A historical perspective of aromatase inhibitors for ovulation induction

This review provides a brief history of the development of letrozole for ovulation induction.

Robert F. Casper, M.D. and Mohamed F. M. Mitwally, M.D., H.C.L.D.

Volume 98, Issue 6, Pages 1352-1355, December 2012

The concept of using aromatase inhibitors in place of clomiphene citrate (CC) for ovulation induction was introduced more than 10 years ago and a brief history of its development is presented. Worldwide usage for ovulation induction, and as an adjunct for intrauterine insemination and in vitro fertilization has occurred despite the absence of definitive data of superiority to CC. The results of two ongoing potentially definitive multicenter trials of efficacy and safety of letrozole compared to CC are eagerly awaited.

  • Isiah Harris

    Firstly, what a fascinating insight into the development of what is a common therapy in our practice, but sounds like nearly was abandoned. I am curious to hear what comments you might have about the use of letrozole for women with endometriosis who require superovulation. You mentioned it in the article, but because of the data suggesting improved pain with aromatase inhibitors for patients with endometriosis, I have preferentially been using letrozole for my endometriosis patients. However I worry that because the rates of multifollicular development are less with letrozole, that I may be ultimately doing them a disservice.

    Also, along the same lines, do you have any theories as to how the pregnancy rates with letrozole are the same as clomid despite the lower rate of multifollicular development? I generally blame the endometrial development, though I don’t believe that is supported by the available studies.

    • Robert F Casper

      Hi Isiah,

      Thanks for your comment. I don’t have any hard data on either question, but we also believe letrozole for ovulation induction in women with endometriosis makes sense just because estrogen levels even at ovulation are lower than other forms on COH. In addition, it is my belief that there is a beneficial effect of letrozole on the endometrium which has been demonstrated in many, but not all studies.

      Best regards,


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