What is the cause of slow follicular growth on Letrozole (letrozole) while taking estrogen for endometrial lining thickening?

From the Guidelines

The cause of slow follicular growth on Letrozole while taking estrogen for endometrial lining thickening is likely due to individual variability in response to the standard letrozole dose, and adjusting the dosage or adding injectable gonadotropins may be necessary to stimulate follicle development. When considering the treatment of slow follicular growth, it is essential to prioritize the patient's morbidity, mortality, and quality of life. According to the study published in the Annals of Oncology 1, the use of letrozole does not reduce the number of mature oocytes obtained or their fertilization capacity. However, some women may be less responsive to standard letrozole doses, requiring adjustments to stimulate follicle growth. Some key points to consider in the management of slow follicular growth include:

• Letrozole works by temporarily reducing estrogen production, which triggers the pituitary to release more FSH to stimulate follicle growth
• Estrogen supplementation for lining thickening, typically estradiol 2mg daily, should not interfere with follicle growth as these medications work through different mechanisms
• Monitoring through ultrasound and blood tests is essential to track progress and make appropriate medication adjustments
• Adjusting the letrozole dosage, typically from 2.5mg to 5mg or 7.5mg daily for 5 days, or extending the treatment duration may be necessary to stimulate follicle development
• Adding injectable gonadotropins like Follistim or Gonal-F may also be considered to stimulate follicle growth It is crucial to weigh the potential benefits and risks of each treatment option and prioritize the patient's overall health and well-being. As noted in the study 1, the efficacy of oocyte and embryo cryopreservation to generate a subsequent pregnancy is tightly connected to the number of mature oocytes retrieved after ovarian stimulation. Therefore, optimizing follicular growth and development is critical to achieving successful treatment outcomes.

From the Research

Causes of Slow Follicular Growth on Letrozole

• The use of letrozole, an aromatase inhibitor, can affect follicular growth by reducing estrogen production, which may lead to slower follicular growth 2.
• Letrozole may not provide the optimal environment for follicular development, as it primarily targets the inhibition of aromatase, which may not be sufficient to support the growth of small antral follicles 2.
• The health of small antral follicles is driven primarily by androgens, which contribute to granulosa cell mitosis, sensitivity to FSH, and resistance to atresia, and letrozole may not effectively promote these benefits 2.

Effect of Estrogen on Endometrial Lining Thickening

• Estrogen is often used to thicken the endometrial lining, which is essential for implantation of the embryo 3, 4.
• Letrozole, when used in combination with FSH, can result in a significant reduction in the FSH dose needed for controlled ovarian hyperstimulation, but its effect on endometrial thickness may vary 3, 5.
• The use of letrozole with estrogen for endometrial lining thickening may not be directly addressed in the available studies, but it is known that letrozole does not deplete estrogen receptors, which could potentially benefit endometrial growth 3, 4.

Interaction between Letrozole and Estrogen

• Letrozole inhibits aromatase, which reduces estrogen production, but it does not deplete estrogen receptors, allowing for the potential benefits of exogenous estrogen on endometrial growth 3, 4.
• The combination of letrozole and estrogen may have varying effects on follicular growth and endometrial thickness, depending on the specific protocol and patient population 3, 5.