Description

Composition:
Each film coated tablet contains:
Letrozole ————- 2.5mg
(USP Specifications)

Indications:

• Ovulation Induction
• Uterine Fibroids/Myomas/Leiomyomas
• Endometriosis
• Moderate to Severe Oligospermia
• Obstructive Azospermia
• Postmenopausal Breast Cancer

Advantages of Letrozole over Clomiphene Citrate:
Letrozole has short half life of 45hrs as compared to clomiphene citrate which has half life from 4-6 weeks.
Significant effect on the endometrial thickness or cervical mucous
Letrozole is effective for increasing follicle recruitment in Unexplained Infertility (Mitwally & Casper, 2000)
For clomiphene citrate resistant patients
Letrozole can replace clomiphene citrate in patients with unexplained infertility undergoing ovulation induction & IUI (Sammouor, 2001).

Mechanism of Action:
Inhibits aromatase in ovaries & peripheral tissues reducing estrogen levels
Negative feedback being active stimulates hypothalamus- pituitary axis.
GnRH release produces FSH-mediated stimulation of follicle.
Rising estrogen level from follicle suppresses FSH leaving a single dominant-follicle.

Committee Opinion 2018
Letrozole should be considered first line therapy for ovulation induction for women with PCOS. Because of increased live birth rates compare with clomiphene citrate. ACOG Committee Opinion. Vol. 131 No. 6, June 2018

Guidelines 2018
Letrozole should be considered first line pharmacological treatment for ovulation induction in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation pregnancy and live birth rates.

Network Meta Analysis
Compared with clomiphene alone, Letrozole is the only treatment showing a significantly higher rate of live birth.
BM/2017, 356-138

SAGE JOURNALS
Elevated levels of aromatase have been found in endometriotic lesions. Letrozole is a drug that inhibits the aromatase enzyme by competitively binding to the cytochrome P450 subunit of the enzyme, resulting in a reduction of letrozole on endometriotic leasions and all revealed that the treatment with letrozole decreases the size of endometriotic lesions (Fang et al., 2002; Bilotas et al., 2009;Yildirim et al., 2009).

Fertility & Sterility
In a randomized controlled trial clomiphene citrate with letrozole for women with unexplained infertility was presented at the American Society for Reproductive Medicine in 2001. The participants were given 2.5mg letrozole or 100mg of clomiphene citrate for 5 days beginning on day 3 of the cycle. On the day of human chorionic gonadotropin (hCG) administration, the number of follicles were greater with clomiphene citrate at 2 versus 1 for letrozole, but the endometrial thickness was greater with letrozole at 8.6 versus 6.9mm. The pregnancy rates were 16,7% for the letrozole group and 5.9% for clomiphene citrate group.

Letrozole in the treatment of azospermia
Fertility and Sterility Volume 92, issue 2, August 2009, pages 829.e1-829.e2

Conclusion:
This is the first study on the use of letrozole to treat male infertility and the first case on the induction of spermatogenesis in a man with using aromatase inhibitor. Letrozole increases spermatogenesis by increasing total serum levels of GnRH thus increasing the level of testosterone and increasing total sperm count.