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词条 Androgen replacement therapy
释义

  1. Medical uses

     Men  Diabetes  Women 

  2. Adverse effects

     Heart disease 

  3. Methods of administration

     Other 

  4. Society and culture

     Regulation  Frequency of use 

  5. Research

  6. See also

  7. References

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Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are replaced. ART is often prescribed to counter the effects of male hypogonadism. It typically involves the administration of testosterone through injections, skin creams, patches, gels, 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.[1] As men enter middle age 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.

Medical uses

{{See also|Testosterone (medication)}}

Men

Androgen replacement is the classic treatment of hypogonadism.[2] It is also used in men who have lost the ability to produce androgens due to disease or its treatment.[3]

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.[4][5] 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."[6]

Women

Androgen replacement is used in postmenopausal women: the indications are to increase sexual desire; and to prevent or treat osteoporosis.[7] The androgens used for androgen replacement in women include testosterone (and esters), prasterone (dehydroepiandrosterone; DHEA) (and the ester prasterone enanthate), methyltestosterone, nandrolone decanoate, and tibolone, among others.[7]

{{Androgen replacement therapy formulations and dosages used in women}}

Adverse effects

{{See also|Testosterone#Adverse effects}}

The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging.[8] The FDA has required that testosterone labels include warning information about the possibility of an increased risk of heart attacks and stroke.[8]

Heart disease

On January 31, 2014, reports of strokes, heart attacks, and deaths in men taking testosterone-replacement led the FDA to announce that it would be investigating this issue.[11] The FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths.[9] Due to an increased rate of adverse cardiovascular events compared to a placebo group, a randomized trial stopped early.[10] Also, in November 2013, a study reported an increase in deaths and heart attacks in older men.[11] 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,[12][13] requested JAMA to retract the article as misleading due to substantial residual errors.[15] Concerns have been raised that testosterone was being widely marketed without the benefit of data on efficacy and safety from large randomized controlled trials.[16] 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.[17][18][19]

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, pill, cream or gel; or depot injections given into fat or muscle.[20]

Other

Other significant adverse effects of testosterone supplementation include acceleration of pre-existing prostate cancer growth in individuals who have undergone androgen deprivation; increased hematocrit, which can require venipuncture in order to treat; and, exacerbation of sleep apnea.[21] 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.[22] Exogenous testosterone may also cause suppression of spermatogenesis, leading to, in some cases, infertility.[23] It is recommended that physicians screen for prostate cancer with a digital rectal exam and prostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy.[24]

Some studies argue that ART increases the risk of prostate cancer, although the results are not conclusive.[25]

Society and culture

Regulation

As of September 2014, testosterone replacement therapy has been under review for appropriateness and safety by the Food and Drug Administration due to the "potential for adverse cardiovascular outcomes".[17][18][19]

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.[26]

A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal products, almost doubled between 2000 and 2010.[27]

Research

Testosterone is being investigated as therapy for the following conditions:

  • Erectile dysfunction[28][29]
  • Osteoporosis[30]
  • Diabetes mellitus[31][32]
  • Chronic heart failure[33]
  • Dementia, but the evidence base is small and the balance of benefit needs to be clarified[34]
  • Transgender hormone therapy for transgender men

