Testosterone, Transdermal Patch

Testosterone is the most important hormone in male physiology. Its chemical structure is based on cholesterol. But different from cholesterol, it has an excellent reputation.

All men want a high testosterone level, and it is the symbol of manhood. It is undoubtedly very important, for different reasons we’re covering in this article.

But in some cases, men experience low levels of testosterone. Aging, genetics and many other factors may contribute. For many years, the only way to increase testosterone levels was through injections. But now other options are available, including transdermal patches.

What is testosterone?

Testosterone is an androgen, a steroid hormone essential for males. As mentioned above, the chemical structure of testosterone is based on cholesterol. But the function of testosterone is very different.

It works as a chemical signal in various tissues. It triggers and modulates cellular proliferation. It activates several genes, with a distinct effect across different tissues.

Testosterone is what causes changes in males during puberty. It is also what maintains sexual activity in men during their lifetime. In nature, testosterone is synthesized and released by the testis. It runs through the blood, either free or bound to transporter proteins.

Bound testosterone remains inactive. However, free testosterone interacts with cell receptors in different tissues and activates several genes and metabolic pathways. As a whole, these changes caused by testosterone modulate the physical appearance and behavior of men (1).

What is testosterone used for?

Testosterone transdermal patches are used to treat the symptoms of low testosterone in men.

It would be ideal if we all had our testosterone concentration intact in the blood. But a lot of males suffer from low testosterone levels. The majority experience slightly low levels, but other causes can be severe. For example, we have hypogonadotropic hypogonadism.

It features insufficient testosterone due to a problem in the testis. These hypogonadal men experience disturbing symptoms such as erectile dysfunction. They also suffer from hypoactive sexual desire disorder. In other words, their sexual function is insufficient and not pleasurable.
That’s why testosterone is administered to certain men.

An external source of the hormone may not only improve sexual health. It also prevents osteoporosis in men, improves mental health, and has other benefits.

Using testosterone for medical purposes is known as testosterone replacement therapy. Unlike what we may think, starting TRT requires a rigorous validation process. Thus, some men who experience symptoms of androgen deficiency may not be candidates for TRT.

It is not fine to use synthetic testosterone just because you believe you have a low level or because you want to increase your muscle mass. Still, that’s another widespread use in our modern society (2).

Experimentally, it is also being used in postmenopausal women with female sexual dysfunction. In these women, testosterone may be useful to relieve depression, treat sexual dysfunction, and reduce vaginal dryness and other menopausal symptoms. Still, using testosterone for this purpose is not yet approved by international regulations (3)

How does it work?

Many clinical trials evaluate how different formulations of synthetic testosterone work. Each one of them is administered differently and for a given group of patients. Some of them should be applied every day or several times a day.

Others are deposited in the body, and their effect lasts for a few weeks. But all of them have proven useful against placebo in treating sexual dysfunction and increasing serum levels of testosterone.

Synthetic testosterone works precisely the same as natural testosterone once coupled to cell receptors. Androgen receptors activate nuclear transcription and modulate cell behavior. This process takes very long as the DNA is stimulated to create new proteins.

But another way is through a cascade of phosphorylation of second messengers. These messengers are slightly modified and trigger a signaling cascade with almost immediate results.

Together, these mechanisms contribute to maintain integrity in the reproductive system, improve sexual desire, induce changes in the musculoskeletal system, trigger modifications in the cardiovascular system, boost the immune system, and much more (1).

Testosterone side effects

Testosterone is essential for males, but not to be taken for granted. There’s a reason why it is so closely controlled and monitored by health authorities. It is because of the side effects.

Testosterone treatment in people who require TRT for medical reasons is not likely to cause many adverse events. They are usually mild and easy to treat. But the severity and number of side effects are higher if you receive testosterone without need.

We can break down the side effects of testosterone into two groups. They are either common side effects or severe side effects.

More common side effects

These are the most common side effects of testosterone replacement therapy (4):

  • Edema: This happens with the majority of steroid hormones. They cause fluid retention, especially in the ankles and the legs. Other tissues with fluid retention include soft tissues and the brain. However, brain edema is a severe side effect, and it is not common.

