From the FDA Drug Label
Letrozole selectively inhibits gonadal steroidogenesis but has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis. No clinically-relevant changes were found in the plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxy-progesterone, ACTH or in plasma renin activity among postmenopausal patients treated with a daily dose of letrozole 0. 1 mg to 5 mg.
The effect of letrozole on luteal phase progesterone levels is not directly addressed in the provided drug label. However, it is mentioned that letrozole selectively inhibits gonadal steroidogenesis, which could imply an effect on progesterone levels.
- Luteal phase progesterone levels are not explicitly mentioned in the label.
- The label does mention that letrozole has no significant effect on adrenal mineralocorticoid or glucocorticoid synthesis, and no clinically-relevant changes were found in the plasma concentrations of several hormones, including 17-hydroxy-progesterone. However, since the label does not directly address the effect of letrozole on luteal phase progesterone levels, a conservative clinical decision would be to say that the information is not available. 1
From the Research
Letrozole does not significantly affect luteal phase progesterone levels, and luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole. The most recent and highest quality study, published in 2023 2, found that luteal phase support with vaginal progesterone does not significantly improve clinical pregnancy rates in patients undergoing ovarian stimulation with letrozole. This study included 492 letrozole ovarian stimulation cycles and found that the unadjusted clinical pregnancy rate per cycle was 11.6% with progesterone and 13.3% without progesterone, with no significant difference between the two groups.
Key points to consider:
- Letrozole is an effective aromatase inhibitor that can induce ovulation by temporarily reducing estrogen levels and stimulating follicle-stimulating hormone release.
- The corpus luteum normally secretes progesterone to maintain the endometrial lining for embryo implantation and early pregnancy support.
- Progesterone supplementation is often recommended to support potential pregnancy, but the latest evidence suggests that it may not be necessary in patients undergoing ovarian stimulation with letrozole.
- The typical regimen for progesterone supplementation involves micronized progesterone 200mg vaginally once or twice daily, starting after ovulation and continuing until pregnancy testing.
- Side effects of progesterone supplementation may include vaginal irritation, breast tenderness, mood changes, and drowsiness, but these are generally well-tolerated.
In terms of the effect of letrozole on luteal phase progesterone levels, a study published in 2015 3 found that progesterone levels after letrozole-associated controlled ovarian stimulation for fertility preservation in breast cancer patients were similarly elevated to those obtained after standard controlled ovarian stimulation without letrozole. Another study published in 2022 4 found that letrozole co-treatment during ovarian stimulation with gonadotropins for IVF did not significantly affect the proportion of women with premature progesterone levels above 1.5 ng/ml at the time of triggering final oocyte maturation.
Overall, the latest evidence suggests that letrozole does not significantly affect luteal phase progesterone levels, and luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole. Therefore, progesterone supplementation during the luteal phase after letrozole treatment may not be necessary, and its use should be individualized based on patient-specific factors and clinical judgment.