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Last updated: Mar 01, 2021
6 min read

Depo-Testosterone: uses and side effects

steve silvestro

Medically Reviewed by Steve Silvestro, MD

Written by Amro Alhelawe, PharmD


If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

The dreaded “low T”—if you’ve got this much-talked-about condition, you might experience fatigue, weight gain, low sex drive, and a whole host of other symptoms. Thankfully, there are great treatments available, including Depo-Testosterone.  


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What is Depo-Testosterone?

Depo-Testosterone is an injectable form of testosterone (T) that is available by prescription only and manufactured by Pfizer. It’s also available as a generic: testosterone cypionate. Testosterone therapy (which brings T levels up to the normal range for adult men) can be beneficial for patients with a few different conditions.

Testosterone cypionate is a so-called “depot” injectable. As a depot form of T, Depo-Testosterone has a longer half-life than other forms of T available (like testosterone propionate) (Petering, 2017). 

Half-life measures the amount of time it takes for a drug to be removed from your body. When the half-life of a drug is long, it has a longer time to work in the body.

T is a male sex hormone—or androgen—that’s known to play a role in sexual health and the development of masculine sex characteristics at puberty. But, T is an essential hormone in both men and women throughout life (Nassar, 2021).

There’s more than meets the eye when it comes to testosterone, as having low levels can lead to health risks that might come as a surprise, including (Saad, 2017):

When is testosterone therapy beneficial? 

Testosterone therapy is beneficial for two primary conditions: hypogonadism and gender dysphoria. 


Having low T, otherwise known as hypogonadism, can lead to symptoms that can significantly impact your life. Some forms of hypogonadism are genetic, and others can be acquired during life as a result of other factors, including (Petering, 2017):

  • Obesity
  • HIV
  • Certain medications
  • Aging 
  • Certain types of cancer

Developing low T can lead to breast discomfort, loss of body hair, and decreased sex drive. T therapy is indicated in those with low T symptoms who are not at high risk for side effects (Mulhall, 2018).

How does T help with these symptoms?

Researchers set out to answer that question in a set of trials known as the T-trials. Researchers compared injection T with placebo in over 700 men who had hypogonadism. Restoring testosterone levels was found to have hefty benefits in these clinical trials, including improvements in (Snyder, 2018):

  • Sexual function
  • Mood and depression
  • Bone mineral density

Scientists involved in the trial also reported risks, with a higher rate in older patients or those with a predisposition for heart problems. For this reason, testosterone replacement therapy is not FDA-approved in patients who have low T due to aging, though it is often used off-label in these cases (Elagizi, 2018). We’ll cover the potential risks of T therapy in a later section.

Gender dysphoria

T therapy also has clinical benefits in treating gender dysphoria (which can lead to severe depression and generalized anxiety) experienced by trans folks. It’s mainly prescribed for trans men who desire masculinization, but it can also help alleviate anxiety and social distress (Gava, 2018).

T therapy can lead to gender-affirming physical changes in men who were assigned female at birth. In scientific research, these changes are dubbed “virilization” and include (Unger, 2016): 

  • Deepening of the voice
  • Increased hair growth on the body
  • Increased development and changes in the distribution of lean muscle. 

People who take T generally notice changes within one month of starting therapy but will usually see significant results after about three months of taking testosterone therapy (Hembree, 2017).

What are the differences between testosterone cypionate and other forms of T?

As mentioned, Depo-Testosterone is a long-acting injection. There are several other forms of T therapy available by prescription, though (Petering, 2017):

  • Testosterone undecanoate, taken by mouth (brand name Jatenzo)
  • Testosterone enanthate, taken by injection (brand name Delatestryl)
  • Testosterone nasal gel, applied to the nose (brand name Natesto)
  • Testosterone topical gel, applied to the skin (brand names Androgel, Fortesta, and Testim)

There are differences in how these forms of T are taken, so pay extra attention to the directions for use on your prescription and carefully follow your healthcare provider’s advice. All of the prescription drugs mentioned above are proven to be safe and effective forms of testosterone therapy.

Testosterone cypionate should be stored at room temperature to avoid solids from forming in the bottle. If this happens, you can use the warmth from the palms of your hands and roll the bottle until the hardened crystals disappear.

Who should avoid taking T?

