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Testosterone levels naturally decline as men age. Low testosterone (low T) can lead to a host of health problems like low sex drive, fatigue, erectile dysfunction (ED), and muscle weakness.
Testosterone replacement therapy (TRT) is the go-to treatment for low T, but it comes with side effects: it can lead to male infertility by lowering the sperm count. That’s why some healthcare providers offer other treatments to treat low T like clomiphene (brand name Clomid). You might have also heard of a drug called anastrozole used to supplement low T levels, however, it’s not routinely recommended.
What is anastrozole?
Anastrozole (brand name Arimidex) is occasionally used to supplement low testosterone. This drug works by decreasing the amount of estrogen the body makes.
It was originally developed to treat what’s called hormone receptor-positive breast cancer in postmenopausal women. Hormone receptor-positive means that the cancer cells grow in response to the hormone estrogen, which explains why anastrozole can treat these kinds of breast cancers.
Currently, anastrozole is only FDA-approved for use in women. But like clomiphene, some providers prescribe anastrozole off-label to treat low testosterone in men. However, there isn’t enough evidence to recommend it as a standard treatment for low T.
Effectiveness of anastrozole in men
There is limited evidence for anastrozole’s effectiveness in men.
In one small study, anastrozole increased testosterone in older men with mild hypogonadism (low T) (Leder, 2004). In another study looking at men with low testosterone and infertility, taking anastrozole led to increased testosterone and increased sperm count in some (Shoshany, 2017).
Although anastrozole may increase testosterone levels, a recent analysis suggests that it doesn’t lead to improvements in sexual function like better erections or higher libido (sex drive). It also doesn’t improve semen quality. Currently, there isn’t sufficient evidence to recommend anastrozole as a routine treatment for low T in clinical practice (Awouter, 2020).
When compared to clomiphene, another off-label treatment for low T, men had significantly higher increases in testosterone than on anastrozole (Helo, 2015).
In some cases, a healthcare professional might consider prescribing low-dose anastrozole for men who receive TRT. The reason is that testosterone injections can increase estrogen levels, sometimes leading to unwanted breast growth (gynecomastia) in men. Arimidex and other aromatase inhibitors may reduce estrogen hormone levels in men and potentially treat gynecomastia (Rhoden, 2004).
How does anastrozole work in men?
We often think of testosterone and estrogen as exclusively male (androgen) and female (estrogen) hormones. However, men and women naturally produce both hormones, and a balance between the two is vital for good health in both sexes.
In men, having too little testosterone or too much estrogen can lead to problems like low sex drive, breast tenderness or enlargement, and erectile dysfunction. The primary sex hormone for men is testosterone, which is made in what are called Leydig cells in the testicles. Men also make a small amount of estradiol, a potent estrogen (de Ronde, 2011).
Estradiol is made directly by the testicles, but the majority comes from the conversion of testosterone into estradiol by the aromatase enzyme. Anastrozole blocks the action of aromatase (called aromatization), which slows down the conversion of testosterone to estradiol. This boosts overall testosterone levels and lowers estradiol (de Ronde, 2011).
Side effects of anastrozole
Most of what we know about the side effects of anastrozole comes from research in women who took it as a cancer treatment. Side effects reported included hot flashes, back pain, arthritis, depression, and bone fractures (FDA, 2011).
One possible side effect of anastrozole in men is decreased bone health, which is another reason why the drug is not recommended as a routine treatment for low T. In older men with low testosterone, a study showed that anastrozole treatment improved T levels, but also decreased spinal bone density (Burnett-Bowie, 2009).
What is low testosterone?
Low T (hypogonadism) affects an estimated 40% of men over 45. Having low testosterone can contribute to bothersome symptoms like erectile dysfunction, low libido, decreased muscle strength, and loss of bone mass (osteoporosis) (Sizar, 2021).
Age is the most common cause of low T. However, other factors that play a role include obesity, sleep apnea, certain medications, and viral infections (Sizar, 2021).
If you think you have a testosterone deficiency, a healthcare provider can perform a blood test to find out for sure. Typically, they’ll order tests to check your total testosterone and free testosterone levels, preferably in the morning (Sizar, 2021).
As we mentioned, a common low T treatment is testosterone replacement therapy. TRT comes in several forms including injections, gels, and patches. TRT works by giving your body exogenous testosterone to raise your baseline hormone levels; when taken as directed, testosterone therapy is safe and effective (Rivas, 2014).
The downside is there are side effects of testosterone therapy, the major one being its negative impact on male fertility. Over time, TRT shuts down your body’s natural sperm and testosterone production, which can eventually lead to infertility (Patel, 2019).
