Transcript Polycystic Ovary Syndrome PCOS A diagnosis oriented approach

Dr . Mouna Dakar
 The
association of amenorrhea with bilateral polycystic
ovaries was first described in 1935 by Stein and Levental
and was known for decades as Stein-Levental syndrome .
 In the past the clinical diagnosis rested on the triad of
hirsutism , amenorrhea and obesity.
‫ً‬
‫املرض الغدي األكثر شيوعا عند السيدات في سن النشاط ‪‬‬
‫التناسلي‪.‬‬
‫‪‬موجود عند ‪ %95‬من السيدات اللواتي يراجعن العيادات‬
‫الخارجية من أجل الشعرانية ‪.‬‬
‫‪‬معدل انتشاره ً‬
‫بناء على أرضية سريرية ‪ % 10 – 5‬من‬
‫السيدات في سن النشاط التناسلي ‪.‬‬
‫‪Poly genic – Oligogenic : Genetic ‬‬
‫ مورثة األنسولين – مورثات الخمائر املشمولة في إنتاج الستيروئيدات ‪.‬‬‫‪Hyper androgenism ‬‬
‫ املصدر الرئيس لالندروجين هو مبيض ي‬‫ يوجد مصدر كظري في ‪ 25%‬من الحاالت‬‫‪Hyper Insulinaemia ‬‬
Defect in Insulin receptor gene -Hyperglycemia
‫‪ - ‬حالة مرضية ال تستجيب الخاليا الهدفية إلى املستويات الطبيعية‬
‫لألنسولين ‪.‬‬
‫‪ : ADA ‬ضعف االستجابة االستقالبية لألنسولين الداخلي والخارجي املنشأ‬
‫شاملة أي من األفعال الحيوية لألنسولين ‪.‬‬
 Decreased
no. of insulin receptors on surface of
target cells
Reduced abundance of insulin receptor mRNA
Impaired transport of receptors to cell surface
Truncated receptor protein
Accelerated receptor degradation
 Defect
in receptor function
Decreased binding affinity for insulin
Decreased insulin stimulated tyrosine kinase
activity of receptor
 Insulin
is a growth factor for the ovary
 Women who are obese sometimes have
insulin resistance (it takes higher and higher
insulin levels to keep glucose in the normal
range)
 Fat cells are insulin resistant, but the ovaries
are not
INSULIN &
OVARY
• Human ovaries have insulin receptors
• Insulin stimulates ovarian androgen production by
directly activating insulin receptors in PCOS subjects
(genetic predisposition)
• Insulin has no effects on androgen production in
normal woman
LH secretion
in IR
Insulin receptors present in pituitary
LH secretory dynamics is changed by
hyperinsulinemia
LH Pulse – Frequency and Amplitude is increased
LH has been shown to act synergistically with
Insulin to promote the production of Androgen by
Ovaries
‫‪ %70 ‬من السيدات املصابات بالـ ‪ pco‬عندهن مقاومة‬
‫لألنسولين بينما يصيب ‪ % 25 – 10‬من السكان بشكل‬
‫عام ‪.‬‬
‫‪‬يبدو أن املقاومة لألنسولين انتقائية (عضالت – كبد –‬
‫نسيج شحمي ) ال تشمل املبيضين ‪.‬‬
‫‪‬تتفاقم املقاومة لألنسولين بالبدانة ‪-‬ولكن ‪ %17‬من‬
‫النحيالت املصابات بالـ ‪ pco‬عندهن مقاومة‬
‫لألنسولين ‪.‬‬
 PCOS
is one of the
most common human
endocrinopathies,
affecting 5–10% of
women of
reproductive age.
 However , PCO
diagnosed by TVS
affects 20-25% of
women.
Hirsutism 70%
Obesity 40-50%
Regular 25%
Infertility 70%
Oligo 51.5%
Menstrual cycle
IGT & DM
IGT 33%
Obese
DM 7.5-10%
IGT 10%
DM 1.5%
IGT 7.8%&DM 1% in normal people
Ameno 23%
Non-obese
Essential update: AACE/ACE and AESSociety release
new guidelinesIn November 2015, the American
Association of Clinical Endocrinologists (AACE),
American College of Endocrinology (ACE), and
Androgen Excess and PCOS Society (AES) released
new guidelines in the evaluation and treatment of
PCOS.[1] Among their opinions and
recommendations are the following[1] :
The major features of PCOS include
menstrual dysfunction, anovulation, and
signs of hyperandrogenism.[2] Other signs
and symptoms of PCOS may include the
following:HirsutismInfertilityObesity and
metabolic syndromeDiabetesObstructive
sleep apnea
Menstrual abnormalities
Menstrual abnormalitiesPatients with PCOS have
abnormal menstruation patterns attributed to
chronic anovulation. Some women have
oligomenorrhea (ie, menstrual bleeding that
occurs at intervals of 35 days to 6 months, with
< 9 menstrual periods per year) or secondary
amenorrhea (an absence of menstruation for 6
months).
Around 25% of women with confirmed PCOS still have regular
menses.
 21% of hyperandrogenic anovulatory women have regular
menses.
 The presence of regular menses does not rule out the diagnosis
of PCOS.
 Just over the half of patients with PCOS have oligomenorrhea.
About 25 % of PCOS patients have amonorrhea.
 The reason for menstrual disturbance are the effect of
androgens on the endometrium as well as the increased levels
of esteron that comes from the peripheral aromatization of
increased androgens to esteron which stimulates the
endometrium to proliferates.

