Late-onset hypogonadism

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Late-onset hypogonadism
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Late-onset hypogonadism (LOH) or testosterone deficiency syndrome (TDS) [1] [2] is a condition in older men characterized by measurably low testosterone levels and clinical symptoms mostly of a sexual nature, including decreased desire for mating, fewer spontaneous erections, and erectile dysfunction. [3] It is the result of a gradual drop in testosterone; a steady decline in testosterone levels of about 1% per year can happen and is well documented in both men and women. [4] [5]

Contents

Signs and symptoms

Some men present with symptoms, but they have normal testosterone levels, while others with low testosterone levels have no symptoms. The reasons for this phenomenon are currently unknown. [3] [6]

In their late 40s and early 50s, some men may experience depression, loss of libido, erectile dysfunction, and other physical and emotional symptoms. These symptoms include irritability, loss of muscle mass and reduced ability to exercise, weight gain, lack of energy, difficulty sleeping, or poor concentration. It is important to note that many of these symptoms may arise from a midlife crisis or as the results of a long-term unhealthy lifestyle (smoking, excess drinking, overeating, lack of exercise) and may be best addressed by lifestyle changes, therapy, or antidepressants. [7]

Causes

Testosterone levels are well-documented to decline with aging at about 1% per year in both men and women after a certain age; the causes are not well understood. [3] [4] [5] [8] [9]

Diagnosis

As of 2016, the International Society for the Study of the Aging Male defines late-onset hypogonadism as a series of symptoms in older adults related to testosterone deficiency that combines features of both primary and secondary hypogonadism; the European Male Aging Study (a prospective study of ~3000 men) [10] defined the condition by the presence of at least three sexual symptoms (e.g. reduced libido, reduced spontaneous erections, and erectile dysfunction) and total testosterone concentrations less than 11 nmol/L (3.2 ng/mL) and free testosterone concentrations less than 220 pmol/L (64 pg/mL). [3]

If a person has symptoms of late-onset hypogonadism, testosterone is measured by taking blood in the morning on at least two days; while immunoassays are commonly used, mass spectrometry is more accurate and is becoming more widely available. [6] The meaning of the measurement is different depending on many factors that affect how testosterone is made and how it is carried in the blood. Increased concentrations of proteins that bind testosterone in blood occur if the person is older, has hyperthyroidism or liver disease, or is taking anticonvulsant drugs (which are increasingly used for depression and various neuropathies), and decreased concentrations of proteins that bind testosterone occur if the person is obese, has diabetes, has hypothyroidism, has liver disease, or is taking glucocorticoids or androgens, or progestins. [6] If levels are low, conditions that cause primary and secondary hypogonadism need to be ruled out. [6] [11] [12]

Screening

Due to difficulty and expense of testing, and the ambiguity of the results, screening is not recommended. [3] [6] While some clinical instruments (standard surveys) had been developed as of 2016, their specificity was too low to be useful clinically. [3]

Management

The significance of a decrease in testosterone levels is debated and its treatment with replacement is controversial. The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established in older men with low testosterone levels. [13] Testosterone replacement therapy should only be started if low levels have been confirmed; [11] in the US, this confirmation is not done about 25% of the time, as of 2015. [12] Testosterone levels should also be monitored during therapy. [11]

Androgen replacement therapy formulations and dosages used in men
RouteMedicationMajor brand namesFormDosage
Oral Testosterone a–Tablet400–800 mg/day (in divided doses)
Testosterone undecanoate Andriol, JatenzoCapsule40–80 mg/2–4x day (with meals)
Methyltestosterone bAndroid, Metandren, TestredTablet10–50 mg/day
Fluoxymesterone bHalotestin, Ora-Testryl, UltandrenTablet5–20 mg/day
Metandienone bDianabolTablet5–15 mg/day
Mesterolone bProvironTablet25–150 mg/day
Sublingual Testosterone bTestoralTablet5–10 mg 1–4x/day
Methyltestosterone bMetandren, Oreton MethylTablet10–30 mg/day
Buccal Testosterone StriantTablet30 mg 2x/day
Methyltestosterone bMetandren, Oreton MethylTablet5–25 mg/day
Transdermal Testosterone AndroGel, Testim, TestoGelGel25–125 mg/day
Androderm, AndroPatch, TestoPatchNon-scrotal patch2.5–15 mg/day
TestodermScrotal patch4–6 mg/day
AxironAxillary solution30–120 mg/day
Androstanolone (DHT) AndractimGel100–250 mg/day
Rectal Testosterone Rektandron, TestosteronbSuppository40 mg 2–3x/day
Injection (IM or SC) Testosterone Andronaq, Sterotate, VirosteroneAqueous suspension10–50 mg 2–3x/week
Testosterone propionate bTestovironOil solution10–50 mg 2–3x/week
Testosterone enanthate DelatestrylOil solution50–250 mg 1x/1–4 weeks
XyostedAuto-injector50–100 mg 1x/week
Testosterone cypionate Depo-TestosteroneOil solution50–250 mg 1x/1–4 weeks
Testosterone isobutyrate Agovirin DepotAqueous suspension50–100 mg 1x/1–2 weeks
Testosterone phenylacetate bPerandren, AndrojectOil solution50–200 mg 1x/3–5 weeks
Mixed testosterone esters Sustanon 100, Sustanon 250Oil solution50–250 mg 1x/2–4 weeks
Testosterone undecanoate Aveed, NebidoOil solution750–1,000 mg 1x/10–14 weeks
Testosterone buciclate a–Aqueous suspension600–1,000 mg 1x/12–20 weeks
Implant Testosterone TestopelPellet150–1,200 mg/3–6 months
Notes: Men produce about 3 to 11 mg testosterone per day (mean 7 mg/day in young men). Footnotes:a = Never marketed. b = No longer used and/or no longer marketed. Sources: See template.

