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Letrozole
Clinical data
ATC code
Pharmacokinetic data
Bioavailability99.9%
Protein binding60%, mainly to albumin
Elimination half-life2 days
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
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Chemical and physical data
FormulaC17H11N5
Molar mass285.303 g/mol

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Letrozole (INN, trade name Femara®) is an oral non-steroidal aromatase inhibitor that has been introduced for the adjuvant treatment of hormonally-responsive breast cancer

Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme. Letrozole blocks production of estrogens in this way by competitive, reversible binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole does not reduce production of mineralo- or corticosteroids. In contrast, the antiestrogenic action of tamoxifen, the major medical therapy prior to the arrival of aromatase inhibitors, is due to its interfering with the estrogen receptor, rather than inhibiting estrogen production.

FDA-approved use

Letrozole is approved by the United States Food and Drug Administration (FDA) for the treatment of local or metastatic breast cancer that is hormone receptor positive or has an unknown receptor status in postmenopausal women. Side effects include signs and symptoms of hypoestrogenism. There is concern that long term use may lead to osteoporosis, which is why prescriptions of Letrozole are often accompanied by prescriptions of osteoporosis-fighting medication such as Fosamax.

Off-label use

It has been in use for the use of ovulation induction by fertility doctors since 2001; having less side-effects than clomiphene citrate (Clomid®) for the patient. A Canadian study presented at the American Society of Reproductive Medicine 2005 Conference suggests that it may increase the risk of birth defects compared with a control group, however a more detailed follow-up study found no basis for concern when letrozole is used for ovulation induction.[1]

The manufacturer, Novartis, has issued letters to doctors in Canada and the United States reiterating that it is not approved for such a use and is not safe to use with pregnant women or women who may become pregnant.

Letrozole has shown to reduce estrogen levels by 98 percent while raising testosterone levels. The anti-estrogen action of letrozole is preferred by athletes and bodybuilders for use during a steroid cycle to reduce bloating due to excess water retention and prevent the formation of gynecomastia related breast tissue that is a side effect of some anabolic steroids. Usage above 2.5 mg/day is known to potentially temporarily kill sex drive. Above 5mg/day for extended periods may cause kidney problems.

Letrozole has also been shown to delay the fusing of the growth plates in adolescents. This may boost the effectiveness of growth hormone, and thus Letrozole is used to treat adolescents and children with short stature.

A related agent is anastrozole.

Letrozole has also been used to treat endometriosis.[2]

References

  1. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Apr 28. PMID 16650422
  2. http://www.endometriosis.org/ESHRE2005-abbamonte.html

See also

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