Hyperandrogenism
70%
PCOS is the most common cause of
hyperandrogenism and hirsutism.
Hyperandrogenism clinically manifests as
excess terminal body hair in a male distribution
pattern. Hair is commonly seen on the upper
lip, on the chin, around the nipples, and along
the linea alba of the lower abdomen. Some
patients have acne and/or male-pattern hair
loss (androgenic alopecia).
ANDROGENS
Terminal hair
Vellus hair
DHT
Thin
Soft
Non-pigmented
5 α reductase
Testosterone
Coarse
Stiff
Pigmented
long
Hirsutism is a sign of increased
androgen action on hair follicles, from
increased circulating levels of
androgens or increased sensitivity of
hair follicles to normal levels of
.circulating androgens
Female pattern baldness
Male pattern baldness

1.
2.
3.
4.
5.

The major Androgen in women are :
Testosterone.
Dihydrotestosterone ( DHT).
Androstendione.
Dehydroepiandrosterone ( DHEA ).
Dehydroepiandrosterone Sulfate ( DHEA-S).
Testosterone is the principal circulating androgen in
normal women.
 There
are three
sources of androgen :
Peripheral conversion
Adrenals
The Ovaries
The ovaries
Adrenals
25%
25%
Testosterone
Androstendion
50%
Peripheral conversion
DHEA
About 70% of PCOS patients may
have different degrees of
subfertility due to anovulation.
Group 2 WHO classification.
Conception may take longer than in other
women, or women with PCOS may have fewer
children than they had planned. In addition,
the rate of miscarriage is also higher in
affected women.
40-50%
Not all PCOS patients are obese
Obesity and metabolic syndrome
Many patients with PCOS have characteristics of
metabolic syndrome; one study showed a 43%
prevalence of metabolic syndrome in women with
PCOS.[25] In women, metabolic syndrome is
characterized by abdominal obesity (waist
circumference >35 in), dyslipidemia (triglyceride
level >150 mg/dL, high-density lipoprotein
cholesterol [HDL-C] level < 50 mg/dL), elevated
blood pressure, a proinflammatory state
characterized by an elevated C-reactive protein
level, and a prothrombotic state characterized by
elevated plasminogen activator inhibitor-1 (PAI-1)
and fibrinogen levels.[2
Male pattern obesity
android obesity
Female pattern obesity
NO PCO/PCOS
YES there is PCO
Diabetes mellitus
ACOG recommends screening for type 2
diabetes and impaired glucose tolerance in
women with PCOS by obtaining a fasting
glucose level and then a 2-hour glucose level
after a 75-g glucose load.[4] Approximately
10% of women with PCOS have type 2 diabetes
mellitus, and 30-40% of women with PCOS have
impaired glucose tolerance by 40 years of age.
Sleep apnea
Many women with PCOS have obstructive sleep
apnea syndrome (OSAS), which is an
independent risk factor for cardiovascular
disease.[5] Ask these patients and/or their
partners about excessive daytime somnolence;
individuals with obstructive sleep apnea
experience apnea/hypopnea episodes during
sleep.[40, 41] For women with PCOS with
suspected OSAS, there should be a low
threshold for referral for sleep assessment.
 Unopposed
estrogen secretion promots endometrial
hyperplasia
 Several
studies have shown that this results in a 2-4
fold excess risk of endometrial carcinoma in
females with PCOS



1.
2.
3.

Increased risk of type 2 D.M.
Increased cardiovascular disease risk.
Increased risk of the following malignancies :
Endometrial carcinoma.
Ovarian carcinoma.
Breast carcinoma.
Increased risk of recurrent pregnancy loss correlated
with increased LH levels.
The diagnostic criteria for PCOS
should include one of the
following three criteria:
chronic anovulation,
hyperandrogenism
(clinical/biologic), and
polycystic ovaries
Use the Rotterdam criteria for diagnosing
PCOS (presence of 2 of the following:
androgen excess, ovulatory dysfunction, or
polycystic ovaries).
 The
absence of PCO on ultrasound does not rule out
the diagnosis of PCOS.