Adverse effects

Adverse effects of testosterone supplementation may include increased cardiovascular (CV) events (including strokes and heart attacks) and deaths, especially in men over 65 and men with pre-existing heart conditions. [3] The potential for CV risks from testosterone therapy led the FDA to issue a requirement in 2015 that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke. [3] [13] However, the data are mixed, so the European Medicines Agency, the American Association of Clinical Endocrinologists, and the American College of Endocrinology have stated that no consistent evidence shows that testosterone therapy either increases or decreases cardiovascular risk. [3]

Other significant adverse effects of testosterone supplementation include acceleration of pre-existing prostate cancer growth; increased hematocrit, which can require venipuncture to treat; and, exacerbation of sleep apnea. [3]

Adverse effects may also include minor side effects such as acne 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, such as finasteride or dutasteride. [14]

Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility. [3]

Prognosis

As of 2015, the evidence is inconclusive as to whether testosterone replacement therapy can help with erectile dysfunction in men with late-onset hypogonadism. [12] It appears that testosterone replacement therapy may benefit men with symptoms of frailty who have late-onset hypogonadism. [12]

Epidemiology

The epidemiology is not clear; 20% of men in their 60s and 30% of men in their 70s have low testosterone; [4] [12] around 5% of men between 70 and 79 have both low testosterone and the symptoms, so are diagnosed with late-onset hypogonadism. [4] The UK National Health Service describes it as rare. [7]

History

The impact of low levels of testosterone has been previously reported. In 1944, Heller and Myers identified symptoms of what they labeled the "male climacteric" including loss of libido and potency, nervousness, depression, impaired memory, the inability to concentrate, fatigue, insomnia, hot flushes, and sweating. Heller and Myers found that their subjects had lower than normal levels of testosterone, and that symptoms decreased dramatically when patients were given replacement doses of testosterone. [15] [16]

Society and culture

The 1997 book Male Menopause [17] [18] by Jed Diamond, a psychologist with a PhD in international health, [19] fueled popular interest in the concept of "andropause".[ citation needed ] Diamond regards andropause as a change of life in middle-aged men which has hormonal, physical, psychological, interpersonal, social, sexual, and spiritual aspects. Diamond claims that this change occurs in all men, that it may occur as early as age 45 to 50 and more dramatically after the age of 70 in some men, and that women's and men's experiences are somewhat similar phenomena. [20] [21] The medical community has rejected the term "andropause" and its supposed parallels with menopause. [22] [23]

Thomas Perls and David J. Handelsman, in a 2015 editorial in the Journal of the American Geriatrics Society , say that between the ill-defined nature of the diagnosis and the pressure and advertising from drug companies selling testosterone and human-growth hormone, as well as dietary supplement companies selling all kinds of "boosters" for aging men, the condition is overdiagnosed and overtreated. [24] Perls and Handelsman note that in the US, "sales of testosterone increased from $324 million in 2002 to $2 billion in 2012, and the number of testosterone doses prescribed climbed from 100 million in 2007 to half a billion in 2012, not including the additional contributions from compounding pharmacies, Internet, and direct-to-patient clinic sales." [24]

Terminology

Late-onset hypogonadism is an endocrine condition as well as a result of aging. [3]

