Maximizing Potential: The Evolution of Testosterone Therapy

Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. British Army Physical Training Instructor.

Testosterone therapy has undergone a remarkable evolution, paving the way for groundbreaking advancements in the field.

With cutting-edge research and innovative techniques, this treatment has transformed the lives of countless individuals.

Testosterone is a critical hormone for development, differentiation, and growth in both the male and female. It progressively declines in men as they age.

The synthesis, pharmacology, and clinical applications of testosterone have changed over the past 80 years. However, many aspects of its application are still unclear and controversial.

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Key Points:

  • Testosterone is a crucial hormone for development and growth in both males and females, declining naturally in men as they age.
  • The history, synthesis, and clinical applications of testosterone have evolved over time, with many aspects still unclear and controversial.
  • Testosterone plays a vital role in male reproductive tissues, secondary sexual characteristics, muscle strength, immune system health, and bone density.
  • Testosterone therapy can improve various health conditions, but its safety and efficacy, especially in prostate cancer, remain under scrutiny.
  • The future of testosterone therapy lies in the development of novel forms and delivery systems to enhance efficacy and safety for patients and clinicians.


The history of testosterone dates back to the time of the Egyptians, when castration of the testes was used for a variety of reasons including punishment and the creation of obedient slaves.

Although it was not known at that time what testosterone was, its role in male reproductive tissues was well-recognized.

In men, testosterone is produced by the ovaries and adrenal glands in much higher levels than in women.

It is a natural sex hormone that plays an essential role in the development of male sex organs, the promotion of secondary sexual characteristics during puberty and maintenance of muscle strength and mass.

It also contributes to the maintenance of a healthy immune system and prevents osteoporosis. In addition, it regulates the release of luteinising hormone and follicle stimulating hormone.

Moreover, it is important in the regulation of the production of red blood cells and in the synthesis of fats. It also affects the development of bones and muscles during growth.

Testosterone's discovery and clinical application were made possible by 3 remarkable pieces of research: Arnold Berthold’s study of roosters in 1849; Charles Brown-Sequard’s work on rejuvenation therapies using auto-injection of animal testicles in 1889; and Gustav Foss’s development of methyl testosterone (MT) in 1935, which simplified the use of steroidal hormones to treat hypogonadism.

The discovery of the relationship between low testosterone and prostate cancer (PCa) was a landmark in modern science, but it has been controversial ever since.

It remains unclear whether the increased testosterone levels found in some men with PCa are a risk factor or just a marker for cancer.

Nevertheless, it is important to acknowledge the potential of testosterone as a potential treatment for prostate cancer. If a positive effect is found, it could be of great benefit to men with advanced prostate cancer.

Testosterone replacement therapy (TRT) is the use of a synthetic version of the male hormone testosterone to restore a man's normal level of the hormone.

It has been shown to increase erectile function, improve sex drive, decrease anemia, boost bone density, enhance lean body mass, and reduce depressive symptoms in patients with low testosterone.

However, the safety of testosterone therapy in prostate cancer has been questioned and the risks associated with its use are being investigated by the FDA.

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Throughout the history of testosterone, its therapeutic potential has been developed to address a wide range of medical conditions.

It is available in a variety of forms, including injectable formulations, topical gels and solutions, tablets, implants, and patches. A further low risk treatment can be in the form of natural 'over the counter' supplements.

Testosterone therapy can be used in males for a variety of purposes, including to treat sexual dysfunction.

In addition, it can be prescribed to increase bone mass and improve quality of life in people with human immunodeficiency virus infection (HIV) and other chronic illnesses.

It can also be prescribed to increase muscle mass and prevent or delay osteoporosis in men with low testosterone levels.

This has been shown in both young and old hypogonadal men and is associated with improvements in areal bone density, volumetric bone mineral density (BMD), and trabecular architecture, as well as increased estimated bone strength.

Syntheis of testosterone

As with other steroid hormones, testosterone is synthesized from cholesterol through the process of oxidative cleavage.

The first step in this process involves the cytochrome P450 CYP11A1 enzyme, which removes six carbon atoms to produce pregnenolone.

The next step is the enzyme CYP17A1 which removes two more carbon atoms to produce testosterone, the principal steroid hormone in both sexes.

Because it is a primary sex hormone, testosterone can affect many different organ systems. It also has a role in promoting secondary sexual characteristics like body hair and muscle mass.

Some of these effects can be mediated by a receptor called sex hormone binding globulin (SHBG). It interacts with sex hormone-binding protein 1 (SBP1), which can then activate a number of different cellular pathways and gene expression.

The development of testosterone as a drug for the treatment of certain diseases has been very fast, and a wide range of therapies have been designed to target it. Among these are polycystic ovarian syndrome (PCOS), congenital adrenal hyperplasia, and ovarian or testicular tumors.

Another important area of interest is the relationship between testosterone and social factors in a person's life.

This can involve the influence of circulating testosterone on the person's SEP, or socioeconomic status (SEP).

Although evidence is circumstantial, it is plausible that circulating testosterone may have causal effects on some aspects of a person's SEP through influences on behavior.

It has been linked with success in some occupations, such as male executives and financial traders.

However, these associations seem to be influenced by the individual's level of exposure in utero or at an earlier point in their life, rather than by a specific biological mechanism.

What is Androgen Insensitivity Syndrome?

