Letrozole mode of action

 

Clomiphene citrate

Contraindications

1.      Liver disease.

2.      Ovarian cyst.

3.      Development of visual symptoms on administration of drug.

4.      Ovarian failure.

5.      Hypothalamic pituitary failure (WHO Group-I) as clomiphene requires an intact hypothalamic-pituitary ovarian axis for its action.

 

Dose

Clomiphene is started from day 2 to 5 of the menstrual cycle but  in amenorrhoeic patients it can be started immediately if pregnancy is ruled out. The starting dose of clomiphene is 50 mg 5 consecutive days. More sensitive patients may be started with a lower dose of 25mg.

Q.1: Why not to initiate from Day 5?? Ans: Giving clomiphene on day 5 results in increased gonadotropins at the time when the dominant follicle is being selected but the negative effect on endometrium will last less receptivity.

q.2: What is the advantage of early start??  Ans: Starting it earlier stimulates more antral follicles .AS a result multiple follicular developments may ensue which is ideal in order to obtain more than oocyte more so if IUI is planned. Dose can be increased every month by 50 mg up to 250 mg till ovulation occurs. However, it is seen that cumulative conception rate does not increase substantially beyond a dose of 150 mgs due to the adverse effect of clomiphene on cervical mucus and endometrium .Duration of treatment can extend to 6 to 12 months but 75 percent conceptions occur in the first 3 months.

Q 3: How to monitor?:

Serum estradiol levels (each follicle secretes 150-300 pg/ ml per follicle)

Method A:--LH surge by home monitoring urine test (best performed by second urination of the day between 7 a.m. and 10 a.m.)

Method B:-Ultrasonography _ Follicular monitoring to be started on Day 9. Optional follicular parameters around ovulation are a follicular size of 18-20 mm with perifollicular blood flow of 50-75 per cent and RI of 0.4-48.

Method C: Serum estradiol levels (each mature follicle secretes 150-300 pg/ ml per follicle)

Method D:-Mid luteal serum progesterone – Greater than 3 ng/ml. is an evidence of ovulation. A level of progesterone more than 10 ng/ml. is taken as an adequate luteal phase.

Q 4. What is clomiphene check?? Before starting the next cycle it is useful to do a ‘clomiphene check’ where previous treatment cycle is reviewed and pelvic exam or ultrasound ensures that no residual cyst is present.

 

Q. 6: What may be rare Side effects and Risks of clomiphene citrate?

  a) Visual disturbances (1.6%)—Blurred vision, diploplia, Scotoma and light sensitivity may occur and need cessation of the drug and change of treatment options. Rarely optic neuropathy develops.

b) Ovarian cysts (6.4%)—Thy resolve without treatment in a few weeks.

C) Ovarian hyperstimulation syndrome (less than 1%)—It can be avoided by establishing and using mini-mum effective dose.

 

LETROZOLE

Q. 1: What it is?? Ans: Letrozole is an aromatase inhibitor. It can be used for ovulation induction.

Q.2: Mechanism of Action

Letrozole competitively binds to the haem subunit of cytochrome P450 aromatase enzyme. It prevents action of aromatase enzyme to convert testosterone to estradiol and androstenedione to estrone. The reduced levels of estrogen cause a release of estrogen negative feedback at hypothalamus and pituitary resulting in gonadotropin secretion and stimulation of ovarian follicle.