How does Clomiphene work?

Clomiphene fools a part of the brain (called the pituitary gland) into thinking that the ovaries are not producing any estradiol, one of three estrogen hormones naturally produced in the body. The pituitary responds to this by increasing the production of Follicle Stimulating Hormone (FSH). When this hormone increases, it stimulates the ovary to produce eggs and follicles. In response to higher levels of FSH, the ovary becomes more likely to produce a mature egg.

In a simpler description—it increases the production of FSH, and FSH is the hormone that induces the ovary to produce follicles and eggs.

What are the Side Effects of Clomiphene?

Clomiphene is associated with a fair number of side effects. A small percentage of women will experience mild headaches, bloating, hot flashes, or visual symptoms. If you experience visual effects, you need to stop the medication and notify your doctor right away. A rather large percentage of couples report that the use of clomiphene results in some emotional instability. If you are taking clomiphene and find that your emotions are a little hard to control, especially in the second half of the cycle, blame it on the clomiphene.

There are no known risks to the fetus or adverse effects on the infant should conception occur. Ovarian cysts may occur in some individuals on clomiphene, but if no additional clomiphene is given, the cysts will almost always resolve on their own.

What are the Advantages of Clomid over Letrozole?

Clomid is the only oral FDA-approved medication for ovulation induction. Letrozole is approved by the FDA exclusively for the treatment of postmenopausal women with breast cancer. Use of letrozole for ovulation induction is an off-label use. Many medications are used for off-label indications.

The use of letrozole for this indication came under fire based on a small Canadian study published by Biljan. This study was poorly controlled and involved very small numbers of patients and birth defects. However, it suggested that the use of letrozole was associated with an increased risk of birth defects. Therefore Novartis Pharmaceutical, the company that makes letrozole has issued a letter advising that letrozole not be used for ovulation induction.

Many studies have since been done and have not shown an increased risk of birth defects with use of letrozole. Letrozole has a half-life of forty hours. When used for ovulation induction, it is completely cleared from your blood by the time of conception. This makes it very difficult to explain how the use of letrozole could result in congenital malformations. There is no question that this medication should not be used during pregnancy, but it is used for ovulation induction only following the onset of normal menses and a negative pregnancy test.

What are the Advantages of Letrozole over Clomid?

1. Side effects—Clomiphene is associated with significant side effects, including hot flashes, vaginal dryness, headaches, and mood swings. Letrozole is essentially side-effect free.
2. Clomid use for many cycles can cause thickening of cervical mucus, which makes it harder for sperm to enter the uterus and find an egg. It can also thin the lining of the uterus which makes it harder for a fertilized embryo to implant into the uterus.
3. Letrozole is less likely to result in a multiple pregnancy.
   Letrozole: Twins approximately 5%, Very rare to have triplets.
   Clomid: Twins approximately 10%, approximately 1% triplets.