What are natural ways to increase testosterone?
What if you want to give your body a natural testosterone boost? Some studies suggest that high-intensity exercise, like sprinting, may be linked to higher T levels (Sato, 2016).
The same goes for high-intensity interval training (HIIT). During HIIT classes, you engage in periods of intense cardio alternated with periods of lower-intensity activity (Riachy, 2020; Hayes, 2019). But even lighter aerobic exercise, such as jogging or walking, may lead to increases in testosterone (Kumagai, 2016).
It also makes sense to cut down on alcohol. The occasional drink most likely won’t affect you, but chronic and heavy alcohol consumption seem to be associated with lower testosterone and decreased sperm quality (Muthusami, 2005).
- Awouters, M., Vanderschueren, D., & Antonio, L. (2020). Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism? Andrology, 8(6), 1590–1597. doi:10.1111/andr.12725. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31696669/
- Burnett-Bowie, S. A., McKay, E. A., Lee, H., & Leder, B. Z. (2009). Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels. The Journal of Clinical Endocrinology and Metabolism, 94(12), 4785–4792. doi:10.1210/jc.2009-0739. Retrieved from https://pubmed.ncbi.nlm.nih.gov/19820017/
- Helo, S., Ellen, J., Mechlin, C., Feustel, P., Grossman, M., Ditkoff, E., & McCullough, A. (2015). A randomized prospective double-blind comparison trial of clomiphene citrate and anastrozole in raising testosterone in hypogonadal infertile men. The Journal of Sexual Medicine, 12(8), 1761–1769. doi:10.1111/jsm.12944. Retrieved from https://pubmed.ncbi.nlm.nih.gov/26176805/
- Leder, B. Z., Rohrer, J. L., Rubin, S. D., Gallo, J., & Longcope, C. (2004). Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. The Journal of Clinical Endocrinology and Metabolism, 89(3), 1174–1180. doi:10.1210/jc.2003-031467. Retrieved from https://pubmed.ncbi.nlm.nih.gov/15001605/
- Kumagai, H., Zempo-Miyaki, A., Yoshikawa, T., Tsujimoto, T., Tanaka, K., & Maeda, S. (2016). Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone. Journal of Clinical Biochemistry and Nutrition, 58(1), 84–89. doi:10.3164/jcbn.15-48. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706091/
- Leproult, R. & Van Cauter, E. (2011). Effect of 1 week of sleep restriction on testosterone levels in young healthy men. Journal of the American Medical Association, 305(21), 2173–2174. doi:10.1001/jama.2011.710. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21632481/
- Muthusami, K. R. & Chinnaswamy, P. (2005). Effect of chronic alcoholism on male fertility hormones and semen quality. Fertility and Sterility, 84(4), 919–924. doi:10.1016/j.fertnstert.2005.04.025. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16213844/
- de Ronde, W. & de Jong, F. H. (2011). Aromatase inhibitors in men: effects and therapeutic options. Reproductive Biology and Endocrinology, 9, 93. doi:10.1186/1477-7827-9-93. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143915/
- Rhoden, E. & Morgentaler, A. (2004). Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole. International Journal of Impotence Research 16, 95–97. doi:10.1038/sj.ijir.3901154. Retrieved from https://pubmed.ncbi.nlm.nih.gov/14963480/
- Rivas, A. M., Mulkey, Z., Lado-Abeal, J., & Yarbrough, S. (2014). Diagnosing and managing low serum testosterone. Proceedings (Baylor University. Medical Center), 27(4), 321–324. doi:10.1080/08998280.2014.11929145. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255853/
- Sato, K., Iemitsu, M., Katayama, K., Ishida, K., Kanao, Y., & Saito, M. (2016). Responses of sex steroid hormones to different intensities of exercise in endurance athletes. Experimental Physiology, 101(1), 168–175. doi:10.1113/EP085361. Retrieved from https://pubmed.ncbi.nlm.nih.gov/26518151/
- Sizar, O. & Schwartz, J. (2021). Hypogonadism. [Updated Jun 29, 2021]. In: StatPearls [Internet]. Retrieved Feb. 2, 2022 from https://www.ncbi.nlm.nih.gov/books/NBK532933/
- Shoshany, O., Abhyankar, N., Mufarreh, N., Daniel, G., & Niederberger, C. (2017). Outcomes of anastrozole in oligozoospermic hypoandrogenic subfertile men. Fertility and Sterility, 107(3), 589–594. doi:10.1016/j.fertnstert.2016.11.021. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28069178/
- U.S. Food and Drug Administration (FDA). (2011). Arimidex (anastrozole) tablet for oral use. FDA. Retrieved Feb. 2, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf
Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.