AIS is a disorder of sex development resulting from varying degrees of resistance to the biological actions of androgens.

There are three phenotypes: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS).

Complete androgen insensitivity syndrome is caused by mutations in the gene encoding the androgen receptor.

These mutations can result in steroid or DNA binding defects that are expressed in genital skin fibroblasts and manifest as feminisation of the genitalia.

Serum testosterone concentrations increase during the neonatal period in infants with CAIS but not as rapidly or as sexually dimorphic as those of normal male infants.

A human chorionic gonadotropin stimulation test can exclude other causes of a similar phenotype.

Infants with CAIS often present with hypospadias, a common congenital malformation in which the testes do not descend into the scrotum (unpublished).

Early gonadectomy with puberty induction later or gonadectomy during adulthood can be performed, depending on the child's age at diagnosis and the parent's wishes.

The child's parents should be informed about the syndrome at an early age, and disclosure can be done gradually as the child approaches pubertal age. Disclosing the syndrome can cause psychological distress and should be done with care.

Women with CAIS are at increased risk of breast cancer, but this is rare. Carcinoma in situ (pregnancy-induced ovarian germ-cell tumour) is also more frequent in girls with this condition than in those who do not have the syndrome.

Early gonadectomy is recommended in this group, but some women choose not to have it.

Clinical Applications

Low testosterone can cause problems with energy, concentration, mood and libido. It may also increase your risk of prostate cancer and heart disease.

If you have low testosterone, your doctor may prescribe medications to treat the problem.

These drugs can help you feel better. Some supplements can also help your body make more of the hormone testosterone.

These medications are called hormone replacement therapy (HRT) and include injectables, tablets, and patches.

You will need to use these medication for several weeks or months, in some cases you may be prescribed the hormone for the rest of your life.

When you get a prescription for testosterone therapy, you should keep track of how much you take each day. You should also ask your doctor to check your blood pressure and cholesterol levels regularly.

Taking too much testosterone can increase your risk of getting a heart attack or stroke, or may lead to other health problems. If you have these problems, you may need to stop using testosterone.

Aside from that, long-term testosterone therapy may increase your risk of developing prostate cancer or polycythemia. These risks aren't life-threatening, but they can be serious.

To reduce your risk of these problems, your doctor may recommend that you take a cholesterol-lowering drug, such as a statin. You should also eat a healthy diet and exercise regularly.

Your doctor may also recommend that you take certain medicines, such as birth control pills, to prevent clotting of your blood. They may also tell you to avoid alcohol or cigarettes.

Other medications, including those that treat depression or low sperm count, can also affect your testosterone levels.

These medications can cause side effects, such as headaches, nausea or vomiting, and changes in your vision.

The clinical application of testosterone is a complex one that involves multiple interactions between the hormone and various tissues. It can act directly on the androgen receptor, by converting to dihydrotestosterone and estradiol, or by acting as an estrogen.

Future Directions

In recent years, testosterone therapy has enjoyed a surge in popularity among men of all ages.

It is widely regarded as a wonder drug with the potential to improve sexual performance, muscle mass, and stamina in older men. However, its safety and efficacy remain a matter of debate.

A few notable studies have thrown light on the pros and cons of testosterone use, but the evidence is still sparse.

For example, a landmark seven-part series funded by the U.S. National Institute on Aging – called the TTrials – has produced mixed results. It was able to demonstrate that testosterone treatment improved bone density, a measure of health.

It also helped to correct anemia, a condition that develops when the body doesn’t make enough healthy red blood cells.

But it did not do a particularly good job of improving memory or preventing heart attacks and strokes.

Testosterone has a long history as a therapeutic agent, from its origins as a hormone derived from the prostate to today’s synthetic versions. Although some physicians still hesitate to prescribe it, it has been shown to have a number of potential benefits.

The future of testosterone therapy will likely be shaped by the continued development of novel forms and delivery systems.

Newer therapies should be easier to administer and provide superior efficacy, while remaining safe for use by both patients and clinicians alike.

One of the most important questions for physicians is deciding which form of therapy is the right choice for their patient.

The most effective strategy involves a well-thought-out evaluation of the patient’s needs and preferences.

This includes assessing his medical history, the type and degree of hypogonadism, current medications and other treatments, and the expected outcomes of treatment.


The hormone testosterone is made by the testicles in men. In women, the ovaries and adrenal glands also make it.

It is made in higher concentrations during puberty, but declines naturally as a man gets older.

Testosterone helps keep a healthy body weight, increases muscle strength and mass, and affects the way a man stores fat. It also plays a role in sexual function, sperm production and the formation of red blood cells.

In addition, testosterone is an important factor in maintaining normal moods. It may also help lower a man's risk of developing osteoporosis and improve the quality of his life, according to researchers.

The most common medical condition that causes a man to not produce enough testosterone is androgen insensitivity syndrome (AIS), which occurs during the development of male fetuses and teenage sexual development. AIS prevents the growth of penis and testicles, and it can cause infertility.

The most powerful treatment for AIS is testosterone therapy, or TTh. It is used to replace testosterone that has been lost in men with AIS or hypogonadism (low levels of testosterone).

The use of TTh has soared in recent years, and it is the most commonly prescribed anabolic steroid in the United States. However, a recent study found that men who use TTh had an increased risk of heart disease and death. 

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