Letrozole vs Clomid for Ovulation: Labels and Trial
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[Fertility · Comparison]

Letrozole vs Clomid: what is the difference for fertility?

FDA status · Dosing · Cycle limits · PCOS trial · Warnings

Short answer: Clomid (clomiphene) is FDA approved to treat ovulation problems in women trying to get pregnant. Letrozole (Femara) is approved only for breast cancer after menopause, so using it to bring on ovulation is off label.12 In one trial of 750 women with polycystic ovary syndrome, letrozole led to more live births than clomiphene: 27.5% vs 19.1%.3

How do letrozole and Clomid compare side by side?

From the US Femara and Clomid labels unless noted.
Letrozole (Femara)Clomiphene (Clomid)
How it worksAromatase inhibitor: lowers estrogen production2Competes with estrogen at estrogen receptors, including in the hypothalamus and pituitary1
FDA-approved useBreast cancer in postmenopausal women only. Not approved for ovulation induction2Ovulation problems in women who want to become pregnant1
Label dose2.5 mg once daily, for breast cancer. No fertility dosing on the label250 mg daily for 5 days, started around day 5 of the cycle; if no ovulation, 100 mg daily for 5 days. No higher1
Course limitsNone for fertility (not a labeled use)2Stop after 3 courses without ovulation, or 3 ovulatory cycles without pregnancy; about 6 cycles in total1
Half-lifeAbout 2 days2No single figure; the zuclomiphene part stayed detectable for more than a month1
PregnancyContraindicated in pregnancy; can cause fetal harm. Pregnancy test before starting2Contraindicated in pregnancy; check for pregnancy before each new cycle1
PCOS trial: live births27.5%319.1%3
PCOS trial: ovulation (per cycle)61.7%348.3%3
PCOS trial: twins3.4%37.4% (difference not significant)3
Common side effectsIn the PCOS trial: more fatigue and dizziness3Label: ovarian enlargement 13.6%, hot flushes 10.4%, visual symptoms 1.5%. In the PCOS trial: more hot flushes13

Reviewed . Half-life figures are shown only where the value Dose Track uses agrees with the cited source.

Is letrozole FDA approved for fertility?

No. The Femara label lists three uses, all breast cancer treatment in postmenopausal women, at 2.5 mg once a day.2 It also says letrozole is contraindicated in pregnancy and asks for a pregnancy test before starting.2 Fertility clinics prescribe it off label, so the timing and dose come from your clinic, not from the label.

Clomid's label is written for ovulation induction: 50 mg a day for 5 days, then 100 mg a day for 5 days only if ovulation does not happen, with ovulation usually 5 to 10 days after a course.1

What did the head-to-head trial show?

Legro and colleagues randomly assigned 750 women aged 18 to 40 with polycystic ovary syndrome to letrozole or clomiphene for up to five cycles, in a double-blind trial.3

  • Live births: 27.5% (103 of 374) with letrozole vs 19.1% (72 of 376) with clomiphene; rate ratio 1.44.3
  • Ovulation: 61.7% vs 48.3% of treatment cycles.3
  • Pregnancy loss and twins: no significant differences (loss 31.8% vs 29.1%; twins 3.4% vs 7.4%).3
  • Birth defects: no significant difference overall; there were four major congenital anomalies with letrozole vs one with clomiphene (P=0.65).3

The trial was only in women with polycystic ovary syndrome, so it does not tell us how the two compare for other causes of infertility.

What does the Clomid label warn about?

  • Vision: blurring, spots or flashes can occur and become more common with higher doses or longer use. Stop and get an eye exam if they happen.1
  • Multiple pregnancy: 7.98% of pregnancies in its trials were multiples, including 6.9% twins.1
  • Ovarian hyperstimulation: OHSS has been reported; the ovaries are checked between cycles.1

More detail: Clomid side effects, Femara side effects, the Clomid and Femara dosing schedules, a missed Femara dose, and how to store Femara and Clomid.

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Frequently asked questions

Is letrozole better than Clomid for getting pregnant?+
In one large trial of women with polycystic ovary syndrome, letrozole led to more live births (27.5% vs 19.1%) and more ovulation.3 That trial did not cover other causes of infertility, and letrozole is not FDA approved for this use.2
Is letrozole FDA approved for ovulation induction?+
No. Femara is approved only for breast cancer in postmenopausal women; fertility use is off label.2
How many cycles of Clomid can you take?+
The label says stop after 3 courses without ovulation or 3 ovulatory cycles without pregnancy, and not to go beyond about 6 cycles in total.1
Do letrozole and Clomid cause twins?+
In the PCOS trial, twins were 3.4% with letrozole vs 7.4% with clomiphene, not a significant difference.3 In Clomid's own trials, 6.9% of pregnancies were twins.1
Can I track letrozole or Clomid cycles in Dose Track?+
Yes. Both are built in. Log each tablet on your cycle days, set reminders for the 5-day course, and keep notes next to your doses.

Sources

  1. Clomid (clomiphene citrate) tablets prescribing information: clinical studies, indications, contraindications, warnings, adverse reactions and dosage. DailyMed, version of January 2025.
  2. Femara (letrozole) tablets prescribing information, sections 1, 2, 4, 5.6, 8.1, 8.3 and 12.3. DailyMed, version of June 2026.
  3. Legro RS, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371:119-129.

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