Androgen replacement therapy

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Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a hormone treatment often prescribed to counter the effects of male hypogonadism. ART typically involves the administration of testosterone, either by injection or by use of testosterone skin creams or gels. ART may also be 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, assessing the benefits and harms of its use in otherwise healthy older men.[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, more body fat. This dissatisfaction with the changes of aging has led to the development of the idea of androgen replacement therapy. Androgen replacement therapy is also used for men who have lost testicular function to disease, cancer, or other causes. For men who have had prostate cancer or at elevated risk, androgen replacement therapy remains controversial because some studies have shown that it increases the risk for prostate cancer; others refute that risk.[2]

History[edit]

Male hormones are called androgens from Greek words andro meaning man, and gen meaning giving birth to. Primary among them is the natural hormone testosterone, which is produced in the testes, ovaries and adrenals. Females also produce testosterone in the adrenals and as a precursor to estrogen, but the amount of circulating testosterone is generally far less than in males. Both sexes also produce an androgen precursor called dihydroepiandrostene (DHEAS) from which the body can make androgens. Androgens cause the secondary sex characteristics of males: facial hair, thicker skin, low body fat, deeper voice, muscularity, penis and scrotal growth and darkening, broad shoulders, body hair, erection of the penis, etc. With increasing age, testosterone production declines, and many of these changes start to reverse.

The decline with age in the physical characteristics of men has given rise to a term, andropause, derived from the term menopause. Menopause is literally defined as the permanent pausing of menstruation, but "menopause" as a medical rather than a physiological condition marks the decline of estrogen and, as with andropause, has given rise to medical treatments to avert such a lowering of the female hormone. The proper scientific term is PADAM, an acronym for Progressive Androgen Deficiency of the Aging Male.

There are several artificial androgens, including nandrolone and various other manipulations of the testosterone molecule. Androgen replacement is administered by patch, tablet, pill, cream or gel; or depot injections given into fat or muscle.[3]

Adverse effects[edit]

Users report an increased alertness and well-being, heightened libido and erection ability, increase in lean muscle mass and concomitant decrease in body fat.

On January 31, 2014, reports of strokes, heart attacks, and deaths in men taking FDA-approved testosterone-replacement led the Food and Drug Administration to announce that it would be investigating this issue.[3] FDA's action followed three peer-reviewed studies of increased cardiovascular events and deaths. A summary of the first study was published online Jan. 29 in the journal PLoS One.[4] But, the full report is also publicly available.[5] Also in November 2013, a study in the "Journal of the American Medical Association" reported an increase of 30% in deaths and heart attacks in older men.[6] The Testosterone in Older Men with Mobility Limitations (TOM) trial, a National Institute of Aging randomized trial, was halted early by the Data Safety and Monitoring Committee because the incidence of adverse cardiovascular events was higher in the testosterone group than the placebo group.[7]

Other adverse effects of testosterone supplementation include minor side effects such as acne and oily skin, and more significant complications such as increased hematocrit which can require venipuncture in order to treat, exacerbation of sleep apnea and acceleration of pre-existing prostate cancer growth in individuals who have undergone androgen deprivation. Another adverse effect may be significant hair loss and/or thinning of the hair. Exogenous testosterone also causes suppression of spermatogenesis and can lead to infertility. 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 hematocrit and PSA levels closely during therapy.

There is the possibility of abuse: some athletes may demand far higher levels of androgen than normal in order to out-perform others, other people may feel they require greater doses in order to achieve what they perceive as a feeling of greater well-being. A UK study in 2013 showed that prescriptions for testosterone replacement, particularly transdermal, almost doubled between 2000 and 2010.[8]

Therapeutic indications[edit]

Androgen replacement has a direct role in the treatment of hypogonadism, and may improve associated features such as anemia,[9] and fatigue.[10]

In addition, a number of other effects of testosterone have led to research into possible therapeutic roles in:

Androgen therapy use in women[edit]

