Testosterone replacement therapy (TRT), also known as androgen replacement therapy (ART), is as the name suggests, is a hormone therapy procedure involving the replacement of male primary sex hormone testosterone or androgen. The basic prescribed use of this therapy is to fill up for the effects of hypogonadism in males. Administration of the hormone through mediums like injections, gels, patches, skin creams or subcutaneous pellets helps in delaying the effects of aging in males. Men entering middle age often go through constricted hormonal changes that are implicated through fatigue, thinning hair, erectile dysfunctionalities, declining muscle mass and strength or weight gain. These hormonal changes are often the reason for men to seek testosterone replacement therapy. However, in the scope of medical science and its advancements, TRT although in vogue is still under scrutiny and subject to numerous clinical trials for more clarity on its short-term and long-term safety.

Prescription Name and Overview

The marketing of testosterone is done under various manufacturer brands around the world. Testosterone replacement therapy is administered through various mediums like injections, gels, patches, skin creams or subcutaneous pellets as a way to curb the effects of hypogonadism. The availability of the same in various countries of the world may differ due to licensed brands marketing their products differently in each geographic zonal region.

In the United States the availability of prescribed non-esterified testosterone is sold in the following formulations:

• Pellet implants: Testopel
• Intranasal gels: Natesto
• Buccal tablets: Striant
• Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone
• Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone
• Topical solutions: Axiron, Testosterone 
• Topical solutions: Axiron, Testosterone 

Intramuscular injective ester prodrugs of testosterone that are available in the United States include the following:

• Testosterone cypionate: Depo-Testosterone, Testosterone Cypionate
• Testosterone enanthate: Delatestryl, Testosterone Enanthate
• Testosterone propionate: Testosterone Propionate
• Testosterone undecanoate: Aveed

Testosterone enanthate and testosterone cypionate were previously available in combination with estradiol valerate and estradiol cypionate under the brand names of Ditate-DS and Depo-Testadiol as oil-based solutions for intramuscular administration. However, it has been discontinued after various medical complications. The United States do not permit the sale of oral testosterone undecanoate, something that is available in Canada, Europe and other countries of the world.

In Canada, testosterone availability is sold under the following branded formulations:

•  topical gels (AndroGel, Testim)
• topical solutions (Axiron)
• transdermal patches (Androderm)
• intranasal gels (Natesto) 
• Testosterone cypionate (Depo-Testosterone
• Testosterone Cypionate
• testosterone enanthate (Delatestryl, PMS-Testosterone Enanthate)
• testosterone propionate (Testosterone Propionate)

Generic Name and Overview

Testosterone is a primary sex hormone in males that is available as a medication for treating conditions like male hypogonadism and certain specific types of breast cancer. Testosterone is the generic name for the hormone in Italian and English and testostérone in French. In Latin, testosterone transforms to testosteronum and in Spanish it is testosterone. However, in languages like Dutch, German, Russian, and any other Slavic languages, it is testosterone. The Cryrillic script counterpart of testosterone is тестостерон.

OTC Name and Overview

The importance of testosterone in the male body encompasses a large spectrum of indispensable functionalities. From the development and maintenance of male sexual characteristics and organs to the growth of muscle tissue, cognitive functions, sex drive, and overall energy, testosterone’s importance is undeniable and one of the most significant ones in the entire physiology of male anatomy. Administration of the hormone through mediums like injections, gels, patches, skin creams or subcutaneous pellets have various over-the-counter names that vary from country to country, their availability and licensed brand manufacturing. However, some of the most widely used testosterone OTC medications include:

• Pellet implants: Testopel
• Intranasal gels: Natesto
• Buccal tablets: Striant
• Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone
• Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone
• Topical solutions: Axiron, Testosterone 
• Topical solutions: Axiron, Testosterone 

     Manufacturer

Testosterone is marketed under a large number of brand names throughout the world. Major brand names of testosterone and its esters include:

• Andriol
• Androderm
• AndroGel
• Axiron
• Delatestryl
• Depo-Testosterone
• Intrinsa
• Nebido
• Omnadren
• Primoteston
• Sustanon
• Testim
• TestoGel
• TestoPatch
• Testoviron
• Tostran.

     Labeled Indications

Testosterone is widely used all across the world as one of the most hormone therapy routines for various reasons. However, along the lines of possible warnings, testosterone also has its own set of labeled indications describing its probable negative impact.