See also

  • List of androgens/anabolic steroids available in the United States

References

1. ^{{cite web |year=2012 |title=Testosterone therapy: Key to male vitality? |url=http://www.mayoclinic.com/health/testosterone-therapy/MC00030 }}
2. ^{{cite journal|last1=Kang|first1=DY|last2=Li|first2=HJ|title=The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis.|journal=Medicine|date=January 2015|volume=94|issue=3|pages=e410|doi=10.1097/MD.0000000000000410|pmid=25621688|pmc=4602637}}
3. ^{{cite journal|last1=Giwercman|first1=A|last2=Lundberg Giwercman|first2=Y|title=Hypogonadism in young men treated for cancer.|journal=Hormones (Athens, Greece)|date=2015|volume=14|issue=4|pages=590–7|doi=10.14310/horm.2002.1650|pmid=26859600}} {{open access}}
4. ^{{cite journal | vauthors = Morales A, Bella AJ, Chun S, Lee J, Assimakopoulos P, Bebb R, Gottesman I, Alarie P, Dugré H, Elliott S | title = A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians | journal = Canadian Urological Association Journal | volume = 4 | issue = 4 | pages = 269–75 | date = August 2010 | pmid = 20694106 | pmc = 2910774 }}
5. ^{{cite journal | vauthors = Morimoto S, Jiménez-Trejo F, Cerbón M | title = Sex steroids effects in normal endocrine pancreatic function and diabetes | journal = Current Topics in Medicinal Chemistry | volume = 11 | issue = 13 | pages = 1728–35 | year = 2011 | pmid = 21463250 | doi = 10.2174/156802611796117540 }}
6. ^{{cite journal | vauthors = Basaria S | title = Male hypogonadism | journal = Lancet | volume = 383 | issue = 9924 | pages = 1250–63 | date = April 2014 | pmid = 24119423 | doi = 10.1016/S0140-6736(13)61126-5 }}
7. ^1 {{cite journal | vauthors = Davis SR | title = The therapeutic use of androgens in women | journal = J. Steroid Biochem. Mol. Biol. | volume = 69 | issue = 1-6 | pages = 177–84 | date = 1999 | pmid = 10418991 | doi = 10.1016/S0960-0760(99)00054-0 | url = }}
8. ^1 {{cite web |author=Staff |title=Testosterone Products: Drug Safety Communication - 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 |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm436280.htm |date=March 3, 2015 |work=FDA |accessdate=March 5, 2015 }}
9. ^{{cite journal | vauthors = Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN | title = Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men | journal = PLOS ONE | volume = 9 | issue = 1 | pages = e85805 | date = January 2014 | pmid = 24489673 | pmc = 3905977 | doi = 10.1371/journal.pone.0085805 | url = http://testosteronedruglawyers.com/wp-content/uploads/2014/03/Study-by-Finkle.pdf }}
10. ^{{cite journal | vauthors = Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S | title = Adverse events associated with testosterone administration | journal = The New England Journal of Medicine | volume = 363 | issue = 2 | pages = 109–22 | date = July 2010 | pmid = 20592293 | pmc = 3440621 | doi = 10.1056/NEJMoa1000485 }}
11. ^{{cite journal | vauthors = Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM | title = Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels | journal = JAMA | volume = 310 | issue = 17 | pages = 1829–36 | date = November 2013 | pmid = 24193080 | doi = 10.1001/jama.2013.280386 | url = http://jama.jamanetwork.com/article.aspx?articleid=1764051 }}
12. ^{{cite web |author=Staff |title=JAMA attacked by Testosterone Money - re "Wall Street Journal" article |url=http://www.dmlawfirm.com/jama-study-attacked-testosterone-money |date=March 27, 2014 |work=DM Law Firm |accessdate=March 18, 2015 }}
13. ^{{cite news |last=Silverman |first=Ed |title=A High Stakes Battle Over Testosterone |url=https://blogs.wsj.com/corporate-intelligence/2014/03/25/a-high-stakes-battle-over-testosterone/ |date=March 25, 2014 |work=The Wall Street Journal |accessdate=August 24, 2015 }}
14. ^|url=http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/4495|
15. ^{{cite web |authors=Abraham Morgentaler; the Androgen Study Group |title=Letter to JAMA Asking for Retraction of Misleading Article on Testosterone Therapy |url=http://www.androgenstudygroup.org/initiatives/letter-to-jama-asking-for-retraction-of-misleading-article-on-testosterone-therapy |publisher=Androgen Study Group |display-authors=etal}}
16. ^{{cite web |last=McCullough |first=Marie |title=As testosterone use grows, questions on risks await answers |url=http://articles.philly.com/2014-04-04/news/48838961_1_testosterone-low-t-male-hormone-replacement |date=April 4, 2014 |work=Philly.com |accessdate=March 19, 2015 }}
17. ^1 {{cite news |last=Tavernise |first=Sabrina |title=F.D.A. Panel Backs Limits on Testosterone Drugs |url=https://www.nytimes.com/2014/09/18/health/testosterone-drugs-fda.html |date=September 17, 2014 |work=The New York Times |accessdate=September 18, 2014 }}
18. ^1 {{cite news |author=Staff |title=FDA Panel To Review Testosterone Therapy Appropriateness and Safety |url=http://ireport.cnn.com/docs/DOC-1167887 |date=September 5, 2014 |work=CNN News |accessdate=September 14, 2014 }}