  • Acne: Testosterone increases the production of sebaceous glands in the skin. Glands and pores get clogged and infected, causing pimples. In severe cases, an additional inflammatory reaction takes place. This can cause acne in the skin.

  • Enlarged breasts: This is a common problem in bodybuilders and whenever testosterone is misused. An excessive dose transforms into female sex hormones and causes an enlargement of the breasts.

  • Mood swings: Testosterone can change a man’s behavior and mood. In some cases, external administration can cause mood swings in males. Aggressive behavior is possible, but not found in every situation.

  • Erythema in the site of injection: This is likely to happen when injected testosterone is chosen. It is not a side effect specific to testosterone. Almost all injected medications have a chance of causing erythema. But it is more likely with testosterone since it changes blood vessel permeability.

  • Pain in the site of injection: This is another common side effect in almost any injected medication. Site pain is more likely with a poor injection technique.

  • A skin reaction: This problem is common if you use a testosterone transdermal patch. The reaction is similar to erythema in the site of injection, featuring redness and sometimes itching.

  • Contact dermatitis: This is a type of allergic reaction to the synthetic materials in transdermal patches. It looks like skin irritation located in the site of application. But similar to other allergic reactions, it often causes severe itching and cracked scaly skin.

  • Cough or dyspnea: This side effect can be severe sometimes, so be careful. It happens immediately after receiving a testosterone shot. Talk to your doctor immediately if you experience a cough with difficulty breathing, chest pain, and dizziness.

Severe side effects

We can also have serious side effects after receiving testosterone. Any form of administration can cause both common or severe adverse reactions. The latter is not as common but requires urgent medical assistance. They are as follows (4):

  • Severe trouble breathing: You may experience a cough or an urge to clear your throat after a testosterone shot. But if this goes as far as to give you trouble breathing, it can be severe. Talk to your doctor right away. Sometimes testosterone causes blood clots in the lungs that can be very dangerous.

  • Depersonalization and paranoia: There are many psychiatric side effects of testosterone. Depression and mood swings can be more common. But sometimes we get patients with psychosis, restlessness, hostility, and anxiety. This is not normal and should be reported immediately.

  • Symptoms of an overdose: Patients with an overdose can experience very severe side effects. Those include blurred vision, slurred speech, temporary blindness, seizures, and confusion.

  • Thrombosis: Testosterone works in the cardiovascular system and increases the number of platelets. But this can get out of hand if the dose is not appropriate. Patients may experience different types of thrombosis with varying effects. Stroke, venous thromboembolism, or deep venous thrombosis are possible consequences.

  • Testicular atrophy: Men with an intact testicular function may cause irreversible damage by using testosterone. An excessive dose maintained in a very long time, sends a signal to the brain. This signal is interpreted as if the testicles are producing enough testosterone. The brain stops stimulating the testicles, and they become atrophied and dysfunctional. This is a potential cause of hypogonadism in previously normal patients.

Important warnings

There are several warnings and precautions around testosterone. These are the most important (1):

  • Certain types of testosterone may increase blood pressure. Thus, some patients may require testing with testosterone before daily administration.

  • Using testosterone for more than 10 years in cases of male hypogonadism can cause breast cancer.

  • Cardiovascular evaluation is essential before starting TRT. Special attention should be given to older men with a high cardiovascular risk.

  • Testosterone may cause gynecomastia and dyslipidemia.

  • Patients with cancer and prolonged immobilization may develop hypercalcemia.

  • Serious hepatic toxicity may arise after using high doses for a long time.

  • Testosterone increases the hematocrit number. Any patient with a count higher than 54% should discontinue TRT.

  • Testosterone improves sexual functioning but may cause priapism (excessive sexual stimulation). This is a cause of discontinuing TRT.

  • Androgens may worsen BPH. Also, they may not be appropriate in some cases of prostate cancer.

