Testosterone Gel - Uses, Mechanism of Action, Precautions and Side Effects

Overview:

Androgen or testosterone deficiency syndrome is a common condition in males. It is associated with certain clinical features like decreased libido, fatigue, or erectile dysfunction. The exact prevalence rate of this condition is unknown, as most men do not seek treatment. The treatment of androgen or testosterone deficiency syndrome (male hypogonadism) is not easy because of the following reasons:

• No adequate data or study suggests the time for initiating the treatment in men or the best treatment option available for a particular patient.

• Sometimes, the general practitioners may also not be familiar with all the treatment options available.

• Presently, the treatment options available in the market are expensive and must be administered in different doses to obtain the desired result.

What Is Testosterone?

Testosterone is a hormone chiefly produced by the testicles in males. The function of this hormone is to maintain the following:

• Facial and body hair.

• Sex drive.

• Sperm production.

• Bone density.

• Red blood cell production.

• Fat distribution.

• Muscle strength and mass.

What Effect Does Aging Have on Testosterone Levels?

Testosterone levels reach the highest during early adulthood. Testosterone levels decline steadily with age. The rate of decline is around one percent every year after 30 or 40 years. It is essential to diagnose if testosterone levels are low due to normal aging or hypogonadism.

Hypogonadism changes the ability to produce normal amounts of testosterone due to some problem in the testicles or the pituitary gland.

Testosterone replacement therapy helps to improve the symptoms of low testosterone in these men. Testosterone replacement therapy is available in the form of:

• Injections.

• Pellets.

• Patches.

• Gels.

Effect of Declining Testosterone Level on Symptoms of Aging:

Men can have many signs and symptoms as they age. The declining testosterone levels do not usually affect the symptoms of aging in men. However, the following symptoms might occur as a result of lower testosterone levels:

1. Physical Changes: Certain physical changes have been noticed that including:

• Increased body fat.

• Reduced muscle bulk and strength.

• Decreased bone density.

• Gynecomastia (swollen or tender breasts).

• Body hair loss.

• Less energy.

2. Emotional Changes: Low testosterone levels can lead to:

• Decrease in motivation and self-confidence.

• Sadness or depression.

• Reduced concentration.

• Forgetfulness.

3. Changes in Sexual Function: This includes:

• Reduced sexual desire.

• Fewer spontaneous erections (during sleep).

• Infertility.

A blood test can be performed to diagnose a low testosterone level. Some of these symptoms might result from other factors like medication side effects, diabetes, thyroid problems, obstructive sleep apnea, and depression. However, sometimes these conditions might lead to low testosterone levels. Hence, treatment can increase testosterone levels.

What Are the Risks Associated With Testosterone Replacement for Normal Aging?

Testosterone replacement therapy includes the following risks:

• Certain skin reactions or acne formation.

• Benign prostatic hyperplasia or noncancerous prostate growth and existing prostate cancer growth.

• Reduced sperm production or shrinkage of the testicles.

• Worsening sleep apnea.

• Enlargement of breasts.

• Increased red blood cell production can lead to the formation of a blood clot.

• Increased risk of heart disease.

When to Consult the Doctor About Testosterone Therapy?

The doctor must be consulted about the risk and benefits of Testosterone therapy. The doctor usually measures the testosterone levels before recommending Testosterone therapy.

Treatment of normal aging with Testosterone therapy is not recommended. Suppose the patient does not have a medical condition that is the reason behind the low testosterone levels. In that case, the doctor may suggest natural ways to boost testosterone, like increasing muscle mass through exercise and losing weight.

Can Testosterone Therapy Help Increase Youth?

Studies have demonstrated that Testosterone therapy can cause a reversal in hypogonadism (a condition where the body produces a decreased amount of the masculine growth and development hormone, testosterone) effects. However, the benefits of this therapy in otherwise healthy men are still unclear.

In some cases, it has been reported that men feel more active and younger after taking Testosterone medications.

The American College of Physicians guidelines reports that Testosterone therapy can increase sexual function in some cases. However, not much evidence proves functions like vitality and energy can be increased.

Warnings:

• Certain precautions must be taken to ensure that others do not come into contact with Testosterone gel applied to the patient. After the Testosterone gel or solution is used, the medication should be allowed to dry for a few minutes. Then clothing must be placed that covers the area so no one can touch the bare skin. After applying the medication, hands must be washed with soap and water to remove the medication and clean the hands properly.

