Clomiphene vs Letrozole: Which Fertility Drug Works Better for You?

When it comes to helping women ovulate, clomiphene, a selective estrogen receptor modulator used for over 60 years to treat anovulation has long been the go-to choice. But in recent years, letrozole, an aromatase inhibitor originally developed for breast cancer that’s now widely used for fertility has gained serious ground. Both drugs stimulate ovulation, but they work in completely different ways—and that difference matters a lot depending on your body, your diagnosis, and your goals.

Clomiphene tricks your brain into thinking estrogen levels are low, which tells your pituitary gland to pump out more follicle-stimulating hormone (FSH). More FSH means more eggs mature. Letrozole, on the other hand, blocks the enzyme that turns androgens into estrogen. Lower estrogen levels send the same signal to your brain—but without affecting cervical mucus or the uterine lining the way clomiphene sometimes does. That’s why many doctors now prefer letrozole for women with PCOS. A 2014 study published in the New England Journal of Medicine found that women with PCOS had higher live birth rates with letrozole than with clomiphene—about 27% vs. 19% over six cycles. That’s not a small gap. It’s the kind of difference that changes treatment plans.

Side effects also vary. Clomiphene can cause hot flashes, mood swings, and blurry vision. Letrozole might give you headaches or joint pain, but it’s less likely to dry out cervical mucus or thin the uterine lining—two things that can hurt your chances of implantation. If you’ve tried clomiphene and didn’t get pregnant after three to six cycles, switching to letrozole is a common next step. And if you’re over 35 or have insulin resistance, letrozole often performs better. Neither drug is perfect. Clomiphene is cheaper and more widely available. Letrozole isn’t FDA-approved for fertility (it’s used off-label), but that doesn’t mean it’s unsafe—it just means the paperwork isn’t done yet. Many clinics now treat letrozole as the first-line option for PCOS-related infertility.

What you won’t find in most brochures is how personal this choice is. One woman’s breakthrough is another’s disappointment. Some respond better to the hormonal nudge of clomiphene. Others need the more direct approach of letrozole. Your doctor will look at your AMH levels, your weight, your insulin sensitivity, and your past treatment history—not just your age or diagnosis. The goal isn’t just to ovulate. It’s to ovulate in a way that gives you the best shot at a healthy pregnancy. That’s why the comparison between these two drugs isn’t just about science. It’s about matching the right tool to your body’s unique needs.

Below, you’ll find real-world comparisons, patient experiences, and clinical insights that help cut through the noise. Whether you’re just starting out or you’ve been through cycles before, these posts give you the facts you need to ask better questions and make smarter choices.