Interactions with other medications

Testosterone replacement and testosterone supplementation have many drug-drug interactions. Luckily, the majority of drugs that interact with testosterone are not very common, as you can see in this list (1):

  • Anisindione, dicumarol, and warfarin: Taking along with testosterone causes easy bleeding and bruising.

  • Carfilzomib: Taking along with testosterone causes dangerous blood clots.

  • Leflunomide, lomitapide, mipomersen, pexidartinib, and teriflunomide: Taking along with testosterone may cause liver toxicity.

More common drugs may also have moderate or minor interactions with testosterone (1):

  • Betamethasone, dexamethasone, budesonide, corticotropin, cortisone, deflazacort: Taking along with testosterone may cause swelling and water retention.

  • Cannabidiol, methotrexate: Taking along with testosterone may cause severe liver problems.

  • Fluconazole, itraconazole: This drug increases blood levels of testosterone and its effects. You may require a dose adjustment.

  • Glimepiride, insulin: Taking along with testosterone may cause hypoglycemia.

Testosterone warnings

Testosterone therapy is not for everyone, and there are many inappropriate ways to use it. For example (5):

  • Abuse and misuse of testosterone: Anabolic-androgenic steroids are sometimes abused for physical performance. Abuse is usually at very high doses and associated with severe side effects. Common adverse events in these patients include cardiovascular and psychiatric problems.

  • Dependence: Testosterone dependence may occur after using excessive doses. The organism becomes dependent on an external source of testosterone. The testis undergoes atrophy and does not produce the hormone by itself.

  • Secondary exposure: Topical application of testosterone should be carefully handled. Skin-to-skin contact may transfer the hormone from one person to the other.

How to take testosterone?

Transdermal testosterone comes as a patch to apply to the skin. It is usually applied each night and left in place for 24 hours. It is usually recommended that you apply testosterone patches at around the same time every evening. Follow the directions on your prescription label carefully and follow the advice of your doctor.

Testosterone patches can be applied on the back, stomach, thighs, or upper arms. When choosing a spot, be sure that it is not oily, hairy, or likely to sweat easily.

The patch should not be applied to the scrotum or broken or irritated skin. Choose a different spot each night and wait at least 7 days before applying another patch to a spot you have already used.

Although this article focuses on the use of a testosterone patch, there are many delivery methods available for TRT. In short, we can summarize them into the following (1):

  • Testosterone injections: Initially, all applications were injected. The dose is variable depending on the testosterone ester you’re using. Some of them should be administered weekly. Others can be applied every 10 days or every 2 weeks. Testosterone cypionate and testosterone enanthate are representative examples.

  • Subcutaneous testosterone: It is not a subcutaneous injection. Instead, it is a quick procedure where small pellets are placed under the skin. It is performed under anesthesia and should be replaced after 3 or 4 months.

  • Testosterone topical applications: This is probably the most popular application of testosterone. It does not require injections, and it is easy to use. It is also known as transdermal testosterone and has many variables. Testosterone patches are attached to the skin, and there are many brands. For example, Androderm patches come in two different doses and can be applied in the abdomen, back, or thighs. Testosterone gels and creams can be used as well. But sometimes they should be applied twice a day to maintain appropriate levels.

  • Oral TRT: Initially, testosterone was only injected because it is metabolized by the liver if taken by mouth. But modern oral TRT uses modified testosterone that is not deactivated. An example is testosterone undecanoate. They are very useful if you’re afraid of injections. But they have a higher chance of liver toxicity. An alternative is a buccal or sublingual testosterone. This is a dissolving tablet you can place under the tongue or against your gums. It is a way to avoid liver toxicity and injections at the same time.

Factors to consider when taking testosterone

Taking testosterone requires constant monitoring and evaluation to avoid potential side effects. Serum testosterone should be measured before, during, and after administration.

We should aim at correcting the problem without reaching an excessively high testosterone concentration. It is also important to know your levels of bioavailable testosterone. Therefore, you might need to measure free and bound testosterone (4).

If you’re using a skin patch, you may experience more variations in your testosterone levels. Therefore, you may need several measurements to make sure you’re receiving the right dose.

