Testosterone Replacement Therapy

What is Testosterone Replacement Therapy

Testosterone Replacement Therapy (TRT) is a collection of medically prescribed and exogenously prepared testosterones that are indicated for the treatment of the symptoms of hypogonadism. Testosterone is the principal androgen / male sex hormone which is also produced in females, but in very minute quantities and it is produced and regulated by the organs that make up the hypothalamic-pituitary-testicular-axis. All the organs responsible for its action work together in a controlled environment. Testosterone is the hormone that is responsible for all the male characteristics which include; the growth and development of male sexual features, and cognitive functions i.e. concentration and memory. It plays a role in regulating mood, libido, bone density and energy levels and it is also responsible for triggering and facilitating the development of male sexual characteristics i.e. voice changes, the growth of pubic and body hair, fat distribution and distribution of muscle mass.
Testosterone Replacement Therapy utilizes testosterone medications to normalize deficient endogenous levels of the hormone in the body. This is done by either diminishing the total hormonal level back to the normal ranges in case of excess concentration or elevating these levels so that they are high enough, but within the normal hormonal levels so as to reverse any negative effects of hypogonadism. It should be noted that just as in other medications, TRT has both its benefits and risks.

Causes of Testosterone Deficiency

Testosterone deficiency occurs when there is a dysfunction within the HPT-axis which results in a condition known as hypogonadism. This condition can be classified into 3 basic types; Primary hypogonadism which originates from the testicles, secondary hypogonadism which involves a dysfunction of the pituitary or the hypothalamus and hypogonadism which is due to idiopathic/unknown causes. More specifically, these three types of hypogonadism can be as a result of other conditions like Klinefelter’s syndrome, hemochromatosis, undescended testes, testicular trauma, Kallmann syndrome, mumps, orchitis, pituitary disorders, HIV/AIDS, inflammatory diseases, andropause, cardiovascular diseases, obesity, alcoholism, chronic illnesses, chronic stress and diabetes.

Symptoms of Hypogonadism

Hypogonadism can be manifested through very many symptoms and these can vary from mild symptoms such as oily skin conditions to very severe disabilities like impotence. However, most of them are greatly related so they can be categorized into various groups. They include;

Physical appearance

Two of the main symptoms of hypogonadism are; a significant decrease in muscle mass and an increased accumulation of body fat. To facilitate a physical diagnosis of this condition, physicians can measure the body fat percentage, the waist to height ratio, the body mass index, the basal metabolic rates and the surface area.

Mood and Irritable Male Syndrome

Andropause / a decline in testosterone levels is believed to contribute to rising rates of depression, especially in older men. The irritable male syndrome is characterized by stress, loss of male identity, an increased frequency of anxiety, depression, confusion, hormonal fluctuations, biochemical changes and a less satisfying quality of life.

Sexual Dysfunction

Declined testosterone levels leads to a decrease in sexual functions which is characterized by a diminished libido, the inability to sustain an erection, low semen volume, and impotence.

General Deteriorated Health

A low testosterone level in the serum is related to a variety of general body health conditions and a diminished quality of life which can include a low insulin resistance, poor sleep quality, reduced cognitive functions, low stamina, body hair loss and brain fog.

How to Diagnose Testosterone

Hypogonadism can be diagnosed using a series of step by step processes that can be conducted on both males and females, even though it is considered a male condition. The typical sequence of diagnosing low testosterone levels in a patient includes self-reporting, the use of standardized questionnaires, analyzing historical information i.e. sexual history, family history, and personal history and finally, conducting physical examinations and blood testing.


A self-report focuses on the current status of sexual functioning and symptoms of secondary sexual characteristics such as muscular strength, beard growth, and decreased energy levels. Men suffering from a testosterone deficiency have statistically notable and rather lower incidences of nocturnal erections, lower degrees of penile rigidity during an erection or sexual intercourse, less frequent sexual thoughts, reduced sexual fantasies and reduced feelings of desire. Additionally, they can experience alterations in their body chemical consumptions which may result in increased body fat and a reduced body mass.

Standardized Testing

The AMS- Aging Male Syndrome Scale and the ADAM-Androgen Deficiency In Aging Men Scale are tests that can be used to quickly assess a patient’s moods, energy levels, quality of life, sleep quality and sexuality. These tests should be administered while a physician compiles an index of these symptoms with the information on the family medical history, personal information and sexual information which should all point towards the patient’s genetic traits and other correlated tendencies.

Historical Profiles

A historical profile should include data that discloses a patient’s:
– Sexual history- cases of delayed puberty, sexual activities, genital abnormalities, the rigidity of an erection, strength, muscle size, body hair, the frequency of sexual thoughts, body hair, changes in energy levels and the ability to gain muscles.
– Personal history entails blood type, chronic illnesses, allergic reactions, current supplements and medications, lifestyle behaviors(smoking and drinking), social relationships, life changes, surgeries, past immunizations, tests and their results and a list of the personal physicians that a patient has had.
– Family history – alcoholism, kidney diseases, cancer, mental illnesses, heart diseases, blood diseases and other conditions.

