Masculinizing hormone therapy: Difference between revisions

The World Professional Association for Transgender Health (WPATH), which sets the standards for transgender care in all countries, says that HRT is "a medically necessary intervention for many transsexual, transgender, and gender-nonconforming individuals with gender dysphoria [...] Some people seek maximum feminization/masculinization, while others experience relief with an androgynous presentation resulting from hormonal minimization of existing secondary sex characteristics".<ref name="soc 33-34">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 33-34. https://wpath.org/publications/soc</ref>  

Most individuals on testosterone will experience a gradual deepening of the voice,<ref name="soc 36">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 36. https://wpath.org/publications/soc</ref> caused by growth of the larynx (voice box). In most cases, this begins after 3 to 12 months, and finished after 1 to 2 years.<ref name="soc 37" /> The changes are permanent, meaning a trans-masculine person's voice will stay as low as it got even if they stop taking HRT. Many individuals who do not want the full effect of voice deepening will take testosterone until their voice deepens to their desired resonance and then stop.

The WPATH says that masculinizing HRT causes a likely increased risk of [[acne]].<ref name="soc 40">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 40. https://wpath.org/publications/soc</ref> Acne is generally worse during only the first two years of testosterone therapy, as with puberty. Can be treated with standard acne therapy. Initial treatment is with increased cleansing (at least twice daily) with an anti-acne or oil reducing scrub. If this doesn't work, additional therapy may be prescribed by a physician. Some physicians see acne as a contraindication to increasing testosterone dose.

Increased skin oiliness and acne happens only when the person is first starting HRT, similar to how cisgender men have oiliness and acne during puberty. Trans-masculine people usually see oiliness and acne start in 1 to 6 months of starting HRT. Then the oiliness and acne usually goes away after 1 to 2 years of HRT.<ref name="soc 37">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 37. https://wpath.org/publications/soc</ref>

[[Polycystic ovary syndrome]] (PCOS), also called polycystic ovarian syndrome, is a set of symptoms with no known cause,<ref name=Fauser2011>Page 836 (Section:''Polycystic ovary syndrome'') in: {{cite journal | vauthors = Fauser BC, Diedrich K, Bouchard P, Domínguez F, Matzuk M, Franks S, Hamamah S, Simón C, Devroey P, Ezcurra D, Howles CM | title = Contemporary genetic technologies and female reproduction | journal = Hum. Reprod. Update | volume = 17 | issue = 6 | pages = 829–47 | year = 2011 | pmid = 21896560 | doi = 10.1093/humupd/dmr033 | pmc=3191938}}</ref><ref name=FertSter_molecular>{{cite journal | vauthors = Legro RS, Strauss JF | title = Molecular progress in infertility: polycystic ovary syndrome | journal = Fertil. Steril. | volume = 78 | issue = 3 | pages = 569–76 | year = 2002 | pmid = 12215335 | doi = 10.1016/S0015-0282(02)03275-2 }}</ref> and no known cure as of 2020.<ref name=NIH2013Cure>{{cite web|title=Is there a cure for PCOS?|url=http://www.nichd.nih.gov/health/topics/PCOS/conditioninfo/Pages/cure.aspx|website=US Department of Health and Human Services, National Institutes of Health|accessdate=13 March 2015|date=2013-05-23|url-status=live|archiveurl=https://web.archive.org/web/20150405021527/http://www.nichd.nih.gov/health/topics/PCOS/conditioninfo/Pages/cure.aspx|archivedate=5 April 2015}}</ref> It correlates with high testosterone levels in people who were assigned female at birth. <ref name=NIH2017Def>{{cite web|title=Polycystic Ovary Syndrome (PCOS): Condition Information |url=https://www.nichd.nih.gov/health/topics/pcos/conditioninfo|publisher=National Institute of Child Health and Human Development |accessdate=19 November 2018|date=January 31, 2017}}</ref><ref>{{cite web|title=Polycystic ovary syndrome (PCOS) fact sheet|url=http://womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html|website=Women's Health|accessdate=11 August 2016|date=December 23, 2014 |url-status=live|archiveurl=https://web.archive.org/web/20160812093306/http://womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html|archivedate=12 August 2016}}</ref> Diagnosis is based on two of the following three findings: no ovulation, high androgen levels, and ovarian cysts. Its symptoms are associated with high testosterone, such as growing extra body hair, menstrual problems, and fertility problems.<ref name="NIH2013Sym">{{cite web|url=http://www.nichd.nih.gov/health/topics/PCOS/conditioninfo/Pages/symptoms.aspx|title=What are the symptoms of PCOS?|website=National Institute of Child Health and Human Development (NICHD)|format=05/23/2013|url-status=live|archiveurl=https://web.archive.org/web/20150303190314/http://www.nichd.nih.gov/health/topics/PCOS/conditioninfo/Pages/symptoms.aspx|archivedate=3 March 2015|accessdate=13 March 2015}}</ref> Some people informally consider PCOS a [[intersex]] condition, even though PCOS usually develops later in life, rather than at birth, as most intersex conditions do. PCOS itself is not harmful, unless if the androgenic symptoms are found distressing by the person who has them, but it does cause a higher risk of obesity, and therefore of Type II diabetes.<ref name=NIH2017Def/> Treatment for PCOS involves lifestyle changes and medications to reduce those risks. For cisgender women, some treatments for PCOS aim to undo masculinization, but that is not desirable to undo for trans-masculine people.