The terms "male menopause" and "andropause" are used in the popular media but are misleading, as they imply a sudden change in hormone levels similar to what women experience in menopause. [7] A decrease in libido in men as a result of age is sometimes colloquially referred to as penopause. [25]

Research directions

As of 2016, research was necessary to find better ways to measure testosterone and to be better able to understand the measurements in any given person, and to understand why some people with low testosterone do not present with symptoms and some with seemingly adequate levels do present with symptoms. [3] Research was also necessary to better understand the cardiovascular risks of testosterone replacement therapy in older men. [3]

A relationship between late-onset hypogonadism and risk of Alzheimer's disease has been hypothesized, and some small clinical studies have been conducted to investigate the prevention of Alzheimer's disease in men with late-onset hypogonadism; as of 2009, results were inconclusive. [26]

See also

Related Research Articles

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 hormone therapy, hormone replacement therapy, androgen replacement therapy (ART), oral contraceptive pills, and transgender hormone therapy.

Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as a "person's inability to participate in a sexual relationship as they would wish". This definition is broad and is subject to many interpretations. A diagnosis of sexual dysfunction under the DSM-5 requires a person to feel extreme distress and interpersonal strain for a minimum of six months. Sexual dysfunction can have a profound impact on an individual's perceived quality of sexual life. The term sexual disorder may not only refer to physical sexual dysfunction, but to paraphilias as well; this is sometimes termed disorder of sexual preference.

Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormonal signs that puberty has begun. In the United States, girls are considered to have delayed puberty if they lack breast development by age 13 or have not started menstruating by age 15. Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14. Delayed puberty affects about 2% of adolescents.

Hot flashes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to 30 minutes for each occurrence.

<span class="mw-page-title-main">Methyltestosterone</span> Chemical compound

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 doses as a component of menopausal hormone therapy for menopausal symptoms like hot flashes, osteoporosis, and low sexual desire in women, and to treat breast cancer in women. It is taken by mouth or held in the cheek or under the tongue.

Hypogonadism means diminished functional activity of the gonads—the testicles or the ovaries—that may result in diminished production of sex hormones. Low androgen levels are referred to as hypoandrogenism and low estrogen as hypoestrogenism. These are responsible for the observed signs and symptoms in both males and females.

Kallmann syndrome (KS) is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypogonadotropic hypogonadism, Kallmann syndrome has the additional symptom of a total lack of sense of smell (anosmia) or a reduced sense of smell. If left untreated, people will have poorly defined secondary sexual characteristics, show signs of hypogonadism, almost invariably are infertile and are at increased risk of developing osteoporosis. A range of other physical symptoms affecting the face, hands and skeletal system can also occur.

Sexual medicine or psychosexual medicine as defined by Masters and Johnsons in their classic Textbook of Sexual Medicine, is "that branch of medicine that focuses on the evaluation and treatment of sexual disorders, which have a high prevalence rate." Examples of disorders treated with sexual medicine are erectile dysfunction, hypogonadism, and prostate cancer. Sexual medicine often uses a multidisciplinary approach involving physicians, mental health professionals, social workers, and sex therapists. Sexual medicine physicians often approach treatment with medicine and surgery, while sex therapists often focus on behavioral treatments.

Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. It may also be combined with blood and saliva testing of hormone levels, and the use of pharmacy compounding to obtain hormones in an effort to reach a targeted level of hormones in the body. A number of claims by some proponents of BHT have not been confirmed through scientific testing. Specific hormones used in BHT include estrone, estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), and estriol.

<span class="mw-page-title-main">Irritable male syndrome</span> Behavioral pattern in seasonally-mating mammals

Irritable male syndrome (IMS) is an annual behavior pattern that has been described in Soay sheep and other mammals with a strictly seasonal breeding pattern and described in a 2002 literature review of animal behavior by Lincoln A. Gerald. IMS is a striking feature in mammals with seasonal breeding patterns; it manifests at the end of the mating season.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.

<span class="mw-page-title-main">Testosterone cypionate</span> Chemical compound

Testosterone cypionate, sold under the brand name Depo-Testosterone among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men. It is also used in hormone therapy for transgender men. It is given by injection into muscle or subcutaneously, once every one to four weeks, depending on clinical indication.

Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, 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.

