POLYCYSTIC

OVARY SYNDROME

Lecture : dr. Johanes Benarto, Sp.OG

by : Gizela Yuanita
 DEFINITION
Polycystic ovarian syndrome is a common
endocrine dysfunction typified by oligo-ovulation or
anovulation, signs of androgen excess, and multiple
small ovarian cysts

Polycystic ovarian syndrome is a generic

description for a broad spectrum of clinical and
morphological findings in women with an endocrine
dysfunction, specifically abnormal androgen
production and metabolism.
SYMPTOMS
 ETIOLOGY

GENETIC
An increased prevalence has been noted
between affected individuals and their sisters
and mothers
ENVIRONMENT
Lifestyle
Androgen exposure
 ETIOLOGY
The syndrome is also associated with
persistently rapid gonadotropin-releasing
hormone pulses, > LH, and insufficient FSH
secretion, which contribute to excessive
ovarian androgen production and ovulatory
dysfunction
PHYSIOLOGY
 PATHOPYSIOLOGY

Abnormal gonadotropin secretion

Excess LH and low FSH
Hypersecretion of androgens
Disrupts follicle maturation
Substrate for peripheral aromatization
Negative feedback on pituitary
Decreased FSH secreation
Insulin resistance, Elevated insulin levels
 GnRH Increased GnRH from
hypothalamus
Excessive LH secretion relative
to FSH by pituitary gland
LH stimulates ovarian thecal
Estrogen cells to produce excessive
androgen
LH,
FSH Ineffective suppression of the
androgen LH pulse frequency by estradiol
and progesterone
Androgen excess increases LH
by blocking the hypothalamic
inhibitory feedback of
progesterone
Anovulation

Intraovarian androgen excess results in excessive

growth of small ovarian follicles
Follicular maturation is inhibited
The PCOS is associated with inherent abnormalities of
ovarian (and adrenal) steroidogenesis:
Cultured ovarian theca cells from women with PCOS
secrete excess androgens and precursors.
Women with PCOS have ex-aggregated ovarian
steroidogenic responses to gonadotropin stimulation
ABNORMAL MORPHOLOGY OF
OVARY
 OBESITY
Prevalence of obesity varies from 40-60%
2/3 of patients with PCOS who are not obese have
excessive body fat and central adiposity
Obese patients maybe have a terminal hair and/or
have menstrual irregularities without having PCOS
 ADRENAL TUMOR
Androgen-secreting ovarian or adrenal tumors are rare,
but they should be considered in patients with abrupt,
rapidly progressive, or severe hyperandrogenism (e.g,.
Virilization, clitoromegaly, a deep voice, and male-
pattern baldness)

Clinical : hyperandrogenemia (total

testosterone>150ng/dL)
 HYPERINSULINEMIA

Hyperinsulinemia can caused by insulin resistance

that happened 80% women with PCOS with central
obese, and 30-40% women without obese.
Insulin resistance is associated with reproductive
abnormalities in women with PCOS
Hyperinsulinemia contributes to hyperandrogenism
through production in the theca cell and through its
suppressive effects on sex hormone binding globulin
(SHBG) production by the liver
Malfunction of -pancreas can be found in PCOS
 INCREASING OF LH
Excessive of LH can be detect once by the blood of
40-50% women with PCOS.
The high LH mostly occur in woman BMI < normal.
Even FSH serum in a normal range, but there are
found an intrinsic inhibitor in FSH
 DIAGNOSIS
These "cysts" are actually immature follicles. The follicles
development stopped at an early antral stage due to the disturbed
ovarian function
Polycystics are >12 or more antral follicles (2-9 mm in diameter) in
either ovary, an ovarian vol that is greater than 10 ml in either ovary
 DIAGNOSIS
Three sets of criteria for the PCOS in women
have been developed

Hyperandrogenis Ovulatory
m disfunction

Polycistic ovarian
morphologic features
 1. HYPERANDROGENISM
Hirsutism : excessive growth of terminal hair
that appears in a male person, may be
quantified with the use of FerrimanGallwey
score.
0 = no terminal hair growth
4 = terminal hair growth
Score 8 abnormal

Single gene cytochrome P45017c17 will

mediated the activity of 17a-hydroxulase and
17-20-desmolase in the ovary
 Androgen assays

Total testosterone assays are relatively inaccurate

at the lower levels detected in women
Free testosterone is the most sensitive test for
hyperandrogenemia in women with PCOS, and
more appropriate to calculate free testosterone
with the use of measurement of total testosterone
and sex hormone-binding globulin
 2. OVULATORY
DISFUNCTION
Typically indicated by unpredictable menses
that occur at <21 to >35 days intervals.
However regular menses do not confirm normal
ovulatory function in women with
hyperandrogenism: 15-40% of women with
hyperandrogenism and regular menses have
ovulatory dysfunction
 Oligo or Amenorrhea
Menstrual irregularity typically begins in the peripubertal
period