Older patients suffering from medical conditions like heart failure or uncontrolled high blood pressure have a greater risk of experiencing severe side effects from taking T (Elagizi, 2018). The FDA issued an official safety notification in 2015 requiring drug manufacturers to change the labels on T-containing products to reflect the risk of heart attacks and other heart problems (FDA, 2015).

People living with severe kidney disease or liver disease should not take testosterone, as the risks can be high with long-term therapy. T is also contraindicated in patients with breast cancer, prostate cancer, and certain blood conditions (specifically, polycythemia) (Nassar, 2021).

What are the possible side effects of injectable testosterone?

Severe allergic reactions to the contents in testosterone cypionate have been reported. If, after taking your first dose, you experience any symptoms of an allergy (hives, swelling, trouble breathing), do not take your second dose and seek immediate medical care (Nassar, 2021).

Testosterone has the potential for abuse, and because of this, is a schedule III controlled substance. Taking higher doses of T than prescribed or combining it with the use of anabolic steroids can lead to severe and life-threatening adverse events (Elagizi, 2018).

T can come with some side effects, but for many people, the benefits often outweigh the risks when it’s indicated. Some possible adverse effects of T include (Nassar, 2021):

  • Acne and changes in the skin
  • Pain at the site of injection, itchiness
  • Gynecomastia (enlargement of the breasts)
  • Headaches
  • Benign enlargement of the prostate
  • High blood pressure
  • Increases in calcium levels
  • Edema (otherwise known as fluid retention)
  • Changes in blood (risk of deep vein thrombosis and increased red blood cell counts)

If you take other medications and are considering starting T, talk to a healthcare professional about all of the medicines you take. It’s possible for T to have drug interactions with other medications that you take—namely, blood thinners (like warfarin) and anabolic steroids.

Combining T with anticoagulants like warfarin can increase your risk of bleeding. If you take a blood thinner, it’s essential to follow a healthcare provider’s medical advice to take your medications safely.

Get the help you need

If you’re suffering from symptoms of low T or gender dysphoria, be sure to seek out help from your healthcare provider. TRT might be right for you in one of its many forms. 


  1. Elagizi, A., Köhler, T. S., & Lavie, C. J. (2018). Testosterone and cardiovascular health. Mayo Clinic Proceedings, 93(1), 83–100. doi: 10.1016/j.mayocp.2017.11.006. Retrieved from 
  2. Gava, G., Mancini, I., Cerpolini, S., Baldassarre, M., Seracchioli, R., & Meriggiola, M. C. (2018). Testosterone undecanoate and testosterone enanthate injections are both effective and safe in transmen over 5 years of administration. Clinical Endocrinology, 89(6), 878–886. doi: 10.1111/cen.13821. Retrieved from
  3. Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., et al. (2017). Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 102(11), 3869–3903. doi: 10.1210/jc.2017-01658. Retrieved from
  4. Mulhall, J. P., Trost, L. W., Brannigan, R. E., Kurtz, E. G., Redmon, J. B., Chiles, K. A., et al. (2018). Evaluation and management of testosterone deficiency: AUA guideline. The Journal of Urology, 200(2), 423–432. doi: 10.1016/j.juro.2018.03.115. Retrieved from
  5. Nassar, G. N. & Leslie, S. W. (2021). Physiology, testosterone. In StatPearls. StatPearls Publishing. Retrieved from
  6. Petering, R. C. & Brooks, N. A. (2017). Testosterone therapy: review of clinical applications. American Family Physician, 96(7), 441–449. Retrieved from
  7. Saad, F., Röhrig, G., von Haehling, S., & Traish, A. (2017). Testosterone deficiency and testosterone treatment in older men. Gerontology, 63(2), 144–156. doi: 10.1159/000452499. Retrieved from
  8. Snyder, P. J., Bhasin, S., Cunningham, G. R., Matsumoto, A. M., Stephens-Shields, A. J., Cauley, J. A., et al. (2018). Lessons from the testosterone trials. Endocrine Reviews, 39(3), 369–386. doi: 10.1210/er.2017-00234. Retrieved from
  9. Unger, C. A. (2016). Hormone therapy for transgender patients. Translational Andrology and Urology, 5(6), 877–884. doi: 10.21037/tau.2016.09.04. Retrieved from 
  10. U. S. Food and Drug Administration (FDA). (2015, March). FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. Retrieved Mar. 5, 2021 from

Dr. Steve Silvestro is a board-certified pediatrician and Manager, Medical Content & Education at Ro.