• Testosterone topical products can harm individuals who touch the area where the gel or solution is applied. For example, if a pregnant woman, or one who is breastfeeding, touches skin covered with topical Testosterone products, it might harm the child.

• The patient must inform others around him to be careful while handling the clothing, bed linens, or other items that may have Testosterone gel or solution.

• If women or children touch skin treated with Testosterone gel, they may develop specific symptoms like:

• Growth of hair in different body regions.

• Acne.

The doctor must be informed immediately about this.

• If a child comes into contact with Testosterone gel, the following symptoms might develop:

• Enlarged genitals.

• Growth of pubic hair.

• Increased erections.

• Increased sexual desire.

• Aggressive behavior.

In most cases, these symptoms disappear once exposure to testosterone is stopped. However, sometimes, the genitals remain enlarged.

• Topical Testosterone can also cause the bones to mature rapidly in children. This might lead to shorter-than-expected adult height as the child stops growing sooner. Even after exposure to Testosterone gel is arrested, the bones of these children remain more mature than expected.

For Patients:

Indications:

Testosterone is FDA-approved as replacement therapy in the following men:

• Men with decreased testosterone levels or hypogonadism.

• Congenital or acquired hypogonadotropic hypogonadism.

• In case of a pituitary-hypothalamic injury, gonadotropin deficiency, or LHRH deficiency resulting from tumors, radiation, or trauma.

Rate of Occurrence of Hypogonadism:

• Men in Their Sixties: 19 %.

• Men in Their Seventies: 28 %.

• Men in Their Eighties: 49 %.

How Should This Medicine Be Used?

• Topical Testosterone comes in the form of a gel and solution that has to be applied to the skin.

• It is usually applied once daily, and it is recommended to use Testosterone gel or solution in the morning.

• Testosterone topical is available in single-use packets or tubes and a multiple-use pump. The pump releases a certain amount of testosterone every time it is pressed. The doctor or pharmacist prescribes the number of times the pump has to be pressed for each dose and the number of doses the pump contains. The pump must be disposed of after the given number of doses, even if it is not entirely consumed.

• It should be applied at around the same time daily to avoid missing the dose.

• The directions on the prescription label must be followed carefully.

• The topical Testosterone must be used exactly as directed by the doctor. It must not be applied more or less and more frequently than prescribed by the doctor.

• Various topical Testosterone products are manufactured differently and have to be used differently. Hence, the patient should know the brand and how and where it must be used.

• The manufacturer's patient guide with the topical Testosterone product should be read carefully.

• The morning bath or shower must be taken before applying topical Testosterone products.

• Testosterone topical products should not be applied to the penis, scrotum, or skin with cuts, sores, or irritation.

• Testosterone gel and solution are combustible and may catch fire. It should be kept away from open flames. Men must never smoke while applying topical Testosterone until the gel or solution has completely dried.

• The doctor can adjust the dose of Testosterone depending on the amount of testosterone present in the blood during treatment.

Testosterone topical is used to control the symptoms, but it does not cure the condition completely. Therefore, topical Testosterone must be continued even after the patient feels well and must not be stopped without the doctor's advice. If topical Testosterone is discontinued abruptly, the symptoms might return.

What Special Precautions Should Be Followed Before Using Testosterone Gel?

Before using Testosterone gel,

Allergies: The doctor should be informed about a known allergy to Testosterone or other medication. The patient should ask for the list of ingredients in the drug that they might be allergic to.

Drug History: The patients must inform the doctor about any prescribed or nonprescribed medications. Further, the doctor should be aware of the patient's vitamins or supplements (nutritional or herbal).

The patients should mention if they are taking the following drugs:

• Anticoagulants (blood thinners) such as Warfarin.

• Insulin.

• Oral steroids such as Dexamethasone.

• Methylprednisolone.

• Prednisone.

Medical History: The patient should tell the doctor about any other illness in the past, or any comorbidities present like:

• Sleep apnea (breathing stops during sleep for a short duration).

• Benign prostate hyperplasia (BPH).

• An enlarged prostate.

• High blood levels of calcium.

• Diabetes.

• Heart, kidney, liver, or lung disease.

• The doctor must be informed of any history of breast or prostate cancer. The doctor will not advise the use of topical Testosterone in such cases.

• Patients 65 years or older must know about the risks and benefits of using topical Testosterone. Older men are usually not advised to use topical Testosterone unless they have hypogonadism.