• Pulmonary oil microembolism

Administration of testosterone is sometimes associated with severe POME or pulmonary oil microembolism and anaphylactoid reaction. The onset of the symptoms may occur immediately after intramuscular injection or during the process that included cough, dyspnea, chest pain, dizziness, throat tightening, and more.

• Myocardial infarction, hypertension, stroke, cardiac complications, heart failure, coronary/artery diseases, thromboembolism. There is an alert issued by the FDA about cardiovascular risks in patients using testosterone products.
• Accidental exposure

Exposure to topical testosterone gel between a child and the pediatric patient has sometimes caused adverse effects like enlargement of genitalia, early development of pubic hair, incremented bone age, excessive libido, and sometimes redundant aggressive behavior.  It is something that can be ruled out with proper measures and hygiene. In women, exposure can result in virilization.

     Active Ingredients

Testosterone is a naturally occurring androstane steroid with chemical name ndrost-4-en-17β-ol-3-one.[98] It has a double bond between the C4 and C5 positions (making it an androstene), a ketone group at the C3 position, and a hydroxyl (alcohol) group at the C17β position.

Esters of testosterone substituted at the C17β position with a lipophilic fatty acid ester moiety of varying chain length. All synthetic AAS are derivatives of testosterone. Unlike testosterone, AAS that is 17α-alkylated, like methandienone and stanozolol, are orally active.

What Is It Used For?

The primary use of this hormonal therapy is for the treatment of males who have constricted testosterone production called hypogonadism in medical terms. The entire treatment of external administration of testosterone is known as hormone replacement therapy or HRT or testosterone replacement therapy or TRT or in specific terms androgen replacement therapy or ART. The entire procedure works towards the maintenance of serum testosterone levels along with the standards of normal physiology. A decline in natural testosterone might occur due to many reasons due to excessive side effects of medicines, aging, etc. This depletion is compensated through synthesized testosterone supplementation.

   How Does it Work?

Endogenous testosterone is the impetus behind sexual maturation for males of all ages. Although it is a naturally occurring steroid, synthetic testosterone is processed from cholesterol. Gonadotropin hormones, luteinizing hormones, and follicle-stimulating hormones get suppressed by a negative-feedback mechanism due to increased androgen plasma concentrations. The hormone affects the balance of blood sugar, blood glucose, and erythropoietin formulation. Testosterone undergoes enzymatic conversion to 5-alpha-dihydrotestosterone and forms a loosely bound complex with cystolic receptors within the cells. Endogenous androgens stimulate the RNA polymerase that results in an increase of protein production, which in return helps in the development of male sexual organs other secondary sexual growth like muscle mass, deepening of the voice and surfacing of pubic hair.

   What are the Approved Uses?

Medical uses- The primary use of this hormonal therapy is for the treatment of males who have constricted testosterone production called hypogonadism in medical terms. A decline in natural testosterone might occur due to many reasons due to excessive side effects of medicines, aging, etc. This depletion is compensated through synthesized testosterone supplementation.

• Deficiency

Deficiency of testosterone also known as hypotestosteronism or hypotestosteronemia in medical terms is referred to the abnormality in terms of low testosterone production in males. The reasons for such an occurrence may include testicular dysfunction or primary hypogonadism, hypothalamic–pituitary dysfunction or secondary hypogonadism that could be acquired or congenital.

• Due to aging

The levels of testosterone in the body decline substantially with age. As per FDA notifications, the benefits and safety have not yet been established for testosterone therapy due to aging.

• Gender change hormonal therapy

Testosterone has virilizing effects in females. As a result, testosterone hormone therapy is an integral part of transgender men.

• Effective use in women

Hypoactive sexual desire disorder in women sometimes is taken through testosterone therapy as a short-term treatment. It is still under research whether the affectivity of testosterone in treating infertility, sexual dysfunction and improvement of metabolic well-being in females has any adverse effects if used on a long-term basis.

Non-medical uses: One of the most widely practiced uses of synthetic testosterone is as a doping formula among athletes to drastically improve performance.

   Production Anecdotes / History

The very first isolation and synthesis of testosterone date back to 1935 and led to the commercial availability of the hormone as a pharmaceutical drug as pellets and ester forms for intramuscular injections. The first oral androgen, methyltestosterone was called off the market due to cases of hepatotoxicity. The mid-1950s saw to the increase in the production and sale of effective testosterone esters that went on to be a medical hit for over half a century. With time and medical science climbing the steps towards revolution, intramuscular testosterone undecanoate became available for medical use in Europe and the USA in the early 2000s and 2014 respectively.

