8. Pathophysiology
• Hyperthecosis
• Increased testosterone from the ovaries
• Defective aromatisation with in ovary
• Hyperandrogenic microenvironment with in ovaries
• Normal aromatisation in periphery
• Unopposed estrogenic action
• Anovulation decreased estrogen
9.
10.
11. Hyperinsulinemia decreased SHBG
hyperandrogenism & hyperestrogenism
Increased insulin can cause
increased androgen release
from ovary
16. Long term complications of PCOS
• Insulin resistance DM
• Increased estrogen endometrial hyperplasia & endometrial
carcinoma
17.
18. Clomiphene
• Racemic mixture of enclomiphene & zuclomiphene
• The orally bioavailable citrate salt of enclomiphene, the trans-isomer
of the nonsteroidal triphenylethylene compound clomiphene, with
tissue-selective estrogenic and antiestrogenic activities. As a selective
estrogen receptor modulator (SERM), enclomiphene binds to
hypothalamic estrogen receptors, blocking the negative feedback of
endogenous estrogens and stimulating the release of gonadotropin –
releasing hormone (GnRH) from the hypothalamus; released GnRH
subsequently stimulates the release of follicle-stimulating hormone
(FSH) and luteinizing hormone (LH) from the anterior pituitary,
resulting in ovulation.
19. • Clomiphene - can sometimes stimulate a man's own pituitary
gonadotropins (when his pituitary is intact) there by increasing
testosterone and sperm production for male infertility
• Clomiphene citrate is non steroidal estrogen antagonist it induces
ouulation in 60% of women with stein-Leventhal syndrome (PCOS)
and is the initial treatment of choice. Adverse effects - Poly cystic
ovaries, multiple pregnancy hot flushes, gastric upset, vertigo, allergic
dermatitis, risk of ovarian tumor may be increased
20. • Clomifene acts by inhibiting the action of estrogen on the
gonadotrope cells in the interior pituitary gland. Since the estrogen
receptors prevented from recycling, the body perceives estrogen
levels to be falsely lower than they actually are. As a result, the body
releases more gonadotropin-releasing hormone from the
hypothalamus, which drives the pituitary secretion of follicle-
stimulating hormone (FSH), leading to a higher rate of ovulation and
hence pregnancy.
21. • Developmnt of follicles with clomiphene
• Ovulation is triggered by
• Beta hCG from urine of pregnant women
• Recombinant beta hCG
• Recombinant LH
22. • Adverse Effects:
• a. Hot flushes (most common)
• b. Ovarian hyperstimulation
• c. Headache, constipation, allergic skin reaction, reversible hair loss.
• Multiple pregnancy: Incidence is about 10%.