Androgen therapy is one method of pharmacological treatments that have been used for hypoactive sexual desire disorder. This is generally more common among women who have had an oophorectomy or who are in a postmenopausal state. However, like most hormonal treatments, this is also controversial and opponents argue that the clinical significance is marginal.[16] Especially among women with surgically induced menopause, the addition of androgens appears to improve libido, enjoyment, ability to reach orgasm, and initiation of sex.[17] One study found that after a 24-week trial, those women taking androgens had significantly higher scores of sexual desire compared to a placebo group.[16] As with all pharmacological drugs, there are side effects in using androgens, which include hirsutism, acne, polycythaemia, increased high-density lipoproteins, cardiovascular risks, and endometrial hyperplasia is a possibility in women without hysterectomy.[16] This is another area in which long-term use has not been demonstrated. In Europe, a patch has been approved for surgically menopausal and postmenopausal women; however, this has not been approved by the FDA in the United States yet.[16]

Notes[edit]

  1. ^ (2012). Testosterone therapy: Key to male vitality? Retrieved from: http://www.mayoclinic.com/health/testosterone-therapy/MC00030
  2. ^ http://www.medscape.com/viewarticle/540617_2
  3. ^ a b http://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf
  4. ^ http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085805?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed:+plosone/PLoSONE+(PLOS+ONE+Alerts:+New+Articles)
  5. ^ http://testosteronedruglawyers.com/wp-content/uploads/2014/03/Study-by-Finkle.pdf |title=Increased Risk of Non-fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men|coauthors=William D. Finkle; Sander Greenland, ;Gregory K. Ridgeway; John L. Adarns; Melissa A. Frasco; Michael B. Cook; Joseph F. Fraumeni, Jr., ;Robert N. Hoover | date=January 2014|
  6. ^ http://jama.jamanetwork.com/article.aspx?articleid=1764051
  7. ^ http://www.nejm.org/doi/full/10.1056/NEJMoa1000485#t=article
  8. ^ Gan, EH; Pattman, S; H S Pearce, S; Quinton, R (October 2013). "A UK epidemic of testosterone prescribing, 2001-2010.". Clinical endocrinology 79 (4): 564–70. PMID 23480258. 
  9. ^ Makipour S, Kanapuru B, Ershler WB (October 2008). "Unexplained anemia in the elderly". Semin. Hematol. 45 (4): 250–4. doi:10.1053/j.seminhematol.2008.06.003. PMC 2586804. PMID 18809095. 
  10. ^ Miner M, Canty DJ, Shabsigh R (September 2008). "Testosterone replacement therapy in hypogonadal men: assessing benefits, risks, and best practices". Postgrad Med 120 (3): 130–53. doi:10.3810/pgm.2008.09.1914. PMID 18824832. 
  11. ^ Farley JF, Blalock SJ (July 2009). "Trends and determinants of prescription medication use for treatment of osteoporosis". Am J Health Syst Pharm 66 (13): 1191–201. doi:10.2146/ajhp080248. PMID 19535658. 
  12. ^ Traish AM, Saad F, Guay A (2009). "The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance". J. Androl. 30 (1): 23–32. doi:10.2164/jandrol.108.005751. PMID 18772488. 
  13. ^ PMID12809074
  14. ^ Caminiti G, Volterrani M, Iellamo F, et al. (September 2009). "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". J. Am. Coll. Cardiol. 54 (10): 919–27. doi:10.1016/j.jacc.2009.04.078. PMID 19712802. 
  15. ^ Cherrier MM (2009). "Testosterone effects on cognition in health and disease". Front Horm Res 37: 150–62. doi:10.1159/000176051. PMID 19011295. 
  16. ^ a b c d Eden, K.J., & Wylie, K.R. (2009). Quality of sexual life and menopause. Women’s Health, 5 (4), 385-396. doi:10.2217/whe.09.24
  17. ^ Nappi, R.E. et al., (2006). Clitoral stimulation in postmenopausal women with sexual dysfunction: A pilot randomized study with hormone therapy. European Menopause Journal, 55, 288-295