30 May
30May

Testosterone Replacement

Testosterone replacement therapy (TRT) is a regimen of physician prescribed synthetic testosterones used to treat hypogonadic (low testosterone) symptoms.  Testosterone is the primary male androgen (sex hormone), which is also naturally produced in smaller amounts within the female body.  Largely produced by and regulated through a joint effort of the glands and organs which make up the Hypothalamic-Pituitary-Testicular-Axis (HPTA), testosterone is the hormone responsible for the normal growth and development of male sex organs, and plays an integral role in:  libido; mood; energy level; bone density; cognitive functions like memory and concentration; and secondary sex characteristics such as voice change, bodily hair growth, muscle mass, fat distribution, etc.

TRT uses synthetic testosterone (medically classified as an anabolic steroid) to support deficient endogenous testosterone levels by either elevating the total hormone levels back into the normal range, or by raising these levels high enough within the normal range to reverse negative hypogonadic symptoms]  It should be noted that as with all medication use, there are both risks and benefits to TRT.

Causes of Low Testosterone

Testosterone deficiency occurs when there is problem with HPTA, resulting in a condition known as hypogonadism, and is typically due to any of three basic hypogonadic conditions: 1) primary hypogonadism - originates from a problem within the testicles; 2) secondary hypogonadism - originates from a problem within the hypothalamus or the pituitary gland; and 3) idiopathic, or unknown causes.  More specifically, these three forms are often caused by:TRT

  • Klinefelter syndrome
  • Undescended testicles
  • Hemochromatosis
  • Testicular trauma
  • Cancer treatment
  • Mumps orchitis
  • Kallmann syndrome
  • Pituitary disorders
  • Inflammatory disease
  • HIV/AIDS
  • Medications
  • Obesity
  • Aging (andropause)
  • Cardiovascular problems
  • Chronic illness
  • Alcoholism
  • Cirrhosis
  • Chronic stress
  • Diabetes

Symptoms Of Hypogonadism

There are a several symptoms associated with low testosterone levels.  Such symptoms vary greatly from mild inconveniences like oily skin, to severe disabilities like impotence.  Hypo-gonadal symptoms are often related and can be largely categorized.

Mood & Irritable Male Syndrome - Often attributed to aging, such age-related gradual decline in testosterone levels (andropause) is known to contribute to the rising rate of depression in older men.  Irritable male syndrome (IMS) is a condition often characterized by its associated biochemical changes, hormonal fluctuations, stress, and loss of male identity.  It includes increased frequency of anxiety, depression, anger, confusion, diminished relationship and sexual life, and a less satisfying overall quality of life.

Sexual Dysfunction - There is a direct correlation between declining testosterone levels and reduced sexual function, i.e., diminished:  libido; impotence; inability to sustain erection; low semen volume; etc. 

Physical Appearance - Two of the primary measures/symptoms physicians use to aid in their physical diagnosis of low testosterone are the recent significant decrease in muscle mass and inversely increased body fat.  Physical health measures include body fat percentage, body mass index (BMI), waist-to-height ratio (WHtR), the basal metabolic rate (BMR), surface area, Willoughby athlete weight calculation, etc.]  Although a variety of internal, external, and even habitual factors are involved in one's physical appearance, low testosterone can be one of the key hidden obstacles to reaching your aesthetic goals

General Health - Low serum testosterone has been correlated with a variety of overall health, or quality of life diminishing symptoms such as decreased or reduced:  cognitive functions like concentration and focus, memory and recall (brain fog); sexual performance; insulin resistance; muscle mass; sleep quality; bone density; stamina; bodily hair; etc.

This condition is diagnosed in a multi-step process, and can be experienced by both genders but is often considered a male condition.  The typical sequence of low testosterone diagnosis is self-reporting, standardized questionnaire, analysis of historical information (personal, sexual, and family), physical exam, and blood test.

Self-Reporting

The self-report reflects the current status of sexual function and secondary sexual characteristics, such as beard growth, muscular strength, and energy level.  Hypogonadal men have statistically significant lower:  incidences of nocturnal erections; degrees of penile rigidity during erection; and frequencies of sexual thoughts, feelings of desire, and sexual fantasies.  Furthermore, alterations in body composition such as increased body fat percentage (adipose, visceral, subcutaneous), and reduced muscle mass are frequently reported by hypo-gonadal men.

Standardized Testing

The Androgen Deficiency in Aging Men (ADAM) and the Aging Males' Symptoms scale (AMS) quickly assess patient mood, energy, quality of life (work and play), sleep, and sexuality.  These tests are usually administered while the physician is compiling an index of symptoms - pertinent sexual, personal, and family medical information all of which aids the physician in the identification of possible genetic traits and tendencies.

Historical Profile

Examples of historical profile data include disclosure of: 

  • Sexual History - birth genital abnormalities; delayed puberty; nocturnal emissions; sexual activity; erection rigidity; sexual though frequency; diminishing body hair; changes in muscular size, strength, and ability to gain muscle; changes in energy levels
  • Personal History - allergic reactions; blood type; past and present major and chronic illnesses; current medications and supplements; surgeries; immunization dates; doctors' names; past positive test results; lifestyle habits (alcohol drinking, smoking, binge eating, etc.); social relationship problems; major life changes
  • Family History - cancer; kidney disease; alcoholism; mental illness; diabetes; blood diseases; and other conditions

Blood Testing

Proper labs should be drawn to determine a diagnosis, and low testosterone levels are measured via blood test.  Although testosterone blood tests vary (especially older ones), a good test uses two samples to measure total testosterone level, and to directly measure or calculate the amount of 'bound' (inactive) testosterone and 'free' (available for function) testosterone within the bloodstream.  Sex hormone-binding globulin (SHBG) is a liver synthesized glycoprotein that binds with and disables circulating both androgens and estrogens, and is also used in the calculation of testosterone levels.  Other measured hormone levels typically include DHEA, FSH, LH, and Estradiol.  All blood testing should be conducted in the morning from 8:00-9:00 AM when blood serum concentrations are at their peak. 