<span class="mw-page-title-main">Enclomifene</span> Chemical compound

Enclomifene (INN), or enclomiphene (USAN), a nonsteroidal selective estrogen receptor modulator of the triphenylethylene group acts by antagonizing the estrogen receptor (ER) in the pituitary gland, which reduces negative feedback by estrogen on the hypothalamic-pituitary-gonadal axis, thereby increasing gonadotropin secretion and hence gonadal production of testosterone. It is one of the two stereoisomers of clomifene, which itself is a mixture of 38% zuclomifene and 62% enclomifene. Enclomifene is the (E)-stereoisomer of clomifene, while zuclomifene is the (Z)-stereoisomer. Whereas zuclomifene is more estrogenic, enclomifene is more antiestrogenic. In accordance, unlike enclomifene, zuclomifene is antigonadotropic due to activation of the ER and reduces testosterone levels in men. As such, isomerically pure enclomifene is more favorable than clomifene as a progonadotropin for the treatment of male hypogonadism.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis, sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones that occur during menopause.

Sexual motivation is influenced by hormones such as testosterone, estrogen, progesterone, oxytocin, and vasopressin. In most mammalian species, sex hormones control the ability and motivation to engage in sexual behaviours.

Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism or primary gonadal failure, is a condition which is characterized by hypogonadism which is due to an impaired response of the gonads to the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and in turn a lack of sex steroid production. As compensation and the lack of negative feedback, gonadotropin levels are elevated. Individuals with HH have an intact and functioning hypothalamus and pituitary glands so they are still able to produce FSH and LH. HH may present as either congenital or acquired, but the majority of cases are of the former nature. HH can be treated with hormone replacement therapy.

Androgen deficiency is a medical condition characterized by insufficient androgenic activity in the body. Androgen deficiency most commonly affects women, and is also called Female androgen insufficiency syndrome (FAIS), although it can happen in both sexes. Androgenic activity is mediated by androgens, and is dependent on various factors including androgen receptor abundance, sensitivity and function. Androgen deficiency is associated with lack of energy and motivation, depression, lack of desire (libido), and in more severe cases changes in secondary sex characteristics.

<span class="mw-page-title-main">Lawley Pharmaceuticals</span> Australian pharmaceutical company

Lawley Pharmaceuticals is a privately owned Australian pharmaceutical company established by pharmacist Michael Buckley in 1995.

<span class="mw-page-title-main">Testosterone (medication)</span> Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.

