Originally Araomatase inhibitors are the drugs for breast cancer for their anti estrogen effect. But they are found effective and in some way better for induction of ovulation particularly in PCOS patients. USFDA and now India government has allowed its use in infertility. Though in most of the company literatures the use of the drug in infertility is not mentioned yet!
Aromatase inhibitors are a serious challenge to replace clomiphene as the first line of treatment for anovulatory women. These are non-steroidal compounds that suppress estrogen biosynthesis by blocking the action of the enzyme aromatase which converts androstenedione and testosterone to estrogens.
Letrozole is the most widely used aromatase inhibitor; it is used orally in a dose of 2.5-5mg per day and is free of any side effects.
There are certain advantages of letrozole over Clomiphene citrate (CC)
1.CC blocks and depletes estrogen receptors. Hence it has a negative effect on the cervical mucous and the endometrium. This does not occur with
letrozole,
2.Though initially estrogen production is impaired with aromatase inhibitors eventually with the rise of FSH, estrogen production also increases with development of follicles as a result of which a negative feedback is activated on the hypo¬thalamus which will modulate an overzealous discharge of FSH which in turn is likely to result in monofollicular ovulation with moderate estrogen concentrations. This is all the more likely since letrozole has a much shorter half life (2days) than CC.
3. Though there is statistically significant data to support letrozole for its advantage over CC but it is true that letrozole is an acceptable alternative to CC as an ovulation induction agent in PCOS. Letrozole may be of benefit for patients in whom CC has failed. CC failure can be defined either as lack of ovulation or a thin endometrial lining resulting in failed implantation. Since it is not possible to identify patients who will have a poor response to CC ahead of time, it seems reasonable to use a treatment that is equally effective in inducing ovulation, but without antiestrogenic adverse effects, as a first-line therapy. For letroz to replace CC as the first line of drug for ovulation induction in general probably some more strong evidence is required.
What are the risks of using aromatase inhibitors (Letrozole)
There are certain concerns raised as to the theoretical possibility of accumulation of androgens in a women with PCOS, however there are no reports which indicate towards manifestation or worsening of clinical and biochemical hyperandrogenism following use of letrozole. In fact these increased androgens may have a stimulatory effect in early follicular FSH receptor expression and therefore amplifying FSH response this may explain the relative success of combined letrozole and FSH for ovulation stimulation in improving the response to FSH.
Pregnancy outcome: In an elegant study by Tulandi et al. where in 911 newborns conceived after infertility treatment with letrozole and clomiphene citrate were accessed for congenital malformations, they found that there was no difference in the overall rates of major and minor congenital malformations among the 2 groups. However, it appeared that congenital cardiac anomaly was less frequent in the letrozole group. Till date there is no data to prove Letrozole is teratogenic.
This article is also published in India study Channel
Showing posts with label Infertility drugs. Show all posts
Showing posts with label Infertility drugs. Show all posts
Thursday, March 5, 2009
Know about Clomiphene – The most common drug used in infertility
What is clomiphene? Why it is used? How long and how much one can take? Are there any side effects?
Full name is Clomiphene citrate and it is an anti estrogen and by inhibiting the effect of estrogen on pituitary gland increases the necessary hormone, Follicular stimulating hormone or, FSH secretion from the pituitary gland to stimulate ovary and induce ovulation.
Clomiphene is prescribed in doses of 50mg per cycle and increased to 250 mg until ovulation is achieved. 75% of clomiphene pregnancies occur at doses of 50-100mg and in first 3 cycles. Doses more than 150 mg has less pregnancy rates. As per RCOG Guidelines not more then 6 cycles continuously and not more than 12 cycles in life time.
Side effects of this drug are formation of cysts, , can cause visual problems (2%), mood swings, headache (1%), depression, dryness and loss of hair (0.3%) .
Clomiphene is contraindicated in liver disease.
How effective is Clomiphene Citrate (CC) and is its effect is predictable?
Clomiphene remains the first choice treatment for inducing ovulation. Approx. 70% receiving clomi¬phene ovulate and about 35-40% conceive. Frequently it takes a couple of cycles in identifying clomiphene resistant patients. If response to clomiphene can be predicted, it will help in identifying patients requiring alternative treatment earlier.
