PCOS

Is a syndrome of ovarian dysfunction along with the cardinal features of hyperandrogenism

and polycystic ovary morphology.
The syndrome acquired its name due to the common sign on US of multiple (poly) ovarian
cysts. These "cysts" are immature ovarian follicles which developed from primordial
follicles, but ("arrested") at an early stage, due to the disturbed ovarian function.
Polycystic ovarian syndrome (PCOS) is the most common endocrine pathology in females
of reproductive worldwide.

Causes

The etiology of PCOS is not completely clear .It is a combination of genetic

abnormality and environmental factors
Epidemiology

Stein and Leventhal initially described it in 1935. The prevalence ranges

between 5% and 15% depending on the diagnostic criteria applied (rotterdam)
It affects around 5–15% of women of reproductive age depending on 2003
Rotterdam criteria. The prevalence of polycystic ovaries seen on ultrasound is
around 25% of all women but is not always associated with the full syndrome.

Classification

Insulin-resistant PCOS. This is one of the most common types of PCOS and occurs
because of high insulin levels in the body. ...
Inflammatory PCOS. ...
Post-pill PCOS. ...
Adrenal PCOS.
 Pathophysiology
Polycystic ovaries develop when the ovaries are stimulated to produce
excessive amounts of androgenic hormones, in particular testosterone,
by either one or a combination of the following :
• Increase GnRh pulsatile release that cause excessive LH release that
act on theca lutien cells to produce more androgen (Androgen cause
arrest follicular maturation ,prevent ovulation & signs of
hyperandrogenism)
• Insulin resistance & Hyperinsulinemia increases GnRH pulse
frequency, which in turn results in an increase in the LH/FSH ratio ;
increased ovarian androgen production and decreased SHBG
binding ,increases the activity of 17α-hydroxylase, which catalyzes
the conversion of progesterone to androstenedione, which is in turn
converted to testosterone.
• Adipose (fat) tissue possesses aromatase, an enzyme that converts
androstenedione to estrone and testosterone to estradiol. The excess of
adipose tissue in obese women creates the paradox of having both
excess androgens (which are responsible for hirsutism and
virilization) and excess estrogens (which inhibit FSH via negative
feedback)
PCOS may be associated with chronic inflammation, with several
investigators correlating inflammatory mediators with anovulation and
other PCOS symptoms. Similarly, there seems to be a relation between
PCOS and an increased level of oxidative stress
1.

2.
Signs&Symp.

Oligomenorrhoea/amenorrhoea in up to 75% of patients,

predominantly related to chronic anovulation.
Hirsutism up to 50- 70% of cases.
Subfertility in up to 75% of women. Obesity in at least 40%
of patients.
Acanthosis nigricans (areas of increased velvety skin
pigmentation occur in the axillae and other area as in the neck
May be asymptomatic polycytic ovaries.
• Complications

Metabolic consequences of PCOS:

Type 2 diabetes.
Cholesterol abnormalities.
Cardiovascular disease.
Obstructive sleep apnoea.
Increased bone mass.
Cancer and PCOS:
Endometrial hyperplasia /malignancy.
No additional risk for ovarian or breast malignancy.

Pregnancy and PCOS:

Higher risk of Gestational diabetes and other complications of
pregnancy(miscairage, PET).
Diagnosis Criteria for DX

(clinical or biochemical)
(Amenorrhea or oligo)

with exclusion of other relevant diseases.

Thyroid dysfunction.
Congenital adrenal hyperplasia (CAH).
Hyperprolactinaemia.
Androgen-secreting tumours.
Cushing syndrome.
Diagnosis Labs

↑ Androgens (testosterone and androstenedione)

↓ SHBG, results in elevated free androgen index
Morning 17-hydroxyprogesterone
↑ or normal LH, normal FSH
DHEAS (DeHydroEpiAndrosterone Sulfate)
↑ Fasting insulin (not routinely measured)
↑ insulin resistance or impaired glucose assessed by GTT)
↑ Estradiol, estrone (neither measured routinely as very wide range of values)
↑ Prolactin

US
presence of 8 or more subcapsullar follicular
cysts in each ovary
measuring <10 mm in diameter,
and/or increased ovarian volume (>10 ml) ,
hyperechoic central stroma peripheral location
of follicles (string of pearls sign)
Treatment Lowering of insulin resistance
Reducing Androgen and Testosterone levels
Restoration of fertility
• Goals
Treatment of hirsutism or acne
Restoration of regular menstruation, and prevention of endometrial
hyperplasia and endometrial cancer
• So it depend on What does the patient complain?
➢ Fertility?
➢ Hirsutism?
➢ Obesity?
➢ Irregular periods?
➢ All off the above!!?
Treatment
Weight reduction and life style modification (Diet, exercise & smoking cessation ) a
General goal of achieving 10–15% weight loss or more, which improves insulin resistance .
measures Orlistat (a lipase inhibitor), significantly reduce body weight and hyperandrogenism.
Bariatric surgery should be performed only when standard weight loss regimes have
failed in PCOS women with a BMI greater than 40kg/m2 or greater than 35kg/m2 with
a high-risk obesity related condition.

