Clinical comparison · PCOS & fertility · Updated 2026-07-02
Letrozole and clomiphene are oral medicines used to induce ovulation in PCOS. This table reproduces labeled and trial-reported facts verbatim, per cell. The PPCOS II trial compared them directly and is summarized below. The page reports the trial result as published and does not add a recommendation.
Every value below is reproduced verbatim from an FDA prescribing-information document or a published clinical trial, and each cell links to its source. This page does not rank the two options, does not declare one safer or more effective, and is not medical advice.
| Dimension | Letrozole | Clomiphene |
|---|---|---|
| Drug class | Aromatase inhibitor[1] | Selective estrogen receptor modulator (SERM)[2] |
| Live-birth rate in PCOS (PPCOS II) | 27.5% live-birth rate[3] | 19.1% live-birth rate[3] |
| Typical fertility dosing | 2.5 mg daily for 5 days (may titrate to 5-7.5 mg)[1] | 50 mg daily for 5 days (may titrate to 100-150 mg)[2] |
| Most common side effect | Hot flashes/flushes 33.5% (Femara label)[1] | Vasomotor flushes 10.4%[2] |
| Distinct labeled caution | Short 5-day course; effects short-lived[1] | Visual disturbances (~1.5%) warrant discontinuation[2] |
| Multiple-pregnancy note | Lower twin rate than clomiphene, still elevated vs natural conception[4] | Multiple pregnancies 7.98% (twins 6.9%)[2] |
What PPCOS II measured (direct head-to-head)
PPCOS II randomized women with PCOS to letrozole or clomiphene for ovulation induction and measured live-birth rate. It reported 27.5% live births with letrozole versus 19.1% with clomiphene. This is a genuine head-to-head result, reproduced as published. PPCOS II (NEJM 2014)
Guideline context
The 2023 International PCOS Guideline and a Cochrane review both address ovulation-induction agents. Their positions are summarized in the sources; this page reproduces numeric endpoints rather than guideline recommendations. International PCOS Guideline (2023)
In women with PCOS, PPCOS II reported a live-birth rate of 27.5% with letrozole versus 19.1% with clomiphene (NEJM 2014).
The FDA Clomid label notes visual disturbances (about 1.5%), which warrant discontinuation. Letrozole is given as a short 5-day course.
Both can raise multiple-pregnancy risk. The Clomid label cites roughly a 7-10% twin rate; a Cochrane review notes letrozole has a lower twin rate than clomiphene but still above natural conception.
Editorial reviews from ClearHormones of telehealth providers in this category. These are not treatment recommendations, and prescribing decisions rest with a licensed clinician.