Clomid vs Letrozole: An Overview
What is Clomid?
Clomid is a brand-name medication that contains the active drug clomiphene. It is no longer available, but its generic version, clomiphene, is still available. Clomiphene is used to treat infertility in females by helping cause ovulation. It is the most commonly used oral agent for the induction of ovulation. It is a nonsteroidal selective estrogen receptor modulator with predominant antiestrogenic action, resulting in long-lasting estrogen receptor depletion.
What is Letrozol?
Letrozole is an active drug that is sometimes used off-label to treat infertility in females. It is an aromatase inhibitor that stops the body from making the hormone estrogen. When estrogen isn't being made, the body can ovulate. Letrozole is often used to treat infertility that's caused by polycystic ovarian syndrome (PCOS), but it can treat other forms of infertility as well. It is utilized similarly to clomiphene citrate but with additional benefits. Letrozole has fewer side effects, a shorter half-life than clomiphene citrate, and no demonstrable effect on the receptivity of the endometrium [1, 2].
Clomid vs Letrozole: Uses
Uses of Clomid
Clomid(clomiphene) is primarily used as a fertility drug to induce ovulation in women who have difficulty conceiving due to certain types of infertility. It works by stimulating an increase in the amount of hormones that support the growth and release of a mature egg during the ovulation cycle [3].
Clomid and Cancer risk: Research suggests that Clomid may have a protective effect against certain types of cancer. For instance, one study found that women who used Clomid had a lower rate of colorectal cancer, particularly among those who first used the drug more than eight years ago. Another study found that the risk of breast cancer was reduced among women who had taken Clomid compared to infertile women who had not used this drug.
Uses of Letrozole
Letrozole is primarily used for treating breast cancer in post-menopausal women. As we previously explained, It works by decreasing the amount of estrogen produced by the body, which can slow or stop the growth of some types of breast cancer cells that need estrogen to grow [4].
Letrozole is used to treat early breast cancer in women who have experienced menopause and have had other treatments, such as radiation or surgery, to remove the tumour. It is also used as a first treatment of breast cancer that has spread within the breast or to other areas of the body or in women whose breast cancer has worsened while they were taking tamoxifen [4].
In addition to its use in cancer treatment, Letrozole has also been utilized in infertile pre-menopausal women because of its ability to enhance FSH production for ovulation induction [5]. It is often used to treat infertility that's caused by polycystic ovarian syndrome (PCOS), but it can treat other forms of infertility as well [4]. Letrozole is sometimes used off-label to treat infertility in females. When estrogen isn't being made, your body can ovulate. To make ovulation happen at the right time in your menstrual cycle, you'll take letrozole for a few days after the start of your period [4].
Letrozole is also emerging as a possible treatment for male infertility of unknown cause, proving to be an effective way of influencing hormonal profiles and increasing various seminal parameters such as sperm motility and concentration, as it inhibits aromatization affecting the feedback mechanism to the hypothalamus [6].
Clomid vs Letrozole: Side effects
Side effects of Clomid
Common side effects of Clomid (clomiphene citrate) include breast tenderness [7, 8], irritability, and mood changes [7, 8, 9]. In one study, 77.8% of women reported experiencing psychological side effects like irritability or mood swings. Additional common side effects include:
- hot flashes which affect around 10% of women ,
- headaches [9],
- bloating and nausea [9],
- visual disturbances such as blurred vision [7, 8, 9].
Severe side effects of Clomid can include:
- ovarian enlargement, which affects around 5% of women , and ovarian hyperstimulation syndrome (OHSS), which may cause abdominal pain.
- visual changes caused by swelling of the pituitary gland [7, 8],
- acceleration of prostate cancer growth in men (if cancer is already present) [7, 8],
- a slightly increased risk of ovarian tumours with long-term use beyond six cycles [9],
- and rare psychotic reactions or severe mood changes requiring medical attention .
These side effects are typically reversible after stopping the medication, but immediate medical attention is advised if severe symptoms occur [7, 8].
Side effects of Letrozole
Letrozole, a medication often used in the treatment of breast cancer, can cause a variety of side effects.
Some of the most common side effects of letrozole include:
- hot flashes,
- bone pain,
- and weakness [10, 4].
- Fatigue or low energy is another side effect some may experience while taking the medication [10].
- Swelling in the arms, hands, legs, or feet,
- increased sweating or night sweats,
- and nausea
have also been reported [10, 4]. Additionally, vaginal bleeding or spotting, vaginal dryness or irritation, and constipation could occur [10]. Weight gain and hair loss are other reported side effects [10, 4], while headaches and joint pain are common [1, 10, 4].
Severe side effects: Letrozole can also cause severe side effects, although these are rare. These include high cholesterol levels, osteoporosis (weakened bones), bone fractures, high blood pressure, cardiovascular side effects (which are related to the heart and blood vessels), such as heart attack and stroke, and depression [10]. A severe allergic reaction is also possible after taking Letrozole, but it's not clear whether this side effect occurred in studies [1, 10, 4].
If you experience any of these side effects, it is essential to consult with your doctor immediately.
Choosing between Clomid and Letrozole
When it comes to choosing between Clomid (clomiphene citrate) and Letrozole for ovulation induction, the decision can be complex as both medications have their benefits and potential drawbacks.
Clomid has been the traditional first-line treatment for anovulatory infertility. However, studies have shown that letrozole can be an effective alternative. A subgroup of women treated with 2.5 mg of letrozole displayed a statistically significant higher rate of clinical pregnancy compared to those treated with 100 mg of Clomid [11].
In a study involving women with polycystic ovary syndrome (PCOS), the ovulation rate was higher in the Letrozole group (86.0%) compared to the Clomid group (72.0%). However, this difference was not statistically significant. The pregnancy rate was slightly higher in the letrozole group (22.0% vs 18.0%) but also not statistically significant [12].
In another study, women with PCOS who received letrozole had more cumulative live births than those who received Clomid (27.5% vs. 19.1%) [13].
In conclusion, both Clomid and Letrozole can be effective for ovulation induction. The choice between the two should be made in consultation with a healthcare provider, considering the patient's specific circumstances and each medication's potential benefits and risks.