Letrozole

 Clomiphene citrate was  the most commonly used pharmacologic agent to induce ovulation in these women since 1962 , but many  women failed to conceive with this therapy. During the past  two decades, aromatase inhibitors have been explored as an primary option for ovulation induction in women with PCO or in women  who fail to conceive with clomiphene citrate.

What is letrozole ? letrozole is a type of Aromatase inhibitors are a class of drugs that block estrogen biosynthesis, thereby reducing negative estrogenic feedback at the pituitary

 

PHARMACOLOGICAL ACTIONS :

Aromatase is a microsomal cytochrome P450 hemoprotein-containing enzyme (P450arom, the product of the CYP19 gene) that catalyzes the rate-limiting step in the production of estrogens: the conversion of androstenedione and testosterone via three hydroxylation steps to estrone and estradiol, respectively .It is a good target for selective inhibition because estrogen production is a terminal step in the biosynthetic sequence. Aromatase activity is present in many tissues, including the ovaries, brain, adipose tissue, muscle, liver, and breast.

Aromatase inhibitors are widely used as adjuvant endocrine therapy for postmenopausal women with breast cancer. They have been used off-label in the treatment of patients with anovulatory infertility  such as polycystic ovary syndrome (PCOS), and for increasing the number of ovarian follicles recruited in ovulatory women undergoing controlled ovarian hyperstimulation (COH)

Letrozole and anastrozole are triazole (antifungal) derivatives that are potent, reversible, competitive, nonsteroidal aromatase inhibitors . In postmenopausal women, at doses of 1 to 5 mg/day, these drugs inhibit estrogen biosynthesis by 97 to >99 percent, resulting in estrogen concentrations below the levels detected by most sensitive immunoassays. They are completely absorbed after oral administration and have a mean terminal half-life of approximately 45 hours (range 30 to 60 hours); clearance is mainly hepatic. By comparison, exemestane, a steroidal aromatase inhibitor, has a circulating half-life of approximately nine hours, but the inhibitory effect is potentially much longer because its effect on aromatase is irreversible