1.
2.
3.



Ovarian morphology remains the most sensitive
marker for the PCOS.
There are ultrasound criteria to diagnose the PCO :
Increased ovary area/volume.
10-15 microcysts less than 10 mm organized in a
peripheral rosary pattern. (generally > 5 cysts)
Increased echogenicity of ovarian stroma.
Transvaginal sonography (TVS) is the gold standard
and the most sensitive method to detect PCO.
The presence of PCO does not mean that the
patient has PCOS.
Around 20-25% of women have PCO detected by TVS
, only about 5-10% have PCOS.
A woman is diagnosed with polycystic
ovaries (as opposed to PCOS) if she has 12
or more follicles in at least 1 ovary
Echodense “white” ovarian stroma
Microcysts in the periphery of the ovary
Microcysts
Multifollicular ovaries (MFO) were first described by Adams and
colleagues in 1985, and are encountered in mid to late normal
puberty, hyperprolactinaemia, hypothalamic anovulation and
weight-related amenorrhoea.
 They differ from PCO, having fewer cysts (6–10 per ovary),
which tend to be larger (up to 10 mm in diameter) and
distributed throughout the ovary with no stromal hypertrophy.
 MFO result from incomplete pulsatile gonadotrophin (GnRH)
stimulation of ovarian follicular development .
 MFO resume a normal appearance following weight gain or
treatment with pulsatile GnRH, whilst PCO retain their
appearance throughout reproductive life, irrespective of time
of cycle, pregnancy or drug treatment, and women with MFO
have normal levels of LH and T and reduced levels of follicle
stimulating hormone (FSH) compared with women with PCO.

.Transvaginal image of a multifollicular ovary
Ovarian stroma is not echodense
Follicle
Confirmation of diagnosis
 Testosterone
 LH
concentrations
concentrate
 Pelvic
US of ovaries and endometrium.
Free testosterone levels are
more sensitive for determining
androgen excess than total T
levels and should be obtained
with equilibrium dialysis
techniques
In addition to clinical findings,
obtain levels of serum 17hydroxyprogesterone and antiMüllerian hormone to aid the
diagnosis of PCOS.

1.
2.
3.
4.
The hypothalamic pituitary compartment also participates
in aspects critical to the development of PCOS.
An increase in the LH pulse frequency is the result of
increased pulse frequency of GnRH.
This increase in LH pulse frequency results typically in
elevated LH to FSH ratio.
FSH is not increased with LH, probably because of the
synergistic negative feedback of chronically elevated
estrogen level and normal follicular Inhibin.
About 25% of patients with PCOS exhibit elevated PRL levels
. This may result in abnormal estrogen feedback to the
pituitary gland. In some patients with PCOS , bromocriptine
has reduced LH levels and restored ovulation.
Lifestyle modifications are considered
first-line treatment for women with
PCOS. Such changes include the
following[3, 4] :Diet
Exercise
Weight loss
treatments are reserved for so-called metabolic
derangements, such as anovulation, hirsutism, and
menstrual irregularities. First-line medical
therapPharmacotherapyPharmacologic y usually
consists of an oral contraceptive to induce regular
menses.If symptoms such as hirsutism are not
sufficiently alleviated, an androgen-blocking agent
may be added. First-line treatment for ovulation
induction when fertility is desired is clomiphene
citrate.[3
Medications used in the management of PCOS
include the following:Oral contraceptive agents
(eg, ethinyl estradiol, medroxyprogesterone).
Antiandrogens (eg, spironolactone, leuprolide,
finasteride).
Hypoglycemic agents (eg, metformin, insulin).
Selective estrogen receptor modulators (eg,
clomiphene citrate)
In October 2013, the Endocrine Society released
practice guidelines for the diagnosis and
treatment of PCOS.
The following were among their conclusions
In adolescents with PCOS, hyperandrogenism is
central to the presentation; hormonal
contraceptives and metformin are treatment
options in this population.
Postmenopausal women do not have a
consistent PCOS phenotype.
For menstrual abnormalities and hirsutism/acne,
hormonal contraceptives are first-line treatment.
For infertility, clomiphene is firstline treatment
.For
metabolic/glycemic abnormalities and for
improving menstrual irregularities, metformin
is beneficial.Metformin is of limited or no
benefit for managing hirsutism, acne, or
infertility.
Good Luck