PCOS/POLYCYSTIC OVARIAN SYNDROME # MEDICINE LECTURES # GYNAECOLOGY # DNB/MD PRESENTATIONS

1. PCOS(POLYCYSTIC OVARIAN
SYNDROME)
DR.SOHAN BISWAS
DNB JR
INTERNAL MEDICINE

2. INTRODUCTION
• Stein and Leventhal initially described it in 1935 – therefore also called Stein
Leventhal syndrome
• Polycystic ovary syndrome (PCOS) is defined by a combination of signs
and symptoms of androgen excess and ovarian dysfunction in the
absence of other specific diagnoses, therefore also called
hyperandrogenic anovulation.
• **polycystic - misnomer
• Aetiology of this syndrome remains largely unknown, but mounting
evidence suggests that PCOS might be a complex multigenic disorder
with strong environmental influences, dietary factors and lifestyle factors

3. ROTTERDAM CRITERIA
• Characterized by two or more of the following:
1)irregular menstrual periods(oligo-anovulation)
2)Hyperandrogenism(clinical - hirsutism or biochemical -
hyperandrogenemia)
3)polycystic ovaries(≥ 12 follicles measuring 2‐9 mm in diameter
and/or an ovarian volume > 10 mL in at least one ovary)
**Hence, ultrasound is not necessary for the diagnosis if features
of both ovulatory dysfunction and hyperandrogenism are present

4. • Hyperandrogenic anovulation has been proposed as a more
accurate and potentially less confusing term, as the ovarian
feature is of multiple follicles and not cysts
• Ovaries may be normal in PCOS, and conversely, polycystic
ovarian morphology (PCOM) may be seen in women without the
syndrome.
• However, it is well accepted that women with PCOS tend to
have larger ovaries with an increased number of follicles.

5. • In patients >8 years post menarche, and using a high-frequency
endovaginal probe:
1) follicle number per ovary (FNPO) ≥20, and/or
2) ovarian volume ≥10ml
• If using transabdominal scanning, or older technology where ovarian
morphology is not well visualized, consider using the ovarian volume
threshold of ≥10 mL on either ovary.

6. • The diagnostic criteria are adjusted in adolescent females
(defined as within 8 years of menarche, or age <20 years), in
whom ultrasound should not be used for the diagnosis of PCOS
due to the high incidence of multi-follicular ovaries in this life
stage.
• This supersedes the initial Rotterdam criteria of ≥12 follicles and
interim recommendations of 24 or 25 follicles per ovary. The
presence of a single multifollicular ovary is sufficient to provide
the sonographic criterion for PCOS .

15. • Obesity (central) is recognized as an important contributory factor.
Apart from excess production of androgens, obesity is also associated
with reduced SHBG. It also induces insulin resistance and
hyperinsulinemia which in turn increases the gonadal androgen
production. PCOS is thought to have a dominant mode of inheritance
as about 50% of first degree relatives have PCOS

16. • Long-term consequences in a patient suffering from PCOS includes:
The excess androgens (mainly androstenedione) either from the
ovaries or adrenals are peripherally aromatized to estrone (E1 ). There
is concomitant diminished SHBG. Cumulative excess unbound E2 and
estrone results in a tonic hyperestrogenic state. There is endometrial
hyperplasia.

19. POSSIBLE LATE SEQUELAE OF PCOS
• Obese women (BMI > 30) are at increased risk of developing diabetes
mellitus (15%) due to insulin resistance.
• Risk of developing endometrial carcinoma due to persistently
elevated level of estrogens. Estrogen effects are not opposed by
progesterone because of chronic anovulatory state.
• Risk of hypertension and cardiovascular disease as dyslipidemia
(↓HDL,↑triglycerides, ↑LDL) is the most common metabolic
abnormality in women with PCOS.
• Obsructive sleep apnea.

21. • Serum values: − LH level is elevated and/or the ratio LH: FSH is > 2:1.
• Raised level of estradiol and estrone — The estrone level is markedly
elevated.
• SHBG level is reduced.
• Hyperandrogenism—mainly from the ovary but less from the adrenals.
Andro-stenedione is raised.
• Raised serum testosterone (> 150 ng/dl) and DHEA–S may be marginally
elevated.
• Insulin Resistance (IR): Raised fasting insulin levels > 25 µIU/ml and fasting
glucose/insulin ratio < 4.5 suggests IR (50%). Levels of serum insulin
response > 300 µIU/ml at 2 hours postglucose (75 gm) load, suggests
severe IR

22. • Hyperinsulinemia causes: (a) Stimulation of theca cells to produce
more androgens. (b) Insulin results in more free IGF-1. By autocrine
action, IGF-1 stimulates theca cells to produce more androgens. (c)
Insulin inhibits hepatic synthesis of SHBG, resulting in more free level
of androgens.

23. • Hyperprolactinemia: In about 20% cases, there may be mild elevation
of prolactin level due to increased pulsitivity of GnRH or due to
dopamine deficiency or both. The prolactin further stimulates adrenal
androgen production.

24. • Anovulation: Because of low FSH level, follicular growth is arrested at different
phases of maturation (2–10 mm diameter).
• The net effect is diminished estradiol and increased inhibin production.
• Due to elevated LH, there is hypertrophy of theca cells and more androgens are
produced either from theca cells or stroma.
• There is defective FSH induced aromatization of androgens to estrogens.
Follicular microenvironment is therefore more androgenic rather than estrogenic.
• Unless there is estrogenic follicular microenvironment, follicular growth,
maturation and ovulation cannot occur.
• There is huge number of atretic follicles that contribute to increased ovarian
stroma (hyperthecosis).
• LH level is tonically elevated without any surge. LH surge is essential for ovulation
to occur

25. • Endometrial hyperplasia causes abnormal uterine bleeding. Chronic
anovulation, hyperestrogenemia, obesity and hyperinsulinemia cause
endometrial hyperplasia even endometrial cancer. Endometrial biopsy
may have to be done.
• Combined oral contraceptives is the treatment of choice to prevent
endometrial hyperplasia and abnormal bleeding

27. INFERTILITY TREATMENT
• First-line therapy for infertility in PCOS patients is clomiphene citrate. This
is a selective estrogen receptor modulator (SERM).
• Clomiphene enhances fertility and ovulation, especially by its effect on the
hypothalamus, where it binds for a prolonged period to estrogen receptors
and depletes them, blocking the negative feedback inhibition effect of
circulating endogenous estrogen.
• This results in the pulsatile release of a hypothalamic gonadotropin-
releasing hormone (GnRH), promoting the secretion of FSH and LH and
indirectly stimulating ovulation.

28. INFERTILITY TREATMENT
• New estrogen modulators such as letrozole has shown that it can be
used in ovulatory infertility. This is an aromatase inhibitor that blocks
estrogen synthesis, reducing negative estrogenic feedback at the
pituitary.

30. THANK YOU