Letrozole, used for treating infertility of women in India, may cause damage to women and their babies. Proper tests are not taken of Letrozole to prove that it is safe and effective treatment for infertility.

The drug sold under name of Femara, developed by Novartis, was approved in 1998 as a treatment drug for breast cancer in post-menopausal women only. Letrozole inhibits the enzymes responsible for producing estrogen. When it is given to women of child-bearing age, it stimulates the follicular development and could be exploited to induce ovulation.

Letrozole used as a fertility drug has been registered as an additional indication of the known drug. Therefore, it has undergone only phase III trials and skipped the phases that establish the safety, determine side effects, dose and regimen.

India’s Drugs and Cosmetics Act Section 122E(b) states, “if a drug is found to have a new indication, it should be considered new and subjected to the gamut of clinical trials. But, if the dosage form is the same, the drugs regulator can waive previous phases provided that drug safety and concept are properly proven.”

Drugs Controller-General of India M. Venkateswarlu, says, “No new toxicity studies were necessary because in the opinion of experts, that is, five gynaecologists who approved the trails, “this is a short-term course (three-five days) and the dosage (2.5mg) is the same. The toxicity information generated from the cancer trials is sufficient.”

Letrozole is embryotoxic and foetoxic as shown by the toxicity information generated from cancer trails and contained in Novartis’ prescribing information.

Company states under “warnings” – “Femara (Letrozole) may cause foetal harm when administered to pregnant women.”

Drug tested on animals showed “intrauterine mortality, increased resorption, increased post-implantation loss, decreased numbers of live fetuses and foetal anomalies, including incomplete ossification of skull, forelegs and hind legs. Repeated doses at the equivalent dose to humans and less “caused sexual inactivity in females and atrophy of reproductive tract in males and females.”

Despite a 2005 warning issued by Novartis against the use of Letrozole in fertility treatment, the drug has been approved.

Dr. Venkateswarlu said based on a 2005 study at the Montreal Fertility Centre, Canada, published in the journal Fertility and Sterility, but that a 2006 study at the same centre found that the drug had nothing to do with the deformities observed in babies in the initial study.

Dr. Venkateswarlu said, “We rely on the opinion of our experts.”

Health Canada, the Canada Health authority, maintains that Letrozole should not be used for infertility treatment, despite such off label studies. A copy of Novartis advisory was sent to all its gynaecologists on November 22, 2005 and is still displayed on their website.

Market approval to treat infertility has not been given in the United States or the United Kingdom.

Sun Pharmaceuticals prescribed information shows that approval has been given based on a collation of separate studies by foreign research institutes and one multi-centric study conducted on 55 women in India.

Sun Pharmaceuticals spokesperson said, “We have submitted the necessary information required for the approval of the drug and based on that we have been given marketing approval.”

Indian generic companies including Sun Pharmaceuticals were caught illegally boosting the drug as an infertility treatment under the brand Letoval.

“Femara (Letrozole) is not approved for use in treatment of infertility and Novartis does not promote Femara for this indication,” said spokesperson for Novartis India.

“Femara is contraindicated and should not be used in women who may become pregnant, during pregnancy and/or while breastfeeding, because there is a potential risk of harm to the mother and the foetus, including risk of foetal malformations,” stated the 2005 Novartis advisory.

Another study is carried out by New York researchers on the stress levels of women undergoing fertility treatment.

The study indicated that stress levels seemed to be unrelated to choice of a women undergoing fertility treatment, to tell her employer and co-workers about it.

Dr. Peter S. Finamore, the UNDNJ-Robert Wood Johnson Medical School in New Brunswick, New Jersey, led the research on 267 women undergoing treatment at university’s fertility clinic.

Researchers speculated that such disclosure might help ease stress for some women. Fertility treatment is time-consuming and bound to require taking time off from work, keeping the reason for work absences secret might, generate added anxiety for some women.

Some women might be stressed by having to tell their boss about such a personal matter.

Finamore’s team found that whether women informed their employer about fertility treatments, made no apparent difference in their reported stress levels.

Researchers write, “the results of this survey suggest that disclosure of one’s infertility status is not a significant factor in either increasing or diminishing persona stress.”