Polycystic Ovary Syndrome (PCOS)

‐ Consider most common endocrine disorder in reproductive age Aetiology

‐ Incidence variable in Jordan 22%, highest incidence in Asia 1. Unknown
‐ Usually, symptomatic 2. PCOS is a multifactorial and polygenic, 40% family Hx (chromosomal related disorder)
‐ Carried long term unwanted health issue like DM, IHD, hyperlipidemia and risk of
endometrial and ovarian cancer
❖ Hyperinsulinaemia and hyperandrogenisim are in the heart of this condition

Significance and genetics

Pathophysiology
‐ Common endocrine disorder
‐ Dysfunction in ovarian function leading to increase androgen production....arising from
‐ A leading cause of infertility 30-40%
exaggerated response of LH by theca cells and augmented by the effect of insulin
‐ May have a profound adverse impact on the health-related quality of life (HRQOL).
binding to IGF- 1&2 ( important regulator for follicular maturation and steroidogenesis)
‐ Tends to cluster in families, considered now autosomal dominant disorder
‐ Dysfunction in hypothalamic function leading to increased LH which stimulates
androgen production
PCOS is higher in those with: ‐ Insulin resistance... From physphorylation of tyrosine and serine residues on receptors →
1. GDM leading to compensatory hyperinsulinaemia , that also ↓ hepatic production of IGF-1&2
2. Premature Adrenarche Binding Protines → ↑ the bioavailability of IGF-1&2
3. Family History of first-degree relatives who have PCOS
Insulin resistance
Criteria for Defining PCOS ‐ Insulin stimulates androgen production from ovary and adrenal and may alter
ESHRE/ASRM (Rotterdam criteria) 2003 VERY IMPORTANT gonadotrophin secretion.
Two of the following in addition to exclusion of related disorders: ‐ ↓SHBG synthesis in the liver = ↑ free testosterone
1. Oligo and/or anovulation (oligo/a menorrhea)
2. Hyperandrogenism “clinical” and/or hyperandrogenemia “biochemical” Other manifestations of PCOS
3. PCO morphology on U/S 1. Central Obesity = ≥ 50% of PCOS patients
≥12 follicles in each ovary, 2-9mm and/or ovarian volume (>10ml) 2. Metabolic syndrome = Type 2 Diabetes, HTN, dyslipidaemia, atherosclerosis & IHD
3. Dermatological = Hirsutism, oily skin, acne, alopecia, Acanthosis nigricans
2-9 mm it’s the size of antral follicles (resting follicles) not dominant one
Long term effects
❖ No clear criteria to diagnosis of PCOS 1. Obesity
❖ First criteria made by NIH (united States national institute of health) 1990 it want clear but the 2. DM
more widely used its ESHRE/ASRM (Rotterdam) 2003 3. Cardiovascular diseases (e.g. HTN, atherosclerosis, IHD, hyperlipidemia)
4. Endometrium & ovarian Ca
Image A Image B
5. PCOS and pregnancy (↑risk of GDM, GHTN, increase rate of CS)
6. Hirsutism
7. Infertility (30-40%)

Obesity
‐ ≥ 50% of patients with PCOS
Image C ‐ Most often a central obesity with an android appearance and an increased waist-to-hip
ratio >0.8
‐ Related to insulin resistance.
❖ Image A = laparoscopic view of the pelvis, uterus anteverted, both tube heathy, 2 white dense ‐ Women with PCOS find it more difficult to lose weight and appear to gain weight more
structure these the ovaries with gray to black spots these are the antral follicles (usually the easily.
antral follicles presented at surface “cortex” so be gentle in surgery to avoid damage the ‐ Treatment of Obesity VERY IMPORTANT
ovarian reserve that lead to premature ovarian insufficiency) 1. Lifestyle changes
❖ Image B = black circles these are the antral follicles (resting) not active not sensitive to FSH, 2. Pharmacological agents
its size around 2-9 mm we need to have at least 12 follicles ‐ Centrally acting serotonin & norepinephrine uptake inhibitor, Sibutramine
❖ Image C = PCO very busy with too many follicles above the normal (↑ovarian reserve) ‐ Peripherally acting lipase inhibitor, Orlistat
3. Bariatric surgery
▪ PCO (polycystic ovary) 25% = only polycystic ovary without other Rotterdam criteria
▪ PCOS (polycystic ovarian syndrome) 75% = polycystic ovary + Oligo and/or anovulation +
Hyperandrogenism and/or hyperandrogenemia
Work up
1. TSH (role out not hypothyroidism)
2. FBS and lipid profile (role out no DM, hyperlipidemia)
3. PRL elevated in 40% of patients with PCOS, secondary to stimulation of the prolactin-
producing cells by chronic oestrogen and not related to the cause of the disease state
4. Free androgen index
5. FSH and oestradiol (E2) to exclude of premature ovarian failure
‐ FSH ≥ 25 IU/l (require 2 tests to confirm)
‐ Associated with oestradiol < 30 pg/mL

Management of PCOS
Treatment depends on needs of patient and preventing long term health
problems

Weight reduction results in improvement in all symptoms of PCOS

‐ 10% wt. Loss will restore normal hormones level
‐ and spontaneous ovulation in 40% of women.

Ovulation induction ‫اذا فشلت خطوة نذهب لالخرى‬

1. Major effect by weight loss to BMI < 30 (reduction of 10 % of body weight induce
ovulation and restore the normal level of all hormones)
2. insulin sensitizer “metformin” used in BMI <30 with Ovulation rate 8%, not for weight
reduction or ovulation induction if BMI > 30
‐ measure MLP to know if she ovulated or not (>9 ng/dl its ovulated)
3. anti-estrogen “clomiphene citrate” used for 6 cycles but not more than 6 months (lead
to ovulation rate 75% and pregnancy rate 62 %) (but with risk of multiple pregnancy and ovarian
hyperstimulation syndrome OHSS)
Started with low dose and increase it if no response (maximum 3 tab per 5 days from day 3-7)
4. if resistant (clomid resistant ovarian syndrome) use aromatase inhibitor
(letrozole)
5. injectable “FSH + LH” gonadotropin or laparoscopic ovarian drilling LOD (both
equal effect on ovulation induction rate 62-65 %, but LOD preferred due to free risk of multiple
pregnancy and OHSS) / (gonadotropin with 25 % risk of multiple pregnancy and OHSS)

Injectable Laparoscopic
30% risk of Multiple pregnancy “the major Free risk of multiple pregnancy
cause of perinatal mortality and morbidity its
mainly due to prematurity”
OHSS its unwanted iatrogenic condition result Free risk of OHSS
from ovulation induction
‐characterized by generalized edema,
intravascular volume depletion, thrombosis
and may lead to death
Laparoscopic with thermal ablation on the
ovary use role of 4 (4 punctures, around 4 mm
depth, for 40 second)

LOD = white organ its ovary, thermal ablation with 4 punctures in ovary
aim to rupture the luteinized that unruptured follicles contain high
amount of androgen result in anovulation → ↓androgen + ↓ LH + will
ovulate