Hyperandrogenism and hyperinsulinemia are key features of PCOS. PCOS emerges in puberty and causes irregular menstrual cycles that persist through reproductive life. Polycystic ovaries contain increased ovarian volume and follicles arranged along the edges. This is caused by hyperplastic stroma containing cells capable of androgen synthesis. Hyperinsulinemia is also common in PCOS due to insulin resistance. Insulin stimulates ovarian hormone production and enhances the effects of gonadotropins, exacerbating hyperandrogenism. Both hyperandrogenism and hyperinsulinemia contribute to the mechanism of anovulation in PCOS.

1. Hyperandrogenism &
Hyperinsulinemia in PCOS
Dr.Debkumar Ray MBBS,MD,DNB
Associate Professor
Department of Biochemistry
Burdwan Medical College

2. Hyperandrogenism
• PCOS emerge in peripubertal years & occationally with premature
pubarche & likely irregular cycles that persist through reproductive life.
• Polycystic overies tend to be enlarged and are characterized by the
presence ˃10 cystic follicles that are between 2-8mm in diameter and
arranged along the subcapsular edge of the overy in a “string of pearls”
fashion.
• The increased ovarian volume and displacement of follicles toword the
periphery may be explained by hyperplastic stroma. The stroma contains
hilar cells & secondary interstitial cells (theca cells) & that are capable of
androgen synthesis.
• Polycystic –appearing overies are very common with the clinical feature
suggestive of hyperandrogenism independent of menstrual disturbances.

3. Hyperandrogenism
• A common clinical sign of hyperandrogenism is hirsutism
• Measurement of androgen levels should play limited role in the
evaluation but there are subsets of amenorrheic patients who are
hyperandrogenemic without clinical manifestations following relative
insensitivity to the circulating androgens.
• Most common androgens such as DHEAS & Testosterone are
measured to exclude other causes of hyperandrogeic anovulation
likely nonclassic adrenal hyperplasia & androgen-secreting tumors.
• Hirsutism is related to higher 5α reductase activity (Increased
sensitivity)

4. Mechanism of anovulation
• PCOS produce both androgen & estrogen (estrone) in excess.
• Functional derangement of LH secretion and mean LH is increased.
The aberration of LH secretion results heightened pituitary
responsiveness and increased hypothalamic GnRH activity.
• Responsiveness of LH for polycystic follicles makes the follicle much
smaller diameter & it produces inappropriate terminal differentiation
of granulosa cells & results in disorganized follicle development.
• Theca cells increase their expression of steroidogenic enzymes from
stimulation by LH .

5. Mechanism of anovulation
• Excess androgen production is a fundamental abnormatity in PCOS.
• Androgens within the overy are produced mainly by the thecal
interstitial cells that surround the follicle and to a lesser extent by the
secondery interstitial cells located in the stroma .
• The CYP 17α complex is the key enzyme in biosynthesis of overian
androgens.
• Under normal condition a large proportion of androgens produced by
theca cells diffuse into granulosa cell layer of the follicle where they
are rapidly converted to estrogen & dysregulation of the hormone
production is most likely responsible for PCOS.

7. Mechanism of anovulation
• Additional studies have found increased expression of the genes
encoding CYP17α hydroxylase,P450scc,the LH receptor & StAR helps
in steroidogenesis & is compounded by the hypertrophy of theca cells
in PCOS.
• DHEAS is elevated in 25-60% of patients with PCOS.

8. Hyperinsulinemia in PCOS
• Hyperinsulinemia is the insulin resistance & that the defect lies in the
post receptor signalling pathway.
• The frequency and degree of hyperinsulinemia with PCOS is amplified
in the presence of obesity.
• Insulin has a stimulatory effect on CYP17α & directly act on ovary.
• Insulin stimulates ovarian estrogen,androgen & progesterone
secretion and that effects are enhanced by gonadrotrophins.
• Administration of insulin sensitizing agent (Metformin/Thiazole
derivative) to obese with PCOS leads to substantial reduction in 17α
hydroxyprogesterone levels,reflecting decreased CYP17α activity.

9. Hyperinsulinemia in PCOS
• Insulin increases secretion of 17α hydroxyprogesterone & DHEAS in
response to ACTH.
• Insulin directly inhibits SHBG production & IGFBP1 .This would
increase IGF 1 & which could modulate ovarian androgen production .
• PCOS have a relation with alteration of Lipid profiles & degree of
dyslipidemia has been correlated with the magnitude of insulin
resistance.
• 30-40% women with PCOS have impaired glucose tolerance.