Blood Testing

A proper laboratory should be used to determine a more accurate diagnosis of hypogonadism. At the lab, this condition can be measured through blood testing even though the testosterone blood levels can vary greatly especially in old folks. A good test can use only two samples to measure the overall total testosterone levels in the serum, or it can calculate the total amount of inactive testosterone and the amount of testosterone that is free for action within the blood stream. The sex hormone binding globulin is a glycoprotein that is synthesized in the liver and its function is to disable circulating androgens and estrogens by binding to them. It also affects circulating testosterone levels. Other hormones that can be measured for the purpose of examining testosterone levels include FSH, LH, DHEA, and Estradiol. All tests should be conducted from 8:00 AM – 9:00 AM when blood serum concentrations of these hormones are at their peak.

The Clinical Rationale For TRT

A therapy using testosterone should approximate the naturally produced endogenous form of this hormone. A normal man should produce 4-7 mg of testosterone in a day in circadian and diurnal patterns. Maximum plasma levels are usually attained early in the morning and they are diminished to the lowest levels in the evening. An ideal testosterone replacement therapy should produce and maintain the normal physiologic serum concentrations without passing adverse side effects or safety concerns. There are several preparations and variations of synthetic testosterone and each has its respective method of action and unique properties.

Types of Testosterone Replacement Therapies

Orally Administered Testosterone

Orally administered testosterone is not recommended for clinical use because it has very many drawbacks, oral agents of testosterone can elevate some liver functions which will lead to abnormalities. Unmodified metabolites of testosterone are also absorbed very fast by the liver before they get to the serum which makes it difficult to achieve the required serum concentrations, other modified testosterones may be required on very high concentrations which will demand multiple administrations. Oral testosterone increases chances for hepatotoxicity, so an oral administration is never the first option when it comes to TRT.

Intramuscular Injections (IM)

For IM injections, testosterone preparations should be shot directly into the muscles. After the administration, it is absorbed directly into the bloodstream through the blood capillaries. IM is the most popular and the most preferred form of administration because it facilitates an extremely accurate dosing, it exhibits varying time-release qualities and it has very insignificant hepatotoxicity levels. Testosterone enanthate and testosterone cypionate are the most frequently used preparations since they can provide an extended release of this hormone during a treatment. Both of these forms have an identical mode of action and minimum side effects.

In men of around 20-50 years, an injection of 200 – 300 mg is sufficient to produce serum concentrations that fall around the normal ranges for about 14 days. Changes in testosterone serum levels can cause variations in body energy levels, moods, libido and sexual functions. Some patients may be inconvenienced by the need for frequent injections, so increasing a dose of this medication to about 300 – 400 mg can maintain eugonadal levels for up to 3 weeks. It should, however, be noted that increasing this dosage further may not lengthen the eugonadal actions for longer.

Transdermal / Topical administrations

Testosterone preparations can be formulated into a gel or cream forms which should be rubbed into the skin where they are absorbed through. Testosterone creams can be prepared into different strengths ranging from 10mg to 200 mg.

How to monitor patients on TRT

Patients on a TRT should be closely monitored so that a physician can ensure that their testosterone levels are within the normal ranges. A prescribing physician should continuously evaluate any fluctuations in the patients’ hypogonadal symptoms and address any side effects of this treatment. Testosterone levels in the serum should be checked after 5 – 7 hours after an application in a case of a trans-dermal delivery since this is when the concentrations are the highest.
It is recommended that men who are 40 years and older have a PSA- prostate specific antigen test before embarking on this treatment. This should be repeated after 3-6 months than repeated annually as the treatment continues. A confirmed increase in PSA over 2 ng/mL or a total PSA of more than 4 ng/nL requires a neurologic evaluation. The hematocrit levels should also be checked at baseline at 3-6 months then annually. A hematocrit level of more than 55% may call for an evaluation for sleep apnea/hypoxia which should be followed by a reduction of the testosterone dosage. Hypogonadal men with osteopenia may consider having their bone mineral density in the femoral necks and the lumbar spine tested after one year.

Contraindications to TRT

TRT is contraindicated in men with bladder and prostate conditions which may include but not limited to Benign prostatic hypertrophy, breast or prostate cancer and lipid abnormalities. However, the effects of TRT on PSA levels and the prostate in some studies of hypogonadism cases are found to be similar and comparable to those in normal men. The PSA levels were at their normal range. Patients on TRT should seek medical attention immediately If they experience any symptoms of a heart attack or stroke which are majorly characterized by; a difficulty in breathing, shortness of breath, chest pains, weakness on one side of the body and slurred speech. Abusing testosterone or administering it in very high dosages than the prescribed amount with other AAS is associated with very serious safety risks that might influence the brain, the liver, and the endocrine system. Reported adverse reactions include heart failure, depression, heart attack, hostility, aggression, male infertility, and strokes. Individuals who have abused high dosage of testosterone also reported some withdrawal symptoms like fatigue, depression, loss of appetite, irritability, decreased libido and insomnia. For more information on this medication and its administration, feel free to contact us.

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