References

  1. ↑ "Middle-age dread". 15 June 2013.
  2. ↑ Jarlath Regan (26 May 2019). "Dr. Andrew Rynne". An Irishman Abroad (Podcast) (297 ed.). SoundCloud. Archived from the original on 27 May 2019. Retrieved 27 May 2019.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Dimopoulou, C; et al. (February 2016). "EMAS position statement: Testosterone replacement therapy in the aging male". Maturitas. 84: 94–9. doi: 10.1016/j.maturitas.2015.11.003 . PMID   26614257.
  4. 1 2 3 4 Samaras, N; Papadopoulou, MA; Samaras, D; Ongaro, F (2014). "Off-label use of hormones as an antiaging strategy: a review". Clinical Interventions in Aging. 9: 1175–86. doi: 10.2147/CIA.S48918 . PMC   4116364 . PMID   25092967.
  5. 1 2 Shifren, JL (October 2015). "Testosterone for midlife women: the hormone of desire?". Menopause. 22 (10): 1147–9. doi:10.1097/gme.0000000000000540. PMID   26397145. S2CID   10928315.
  6. 1 2 3 4 5 Basaria, S (5 April 2014). "Male hypogonadism". Lancet. 383 (9924): 1250–63. doi:10.1016/s0140-6736(13)61126-5. PMID   24119423. S2CID   30479724.
  7. 1 2 3 "Male Menopause". www.nhs.uk. NHS Choices. April 8, 2016. Retrieved October 7, 2016.
  8. ↑ "Could you have low testosterone?: MedlinePlus Medical Encyclopedia". NIH: Medline Plus. September 18, 2014.
  9. ↑ Huhtaniemi, I (2014). "Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment". Asian Journal of Andrology. 16 (2): 192–202. doi: 10.4103/1008-682x.122336 . PMC   3955328 . PMID   24407185.
  10. ↑ Wu, FC; EMAS Study Group; et al. (8 July 2010). "Identification of late-onset hypogonadism in middle-aged and elderly men" (PDF). The New England Journal of Medicine. 363 (2): 123–35. doi:10.1056/NEJMoa0911101. hdl: 10044/1/19214 . PMID   20554979. S2CID   15635078.
  11. 1 2 3 Bhasin, S; Cunningham, GR; Hayes, FJ; Matsumoto, AM; Snyder, PJ; Swerdloff, RS; Montori, VM; Task Force, Endocrine Society (June 2010). "Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline". The Journal of Clinical Endocrinology and Metabolism. 95 (6): 2536–59. doi:10.1210/jc.2009-2354. PMID   20525905. S2CID   20816995.
  12. 1 2 3 4 5 Seftel, AD; Kathrins, M; Niederberger, C (August 2015). "Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis". Mayo Clinic Proceedings. 90 (8): 1104–15. doi: 10.1016/j.mayocp.2015.06.002 . PMID   26205546.
  13. 1 2 Staff (3 March 2015). "FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke". FDA . Retrieved 5 March 2015.. NEJM Perspective piece: Nguyen, CP; et al. (20 August 2015). "Testosterone and "Age-Related Hypogonadism"--FDA Concerns". The New England Journal of Medicine. 373 (8): 689–91. doi:10.1056/nejmp1506632. PMC   8905399 . PMID   26287846.. Popular summary: Tavernise, Sabrina (March 3, 2015). "Drugs Using Testosterone Will Label Heart Risks". New York Times . Retrieved March 19, 2015.
  14. ↑ Grech, Anthony; Breck, John; Heidelbaugh, Joel (7 October 2016). "Adverse effects of testosterone replacement therapy: an update on the evidence and controversy". Ther Adv Drug Saf. 5 (5): 190–200. doi:10.1177/2042098614548680. PMC   4212439 . PMID   25360240.
  15. ↑ Gabrielsen, JS; Najari, BB; Alukal, JP; Eisenberg, ML (May 2016). "Trends in Testosterone Prescription and Public Health Concerns". The Urologic Clinics of North America. 43 (2): 261–71. doi:10.1016/j.ucl.2016.01.010. PMID   27132584.
  16. ↑ Heller, CG; Myers, GB (21 October 1944). "The male climacteric, its symptomatology, diagnosis and treatment". Journal of the American Medical Association. 126 (8): 472. doi:10.1001/jama.1944.02850430006003.
  17. ↑ Diamond, Jed (1997). Male Menopause (reprint ed.). Sourcebooks. ISBN   9781570711435 . Retrieved 7 August 2020.
  18. ↑ Diamond, Jed (1998). Male Menopause. Naperville, Ill: Sourcebooks. ISBN   978-1-57071-397-2.
  19. ↑ James, Susan Donaldson (8 August 2009). "Low-T Syndrome: Another Word for Male Menopause". ABC News. ABC News Internet Ventures. Retrieved 7 August 2020. 'Male menopause is real,' said Jed Diamond, a psychologist and author of a series of books on the topic, including, 'Irritable Male Syndrome.' [...] 'Men are more in denial about this than women,' said Diamond, who has a Ph.D. in international health and a master's degree in social work.
  20. ↑ Diamond, Jed (2000). Surviving Male Menopause. A Guide for Women and Men. Naperville, Ill: Sourcebooks. ISBN   978-1-57071-433-7.
  21. ↑ Tan, Robert S. (2001). The andropause mystery: unraveling truths about the male menopause. Houston, Tex: AMRED Pub. ISBN   978-0-9707061-0-2.
  22. ↑ "The 'male menopause'". NHS. NHS. 19 February 2019. Retrieved 7 August 2020. The 'male menopause' (sometimes called the andropause) is an unhelpful term sometimes used in the media.
  23. ↑ Compare: Gorski, David (November 25, 2013). ""Low T": The triumph of marketing over science « Science-Based Medicine". Science-Based Medicine. There is a paucity of evidence that 'low T' is the problem that it is advertised to be and even less evidence that testosterone replacement therapy corrects the problems attributed to 'low T.' Before pharmaceutical companies launch big money campaigns to make millions of men 'aware' of low T, they should be required to do what they have to do before introducing a new drug for a new indication: the appropriate large-scale randomized trials to demonstrate that testosterone therapy for otherwise-healthy aging men whose testosterone levels are below the normal range for young men does more good than harm. Right now, we don't have that evidence, and we're not likely to get it from pharmaceutical companies.
  24. 1 2 Perls, T; Handelsman, DJ (April 2015). "Disease mongering of age-associated declines in testosterone and growth hormone levels". Journal of the American Geriatrics Society. 63 (4): 809–11. doi: 10.1111/jgs.13391 . PMID   25809947.
  25. ↑ Gooren, L. J. G. "The age‐related decline of androgen levels in men: clinically significant?." British journal of urology 78.5 (1996): 763-768.
  26. ↑ Cherrier, MM (2009). Testosterone effects on cognition in health and disease. Vol. 37. pp. 150–62. doi:10.1159/000176051. ISBN   978-3-8055-8622-1. PMID   19011295.{{cite book}}: |journal= ignored (help)
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