A number of factors have been studied to predict clomiphene response:
Free androgen index: FAI [testosterone/sex hormone binding globulin (SHBG) ratio ] is an important indicator of clomiphene responsiveness.
High FAI is also usually associated with hyperinsuilaemia and insulin resistance. These two factors together diminishes the CC responsiveness.
Leptin levels: Leptin is a product of the obesity gene and is primarily produced by adipocytes. Leptin plays an important role in regulation of menstrual cycle and it has been shown that it is increased in clomiphene non-responders and unexplained infertility.
BMI: There have been some studies linking the dose requirement of clomiphene and body weight. This again may be related to leptin levels. In very thin women less than 45 kg, clomiphene should be started at lower dose of 25 mg, whereas in obese women higher dose of 100 mg may be required. Obese women are more likely to have poor response with CC.
Ovarian volume and antral count: Ovarian volume and antral foUicle count have also been closeJy linked to ovarian response. Low ovarian volume as well as very high volume f > 10 ml, suggestive of PCOS; are indicators of poor response. Antral follicles are small follicles measuring 2 to 8 mm in the baseline state. They are indicative of the relative number of microscopic primordial follicles remaining in the ovary. If the antral follicle count is <> 30 as in PCOS, chances of hyperstimulation are very high.
In general, an obese, amenorrhoic woman with hyper insulinemia and high FAI is very likely to have a poor response with clomiphene citrate.
This article is also published in India study Channel
Full name is Clomiphene citrate and it is an anti estrogen and by inhibiting the effect of estrogen on pituitary gland increases the necessary hormone, Follicular stimulating hormone or, FSH secretion from the pituitary gland to stimulate ovary and induce ovulation.
Clomiphene is prescribed in doses of 50mg per cycle and increased to 250 mg until ovulation is achieved. 75% of clomiphene pregnancies occur at doses of 50-100mg and in first 3 cycles. Doses more than 150 mg has less pregnancy rates. As per RCOG Guidelines not more then 6 cycles continuously and not more than 12 cycles in life time.
Side effects of this drug are formation of cysts, , can cause visual problems (2%), mood swings, headache (1%), depression, dryness and loss of hair (0.3%) .
Clomiphene is contraindicated in liver disease.
How effective is Clomiphene Citrate (CC) and is its effect is predictable?
Clomiphene remains the first choice treatment for inducing ovulation. Approx. 70% receiving clomi¬phene ovulate and about 35-40% conceive. Frequently it takes a couple of cycles in identifying clomiphene resistant patients. If response to clomiphene can be predicted, it will help in identifying patients requiring alternative treatment earlier.
A number of factors have been studied to predict clomiphene response:
Free androgen index: FAI [testosterone/sex hormone binding globulin (SHBG) ratio ] is an important indicator of clomiphene responsiveness.
High FAI is also usually associated with hyperinsuilaemia and insulin resistance. These two factors together diminishes the CC responsiveness.
Leptin levels: Leptin is a product of the obesity gene and is primarily produced by adipocytes. Leptin plays an important role in regulation of menstrual cycle and it has been shown that it is increased in clomiphene non-responders and unexplained infertility.
BMI: There have been some studies linking the dose requirement of clomiphene and body weight. This again may be related to leptin levels. In very thin women less than 45 kg, clomiphene should be started at lower dose of 25 mg, whereas in obese women higher dose of 100 mg may be required. Obese women are more likely to have poor response with CC.
Ovarian volume and antral count: Ovarian volume and antral foUicle count have also been closeJy linked to ovarian response. Low ovarian volume as well as very high volume f > 10 ml, suggestive of PCOS; are indicators of poor response. Antral follicles are small follicles measuring 2 to 8 mm in the baseline state. They are indicative of the relative number of microscopic primordial follicles remaining in the ovary. If the antral follicle count is <> 30 as in PCOS, chances of hyperstimulation are very high.
In general, an obese, amenorrhoic woman with hyper insulinemia and high FAI is very likely to have a poor response with clomiphene citrate.
This article is also published in India study Channel
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