Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of

hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...

in which

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

s, often

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

, are supplemented or replaced. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. ART is often prescribed to counter the effects of male

hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...

. ART is also prescribed to lessen the effects or delay the onset of normal male aging. However, this is controversial and is the subject of ongoing clinical trials. As men enter

middle age Middle age (or middle adulthood) is the age range of the years halfway between childhood and old age. The exact range is subject to public debate, but the term is commonly used to denote the age range from 45 to 65 years. Overall This time span ...

they may notice changes caused by a relative decline in testosterone: fewer erections, fatigue, thinning skin, declining muscle mass and strength, and/or more body fat. Dissatisfaction with these changes causes some middle age men to seek ART. Androgen deficiencies in women have also, as of 2001, been recognized as a medical disorder that can be treated with ART. As with men, symptoms associated with androgen deficiency are most prevalent with age, and androgen replacement therapy has been shown to help with symptoms of

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

Medical uses

Males

Androgen replacement is the classic treatment of

. It is also used in men who have lost the ability to produce androgens due to disease or its treatment.

Diabetes

The risks of diabetes and of testosterone deficiency in men over 45 (i.e., hypogonadism, specifically hypoandrogenism) are strongly correlated. Testosterone replacement therapies have been shown to improve blood glucose management. Still, "it is prudent not to start testosterone therapy in men with diabetes solely for the purpose of improving metabolic control if they show no signs and symptoms of hypogonadism."

Females

Androgen replacement is used in

postmenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

women: the indications are to increase sexual desire; and to prevent or treat

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

. Other symptoms of androgen deficiency are similar in both sexes, such as muscle loss and physical fatigue. The androgens used for androgen replacement in women include

(and

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s), prasterone (dehydroepiandrosterone; DHEA) (and the ester prasterone enanthate),

methyltestosterone Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low ...

, nandrolone decanoate, and tibolone, among others.

Adverse effects

The

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke.

Heart disease

On January 31, 2014, reports of

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

s, and

death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...

s in men taking testosterone-replacement led the FDA to announce that it would be investigating this issue. The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths. Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early. Also, in November 2013, a study reported an increase in deaths and heart attacks in older men. Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials. As a result of the "potential for adverse cardiovascular outcomes", the FDA announced, in September 2014, a review of the appropriateness and safety of testosterone replacement therapy. However, when given to men with hypogonadism in the short- and medium-term, testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks and other heart diseases). The long-term safety of the therapy is not known yet.

Other

Other significant adverse effects of testosterone supplementation include acceleration of pre-existing

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

growth in individuals who have undergone androgen deprivation; increased hematocrit, which can require

venipuncture In medicine, venipuncture or venepuncture is the process of obtaining intravenous access for the purpose of venous Sampling (medicine)#blood, blood sampling (also called ''phlebotomy'') or intravenous therapy. In healthcare, this procedure is p ...

in order to treat; and, exacerbation of sleep

apnea Apnea (also spelled apnoea in British English) is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the ...

. A 2014 review said there was some evidence men with certain comorbidities may be at risk of adverse effects including sleep apnoea, metabolic syndrome and cardiovascular disease. Exogenous testosterone may also cause suppression of

spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...

, leading to, in some cases, infertility. It is recommended that physicians screen for

with a digital rectal exam and prostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy. Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.

Methods of administration

There are several artificial androgens, many of which are manipulations of the testosterone molecule referred to as anabolic-androgenic steroids. Androgen replacement is administered by patch, tablet, capsule, cream or gel; or depot injections given into fat or muscle.

Society and culture

MMA

Some UFC fighters used TRT until 2014 when the Nevada State Athletic Commission banned its use.

Regulation

As of September 2014, testosterone replacement therapy has been under review for appropriateness and safety by the

due to the "potential for adverse cardiovascular outcomes".

Frequency of use

In the United States usage increased from 0.5% in 2002 to 3.2% in 2013 and have since decreased to 1.7% in 2016. A UK study in 2013 showed that prescriptions for testosterone replacement, particularly

transdermal Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointm ...

products, almost doubled between 2000 and 2010.

Research

Testosterone is being investigated as therapy for the following conditions: *

Erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

Diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

Chronic heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pre ...

Dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

, but the evidence base is small and the balance of benefit needs to be clarified

References

{{Androgen receptor modulators Endocrine procedures Testosterone Medical treatments