Reduction in ovulatory events leads to deficient

progesterone secretion
Chronic estrogen stimulation of the endometrium with
no progesterone for differentiationintermittent
breakthrough bleeding or dysfunctional uterine bleeding
Increased risk for endometrial hyperplasia and/or
endometrial CA
 3. POLYCYSTIC
OVARIAN
MORPHOLOGIC
12 or more antral follicles in either ovary

Ovarian USG is not required for diagnosis when both

hyperandrogenism and ovulatory dysfunction are present
 Androgen-secreting ovarian or adrenal tumors are
rare, but they should be considered in patients with
abrupt, rapidly progressive, or severe
hyperandrogenism
(e.g., virilization, clitoromegaly, a deep voice)

Screening for cardiometabolic risk factors is

recommended in women with PCOS (BMII, waist
circumference, blood pressure each visit, fasting lipid
levels every 2 years (or sooner if the woman has
gained weight)
Most guidelines regarding the PCOS suggest
screening for:
impaired glucose tolerance
Type 2 DM with 2 hr oral glucose-tolerance test
(every 1-5yrs)

USG and biopsy as a provide support for referral to a

gynecologist in patients with prolonged amenorrhea
or persistently abnormal vaginal bleeding
 SIDE EFFECTS OF
PCOS
Short-term Long-term
consequences consequences

Irregular menses Diabetes

Hirsutism/acne/androge mellitus(DM)
nic alopecia
Cardiovascular
Infertility
disease(CVD)
Obesity
Metabolic disturbances:
Endometrial cancer
Abnormal lipid Hyperplasia/cancer
levels/glucose
intolerance
Hyperplasia/cancer
 LABORATORY
Suspect
PCOS Adrenal Idiopathic
Tumor
T DS T & DS T > 200
Elevated Elevated Normal ng/dl
DS DS > 700
Elevated g/dl

Total Testosterone (T)

DHEA-S (DS)
17-hyroxyprogesterone (17-OHP)
 MANAGEMENT
Lifestyle
Modification
(weight loss)
Reduced androgen levels likely, but effect on
hirsutism uncertain
No specific diet/exercise regimen has been proved to
be superior in PCOS
90% of anovulatory women restored to full ovulation
despite relatively small amounts of weight loss
following exercise and change of diet
Clomiphene
Considered as a first-line agent for induction of
ovulation in women with the PCOS
CC is a selective estrogen receptor modulator (SERM)
Clomiphene blocks negative feedback to
hypothalamus & pituitary
A randomized trial of ovulation induction involving
women with PCOS and infertility showed a higher
live birth rate among women who received
clomiphene than with metformin alone
Anti Androgen OCPs: first option when fertility
is not desired
Decrease in LH secretion and decrease in androgen
production
Increase in hepatic production of sex-hormone
binding globulin(SHBG)
Decreased bioavailablity of testosterone
Decreased adrenal androgen secretion
Regular withdrawal bleeding
Prevention of endometrial hyperplasia
 Spironolakto
n
Androgen receptor blockade
Steroid enzyme inhibition
Aldosterone antagonism
Lower blood pressure
Potassium sparing
Start at 2 x 50 mg, increasing to 2 x 100mg as
needed
Avoid in pregnancy
Metformin
Reduces hyperinsulinemia and lowers serum
testosterone levels by approximately 20-25% in PCOS
Effects on hirsutism are modest at best
Improved ovulatory function
will restore ovulation and menses in > 50% of
patients
added to clomid, improves ovulatory rates
Progestin
Prevention of endometrial hyperplasia and cancer
Oral micronized progesterone (200 mg at bedtime) or
oral medroxyprogresterone acetate (5-10 mg daily)
for 10-14 days
Insulin
Sensitizing
Agents
Induction of ovulation
Some reduced hair growth
Improved glucose utilization
Lowered serum insulin
Lipid lowering properties
 LAPAROSCOPIC
OVARIAN DRILLING
LOD is a surgical treatment that can trigger
ovulationin women who havePCOS
Electrocautery or a laser is used to destroy parts of
the ovaries

Fritz MA, Speroff L (2011). Induction of ovulation. In Clinical Gynecologic Endocrinology and infertility,
8th ed., pp. 1293-1330. Philadelphia: Lippincott Williams and Wilkins.
 CONCLUSIONS
Polycystic ovary syndrome is diagnosed in women with at
least 2 of the following otherwise unexplained
abnormalities
Women with PCOS are at increased risk for infertility,
endometrial hyperplasia and cancer, abnormal glucose
metabolism, dyslipidemia
Lifestyle modification is important for patients who are
overweight/those with other coexisting metabolic
conditions
Pharmacologic therapies can be used like spironolactone
for hirsutism, progestin for endometrial protection,
metformin for abnormal glucose tolerance