Polycystic Ovarian

Syndrome
CHAUDHARY,JITENDRA
(PGI)
 Polycystic Ovarian Syndrome

• 1st described by Irving Stein and Michael Leventhal as a

triad of amenorrhea, obesity and hirsutism (1935)

• He observed the relationship between obesity and reproductive

disorder, what is now known as the “syndrome O” (over-
nourishment, overproduction of insulin, ovarian confusion, and
ovulation disruption).

• Since then, this condition is considered to be the most common

endocrine disorder of pre-menopausal women, affecting an
estimated 5% of the population.
 PCOS Presentation

• PCOS is heterogeneous endocrine disorder, a syndrome

not a disease, in which no single criterion is sufficient for
diagnosis due to the multiple etiologies and presentations.

• Defining characteristics include menstrual dysfunction,

hyperandrogenism, ovarian morphology on Ultrasound,
with the exclusions of other endocrine abnormalities
(Cushing’s syndrome, thyroid abnormality, hyper-
prolactinemia, etc.).
 Etiology & Pathopysiology

• Abnormal gonadotropin secretion

– Excess LH and low, tonic FSH

• Hypersecretion of androgens
– Disrupts follicle maturation
– Substrate for peripheral aromatization

• Negative feedback on pituitary

– Decreased FSH secreation

• Insulin resistance, Elevated insulin levels

 Pathology

• Ovaries:
enlarged and/or polycystic ovaries

• Endometrium: Lack of ovulation for an extended

period of time may cause excessive thickening of the
endometrium (the lining of the uterus).
 PCOS Symptoms and Signs
• Two of the following symptoms:
–Polycystic ovaries (PCOS)
–Hyperandrogenism
–Anovulation
No single criteria is sufficient for clinical diagnosis.

• Additional features may include:

Excessive hair growth Abnormal bleeding
Obesity Hair loss
Acne
Infertility
 PCOS Presentation

• NIH-Sponsored Conference on PCOS (1990

Criteria)

• Rotterdam ESHRE/ASRM-Sponsored PCOS

Consensus Workshop Group (2003 Criteria)
Comprhensive gynecology, 7th edition
Symptoms

• Hirsutism : Excessive
body hair. In women with
PCOS dark, coarse hair
will appear on the face,
neck, chest, arms, and
in between the legs.
Symptoms

• Weight Problems :
Depending on the
woman, there could
be a decrease of
weight or a rapid
fluctuation of weight
that settles around
the stomach that will
lead to morbid
obesity.
Symptoms

• Acne : Because
women with PCOS are
producing more male
hormone, that
produces more sebum
( skin oils and old
tissue) and causes
blocked pores and
more acne around the
jawline, arms and
chest.
 Genetic Link
• Familial clustering of PCOS commonly
– 1st degree relatives of patients with PCOS may be at
high risk for diabetes and glucose intolerance
– Mothers and sisters of PCOS patients have higher
androgen levels than control subjects

Heritability: Due to the observable trends within families

concerning insulin resistance, the question remains
whether PCOS has a genetic connection. For instance,
first degree relatives inherit B-cell dysfunction (secretory
deficits).
 PCOS: Metabolic Disorder
• Insulin Resistance
– High association with PCOS
– 10% have Type 2 Diabetes
– 30%-35% have Impaired Glucose Tolerance (IGT)

• Obesity
– 50% of PCOS patients are obese
– Amplifies biochemical and clinical abnormalities of
PCOS
 PCOS: Metabolic Disorder

• Endometrial Cancer
 Due to the high estrogen levels and lack of normal
ovulation cycles, there is a risk for endometrial cancer in
PCOS women.

 Endometrial cancer-described as early as 1949 by

Speer : cystic ovaries and EC-persistent estrogen
stimulation; hyperplasia-lack of differentiation to
secretory endometrium. Prolonged stimulatory effect of
estrogen with unopposed inhibition by progesterone.
 PCOS: Metabolic Disorder

• Cardiovascular Disease :
 Putting into consideration the rates of insulin resistance
and obesity together plus the complications of high blood
pressure and increased lipids values;

 PCOS patients are also at risk for CVD. CVD-

associated with both increase in androgen and increase
in levels of inflammatory cytokines-IL6, TNF alpha-
increased lipids, BP, obesity, IR-associate with CVD.
Higher BMI-greater risk for both conditions.
 PCOS: Metabolic Disorder
• Sleep Apnea
– Increased Sleep Disordered Breathing (SDB) and
daytime sleepiness in PCOS

• Depression
– Higher prevalence in PCOS patients, associated
with higher body mass index (BMI, P=0.05) and
greater insulin resistance (P=0.02)
 Pregnancy Complications