Metformin As an insulin sensitizing agent. It improves parameters of insulin

resistance, hyperandrogenaemia,anovulation and acne in PCOS.
 Combined oral contraceptive pill (COCP) :
Oligomen • Increase sex hormone binding globulin production, which increases binding of free
orrhea Tx
testosterone. This reduces the symptoms of hirsutism caused by high testosterone
and regulates return to normal menstrual periods
Cyclical oral progesterone induce regular menstruation and to protect
endometrium. e.g. MPA- 10mg daily for 10 days.
Alternative medicine:
• Review concluded that while both myo-inositol and D-chiro-inositols may regulate
menstrual cycles and improve ovulation, there is a lack of evidence regarding
effects on the probability of pregnancy.
• Myo- inositol reduces the amount of gonadotropins and the length of controlled
ovarian hyperstimulation in women undergoing in vitro fertilization
 Hirsutism
Tx

➢ medical :
Eflornithine cream (Vaniqua™) applied [Link] irreversibly inhibits the enzyme ODC,
which is essential for the synthesis of polyamines which is needed for rapid cell proliferation and
differentiation into hair
Cyproterone acetate (an antiandrogen contained in the Dianette™ contraceptive pill, sometimes used
alone)
Anti-androgens such as finasteride(5α-Reductase inhibitors), flutamide, spironolactone, do not show
advantages over oral contraceptives, but could be an option for people who do not tolerate them
Metformin: hyperandrogenemia, improves parameters of anovulation insulin and acne in PCOS
GnRH be analogues reserved with for low-dose women intolerant HRT: this of regime other
therapies;
➢ Mechanical:
Shaving
Waxing
Electrolysis
Laser ablation
 Infertility
Tx
➢ 1st line of treatment

Weight loss 5-10% of body weight (>50% return of ovulatory cycles).

Metformine :to reduce hyperinsulinimia .Metformin is a medication commonly used in
type 2 diabetes mellitus to reduce insulin resistance, and used to treat insulin resistance
seen in PCOS
First line drugs triggers ovulation in 80% : Clomiphene Citrate / Tamoxifen/ letrezole.
Second line drug Gonadotrophin therapy. Ovulation is triggered by hCG injection when
1-3 follicles are 18mm diameter (Risks of multiple pregnancy & OHSS)
Assisted reproductive technology procedures such as controlled ovarian hyperstimulation
with FSH injections followed by IVF. For women not responsive to letrozole or
clomiphene ,gonadotrophin and diet and lifestyle modification
➢ 2nd line of treatment
Laproscopic Ovarian drilling (LOD) (reserved for
selected anovulatory women with a normal BMI.)
Though surgery is not commonly performed,
Procedure

Puncture of 4–10 small follicles with electrocautery or laser ,The most accredited strategy consists of
performing four punctures bilaterally, for a depth of 3–4 m, each for 4 s at 40 W (rule of 4).
(Ovarian wedge resection is no longer used as much due to complications such as adhesions and the presence
of frequently effective medications.)

Mechanism
The most possible mechanism is the destruction of ovarian follicles and stroma resulting in a decrease in
androgen and inhibin levels and a secondary rise in follicle-stimulating hormone (FSH) levels
Production of inflammatory growth factors like insulin-like growth factor-1, in response to thermal injury,
further potentiates the actions of FSH on folliculogenesis, while increased blood flow to the ovary provoked by
surgery, facilitates increased delivery of gonadotropins
The goal of this technique is to decrease the androgen producing tissue , which often results in either
resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH.
Indications

The main indication is CC-resistant PCOS - as a second-line therapy for anovulatory

infertile PCOS cases
All recommend its use in highly selected cases, particularly in those with hypersecretion
of LH , normal body mass index, those needing laparoscopic assessment of the pelvis or
who live too far away from the hospital for the intensive monitoring required during
gonadotropin therapy. Despite its theoretical advantages, LOD is not superior to CC,
neither as a first line therapy for OI nor for CC-failure or prior to in vitro fertilization
(IVF).
CC-resistance refers to the failure to ovulate with 150 mg of CC for at least 3 cycles,
while CC-failure is defined as failure to conceive with CC despite successful regular
ovulation for 6-9 cycles
 Prognosis
multiple punctures are done on each ovary by electrocautery through unipolar hook Ovarian drilling is a
one-time treatment unlike fertility medicines that have to be taken every month. Having twins or triplets
is not as likely with ovarian drilling as with fertility medicines. However, the benefits of ovarian drilling
are not permanent.
The outcome of LOD in achieving ovulation and pregnancy rate : ovulation rates of 80% ,the pregnancy
rates of 60% . LOD increases the sensitivity of gonadotrophins in PCOS.
There are, however, concerns about the long-term effects of ovarian drilling on ovarian function.

Complications

One of the main shortcomings complication of LOD is iatrogenic adhesions due to bleeding from the
ovarian surface or premature contact between the ovary and the bowel after cauterization
Another potential risk is premature ovarian failure(POF) , especially if the ovarian blood supply is
damaged inadvertently or if large number of punctures are made, leading to excessive destruction of
ovarian follicular pool or production of anti-ovarian antibodies
Anesthetic complications.