Clomid and Letrozole By Mike Dougherty on September 24, 2023

There are often many options for patients who are trying to conceive.  An individual’s age, history, prior treatments, and many other factors play a role in decide which management strategy is optimal for that specific patient.  Today, I will address two of the most common oral ovulation induction medications.

To understand how these medications work, we will need to understand how the ovary, and pituitary gland talk to each other (in simplified terms).  The pituitary gland is this little ball like gland that sits beneath your brain.  This is the "command center" for a lot of regulatory factors in the body.  The factors we will focus on here are FSH (follicle stimulating hormone) and LH (luteinizing hormone).  With normal function, these two chemicals are released from the pituitary gland when estrogen levels are LOW.  This is because the primary role of FSH, as the name suggests, is to create a follicle.   A follicle is a fluid filled sac with an egg inside of it.  FSH causes these follicles to grow, and develop and LH helps with growth and maturation of these follicles.  As the follicle grows, it produces estrogen.  As estrogen levels increase in your system, they reach the pituitary gland and let it know the ovary is doing its job and results in decreased levels of FSH.  Elevated estrogen levels are also believed to please a role in initiation of ovulation.  Oral ovulation induction agents allow us to take advantage of the way your body naturally responds to estrogen, to help further nourish and support growth of a mature follicle.

The first medication we will discuss is clomiphene citrate (CC) which falls in the class of drugs called SERM's or Selective Estrogen Receptor Modulators.  As the name suggest it binds to and modifies the way estrogen receptors recognize estrogen.  It binds to these receptors and prevents the pituitary gland from recognizing estrogen.  If your pituitary gland doesn't see estrogen, as we know from above, it will send more FSH down to the ovary to make it work harder to do its job.

The same premise stands true with use of letrozole.  However, this medication works on a different enzyme called Aromatase, and falls in the class of drugs called aromatase inhibitors.  The main secondary location estrogen is produced from besides the ovary is adipose tissue (fat cells).  These cells contain aromatase which converts male hormone (testosterone) into female hormone (estrogen).  When we give patients letrozole, aromatase does not covert as much male hormone to female hormone and the pituitary gland sees less estrogen and sends a stronger signal to the ovary.

This is why timing of the medication is so important.  Patients can take these medications for 5 days in the beginning of their cycle.  Whether the medication is taken from cycle days 3-7 or cycle days 5-9 results in equal outcomes.  However, it is important they are taken in the beginning of the cycle so they can have the desired effect.  The use of oral ovulation induction medications with or without intrauterine insemination is a common first line approach to management of infertility.

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Dr. Louis R. Manara

Center for Reproductive Medicine and Fertility

Dr. Louis R. Manara and the Center for Reproductive Medicine and Fertility team are dedicated to helping families achieve parenthood through safe, versatile, and personalized treatment options. We are affiliated with several noteworthy organizations including:

  • American Society for Reproductive Medicine
  • Society for Assisted Reproductive Technology
  • American Osteopathic Association®

​If you are struggling with infertility, a professional diagnosis is the best way to explore your treatment options. Schedule your initial consultation today by contacting us online or calling us at (856) 767-0009.

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