Letrozole may be better than Clomid for women with PCOS

Letrozole (Femara) was associated with roughly a 42% increase in the pregnancy rate, compared with clomiphene citrate (Clomid) in infertile women with polycystic ovary syndrome in a double-blind, randomized study.

The pregnancy rate was 61.2% with letrozole versus 43% with clomiphene. There also was a trend toward more live births with letrozole (48.8% vs. 35.4%).

“We now have convincing evidence that letrozole is better than clomiphene and we should seriously consider moving on to letrozole,” principle investigator Dr. Saad Amer said at the annual meeting of the European Society of Human Reproduction and Embryology.

The results are consistent with the most recent Cochrane meta-analysis, which called for further research comparing letrozole with clomiphene as a primary ovulation induction agent in polycystic ovary syndrome (PCOS) because of low-quality evidence.

A recent robust U.S. study (N. Engl. J. Med. 2014;371:119-29) showed higher live-birth and ovulation rates with letrozole vs. clomiphene in women with PCOS, but it included a markedly obese population with a mean body mass index (BMI) of 35 kg/m2 and thus does not reflect clinical practice worldwide, Dr. Amer said.

The current results are more generalizable, especially in Europe, because the patients fulfilled the widely accepted Rotterdam diagnostic criteria for PCOS and had a median BMI of 27.7 kg/m2 in the clomiphene group and 27.5 kg/m2 in During a discussion of the results, reproductive medicine specialist Dr. Roy Homburg of Homerton University Hospital, London, said that it’s time for letrozole to recognized as the superior choice.

“Every study that has been done on the subject, every randomized controlled trial, every meta-analysis, every Cochrane database has shown exactly what you have shown – the superiority of letrozole over clomiphene,” Dr. Homburg said. “ I think it’s about time people start believing this and make sure letrozole is on-label rather than off-label.”

Dr. Amer agreed. “It’s now time for clomiphene to retire,” he said, receiving a round of applause from the audience.

Although this sounds pretty convincing, not all doctors may be ready to accept this for all PCOS patients so many doctors may still be prescribing Clomid.

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