Understanding Testosterone Replacement Therapy

Testosterone serves as the predominant male hormone, playing a central role in overseeing sex differentiation, the development of male sexual characteristics, spermatogenesis, and fertility (Nassar et al 2023). Other roles of testosterone include boosting bone density and strength; testosterone also stimulates hematopoiesis, has a cardioprotective impact, and builds muscle (Gruenewald et al 2003). Both males and females have testosterone, but it is naturally more abundant in males.

Hypogonadism refers to a condition where the body produces insufficient testosterone, and it often manifests with symptoms such as reduced energy, diminished libido, and changes in mood. The symptoms associated with hypogonadism are particularly prevalent in aging men (Tsametis et al 2003). Despite being a common ailment, it is frequently misdiagnosed and poorly treated. Low testosterone levels as well as hypogonadism symptoms and manifestations are prerequisites for the prescription of TRT (Basil et al 2009). Studies have shown that the benefits of TRT are noticeable only when a person has low testosterone levels (total testosterone < 12 nmol/L) (Rastrelli et al 2009).

To diagnose low testosterone, doctors initially take an adequate history and physical exam, followed by measuring the total testosterone level in the morning. If it is low and the person reports reduced libido, the doctor checks prolactin levels, which, if high, may suggest a pituitary issue. When prolactin levels are normal or low, luteinizing hormone (LH) levels are measured to distinguish between testicular and pituitary abnormalities. High LH often indicates primary testicular disease. If testosterone is low and LH is elevated, TRT may be recommended to address the deficiency (Hellstrom 2004). To maximize the advantages of TRT and reduce any possible TRT health risk, regular monitoring of testosterone levels and continued medical supervision are crucial.

Caution: Using testosterone on one’s own or without a doctor’s supervision can have negative effects and pose health hazards. To ascertain whether testosterone replacement therapy is appropriate for them based on their unique health condition and symptoms, anyone thinking about the treatment should speak with a medical practitioner.

Types of Testosterone Replacement Therapy

An optimal TRT aims to achieve and sustain natural levels of the hormone and its active byproducts, ensuring minimal side effects and safety concerns. Various types of testosterone therapy are available, such as tablets, injectables, patches, implants, pellets, creams, and gels, each designed to deliver the hormone in a way that aligns with physiological concentrations. Let us understand each of them in brief.

Testosterone Injections

Testosterone injections for men (intramuscular or subcutaneous) are effective in overcoming low testosterone levels. The types of testosterone injections available are (Figueiredo et al 2022):

Testosterone enanthate:

• Injected once weekly via the intramuscular (gluteal muscle) route.

Testosterone cypionate:

• Injected one to three times weekly via intramuscular route.

Testosterone undecanoate:

• Injected via intramuscular route.

Testosterone shots for men are often prescribed by doctors to address low testosterone levels and associated symptoms. If a standard testosterone product is not suitable, your doctor might recommend a customized option through compounding, typically in the form of an injection. For more details, consult your doctor or connect with specialists within Science and Humans.

Pros and cons of testosterone injections

Pros:

• Inexpensive

• Infrequent administration.

• Can be self-administered

Cons

• Injection site reactions (pain, redness, bruise in the injection site)

• Episodes of sudden-onset, non-productive cough are associated with faintness associated with enanthate (Mackey et al 1995)

Testosterone Patches

Testosterone replacement patches (like androderm and testoderm) can be applied to the skin (back, abdomen, upper arms, or thighs) once daily, at the same time each day, as directed by the healthcare practitioner.

Advantages and disadvantages of TRT patches

Advantages:

• Easy to apply

• Regulated and sustained release of testosterone aids in sustaining consistent hormone levels throughout the day.

• No risk of an injection site reaction.

Disadvantages:

• Can cause skin irritation.

• Decreased compliance in the presence of sweating.

• It is not suitable for individuals with skin conditions and hypersensitivity

• It is not recommended to use the same patch site for 7 days

Testosterone Gels

The effectiveness of testosterone therapy gels (like AndroGel TRT and Testim) in influencing sexual function and mood is comparable to that of TRT patches and injectable forms. These are alcohol-based formulations and are applied once daily in the prescribed doses. The excellent tolerance and flexibility in dosing make testosterone gel a preferred choice over alternative methods of testosterone replacement (Lakshman et al 2009).

Application methods and dosage guidelines

Testosterone gel is applied to clean and dry skin of the upper arms and shoulders (preferably at the same time every day). The application of the gel is restricted to the specific area covered by the patient’s short-sleeve T-shirt. Applying the gel to any other body parts, including but not limited to the genitals, chest, armpits (axillae), knees, or back, should be avoided. Once the testosterone therapy gel is applied, it is important to let the application site dry before dressing. After application, it is recommended to wash hands thoroughly with soap and water (AndroGel Prescribing Information 2022).

Side effects and precautions

Testosterone gels have a lower occurrence of application site reactions compared to testosterone therapy patches, which is a notable advantage. Yet, there is a potential issue with inter-personal transfer when using testosterone gel, particularly if adequate precautions are not observed. This means that care must be taken to prevent unintended exposure or transfer of the gel to others during close contact. One issue linked to the application of testosterone gel is its inadvertent transfer to children or women through skin contact with the application site. A case study has reported hyperandrogenism in a female as a result of her partner using testosterone gel (de Ronde 2009).

