Anastrazole / Arimidex for Male Infertility
Introduction to Anastrazole / Arimidex and Male Infertility
Anastrazole is a non-steroidal aromatase inhibitor. Aromatase is an enzyme located in the testicles, fat cells, and the liver that converts part of the testosterone in the bloodstream into estradiol. Anastrazole decreases the action of aromatase, which results in higher testosterone levels and lower estradiol levels. Anastrazole can also raise FSH and LH levels through an inhibition of the negative feedback that estradiol plays on the pituitary gland.
For fertility, anastrazole is commonly used in men with elevated estradiol levels (>60 pg/mL) or abnormal testosterone-to-estradiol ratios (<10:1). For these men, anastrazole has proven effective in improving abnormal semen parameters. [Raman J. JUrol 2002]
Libido, Sexual function, and Bone Health
A common misconception is that mildly increased estradiol levels play a negative role in men’s health, and specifically that it decreases libido and sexual function. Actually, maintaining adequate estradiol appears to play several important roles in maintaining good sexual health, as recent studies have also shown that very low levels of estradiol can lead to an increased risk of low libido and sexual problems in men. The clearest role of estradiol seems to be in maintaining normal bone health (along with testosterone).
High levels of estradiol can potentially decrease sperm production and sperm quality. Another issue is that prolonged elevation of estradiol can also lead to gynecomastia (abnormal breast development in men).
HOW ANASTRAZOLE IS USED
Anastrazole comes in 1 mg tablets. The typical starting dosage in men is 1 mg every other day (although some clinicians have begun to use smaller doses, such as 0.25 mg daily; the smaller-dose tablets must be made by specialty compounding pharmacies). I usually recommend follow-up testing two weeks after starting anastrazole, or two weeks after any change in dosage or medications. Dosages can then be adjusted depending on the findings of the follow-up blood hormone tests.
Here is a sample range of dosages:
• 1 mg every third day
• 1 mg every other day
• 1 mg every day (typical starting dosage)
It is generally not recommended to take more than 1 mg daily because of the potential risk of liver toxicity.
COST OF ANASTRAZOLE
Anastrazole may be covered by your insurance company. However, if you do not have insurance coverage for your medications, you may want to consider the use of on-line coupons such as www.GoodRx.com which have some really good prices for many medications. For more information see the "Fertility Medications Cost" section of this website.
Side Effects of Anastrazole
Similar to clomiphene, the majority of men taking anastrazole generally do not experience significant adverse side effects and some feel better because of the higher testosterone level.
A review of men taking anastrazole showed that <5% showed decreased libido and another 7.4% had mild elevations of their liver enzymes which was not felt to be clinically significant. [Raman JD JUrol 2002]
When combined with other medications, side effects can be more frequent. A study of 51 men taking anastrazole along with clomiphene reported the following side effects:
1) Anxiety/irritability 9.8%
2) Decreased libido 7.8%
3) Increased hematocrit 3.9%
Other rare potential side effects with the use of anastrazole include increased blood pressure, rash, paresthesia (sensations of skin tingling, pricking, or burning), malaise, peripheral edema, glossitis (inflammation or swelling of the tongue), anorexia (lack of appetite), alopecia (hair loss; usually resolves spontaneously when the medication is discontinued), erectile dysfunction, and acne (due to increased skin gland oil production; usually subsides after a few months of treatment).
Patients who experience significant adverse side effects should stop their medication and contact your doctor for further guidance.
Osteoporosis
Decreased estradiol levels and the use of aromatase inhibitors have been associated with lower bone mineral densities in men. [Burnett-Bowie SM. JClinEndocrinMet 2009]. When estradiol levels are low (under 20 pg/mL) over extended periods of time, there may be an increased risk of developing osteoporosis. Short-term use of anastrazole (up to a few years) with proper monitoring and prevention strategies is typically fine in most men, but prolonged use may increase the risk of fractures. If men are going to be taking anastrazole for more than 1-2 years, baseline DEXA scanning may be indicated. For more information, see the “Osteoporosis” section of this website.
Other aromatase inhibitors
Several other aromatase inhibitors exist. Testolactone is a steroidal aromatase inhibitor that is currently not available in the United States. Although similar outcomes to anastrazole had been noted in terms of hormonal and semen parameter responses, the steroidal activity of testolactone increased the risk of adrenal suppression with the need to replace corticosteroids and mineralocorticoids. [Schlegal PN. FertSteril 2012]
Letrozole (Femara)
Letrozole is another non-steroidal aromatase inhibitor that is commonly used in female fertility. It is actually a more potent inhibitor of the aromatase enzyme than anastrazole, but not necessarily more clinically beneficial. Letrozole also seems to have a higher side effect profile in men, with an increased risk of decreased libido, nervousness, rash, and headaches. [Schlegal PN. FertSteril 2012]. However, it can be used as a possible alternative in men who are either allergic to anastrazole or cannot tolerate that medication for some reason. Dosing for letrozole in men is typically 2.5mg daily. [Schlegal PN. FertSteril 2012].