Polycystic Ovary Syndrome (PCOS) is a common hormonal disorder affecting individuals of reproductive age, often leading to irregular or absent ovulation, known as anovulation. This anovulation is a primary reason many individuals with PCOS experience difficulty conceiving. Letrozole has emerged as a widely used oral medication designed to induce ovulation in those diagnosed with PCOS, helping them pursue pregnancy.
Mechanism of Action for Ovulation Induction
Letrozole functions as an aromatase inhibitor, temporarily blocking the aromatase enzyme. This enzyme converts androgens into estrogen. By inhibiting aromatase, letrozole causes a temporary reduction in the body’s estrogen levels, which can be as significant as 97% to 99%.
This drop in estrogen levels sends a signal to the pituitary gland to increase its production of Follicle-Stimulating Hormone (FSH). Elevated FSH levels directly stimulate the ovaries, encouraging the development of one or more ovarian follicles. The growth of these follicles culminates in the release of a mature egg, initiating ovulation.
The Letrozole Treatment Cycle
A typical letrozole treatment cycle begins with the medication taken daily for five days, usually starting between cycle day 3 and 5 following a menstrual period. The common initial dosage is 2.5 milligrams (mg) per day. If ovulation does not occur in the first cycle, the dosage may be increased in subsequent cycles, typically in 2.5 mg increments, up to a maximum of 7.5 mg daily.
Throughout the treatment, healthcare providers monitor progress using transvaginal ultrasounds. These ultrasounds track the growth of ovarian follicles, aiming for one or two dominant follicles. Monitoring also includes assessing the thickness of the endometrial lining to support a potential pregnancy. In some cases, once a follicle reaches an appropriate size, a trigger shot of human chorionic gonadotropin (hCG) may be administered to precisely time the release of the egg.
Efficacy and Expected Outcomes
Letrozole is often considered a first-line treatment for ovulation induction in individuals with PCOS, frequently preferred over clomiphene citrate due to its favorable outcomes. Studies indicate high ovulation rates, with some reporting that approximately 62% to 93% of women with PCOS ovulate when using letrozole.
While ovulation rates are high, the live birth rate per cycle is lower, ranging from about 25.4% to 28%. One study showed a live birth rate of 27.5% for women with PCOS receiving letrozole over five cycles, compared to 19.1% for those on clomiphene. The chance of multiple pregnancies, such as twins, is lower with letrozole compared to clomiphene, typically around 2-3%. This reduced risk occurs because letrozole tends to promote the development of fewer dominant follicles, decreasing the likelihood of multiple eggs being released and fertilized.
Potential Side Effects
Individuals taking letrozole may experience side effects, largely due to temporary hormonal fluctuations caused by the medication. Common side effects include hot flashes, fatigue, dizziness, and headaches. Some may also report bone, muscle, or joint pain, or upset stomach.
Less common, but more serious, is the potential for Ovarian Hyperstimulation Syndrome (OHSS). This condition involves swollen, painful ovaries, ranging from mild symptoms like bloating and nausea to severe complications such as excessive weight gain, abdominal swelling, and difficulty breathing. While OHSS can occur with fertility treatments that stimulate the ovaries, it is rare with oral medications like letrozole, particularly compared to injectable fertility drugs.