What is the role of Clomiphene (Clomifene) in the treatment of Polycystic Ovary Syndrome (PCOS)?

From the Guidelines

Clomiphene citrate is the recommended first-line treatment for ovulation induction in women with PCOS who wish to conceive, due to its effectiveness as stated by the ACOG guidelines 1. The treatment typically starts with a dose of 50mg daily for 5 days, beginning on day 3-5 of the menstrual cycle, and can be increased by 50mg increments in subsequent cycles if ovulation doesn't occur. According to the ACOG guidelines, about 80 percent of women with PCOS ovulate and one half of these patients conceive when treated with clomiphene citrate 1. Some key points to consider when using clomiphene citrate for PCOS include:

• Starting with a low dose and increasing as needed to minimize side effects
• Limiting treatment to 6 ovulatory cycles, as pregnancy rates don't significantly improve beyond this point
• Tracking ovulation using basal body temperature, ovulation predictor kits, or mid-luteal progesterone levels, and timing intercourse accordingly
• Using ultrasound monitoring to track follicular development and reduce the risk of multiple pregnancies
• Being aware of potential side effects, such as hot flashes, mood swings, breast tenderness, and visual disturbances If pregnancy doesn't occur after 3-6 ovulatory cycles, alternative treatments like letrozole, gonadotropins, or referral for assisted reproductive technologies should be considered, as recommended by the ACOG guidelines 1.

From the FDA Drug Label

Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome Clomiphene citrate should not be used in patients with ovarian enlargement except those with polycystic ovary syndrome

Clomiphene for PCOS: Clomiphene citrate is indicated for the treatment of ovulatory dysfunction in women with Polycystic Ovary Syndrome (PCOS) who desire pregnancy.

• Key points:
  • Clomiphene citrate is effective in patients with PCOS.
  • Patients with PCOS are among those most likely to achieve success with clomiphene therapy.
  • Clomiphene citrate can be used in patients with PCOS, even if they have ovarian enlargement. 2

From the Research

Clomiphene for PCOS

• Clomiphene citrate (CC) is a commonly used medication for inducing ovulation in women with polycystic ovary syndrome (PCOS) 3, 4, 5, 6, 7.
• Studies have compared the efficacy of CC with other treatments, such as metformin, letrozole, and gonadotropins, for ovulation induction in PCOS patients 3, 5, 6.
• A study published in 2007 found that CC and metformin were equally effective in inducing ovulation in PCOS patients, with no significant difference in pregnancy rates 3.
• Another study published in 2018 found that intermittent CC treatment was effective in inducing ovulation in PCOS patients who were resistant to standard CC treatment, with an overall success rate of 80.8% 4.
• A meta-analysis published in 2019 found that letrozole was more effective than CC in inducing ovulation and achieving live birth in PCOS patients, and that CC plus metformin may be more effective than CC alone in improving clinical pregnancy rates 5.
• A randomized clinical trial published in 2018 found that letrozole was more effective than CC combined with metformin in inducing ovulation and achieving clinical pregnancy in CC-resistant PCOS patients 6.
• A review published in 2012 discussed the use of CC alternatives for the initial management of PCOS, including weight loss, insulin-sensitizing drugs, aromatase inhibitors, and gonadotropins 7.

Efficacy of Clomiphene for PCOS

• The efficacy of CC for ovulation induction in PCOS patients has been established in several studies, with ovulation rates ranging from 55.4% to 82% 3, 4, 6.
• The cumulative pregnancy rate with CC treatment has been reported to be around 62.9% to 48.6% 3.
• However, some studies have found that letrozole may be more effective than CC in achieving live birth and clinical pregnancy in PCOS patients 5, 6.

Comparison with Other Treatments

• CC has been compared with other treatments, such as metformin, letrozole, and gonadotropins, for ovulation induction in PCOS patients 3, 5, 6.
• Letrozole has been found to be more effective than CC in inducing ovulation and achieving live birth in PCOS patients 5, 6.
• CC plus metformin may be more effective than CC alone in improving clinical pregnancy rates 5.