What Should Special Dietary Instructions Be Followed?

A normal diet must be followed unless the doctor recommends changes.

What Should Be Done in Case of a Missed Dose?

The missed dose should be applied once the patient remembers about it. However, if it is almost time for the next dose, the dose should be skipped, and a regular dosing schedule should be followed. For example, a double dose should not be taken to compensate for a missed one.

Side Effects:

Serious side effects have been documented in people who use high doses of Testosterone and other male sex hormone products without the doctor's advice. These side effects include:

• Heart attack.

• Heart failure.

• Other heart problems (stroke and mini-stroke).

• Seizures.

• Mental health changes such as depression, mania (abnormally excited mood), aggressive or unfriendly behavior, hallucinations (seeing things or hearing voices that do not exist), or delusions (having strange thoughts or beliefs that have no basis in reality).

• Liver disease.

• Difficulty urinating.

• Lower leg pain, swelling, or redness.

• Shortness of breath.

• Swelling of the hands, ankles, or lower legs.

• Nausea or vomiting.

• Difficult speech.

• Dizziness or faintness.

• Weakness or numbness of an arm or leg.

• Chest pain.

• Yellowing of the skin or eyes.

People with higher doses of Testosterone than recommended by a doctor may lead to the following withdrawal symptoms if the application is suddenly stopped:

• Depression.

• Extreme tiredness.

• Restlessness.

• Loss of appetite.

• Decreased sex drive.

• Craving.

• Irritability.

• Inability to fall asleep or stay asleep.

The common side effects of topical Testosterone include:

• Decreased sexual desire.

• Acne.

• Depression.

• Dry or itchy skin.

• Diarrhea.

• Mood changes.

• Headache.

• Teary eyes.

• Skin redness or irritation.

Testosterone topical may cause a decrease in the number of sperm (male reproductive cells) produced, especially if it is used at high doses.

How to Store and Dispose of This Medicine?

• The container of Testosterone should be tightly closed and kept out of reach of children.

• Testosterone gel should be stored at room temperature and not exposed to excessive moisture and heat.

• If Testosterone gel is no longer required, it should be disposed of properly so that pets and children do not consume the medications by mistake.

Other information:

• The patient should not advise others to take this medication without consulting a doctor.

• The patient can ask the pharmacist any questions about refilling the prescription.

• Maintaining a written list of all the prescribed and non-prescribed (over-the-counter) drugs that are being taken by the patient, including other supplements like vitamins or minerals. The patient should carry this list for every visit to a doctor or a hospital. It is extremely important in case of emergencies.

• The gel should not be used by anyone else as Testosterone gel is a controlled substance.

For Doctors:

Indications:

Testosterone is FDA-approved as replacement therapy in the following men:

• Men with low testosterone levels and symptoms of hypogonadism.

• Congenital or acquired hypogonadotropic hypogonadism.

• In case of a pituitary-hypothalamic injury, gonadotropin deficiency, or LHRH deficiency resulting from tumors, radiation, or trauma.

Establishing the difference between primary (testicular) and secondary (pituitary-hypothalamic) hypogonadism is important.

Symptoms that highly suggest hypogonadism include:

• Decreased spontaneous erections.

• Decreased libido.

• Decreased beard growth.

• Decreased nocturnal penile tumescence.

• Shrinking testicles.

In males, the normal range for testosterone:

• 300 ng/dL to 1000 ng/dL (early morning).

In hypogonadism, serum testosterone level:

• Less than 300 ng/dL (early morning).

However, accurate clinical judgment is essential to diagnose hypogonadism in patients with persistent testosterone deficiency symptoms with testosterone levels in the normal range.

Testosterone levels:

• Senior Men: 500 and 800 ng/dL.

• Young Adults: 600 and 900 ng/dL.

In cases of testosterone levels lower than normal, along with clinical symptoms, further testing is necessary to detect free or bioavailable testosterone. The following tests should be performed to calculate the bioavailable testosterone:

• Sex hormone-binding globulin (SHBG).

• Albumin.

Sex hormone-binding globulin (SHBG) and albumin can be affected by the following:

• Obesity.

• Hypothyroidism.

• Type 2 diabetes.

• Liver disease.

The following tests can be performed to rule out the suspicion of a secondary cause:

• Semen analysis.

• Pituitary MRI.

• Testicular ultrasound.

