Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT) or hormone replacement therapy (HRT), 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 oncologic horm ...

in which

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

s, often

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

, are supplemented or replaced

exogenously In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...

. ART is often prescribed to counter the effects of male

hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...

. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. 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 In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the post-classical period of global history. It began with the fall of the Western Roman Empire a ...

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 A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that ar ...

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 in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

Medical uses

Men

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."

Women

Androgen replacement is used in

postmenopausal Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

women: the indications are to increase

sexual desire Sexual desire is an emotion and motivational state characterized by an interest in sexual objects or activities, or by a drive to seek out sexual objects or to engage in sexual activities. It is an aspect of sexuality, which varies significantly ...

; 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 bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

. 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 oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

s),

prasterone Prasterone, also known as dehydroepiandrosterone (DHEA) and sold under the brand names Intrarosa, Diandrone, and Gynodian Depot among others, is a medication as well as over-the-counter dietary supplement which is used to correct DHEA deficienc ...

(dehydroepiandrosterone; DHEA) (and the ester

prasterone enanthate Prasterone enanthate, also known as dehydroepiandrosterone enanthate (DHEA-E) and sold in combination with estradiol valerate under the brand name Gynodian Depot among others, is a weak androgen, estrogen, and neurosteroid medication which is u ...

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 Nandrolone decanoate, sold under the brand name Deca-Durabolin among others, is an androgen and anabolic steroid (AAS) medication which is used primarily in the treatment of anemias and wasting syndromes, as well as osteoporosis in menopausal wo ...

, and

tibolone Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated ...

, 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 respon ...

(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 A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...

s, and

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

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 Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dieta ...

, a randomized trial stopped early. Also, in November 2013, a study reported an increase in deaths and heart attacks in older men. Even after a correction was published, the "Androgen Study Group", a group with many members who have relationships with drug companies in the testosterone market, requested JAMA to retract the article as misleading due to substantial residual errors. 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.

Methods of administration

There are several

artificial androgen Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone (medication), testosterone as well as synthetic androgens that are structurally related ...

s, many of which are manipulations of the testosterone molecule referred to as

anabolic-androgenic steroids Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects ...

. Androgen replacement is administered by patch, tablet, capsule, cream or gel; or depot injections given into fat or muscle.

Other

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

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

growth in individuals who have undergone androgen deprivation; increased

hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is norm ...

, which can require

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

in order to treat; and, exacerbation of sleep

apnea Apnea, BrE: apnoea, is the temporal 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 airways are ( patency), there ...

. Adverse effects may also include minor side-effects such as

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

and oily skin, as well as, significant hair loss and/or thinning of the hair, which may be prevented with 5-alpha reductase inhibitors ordinarily used for the treatment of

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...

, such as

finasteride Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women and as a part of horm ...

. 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 testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubule ...

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

with a digital rectal exam and

prostate-specific antigen Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted b ...

(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.

Society and culture

MMA

UFC The Ultimate Fighting Championship (UFC) is an American mixed martial arts (MMA) promotion company based in Las Vegas, Nevada. It is owned and operated by Zuffa, a wholly owned subsidiary of Endeavor Group Holdings. It is the largest MMA ...

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 ointme ...

products, almost doubled between 2000 and 2010.

Research

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

Erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

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

Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

Chronic heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

Dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

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

Transgender hormone therapy Transgender hormone therapy, also called hormone replacement therapy (HRT) or gender-affirming hormone therapy (GAHT), is a form of hormone therapy in which sex hormones and other hormonal medications are administered to transgender or gender nonc ...

for

transgender men A trans man is a man who was assigned female at birth. The label of transgender man is not always interchangeable with that of transsexual man, although the two labels are often used in this way. ''Transgender'' is an umbrella term that inclu ...

References

{{Androgen receptor modulators Endocrine procedures Testosterone