Ans. is 'd' i.e., Aromatase inhibitors Aromatase inhibitorso Aromatase inhibitors are drugs which inhibit the enzyme Aromatase.o Aromatase is an enzyme responsible for the conversion of testosterone (androgens) to estrogens.o This conversion of androgens to estrogens occur in several tissues including ovary, adrenal cortex, peripheral tissues.o Inhibition of Aromatase leads to decrease in estrogen level.o Aromatase inhibitors prevent the conversion of androgens to estrogens only in postmenopausal women, not in premenopausal women.o In premenopausal women, as the level of estrogens decrease it activates the pituitary hypothalamic axis. Activation of pituitary hypothalamic axis leads to increased secretion of pituitary gonadotropins. The pituitary gonadotropins inturn increase the secretion of estrogens. Thus the estrogen level returns back to their normal level.o On the other hand aromatase inhibitors effectively decrease the secretion of estrogen in postmenopausal women.o In postmenopausal women, the production of estrogen from androgens occurs, only in extraovarian sites such as peripheral tissues where the conversion of androgens to estrogens is blocked by aromatase inhibitors.Use of aromatase inhibitorso Aromatase inhibitors are used in the t/t of Hormone receptor positive breast carcinomas in postmenopausal women. They are not effective in premenopausal women.How are Aromatase inhibitors useful in Breast carcinomas ?o In breast carcinomas, estrogen delivers growth signals to the hormone receptors. The hormone receptors upon receiving the growth signals, cause the proliferation of tumor cells,o After the inhibition by aromatase inhibitors, estrogen level decreases, this leads to lesser delivery of growth signals and in turn lesser proliferation of tumor cells.Aromatase inhibitors are of two types :o Type I (steroidal) aromatase inhibitor - They cause irreversible inhibition of aromatase, e.g. Exmestane. formestane.o Type II (non-steroidal) aromatase inhibitor - They cause reversible inhibition of aromatase e.g. Anastrazole, Letrozole, vorozale.o Above classification is based on chemical structure (steroidal or non-steroidal ) and type of inhibition (reversible or irreversible). Based on the evolution the aromatase inibitors are:First generation - AminoglotethimideSecond generation - Steroidal type I(Example, formestane), non-steroidal type II (Anastrazole, Letrozole, Vorozole, fadrozole)o Side effects - Hot flushes, nausea, diarrhoea, dyspepsia, thinning of hair and Joint Pain (Arthralgia) and increased risk of fracture.o There is no endometrial proliferation (no risk of endometrial carcinoma), no risk of venous thromboembolism and no deterioration of lipid profile.Remembero Anastrozole and letrozole are nonsteroidol compound, while exemestane is steroidol.o Exemestane also has weak androgenic activity',o Anastrozole is more potent than letrozole.o First generation aromatase inhibitors - Aminoglutethimide.o Second generation aromatase inhibitors - Letrozole, anastrozole, fadrozole and exemestone.