Estrogen blockers / Aromatase inhibitors

The majority of estrogen in the male body is a breakdown product of testosterone. It is well known that men on testosterone therapy will have a corresponding rise in their estrogen level. Monitoring and managing estrogen levels is paramount to optimizing testosterone therapy results.  

A clear indication for the treatment of high estradiol levels in men on testosterone therapy is the development of gynecomastia (breast tenderness or enlargement of breast tissue) and/or erectile dysfunction. 

Not all men need estrogen blockers as part of their testosterone replacement therapy, but they can help to alleviate certain symptoms associated with low testosterone levels.

In men on testosterone replacement therapy who want to optimize performance, sex drive, muscle growth and weight loss, estrogen management must also be a component of therapy.  There is a greater increase in estradiol levels in older men and more obese men on testosterone.  

Aromatase is the enzyme responsible for conversion of androgens to estrogens. It is predominately found in adipose tissues, principally in the central fat deposits of the abdomen.  

When estrogen levels are too high in men the result can be a decrease in testosterone production. When men undergo testosterone replacement therapy, the enzyme aromatase will act to breakdown newly injected testosterone into estrogen. Blocking the aromatizing enzyme can improve and maintain injected testosterone.   

The most widely used medication to manage estrogen levels during testosterone treatment is Arimidex (Anastrozole). Arimidex is an aromatase inhibitor (AI). Aromatase inhibitors can be used in men with elevated estrogen levels for the primary treatment of hypogonadism and increase testosterone levels without impairing fertility. 

While Arimidex is known to reduce estrogen in men by inhibiting aromatase, the medication can also increase testosterone production. Arimidex prevents estrogen from blocking pituitary signals that stimulate testosterone production, mainly LH and FSH.

According to the American Urologic Association guideline, Arimidex is used for off label use in men. Side effects of the medication include hot flashes, dyspnea, peripheral edema, and bone pain.  

We also prescribe letrozole and exemestane.

Tamoxifen blocks the estrogen receptors in target tissues and glands. This is different from Anastrozole which inhibits the enzymes that converts testosterone in to estrogen. By blocking the estrogen receptor, estrogen is unable to impact signaling hormones that stimulate testosterone production.  

Tamoxifen is an off-label medication used in men to prevent and treat gynecomastia. Gynecomastia is enlargement of male breast tissue and is a result of an imbalance between testosterone and estradiol levels. Tamoxifen exerts an effect by binding to estradiol (E2) receptors in estrogen sensitive tissues (such as the male breast) and prevents estrogen from exerting an effect. 

 Clomiphene Citrate (Brand name Clomid) was initially developed in the 1960’s to treat female infertility. Today, Clomid is commonly used off-label in men to treat male infertility and low testosterone. 

In men with low testosterone, Clomid is an excellent and effective oral medication to raise serum testosterone levels and improve the testosterone to estradiol ratio. Clomid works by blocking the estrogen receptor leading to an increase in both FSH and LH. These two signaling hormones released by the pituitary stimulate the testis to raise testosterone levels and enhance sperm production.

Clomid is also used after testosterone therapy to help the body raise its natural production of testosterone.