19. ^1 {{cite web |author=Staff |title=Joint Meeting for Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety And Risk Management Advisory Committee (DSARM AC) - FDA background documents for the discussion of two major issues in testosterone replacement therapy (TRT): 1. The appropriate indicated population for TRT, and 2. The potential for adverse cardiovascular outcomes associated with use of TRT |url=http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM412536.pdf |date=September 17, 2014 |work=Food and Drug Administration |format=PDF |accessdate=September 14, 2014 }}
20. ^1 {{cite web |author=Staff |title=FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products |url=http://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf |publisher=U.S. Food and Drug Administration |date=January 31, 2014 |format=PDF |accessdate=September 17, 2014 }}
21. ^{{cite journal | vauthors = Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M | title = Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy | journal = The Journal of Urology | volume = 190 | issue = 2 | pages = 639–44 | date = August 2013 | pmid = 23395803 | doi = 10.1016/j.juro.2013.02.002 | pmc=4544840}}
22. ^{{cite journal|title=Adverse effects of testosterone replacement therapy: an update on the evidence and controversy | pmc=4212439 | pmid=25360240 | doi=10.1177/2042098614548680 | volume=5 | year=2014 | journal=Ther Adv Drug Saf | pages=190–200 |vauthors=Grech A, Breck J, Heidelbaugh J }}
23. ^{{cite journal | vauthors = | title = Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility | journal = Lancet | volume = 336 | issue = 8721 | pages = 955–9 | date = October 1990 | pmid = 1977002 | doi = 10.1016/0140-6736(90)92416-F }}
24. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK216164/#ddd00024/|title=Introduction - Testosterone and Aging - NCBI Bookshelf }}
25. ^{{cite web|url=http://www.medscape.com/viewarticle/540617_2%7cwork=Medscape|title=Medscape: Medscape Access|work=medscape.com}}
26. ^{{cite journal |last1=Baillargeon |first1=Jacques |last2=Kuo |first2=Yong-Fang |last3=Westra |first3=Jordan R. |last4=Urban |first4=Randall J. |last5=Goodwin |first5=James S. |title=Testosterone Prescribing in the United States, 2002-2016 |journal=JAMA |date=10 July 2018 |volume=320 |issue=2 |pages=200 |doi=10.1001/jama.2018.7999}}
27. ^{{cite journal | vauthors = Gan EH, Pattman S, Pearce S, Quinton R | title = A UK epidemic of testosterone prescribing, 2001-2010 | journal = Clinical Endocrinology | volume = 79 | issue = 4 | pages = 564–70 | date = October 2013 | pmid = 23480258 | doi = 10.1111/cen.12178 }}
28. ^{{cite journal|last1=Walther|first1=Andreas|last2=Mahler|first2=Fiona|last3=Debelak|first3=Rudolf|last4=Ehlert|first4=Ulrike|title=Psychobiological Protective Factors Modifying the Association Between Age and Sexual Health in Men: Findings From the Men’s Health 40+ Study|journal=American Journal of Men's Health|date=13 February 2017|volume=11|issue=3|pages=737–747|doi=10.1177/1557988316689238}}
29. ^{{cite journal|last1=Finkelstein|first1=Joel S.|last2=Lee|first2=Hang|last3=Leder|first3=Benjamin Z.|last4=Burnett-Bowie|first4=Sherri-Ann M.|last5=Goldstein|first5=David W.|last6=Hahn|first6=Christopher W.|last7=Hirsch|first7=Sarah C.|last8=Linker|first8=Alex|last9=Perros|first9=Nicholas|last10=Servais|first10=Andrew B.|last11=Taylor|first11=Alexander P.|last12=Webb|first12=Matthew L.|last13=Youngner|first13=Jonathan M.|last14=Yu|first14=Elaine W.|title=Gonadal steroid–dependent effects on bone turnover and bone mineral density in men|journal=Journal of Clinical Investigation|date=22 February 2016|volume=126|issue=3|pages=1114–1125|doi=10.1172/JCI84137|pmc=4767351}}
30. ^{{cite journal | vauthors = Farley JF, Blalock SJ | title = Trends and determinants of prescription medication use for treatment of osteoporosis | journal = American Journal of Health-System Pharmacy | volume = 66 | issue = 13 | pages = 1191–201 | date = July 2009 | pmid = 19535658 | doi = 10.2146/ajhp080248 }}
31. ^{{cite journal | vauthors = Traish AM, Saad F, Guay A | title = The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance | journal = Journal of Andrology | volume = 30 | issue = 1 | pages = 23–32 | year = 2009 | pmid = 18772488 | doi = 10.2164/jandrol.108.005751 }}
32. ^{{cite journal | vauthors = Boyanov MA, Boneva Z, Christov VG | title = Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency | journal = The Aging Male | volume = 6 | issue = 1 | pages = 1–7 | date = March 2003 | pmid = 12809074 | doi=10.1080/tam.6.1.1.7}}
33. ^{{cite journal | vauthors = Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM | title = Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study | journal = Journal of the American College of Cardiology | volume = 54 | issue = 10 | pages = 919–27 | date = September 2009 | pmid = 19712802 | doi = 10.1016/j.jacc.2009.04.078 }}
34. ^{{cite journal | vauthors = Cherrier MM | title = Testosterone effects on cognition in health and disease | journal = Frontiers of Hormone Research | volume = 37 | issue = | pages = 150–62 | year = 2009 | pmid = 19011295 | doi = 10.1159/000176051 }}
{{Androgens and antiandrogens}}{{Androgen receptor modulators}}

2 : Endocrine procedures|Testosterone
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