On the other hand, the reality of distinct differences between the brains of men and women is disputed by various neurologists. British neuroscientist Gina Rippon, author of the 2019 book ''Gendered Brain: The New Neuroscience that Shatters the Myth of the Female Brain'', argues that there is not a "single item type as a male brain or a female brain", instead that "everybody is actually made up of a whole pattern of things, which is maybe due to their biology and maybe due to their different experiences in life."<ref name=":2">{{Cite news|title='Every brain is different from every other brain’: Author Gina Rippon challenges gender stereotypes|url=https://www.theglobeandmail.com/life/health-and-fitness/article-every-brain-is-different-from-every-other-brain-author-gina-rippon/|access-date=2020-08-06}}</ref> She puts forward the idea that "every brain is different from every other brain".<ref name=":2" /> Rippon is opposed to the "continued emphasis on '[[gender essentialism|essentialist]]', brain-based explanations in both public communication of, and research into, many forms of gender imbalance."<ref>{{cite journal | last = Rippon | first = Gina | title = The trouble with girls? | journal = [[The Psychologist (magazine)|The Psychologist]] | volume = 29 | issue = 12 | pages = 918&ndash;922 | publisher = British Psychological Society | date = December 2016 | url = https://thepsychologist.bps.org.uk/volume-29/december-2016/trouble-girls | ref = harv }}</ref>

https://pubmed.ncbi.nlm.nih.gov/29175227/</ref> Many transgender men, however, report improved mood, decreased emotional lability, and a lessening of anger and aggression.{{citation needed|date=November 2018}}

The WPATH says that masculinizing HRT carries a possible increased risk of high cholesterol, also called hyperlipidemia,<ref name="soc 40" /> which means abnormally high levels of fats (lipids) in the blood. High cholesterol can be inherited, or can be caused by unhealthy habits (including eating mostly unhealthy foods, not getting enough exercise, drinking too much alcohol, and smoking).<ref>"Hyperlipidemia." ''Healthline.'' https://www.healthline.com/health/hyperlipidemia</ref> This means that trans-masculine people on HRT have reason to make healthy choices about food, exercise, and substances, just as cisgender men do.

