Letrozole ingestion increases pit gonadotrophins.

 

How does letrozole increases Gonadotrophin secretion and decreases already existing oestrone in peripheral blood?? As an aromatase inhibitor, Letrozole prevents the conversion of androgens to estrogen in the peripheral blood stream. The subsequent feedback to the hypothalamus containing reduced estrogen levels, triggers a compensatory increase in hypothalamic gonadotropin-releasing hormone (GnRH) secretion, and thus an increased release of pituitary gonadotropins (follicle stimulating hormone and luteinizing hormone). These gonadotropins subsequently promote growth of the follicles and stimulate ovulation. In contrast, CC is a selective estrogen receptor modulator (SERM). CC functions as an estrogen receptor antagonist in the hypothalamus, thus stimulating GnRH and subsequent FSH secretion.What is the “stair step” protocol in relation to letrozole ?? Ans:    . Stair-Step protocols with CC for ovulation induction has been thoroughly explored . Diagnosis of PCOS was based on the 2003 Rotterdam definition requiring oligo/anovulation and either the presence of clinical or biochemical signs of hyperandrogenism, oligoovulation/anovulation or polycystic ovaries, with exclusion of other causes of excess androgen activity. Exclusion criteria : who had a Day 3 FSH > 10 or BMI > 40. Patients with BMI > 40 were excluded from any treatment with ovulation 

Stair step protocol : Women were prescribed the lowest dose of ovulation induction medication (50 mg CC or 2.5 mg Letrozole) for 5 days beginning with either menstrual cycle day 3–5 if they had spontaneous menses or were randomly started irrespective of past bleeding timing. Established doses of both medications were used in the respective stair-step protocols starting at the lowest dose: CC 50 mg increasing to 150 mg and up to 250 mg as needed; Letrozole 2.5 mg increasing to 5 mg and up to 7.5 mg as needed. A transvaginal ultrasound was performed approximately 1 week (5–7 days) after the last pill (Fig. 1.). If no response (all follicles < 10 mm) was noted on ultrasound, the patient was immediately given the sequential higher dose and an ultrasound was repeated in 1 week (5–7 days). The protocol was continued until a max of 7.5 mg for Letrozole or 250 mg for CC. Successful ovulation was defined with a positive ovulation predictor kit or ultrasound documentation of a preovulatory follicle of at least 18 mm that presumably would ovulate on its own. Documentation of ovulation type (spontaneous or triggered) was not performed in the CC group. Of note, when a 18 mm dominant follicle was noted on ultrasound, the patients were triggered with 10,000 IU HCG. Measurement of mid-luteal progesterone was not performed.