• Genetic studies.

• Biopsy.

The FDA does not recommend Testosterone therapy to treat women with low libido.

Mechanism of Action:

Testosterone shows various biologic effects because it acts as three hormones:

• It can act directly on the androgen receptor.

• It acts on the tissues by converting to dihydrotestosterone (DHT) by the enzyme 5-alpha reductase.

• It acts as an estrogen after conversion to estradiol by aromatase.

The three actions are essential to understand the indications and adverse effects of androgen replacement therapy.

1. In most tissues, the activity of testosterone depends upon its reduction to DHT.

2. DHT then binds to cytosol receptor proteins.

3. After being transported to the nucleus, the steroid-receptor complex starts transcription and cellular changes.

Pharmacokinetics:

Half-Life:

• Directly proportional to the free testosterone concentration in plasma.

• Testosterone Cypionate (IM): Eight days (approximately).

Excretion:

• Around 90 % of testosterone is excreted in the urine as glucuronic or sulfuric acid conjugates of testosterone.

• It is converted into an inactive form by the liver.

Administration:

Monitoring:

Various laboratory tests must be performed before starting the Testosterone therapy, including:

• Hemoglobin (Hgb).

• Hematocrit (Hct).

• Liver Functional Tests (LFTs).

• Lipid profile.

• Two-morning testosterone levels.

• DEXA scan (dual-energy X-ray absorptiometry scan).

Monitoring Over a Period of Time:

One month after treatment:

• Morning testosterone level.

Three to six months after treatment within one year:

• Morning testosterone level.

• Lipid profile.

• Liver function test.

• Estradiol.

• Blood pressure.

• Hematocrit.

• Hemoglobin.

Annually after one year:

• Morning testosterone level.

• Liver function tests.

• Lipid profile.

• Estradiol.

• Hematocrit.

• Hemoglobin.

• Blood pressure.

Adverse Effects:

It is essential to monitor different adverse effects at every visit:

• Patients on Testosterone replacement therapy must be evaluated at an interval of three months for prostate cancer and one year after initiating the treatment.

• Patients are advised to put a cloth over the application site and wash their hands or skin before having skin-to-skin contact to avoid transfer to a woman or child who comes in contact with the gel.

• Testosterone patches can lead to skin reactions, and injections can cause mood, energy, and libido fluctuations.

• Testosterone use can be related to erythrocytosis associated with hematocrit, further developing the risk of venous thromboembolism.

• No significant effects of testosterone on lower urinary tract symptoms and benign prostatic hyperplasia. The doctors or physicians must carefully address Testosterone therapy's risks and benefits before starting the treatment.

• In 2015, the FDA (food and drug administration) reported an increased cardiovascular risk associated with Testosterone use.

Contraindications:

Testosterone replacement therapy is contraindicated in the following conditions:

• Uncontrolled heart failure.

• Myocardial infarction.

• History of breast cancer.

• Prostate cancer.

• Cerebrovascular accident within the past six months.

• A palpable undiagnosed prostate nodule.

• Untreated obstructive sleep apnea.

• Hematocrit above 48 %.

• Men planning fertility.

• An elevated PSA (prostate-specific antigen) above 4 ng/ml.

• An increased PSA level above three ng/mL in high-risk patients.

Toxicity:

No cases of acute overdosage with Testosterone therapy have been reported.

Improving Healthcare Team Outcomes:

• The interprofessional team, including physicians, pharmacists, and nurses, must know the risks, benefits, and contraindications associated with Testosterone replacement therapy.

• Clinicians can prescribe androgen replacement therapy by using a risk-benefit assessment of the patient's needs and considering the risk of adverse reactions.

• Low testosterone levels are related to an increased risk of coronary artery disease. In 2017, a study documented that Testosterone replacement was associated with a lower risk of cardiovascular issues.

• The American Association of Clinical Endocrinologists (AACE) issued a guideline that there is no significant evidence that Testosterone therapy increases cardiovascular risk. However, testosterone deficiency is related to sarcopenia, osteopenia, frailty, and osteoporosis.

• Pharmacists should provide thorough counseling before administration, depending on the formulation. Nurses can also counsel patients on administration and dosing and assess the effectiveness of the treatment.

• Both pharmacists and nurses must inform the doctor about concerns they encounter to establish a proper communication channel between team members. Desired outcomes can be achieved with interprofessional patient monitoring with the least adverse effects.