• Spontaneous Abortions
– Increased in high BMI/PCOS patients

• Gestational Diabetes

• Hypertension

• Small for Gestational Age

 Infertility

• >75% of women with anovulation infertility

• Franks and colleagues suggested that over 75% of the
patients with anovulation were PCOS patients.
• PCOS involves primary ovarian dysfunction. This
intrinsic ovarian abnormality caused an increased
density of small preantral follicles, primordial not
different, same for ovulatory and anovulatory.
• Early follicular growth is excessive since the selection of
1 single follicle from the follicular pool to mature to the
dominant one not occur.
 Diagnosis

• BBT (basal body temperature)

• Ultrasound:
- multiple small ovarian cysts
- enlarged ovary
• Endometrium biopsy(Curettage )
before menses reveal to proliferative glands
• Determination of LH,FSH,E2,P,T,PRL，Ins，
(LH:FSH≧3:1)
• Laparoscopy
 Treatment

• Treatment of women with PCOS should be directed at

the specific complaint. These concerns fall into three
main categories:
• androgen excess and symptoms of hyperandrogenism;
irregular bleeding
• risks of endometrial disease due to unopposed estrogen
stimulation from anovulation;
• fertility concerns and subfertility, mostly due to
anovulation.
 Treatment

• Androgen excess (acne, hirsutism, and alopecia) occurs

in the majority of women with PCOS, but not in all
women.

• At times the symptoms are sufficiently mild that the

treatment focus is on other concerns such as subfertility.
 Treatment
• Treatment of Skin Manifestations of Androgen
Excess
1) Oral Contraceptive Steroids :
 Oral Contraceptive Steroids suppress ovarian androgens
by inhibiting LH stimulation of the ovary.
 They also decrease adrenal androgens (DHEAS) by
about 30% and inhibit 5α-reductase activity
 Among the various preparations, it would seem logical to
use a less androgenic progestogen (norgestimate,
desogestrel, drospi- renone) than more potent ones
(levonorgestrel) , to use lower-dose estrogen products
(20 μg)
• Antiandrogens
• Peripheral androgen blockade with antiandrogens is
dose related. Receptor blockade with spironolactone
and flutamide and a specific 5α-2 inhibitor, finasteride,
are the agents most com- monly used.
• a dose of 200 mg/ day of spironolactone is more
effective than 100 mg/day (Lobo, 1985).
• Barth and associates have found a clinically evident
response of decreased hair after 3 months of
spironolactone, 200 mg/day (Barth, 1989).
 Treatment

2) Other Agents for Treatment :

 In severe cases, use of a GnRH agonist with estrogen
or an OC add-back has been shown to be successful
(Andreyko, 1986; Bayhan, 2000).

 However, this is expensive and cannot be used for long-

term therapy. It has been used in women with high lev-
els of circulating androgens.
 Treatment

• Ketoconazole :
It blocks adrenal and gonadal steroidogen- esis by
inhibiting cytochrome P450–dependent enzyme pathways,
has been used in dosages of 200 mg, twice daily, to treat
hyperandrogenism associated with PCOS and idiopathic
hirsutism.
 Treatment

• Insulin sensitizers
 It has been proposed as agents to treat androgen
excess and have been used in women with PCOS.

 Although some agents have shown some minor

beneficial effects,

 these are not recommended as a primary therapy for

manifestations of androgen excess .
 Treatment

• Eflornithine cream 13.9% :

 It is a topical treatment that has been approved by the

U.S. Food and Drug Administration (FDA) for facial
hirsutism.

 Eflornithine is an inhibitor of ornithine decarboxylase,

which is an enzyme necessary for the growth and
development of the hair follicle.
 Treatment of subfertility

• Ovulation induction may be accomplished by a variety of

agents, including metformin, clomiphene, letrozole,
gonadotropins, and pulsatile GnRH

• Although metformin had been used as a first-line

treatment for infertility

• more recent randomized trials with a focus on live births

as an end point have suggested that clomiphene is
superior to metformin for first-line therapy (Legro, 2007)
Treatment of subfertility
 Treatment of subfertility

• Clomiphene has been the mainstay for ovulation

induction.

• Most pregnancies occur within the first few cycles.

Accordingly, it is reasonable to use clomiphene, with or
without metformin, as an initial approach, after obtaining
a semen analysis, but not for more than three or four
ovulatory cycles before a more comprehensive workup is
undertaken.
 Treatment of subfertility

• Letrozole (2.5 to 5 mg/day, 5 days) has proved to be

efficacious as an alternative to clomiphene,

• and it is particularly suited for women who have side

effects with clomiphene.

• In a randomized head-to head comparison of

clomiphene and letrozole in women with PCOS, letrozole
was found to be superior (Legro, 2014)
Thank you