From the Guidelines
Clomiphene citrate is the most recommended medication to help induce ovulation in women experiencing ovulatory disorders, as it has been shown to be effective in inducing ovulation in about 80% of women with PCOS, with approximately half of these patients conceiving 1. The typical regimen involves taking 50mg daily for 5 days, usually starting on day 3-5 of the menstrual cycle. If ovulation doesn't occur at this dose, it may be increased in subsequent cycles up to 150mg daily.
Alternative Options
Letrozole (Femara) is an alternative that is increasingly preferred by many fertility specialists, taken at 2.5-7.5mg daily for 5 days, as it has been shown to be effective in inducing ovulation while keeping estrogen levels near physiologic levels 1. Both medications work by blocking estrogen receptors, which triggers the pituitary gland to release more follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stimulating the ovaries to develop and release eggs.
Additional Considerations
For women who don't respond to these oral medications, injectable gonadotropins like Follistim or Gonal-F may be necessary, though these require closer monitoring due to increased risk of multiple pregnancies. Women should be aware that ovulation typically occurs 5-10 days after the last pill, making this the optimal time for intercourse or insemination. Some potential side effects may include hot flashes, mood swings, breast tenderness, and in rare cases, ovarian hyperstimulation syndrome. It's worth noting that more recent studies, such as the one published in 2025 1, do not support the use of clomiphene citrate as a first-line treatment for functional hypothalamic amenorrhea, but this does not apply to the general recommendation for ovulation induction in women with PCOS.
From the FDA Drug Label
Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. The therapeutic objective should be balanced with potential risks and discussed with the patient and others involved in the achievement of a pregnancy. Treatment of the selected patient should begin with a low dose, 50 mg daily (1 tablet) for 5 days.
The recommended medication to help ovulation is clomiphene citrate.
- The initial dose is 50 mg daily for 5 days.
- The dose may be increased to 100 mg daily for 5 days if ovulation does not occur after the first course of therapy.
- Clomiphene citrate therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders 2.
- Long-term cyclic therapy is not recommended beyond a total of about six cycles 2.
From the Research
Recommended Medication for Ovulation Induction
The recommended medication for ovulation induction can vary depending on the specific condition and patient population.
- For women with polycystic ovary syndrome (PCOS), studies have compared the efficacy of letrozole and clomiphene citrate (CC) for ovulation induction 3, 4, 5, 6, 7.
- Letrozole has been shown to have a higher ovulation rate compared to CC in some studies 4, 5, 6, 7.
- A systematic review and meta-analysis found that letrozole had a higher probability of ovulation compared to CC in infertile women with PCOS 7.
- However, another study found that CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS 3.
- Letrozole has also been compared to human menopausal gonadotropin (HMG) for ovulation induction in clomiphene-resistant PCOS patients, and was found to have similar ovulation and pregnancy rates, but with a lower risk of ovarian hyperstimulation syndrome 4.
Comparison of Letrozole and Clomiphene Citrate
- Letrozole has been shown to have a higher ovulation rate and clinical pregnancy rate compared to CC in some studies 5, 6, 7.
- However, CC is still widely used as a first-line treatment for ovulation induction in women with PCOS 3.
- The choice of medication may depend on individual patient factors, such as medical history and fertility goals.
Safety and Efficacy
- Letrozole has been found to have a lower risk of ovarian hyperstimulation syndrome compared to HMG 4.
- However, the use of letrozole for ovulation induction is not FDA or EMA approved, and its use is "off-label" 7.
- Further research is needed to fully understand the safety and efficacy of letrozole and CC for ovulation induction in women with PCOS.