Anastrazole (Arimidex) is an aromatase inhibitor (AI). Like other AIs, anastrazole prevents the synthesis of estrogen by inhibiting the enzyme aromatase. Anastrazole is approved as a treatment for metastatic and post-surgical breast cancer in pre- and post-menopausal women. Off-label uses of anastrazole include treatment of drug-induced gynecomastia, as a fertility treatment for men, occasionally as an androgen substitute monotherapy for hypogonadal men, as part of a hormone replacement therapy regimen for men, and as part of a transitional hormone cocktail for female-to-male (FTM) individuals. Like other AIs anastrazole is sometimes used as part of a short stature syndrome treatment regimen.
In the human body, estrogen is created via reduction from androgens and related prohormones, through an enzyme called aromatase. AIs such as anastrazole bind to aromatase and render it inactive. “Reversible” AIs such as anastrazole and letrozole do not bind permanently to aromatase; irreversible AIs create a circulating aromatase complex that is permanently inactive.
The most common uses for anastrazole are treating metastases in post-menopausal women and as a follow-up treatment to surgery; estrogen drives the growth of some breast cancer cells, meaning that the disruption of estrogen production via aromatase inhibition improves patient outcomes. Howell et all conclude in a trial of over 9000 women that for patients with local estrogen-receptor positive (ER-positive) breast cancer anastrazole should be preferred to tamoxifen. The most concerning side-effect is possible disrupted bone metabolism resulting in an increase in fractures.
Holbrook and Cohen find that while anastrazole is effective to treat idiopathic hypogonadotrophic hypogonadism (low testosterone occurring due to a lack of hypothalamic, or pituitary, activity), it does not assist men in that demographic suffering from premature ejaculation with their ejaculation issues.
After two to three years of therapy for short stature syndrome, anastrazole increased adult height potential while still allowing for normal pubertal development trajectory. Mauras et al recommend it as a safe and effective treatment for GH deficient short stature syndrome.
Anastrazole is especially helpful and appropriate for men who have higher estrogen levels due to obesity and are suffering from resulting hypogonadism or infertility,, according to some researchers and clinicians. Roth et al report:
A 29-year-old man presented to a clinic with infertility and hypogonadism in the setting of morbid obesity. On presentation, he had notable gynecomastia and a low testicular volume. The patient's weight was 154 kg and his height was 168 cm (BMI 54.5 kg/m(2)). Before referral to the clinic, the patient had been treated with testosterone therapy for 4 months for hypogonadism. This treatment had caused his initially low sperm concentration to fall to undetectable levels. [...] Treatment with an aromatase inhibitor, anastrozole, led to normalization of the patient's testosterone, luteinizing hormone and follicle-stimulating hormone levels, suppression of serum estradiol levels, and to normalization of spermatogenesis and fertility.
Because of the nature of most hypogonadotrophic hypogonadism, reducing estrogen levels activates the male hormonal axis regardless of whether hyperestrogenism is present. Older men with hypogonadism responded favorably to anastrazole monotherapy without necessarily having high estrogen levels previously: "anastrozole administration normalized androgen production in older hypogonadal men and decreased estradiol production modestly."
Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 365 (9453): 60–2. 2005.
R. Jakesz et al. Review of: Arimidex After Two Years of Tamoxifen Reduces Recurrence in Post-Menopausal Women. The Lancet, August 6, 2005.
Holbrook JM, Cohen PG. Aromatase inhibition for the treatment of idiopathic hypogonadotropic hypogonadism in men with premature ejaculation. South Med J. 2003 Jun;96(6):544-7.
Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, Klein KO, Singh RJ, Miyamoto A, Bishop K. Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years. J Clin Endocrinol Metab. 2008 Mar;93(3):823-31. Epub 2007 Dec 28.
 Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab. 2008 Jul;4(7):415-9.
Burnett-Bowie SA, Roupenian KC, Dere ME, Lee H, Leder BZ. Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). 2008.