Beginning in the mid-forties, men may also experience a range of general symptoms, including hot flashes, sleep disturbances, fatigue, nervousness, and depressed mood. Libido and sexual activity decline with age: compared with men at age 30, sexual activity decreases by approximately 50% by age 50 and to about 20% by age 75. Testosterone deficiency also leads to loss of muscle mass, reduced bone mineral density, and decreased physical performance. The scientifically preferred terms for this condition are age-related hypogonadism or PADAM (Partial Androgen Deficiency of the Aging Male).

Terminology Used for Age-Related Testosterone Deficiency

Several terms are used to describe age-related testosterone deficiency:

• Andropause
• Andropenia
• Male climacteric
• Male menopause
• Partial Androgen Deficiency of the Aging Male (PADAM)
• Age-related testosterone deficiency

Hormonal Changes in Men Occur Gradually

Average testosterone blood levels decline slowly between the ages of 40 and 70:

• Total testosterone decreases by approximately 0.4% per year
• Free testosterone decreases by approximately 1.2% per year
• SHBG (sex hormone-binding globulin) increases by approximately 1.2% per year

As a result, biologically active testosterone declines by about 30% over this period. (Massachusetts Male Aging Study, Gray et al., 1991).

Typical Symptoms of Testosterone Deficiency

Common clinical symptoms include:

Musculoskeletal Symptoms

• Osteoporosis with associated bone pain
• Loss of muscle mass and strength
• Increased body fat, especially around the abdomen

Psychological and Cognitive Symptoms

• Reduced motivation
• Depressive mood
• Declining cognitive function

Sexual Symptoms

• Loss of libido
• Reduced sexual fantasies and interest
• Erectile dysfunction

Low testosterone may contribute to erectile dysfunction in approximately 20% of affected men and may be the sole cause in about 3% of cases.

Blood-Related Symptoms

• Anemia (reduced red blood cell count and hemoglobin levels)
• Fatigue and reduced physical performance

Diagnosis of Testosterone Deficiency

According to a consensus statement from German professional societies in andrology, dermatology, endocrinology, and urology, treatment-requiring testosterone deficiency is diagnosed when:

• At least two characteristic symptoms are present, and
• Total testosterone is below 3 ng/mL.

Symptoms Considered in Diagnosis

• Sexual dysfunction
• Changes in body composition (fat distribution and muscle mass)
• Symptoms related to osteoporosis
• Vasomotor symptoms (hot flashes and sweating)
• Psychosomatic symptoms (depressed mood)

Testosterone Replacement Therapy (TRT)

When testosterone deficiency (hypogonadism) has been confirmed through both symptoms and laboratory testing, testosterone replacement therapy (TRT) may be considered. The goal of treatment is to restore testosterone levels to the normal physiological range and improve symptoms such as reduced libido, erectile dysfunction, fatigue, depressed mood, loss of muscle mass, and reduced bone density.

Several formulations are available, including injections, topical gels, oral capsules (in some countries), and long-acting implants.

Injectable Testosterone Preparations

Injectable testosterone remains one of the most commonly prescribed forms of TRT because of its effectiveness and relatively low cost.

Short-Acting Injections

Characteristics

Advantages

• Low cost
• Effective symptom relief
• Widely available

Disadvantages

• Testosterone peaks shortly after injection
• Levels gradually decline before the next injection
• May produce fluctuations in mood, energy, libido, and sexual function (“sawtooth effect”)

Long-Acting Injections

Characteristics

Advantages

• Stable testosterone levels
• Fewer injections
• Less fluctuation in symptoms
• Improved convenience

Disadvantages

• Higher cost
• Requires administration by trained healthcare personnel in some countries

Long-acting testosterone undecanoate is often considered the preferred injectable option for long-term treatment because it more closely mimics physiological testosterone levels.

Testosterone Gels

Testosterone gels are applied once daily and provide relatively stable hormone levels.

Common Gel Preparations

Application Sites

Advantages

• Mimics natural daily testosterone production
• Avoids injections
• Stable testosterone levels
• Easy dose adjustment

Disadvantages

• Daily application required
• More expensive than injections
• Risk of transferring testosterone to partners or children through skin contact

Important Safety Measures

After applying testosterone gel:

• Wash hands thoroughly.
• Allow the gel to dry completely.
• Cover the application site with clothing.
• Avoid skin-to-skin contact until the area is dry.

Oral Testosterone

Oral testosterone formulations are available in some countries.

Advantages

• No injections
• Convenient oral administration

Disadvantages

• Requires daily dosing
• Absorption can vary with food intake
• Generally more expensive than injectable preparations

Testosterone Pellets (Implants)

Small testosterone pellets can be implanted under the skin and provide long-term hormone replacement.

Characteristics

• Effective for 3–6 months
• No daily treatment required
• Minor surgical procedure necessary

Comparison of Testosterone Formulations

Choosing the Right Therapy

The optimal testosterone formulation depends on:

• Patient preference
• Cost and insurance coverage
• Availability in the country of residence
• Desire to avoid injections
• Need for stable hormone levels
• Ability to adhere to daily treatment

Typical Clinical Preference

For many men with diabetes and age-related hypogonadism, long-acting testosterone undecanoate (Nebido®/Aveed®) or daily testosterone gel are often considered the most physiologic and convenient treatment options because they provide relatively stable testosterone levels with fewer hormonal fluctuations.

by clothing.

Monitoring During Testosterone Therapy

Regular monitoring is essential during testosterone replacement therapy.

Initially Every Three Months, Later Every Six Months

• Prostate examination (digital rectal exam, PSA testing, and/or ultrasound)
• Testosterone level measurement
• Estradiol measurement
• Prolactin measurement
• LH and FSH measurement

Additional Monitoring

• Blood lipid levels
• Liver function tests
• Complete blood count

These tests are generally recommended every six months.

Possible Side Effects of Testosterone Therapy

Although testosterone therapy is generally considered safe, several important risks must be considered.

Prostate

Testosterone can accelerate the growth of an existing prostate cancer. Therefore:

• Men with prostate cancer should not receive testosterone therapy.
• Prostate cancer must be ruled out before treatment begins.

However, current evidence indicates that testosterone replacement itself does not increase the risk of developing a new prostate cancer.

Breast Enlargement

• Gynecomastia (breast enlargement) may occur.

Sleep Apnea

• Existing sleep-related breathing disorders may worsen.

Polycythemia

• Increased red blood cell production can occur.
• This may increase the risk of thrombosis (blood clots).

Testosterone Deficiency and Diabetes

Men with Type 2 diabetes frequently have low testosterone levels.

Normally, low testosterone should trigger the hypothalamus and pituitary gland to increase the production of GnRH, LH, and FSH, thereby stimulating testosterone production. However, many men with Type 2 diabetes are also obese. In obesity, LH and FSH levels often remain low despite low testosterone levels. As a result, the testes receive insufficient stimulation to produce testosterone.

This can create a vicious cycle:

• Testosterone levels decline.
• Muscle mass decreases.
• Fat mass increases.
• Insulin resistance worsens.
• Diabetes control becomes more difficult.

Research Findings on Testosterone Therapy

An English study compared:

• 113 men with Type 2 diabetes treated with testosterone undecanoate
• 117 untreated control subjects

After eight years:

• Treated patients reduced their body weight by 18%.
• The control group gained weight despite receiving dietary counseling.
• HbA1c decreased by 2.5% in the testosterone-treated group.
• HbA1c increased by 0.47% in the control group.
• Blood lipid profiles also improved in the treated group.

The study concluded that testosterone therapy had a positive effect on several components of metabolic syndrome in hypogonadal men with Type 2 diabetes.