Testosterone Creams

Many patients choose testosterone creams due to their convenience, as they are much simpler than self-administering a daily subcutaneous injection. Testosterone creams with the correct base compound can be applied to the scrotum. The scrotal skin, being thin and highly permeable to steroids, is a suitable application site. It is crucial to refrain from using a cream or gel containing alcohol, as alcohol can be detrimental to the health of the scrotal skin. Studies have shown that serum testosterone levels were in a normal range during a 2- week period when trans-scrotal TRT cream was applied to hypogonadal men (Bals-Pratsch et al 1986).

Pros and cons of TRT creams

Pros:

• The absorption of trans-scrotal testosterone creams occurs more rapidly, and the bioavailability of testosterone is several times greater compared to injections or the application of cream to other areas of the body, such as the armpits, thighs, or abdomen.

• Applying testosterone to the scrotal skin can significantly increase serum dihydrotestosterone (DHT), which can enhance sexual arousal, improve erectile strength, and contribute to longer-lasting erections. This can be particularly advantageous for individuals experiencing erectile dysfunction (ED) (Ahmed et al 1988).

Cons:

• Application site irritation

• Require refraining from certain activities, including sexual activity, exercise, and showering, for up to 90 minutes.

• It needs a periodic monitoring of the DHT level. A high DHT level can lead to hair loss, acne, an increased PSA level, and sometimes may prove dent to libido.

Oral Medications

Testosterone oral medications are the least prescribed by healthcare professionals. Traditionally, testosterone cannot be administered orally because of its low bioavailability resulting from extensive hepatic first-pass metabolism. The sole oral form of ester testosterone preparation is testosterone undecanoate (Ahmed et al 2022).

Pros and cons

Pros:

• Oral testosterone replacement therapy has ease of administration as this is a non-invasive method when compared with injections or patches.

• Oral TRT therapy may reduce the chance of any skin irritation.

Cons:

• The capsules should be consumed 2 to 3 times a day, preferably with a meal containing dietary fats to facilitate absorption. (Bagchus et al 2003).

• It require periodic blood pressure measurements. The oral TRT therapy comes along with the warning of blood pressure increases associated with adverse cardiovascular events (FDA 2019).

Testosterone Pellets

Long-lasting TRT pellets (like Testopel and Organon) are crystalline testosterones that are placed under the skin (subcutaneously) and release the drug product over time (McCullough 2014).

Pros and cons

Pros:

• Implantable testosterone pellets slowly release the testosterone over time, thereby reducing the effort of multiple administrations and applications.

• There is no risk of transfer from one person to another.

Cons:

• Require surgery for placing the pellets in the subcutaneous site.

• TRT pellets are less flexible for dosage adjustment as compared to other dosage forms (Testopel prescribing information).

• Chances of implant site infections associated with pain, itching, inflammation, etc. Higher cost (Kovac et al 2014).

Testosterone Implants

“TRT pellets” and “TRT implants” are typically the same. These implants are placed beneath the skin, commonly in the abdominal or buttock area.

Duration of effectiveness and monitoring after implantation.

Subcutaneous testosterone implant for men offer a consistent and prolonged release of testosterone, maintaining steady levels for 3 to 6 months (Cavendar et al 2009). Monitoring the effectiveness of replacement therapy is crucial, as with any form of such treatment.

Side effects and risks

Other than what is discussed under the cons of TRT pellets, testosterone implants for men have reported an incidence of pellet extrusion (Behre et al 2004). A case study has also shown that within 28 days of the subcutaneous insertion of TRT implant pellets, dermatitis emerged, characterized by red plaques and patches on the buttocks and thighs (Heldt Manica et al 2017). The dermatitis was resolved using topical corticosteroids.

Choosing the Right Option

With the rising popularity of testosterone replacement therapy, there is a growing emphasis on developing innovative administration methods to minimize associated side effects. Presently, individuals with hypogonadism have multiple treatment options, allowing them to select the most advantageous method tailored to their individual condition (Fink et al 2023). Ideally, TRT is required in the following situations (Hellstrom 2004):

• To enhance libido and erectile function.

• To maintain or restore secondary sexual characteristics.

• To improve mood and energy To enhance body composition.

• To stabilize or increase bone density.

The choice of TRT depends on various factors like medical conditions, safety, preferences, injection site, insurance coverage, and cost. Given that testosterone is a controlled substance, a healthcare practitioner can determine the most suitable injection for you.

Common side Effects and Risks Associated with TRT

Common side effects of TRT other than those discussed above include:

• breast enlargement or pain

• acne

• tiredness

• hoarseness

• weight gain 

• Toback and join pain

• headaches

• sleep disorders

• mood swings

Men with untreated prostate and breast cancer should avoid TRT. Those undergoing TRT should be regularly monitored for potential side effects, including polycythemia, peripheral edema, and cardiac or hepatic dysfunction (Osterberg et al 2017). The long-term disadvantages of TRT can include potential risks such as increased red blood cell production and a potential impact on cardiovascular health (Grech et al 2014). Monitoring by a healthcare professional is essential to assess and manage any potential long-term TRT health risk. ).

Conclusion

Physicians might recommend testosterone in dosage forms like injections, creams, gels, etc to address low testosterone in males due to specific medical conditions. It is important for people to be careful about possible problems that can happen soon or later when using testosterone. Before giving someone testosterone treatment, a physician should thoroughly check them and talk about the good and not-so-good things it might do for them. For more information on TRT, connect with experienced healthcare professionals of Science and Humans (ScienceandHumans ).