Precautions

• Benzoic acid hypersensitivity
• benzyl alcohol hypersensitivity
• polyoxyethylated castor oil hypersensitivity
• serious hypersensitivity reactions or anaphylaxis
• sesame oil hypersensitivity
• soya lecithin hypersensitivity
• Pulmonary oil microembolism
• Breast cancer
• prostate cancer
• prostatic hypertrophy
• Cardiac disease
• coronary artery disease
• heart failure
• hypertension
• myocardial infarction
• stroke
• thromboembolism
• Obesity
• pulmonary disease
• sleep apnea
• Polycythemia
• Hepatic disease
• renal disease
• Diabetes mellitus
• Hypercalcemia
• Depression
• suicidal ideation
• Substance abuse
• Nasal polyps
• nasal septal perforation
• nasal surgery
• nasal trauma rhinorrhea
• Sjogren’s syndrome
• Infertility
• Accidental exposure
• reproductive risk

Long-term Use Considerations

Testosterone replacement therapy (TRT), also known as androgen replacement therapy (ART), is as the name suggests, is a hormone therapy procedure involving the replacement of male primary sex hormone testosterone or androgen. The basic prescribed use of this therapy is to fill up for the effects of hypogonadism in males. Administration of the hormone through mediums like injections, gels, patches, skin creams or subcutaneous pellets helps in delaying the effects of aging in males. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

Drug Interactions

Like any other synthetic drug, testosterone administration has interactive effects with various drugs if taken together.

  Can Interact with the Following

• Abarelix
• Acarbose
• Alogliptin
• Ambrisentan
• Boceprevir
• Cabozantinib
• Canagliflozin
• Cobicistat
• Cobimetinib
• Corticosteroids
• Daclatasvir
• Darbepoetin Alfa
• Darunavir
• Dronedarone
• Empagliflozin
• Incretin Mimetics
• Insulins
• Miglitol
• Nafarelin
• Propranolol
• Ritonavir
• Sitagliptin
• Telaprevir
• Ticagrelor
• Vinblastine
• Warfarin
• Zonisamide

   Can’t Interact with the Following

No studies have been concluded on this.

When To Stop Taking

The list of major, moderate and minor side effects are so vast with testosterone replacement therapy that it is difficult to specify a certain trait that will lead to its discontinuation. However, consulting the doctor irrespective of whether there are any surfacing side effects is recommended. Mostly, a patient undergoing TRT is kept under constant monitoring to eradicate the risks of adverse side effects.

Long-Term Side Effects

The long-term side effects of testosterone use include:

• Cardiovascular disease

Long-term use may increase the risks of strokes and heart attacks, something that might get fatal in isolated cases, especially among aged men. There have been many ongoing studies and clinical research to specify these effects. It has also been associated with thrombosis and pulmonary embolism.

• Prostate cancer

Testosterone increases the growth rate of slow-growing prostate cancer. Although there is no proof regarding the same, doctors and medical practitioners associate the risk of cancer with testosterone supplementation.

FDA Warnings (History Of)

As per the U.S Food and Drug Administration (FDA), prescription testosterone has the approval for use in men with only certain medical complications. Low testosterone levels due to aging and its external administration for recovery still does not have any concrete beneficial or medical safety side. FDA requires drug manufacturers to put more clarity on their labeled indications. According to DFA, various side effects of moderate and adverse intensity associated with the use of externally administered testosterone should be taken into account and put into perspective studies for more substantiality.

Other Common Side Effects

• Obesity
• pulmonary disease
• sleep apnea
• Polycythemia
• Hepatic disease
• renal disease
• Diabetes mellitus
• Hypercalcemia
• Depression
• suicidal ideation
• Substance abuse
• Nasal polyps
• nasal septal perforation
• nasal surgery
• nasal trauma rhinorrhea
• Sjogren’s syndrome
• Infertility
• Accidental exposure
• reproductive risk

Lawsuits

Over the years of extensive medical use of testosterone as a synthetic steroid, there have been numerous lawsuits filed against the manufacturers due to the extremities of its side effects. In spite of FDA warnings, the use of synthetic testosterone is still an ongoing fad that requires more assurance with clinical research. Lawsuits are customized as per the reported files and the prerequisites are extensively researched before any further legal steps can be taken. Medical research on the effects of testosterone usage is still under extensive clinical study with the manufacturers sitting amidst the dusty air of uncertainty.