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