Older patients receiving testosterone may have an increased risk of BPH and prostate cancer. It is also important to measure liver functioning and evaluate the patient thoroughly. Therefore, do not attempt to start TRT by yourself and without proper guidance (4).

How to naturally increase testosterone

Hypoactive sexual desire is not always due to extremely low testosterone levels. You might have slightly lower levels and not being a candidate for TRT. Even if you are, you might want to try natural alternatives first. You’re probably not into injections and not even into testosterone patches. But there are other alternatives to consider:

  • Magnesium: Eating more magnesium-rich foods may improve your testosterone levels. Only 10 mg of magnesium for a kilogram of body weight may increase your testosterone by 24% (6).

  • Zinc: This nutrient is also important to synthesize testosterone. You can find it in oysters, seafood, or as testosterone booster supplements (7).

  • Boron: This nutrient is mandatory if you want to increase your testosterone levels. Boron reduces the ratio of bound testosterone. Thus, you will have more free testosterone around, which is more active (8).

  • Vitamin D: Consider supplementing with this vitamin if you live in a northern country, have darker skin, or during winter. It is fundamental to create testosterone and helps you increase your vitamin d levels naturally (9).

  • Ashwagandha: Out of many herbs and plants, Ashwagandha increases testosterone levels exponentially. It lowers cortisol levels and boosts testosterone production (10).


Testosterone is a star hormone for males, especially for those with an impaired sexual function. Replacement therapy may increase your low sexual desire, but it is not without side effects. Therefore, it is not for everyone.

If you are a candidate to receive testosterone, there are many ways to choose from: endoderm testosterone patches, oral and sublingual testosterone, and more. You can stick to testosterone injections, too.

In any case, ask your doctor which one is better for you and follow indications. Remember that TRT has risks as everything else in medicine. But they will be minimized when we are properly monitored and evaluated by a skilled professional.


  1. Hohl, A. (Ed.). (2017). Testosterone: From Basic to Clinical Aspects. Springer.
  2. Rastrelli, G., Reisman, Y., Ferri, S., Prontera, O., Sforza, A., Maggi, M., & Corona, G. (2019). Testosterone Replacement Therapy. In Sexual Medicine (pp. 79-93). Springer, Singapore.
  3. Achilli, C., Pundir, J., Ramanathan, P., Sabatini, L., Hamoda, H., & Panay, N. (2017). Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertility and sterility, 107(2), 475-482.
  4. Corona, G., Sforza, A., & Maggi, M. (2017). Testosterone replacement therapy: long-term safety and efficacy. The world journal of men’s health, 35(2), 65-76.
  5. Iyer, R., & Handelsman, D. J. (2017). Testosterone Misuse and Abuse. In Testosterone (pp. 375-402). Springer, Cham.
  6. Cinar, V., Polat, Y., Baltaci, A. K., & Mogulkoc, R. (2011). Effects of magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biological trace element research140(1), 18-23.
  7. Kilic, M., Baltaci, A. K., Gunay, M., Gökbel, H., Okudan, N., & Cicioglu, I. (2005). The effect of exhaustion exercise on thyroid hormones and testosterone levels of elite athletes receiving oral zinc. Neuro endocrinology letters27(1-2), 247-252.
  8. Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M. S. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of trace elements in medicine and biology25(1), 54-58.
  9. Holt, R., Mortensen, L. J., Poulsen, K. H., Nielsen, J. E., Frederiksen, H., Jørgensen, N., … & Jensen, M. B. (2020). Vitamin D and sex steroid production in men with normal or impaired Leydig cell function. The Journal of Steroid Biochemistry and Molecular Biology, 105589.
  10. Ambiye, V. R., Langade, D., Dongre, S., Aptikar, P., Kulkarni, M., & Dongre, A. (2013). Clinical evaluation of the spermatogenic activity of the root extract of Ashwagandha (Withania somnifera) in oligospermic males: a pilot study. Evidence-Based Complementary and Alternative Medicine2013.


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