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The following article discusses the subject of co-administering anastrozole with testosterone therapy.
As a side note, The Endocrine Society currently does not recommend for or against the use of anastrozole. Some physicians do prescribe it to mitigate symptoms of high estradiol levels, like gynecomastia and edema.
With this being said, estradiol plays an important role, even in men, so taking it in the absence of clinically diagnosed high estradiol levels and related symptoms may be counterproductive. At this time, there is no consensus on its use or on the optimal estradiol range in men.
Estradiol in Men
Most men think of estrogen as exclusively a female hormone, but men also produce it. In fact, testosterone is the precursor of estradiol, an estrogen and the primary female sex hormone. Testosterone is converted into estradiol via the aromatase enzyme.
Because testosterone can be converted into estradiol, taking testosterone via testosterone replacement therapy (TRT) can potentially elevate estrogen levels. Fortunately, most men on standard TRT dosages do not experience high estradiol levels.
Nevertheless, genetically predisposed men may experience symptoms associated with high levels, which may lead to certain unwanted side effects.
Side Effects of High Estradiol Levels in Men
As mentioned, testosterone replacement therapy dosages that do not raise testosterone above normal generally do not lead to high estradiol levels. Consequently, the feminizing effects associated with high levels are generally not seen with TRT dosages. Unfortunately, genetically predisposed men on TRT may experience symptoms associated with high estrogen levels.
Symptoms of high estradiol levels in men include two of the most common side effects of testosterone therapy. These are 1) gynecomastia (male breast development and enlargement) and 2) edema (fluid retention in the extremities).
Gynecomastia is breast enlargement in men due to benign (non-cancerous) breast tissue growth. Breast tissue contains receptors for estrogen. As such, high levels of estrogens promote breast tissue growth and lead to gynecomastia.1 Unfortunately, medical treatment of gynecomastia that has persisted beyond a year is often ineffective. After one year, most cases must be treated via surgical excision.
Edema is soft tissue swelling caused by fluid retention. Fluid retention may occur in the arms and legs at the beginning of testosterone therapy. It generally resolves after the first few months of treatment, if treatment dosages is reduced, or if treatment is stopped. Nonetheless, edema may persist and may cause pain.
Co-administration of Anastrozole (Arimidex)
To begin, The Endocrine Society’s Clinical Practice Guidelines for Testosterone Therapy in Adult Men with low testosterone does not address the potential issue of high estradiol levels during TRT.
As such, The Endocrine Society does not recommend for or against any treatments that lower estradiol levels. Also, there is currently a lack of guidelines as to the critical level whereby intervention is needed to treat high levels.
With this being said some physicians do treat men on TRT with high estradiol levels by co-administering anastroloze (brand name Arimidex) with TRT at 0.25 mg per day or 0.5 mg every other day.
Anastrozole is an aromatase-inhibiting drug that comes in the form of a pill and is taken orally. It inhibits the ability of the aromatase enzyme to convert testosterone to estrogen. Thus, it lowers the level of circulating estradiol quite effectively.
Anastrozole is actually FDA-approved for the treatment of breast cancer in women after surgery. As such, its use in men on testosterone replacement therapy is considered to be off-labeled.
What are High Estradiol Levels in Men
The definition of high estradiol levels in men varies by laboratory and type of analytical method. Unfortunately, there is also no consensus on what type of test (regular or ultrasensitive) is best.
Lab Corp uses an electro-chemiluminescence immunoassay methodology and defines high estradiol as equal to or above 42.6 pg/mL.
Role of Estradiol in Men: Is Estradiol Important
Many men assume that estradiol is simply bad.
They think that because estradiol is one of the primary female hormones and because high levels may cause gynecomastia and/or edema, estradiol should be reduced as much as possible. However, this is not true.
While high levels cause certain side effects in genetically susceptible, estradiol plays many important roles in men. For example, it plays an important role in determining bone mineral density in men. Low levels may well be the major cause of bone loss in elderly men.
Low estradiol levels are associated with increased fat and decreased sexual desire and erectile function compared to higher levels.
While there is currently not enough data and/or information to know what is the optimal estradiol range in men, low estradiol levels are evidently not good. As such, taking anastrozole in the absence of clinically diagnosed high estradiol levels along with associated symptoms (gynecomastia and edema) is likely counterproductive for men on testosterone therapy.
