that’s what I did at
05:27
my first appointment I walked out with
05:31
like two pages of blood work to get done
05:34
ranging from thyroid to hormone to check
05:39
for diabetes everything so I went and I
05:44
got that blood work done and when I came
05:47
back to review and when I came back to
05:50
review the results for that blood work I
05:52
found out that I had Hashimoto’s which
05:56
is an autoimmune disease and my
05:59
testosterone was way too high
06:01
on my test zero to ten is normal for a
06:05
woman mine was seventeen point six which
06:08
is almost double and so we decided to go
06:12
ahead and do some further testing so I
06:14
got a cat scan to look at other other
06:17
things but for me I wanted to know if I
06:22
had two cysts on my ovaries and I did so
06:27
I deal with everything so if you’re on
06:34
this video you’re probably familiar with
06:36
the Rotterdam criteria where you need to
06:39
have two of the three so
06:40
thumbs that are excess androgen levels
06:43
irregular period and cysts on your
06:48
ovaries and I have all three so this is
06:52
quite the struggle and that’s when she
06:55
my doctor decided to put me on metformin
06:58
so I’m currently on metformin I’m hoping
07:00
that it works I I don’t know I don’t
07:06
know if it’ll work but I just wish that
07:08
I would have gotten into a doctor a lot
07:09
sooner I wish I had better guidance as a
07:12
child to to figure out what was wrong
07:17
with me a lot sooner you know there’s a
07:19
lot of frustration with that but you
07:23
know I’m an adult now and I need to take
07:25
care of myself so that’s my story
07:28
I know I’m not the only one that’s gone
07:31
done diagnosed with PCOS for a long time
07:36
I know there were women out there that
07:38
are even now are not diagnosed and I
07:42
just hope that they can find a doctor
07:44
that will listen to them and who won’t
07:47
just brush it off anyways so that’s all
07:52
that I have for today
07:53
if you have any comments or any
07:55
questions let me know I would love to
07:58
answer them and I will see you guys next
08:01
video bye