The Clinical Rational For TRT

Testosterone replacement should approximate the natural, endogenous production of the hormone.  The average male produces 4-7 mg of testosterone per day in a circadian pattern, with maximal plasma levels attained in early morning and minimal levels in the evening.  Ideal testosterone replacement therapy produces and maintains physiologic serum concentrations, without significant side effects or safety concerns.  There are different variations (preparations, esters, blends, etc.) of synthetic testosterone each with its own unique properties, and respective methods of action.  

Types of Testosterone Replacement Therapy

Ideal testosterone replacement therapy produces and maintains physiologic serum concentrations of the hormone and its active metabolites without significant side effects or safety concerns. 


Oral Testosterone

Oral agents may cause elevations in liver function tests and abnormalities at liver scan and biopsy. Unmodified testosterone is rapidly absorbed by the liver, making satisfactory serum concentrations difficult to achieve. Modified 17-alpha alkyltestosterones, such as methyltestosterone or fluoxymesterone, also require relatively large doses that must be taken several times a day. Due to it's potential for hepatotoxicity, these formulations are not recommended for clinical use.

 

Intramuscular Injections (IM) 

Testosterone preparations are shot directly into the muscle, and then absorbed into the bloodstream via the capillaries.  This is an extremely popular preparation due to its highly accurate dosing, varying time release qualities, and insignificant hepatotoxicity levels.  Testosterone Cypionate and Testosterone Enanthate are frequently used parenteral preparations that provide a safe means of extended release hormone replacement in hypogonadal men. The kinetics of testosterone enanthate and cypionate are identical. In men 20-50 years of age, an intramuscular injection of 200 to 300 mg testosterone enanthate is generally sufficient to produce serum testosterone levels that are supranormal initially and fall into the normal ranges over the next 14 days. Fluctuations in testosterone levels may yield variations in libido, sexual function, energy, and mood. Some patients may be inconvenienced by the need for frequent testosterone injections. Increasing the dose to 300 to 400 mg may allow for maintenance of eugonadal levels of serum testosterone for up to three weeks, but higher doses will not lengthen the eugonadal period. Testosterone Propionate is available for patients requiring a faster acting dose.


Testosterone (enanthate, cypionate, and propionate) is approved by the U.S. Federal Drug Administration (FDA) to treat hypogonadism as it improves mood, memory, energy, libido, and erectile function; increases muscle mass, strength, and bone density; and reduces subcutaneous, visceral, and adipose fat.

Testosterone preparations can be made in cream or gel forms and are rubbed into the skin, then absorbed through it.  Transdermals can be provided in different strengths ranging from 10 mg to 200 mg per milliliter.  For optimal benefit, twice daily doses are recommended once upon waking, and again later in the day at consistent times.  

Monitoring Patients On Testosterone Replacement

Patients on testosterone replacement therapy should be monitored to ensure that testosterone levels are within normal ranges.  The prescribing physician should continually evaluate changes in hypogonadic symptoms, and address treatment side effects.  Serum testosterone levels should be checked 5 to 7 hours after the application of transdermal delivery systems, when concentrations are highest.

Men forty and older should have a Prostate Specific Antigen (PSA) prior to therapy.  The PSA test should be repeated in 3-6 months, and then checked annually.  A confirmed increase in PSA >2 ng/mL, or a total PSA >4.0 ng/mL requires urologic evaluation.  The hematocrit level should also be checked at baseline, at 3-6 months, and then annually.  A hematocrit >55% warrants evaluation for hypoxia and sleep apnea, and/or a reduction in the testosterone therapy dosage.  Hypogonadal men with osteopenia should be having bone mineral density of the lumbar spine and/or the femoral necks tested after one year.

Contraindications To TRT

TRT is traditionally contraindicated in men with prostate and bladder conditions which include but may not be limited to:  Benign Prostatic Hypertrophy (BPH); cancer or carcinoma of the breast or prostate; and lipid abnormalities.  However, the effects of TRT on prostate size and PSA levels in some studies of hypogonadal men were found to be comparable to those in normal men, and PSA levels were within the normal range.

Benefits of Testosterone Replacement Therapy

A number of benefits of testosterone replacement therapy have been recorded, including better stability with moods, energy levels, and libido. Testosterone replacement has also been shown to enhance libido, the frequency of sexual acts and sleep-related erections. Transdermal testosterone replacement therapy, in particular, has been linked to positive effects on fatigue, mood, and sexual function, as well as significant increases in sexual activity. More specifically, testosterone replacement therapy has been shown to improve positive mood parameters, such as feelings of friendliness and reduction of negative mood parameters, such as anger and irritability.

Testosterone replacement therapy is also associated with potentially positive changes in body composition. In hypogonadal men, testosterone replacement therapy has demonstrated a number of effects, including an increase in lean body mass and decrease in total body fat.

Improvements in bone density have also been shown with testosterone replacement therapy. Increases in spinal bone density have been realized in hypogonadal men, with most treated men maintaining bone density above the fracture threshold.

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