Testosterone increases body weight (and increases appetite). The form that this weight gain will take depends on diet and exercise as well as genetic factors. Since testosterone has anabolic effects, gain of lean muscle mass will be easier than it previously was for transgender men. Moderate amounts of exercise will cause greater gains and will ameliorate some of the adverse effects of testosterone. Many transgender men report an increased energy level, decreased need for sleep, and increased alertness after testosterone therapy. In cisgender men, abnormally high or low levels of testosterone are both associated with insulin resistance (which eventually can result in Type II diabetes). So mid-normal levels of testosterone are the target for androgen therapy. In women, increased levels of either estrogen or androgens are associated with decreased insulin sensitivity (which may predispose to diabetes). In a study of transgender males and females, decreased insulin sensitivity was found in both populations after four months of hormonal treatment.<ref>{{cite journal | author = Polderman K |display-authors=etal | year = 1994 | title = Induction of insulin resistance by androgens and estrogens | url = | journal = Journal of Clinical Endocrinology & Metabolism| volume = 79 | issue = 1| pages = 265–71 | doi=10.1210/jc.79.1.265}}</ref>

'Depot' drug formulations are created by mixing a substance with the drug that slows its release and prolongs the action of the drug. The two primarily used forms in the United States are the testosterone esters [[testosterone cypionate]] (Depo-Testosterone) and [[testosterone enanthate]] (Delatestryl) which are almost interchangeable. Testosterone enanthate is purported to be slightly better with respect to even testosterone release, but this is probably more of a concern for bodybuilders who use the drugs at higher doses (250–1000&nbsp;mg/week) than the replacement doses used by transgender men (50–100&nbsp;mg/week). These testosterone esters are mixed with different [[oil]]s, so some individuals may tolerate one better than the other. Testosterone enanthate costs more than testosterone cypionate and is more typically the one prescribed for hypogonadal males in the United States. Testosterone cypionate is more popular in the United States than elsewhere (especially amongst [[bodybuilder]]s). Other formulations exist but are more difficult to come by in the United States. A formulation of injected testosterone available in Europe and the United States, [[testosterone undecanoate]] (Nebido, Aveed)<ref>{{cite web|url=https://www.drugs.com/history/aveed.html|title=Aveed (testosterone undecanoate) FDA Approval History|website=Drugs.com|accessdate=9 May 2019}}</ref><ref>{{cite web|author1=Miriam E. Tucker|title=FDA Approves Aveed Testosterone Jab, with Restrictions|url=http://www.medscape.com/viewarticle/821632|website=[[Medscape]]|accessdate=December 13, 2016|date=March 7, 2014}}</ref>  provides significantly improved testosterone delivery with far less variation outside the eugonadal range than other formulations with injections required only four times yearly. However, each quarterly dose requires injection of 4&nbsp;mL of oil which may require multiple simultaneous injections. Testosterone undecanoate is also much more expensive as it is still under [[patent protection]]. [[Testosterone propionate]] is another testosterone ester that is widely available, including in the United States, Canada, and Europe, but it is very short-acting compared to the other testosterone esters and must be administered once every 2 or 3&nbsp;days, and for this reason, is rarely used.

Implants, as subcutaneous pellets, can be used to deliver testosterone (brand name Testopel). 6 to 12 pellets are inserted under the skin every three months. This must be done in a physician's office, but is a relatively minor procedure done under local anesthetic. Pellets cost about $60 each, so the cost is greater than injected testosterone when the cost of the physician visit and procedure are included. The primary advantages of Testopel are that it gives a much more constant blood level of testosterone yet requires attention only four times yearly. One common risk of any kind of implants is that the body can reject them. This often happens with testosterone implants, causing the implant to emerge from deep and painful skin lesions. One trans-masculine blogger, K-CON, posted weekly blog updates about being on Testopel for over a year, and his resulting complications (pellets failing to dissolve at the rate claimed by the manufacturer, implant rejection, leading to infection, pain, and surgery under general anesthesia to remove the pellets and the damaged tissue). He summarized his experience in [https://k-con.today/post/172598026877/whats-testopel a post where he explains why he would not recommend Testopel to anyone].<ref>K-CON. "What's Testopel?" ''K-CON'' (personal blog). 2018. https://k-con.today/post/172598026877/whats-testopel</ref>  

[[Dihydrotestosterone]] (DHT) (referred to as androstanolone or stanolone when used medically) can also be used in place of testosterone as an androgen. The availability of DHT is limited; it is not available in the United States or Canada, for instance, but it is available in certain European countries, including the [[United Kingdom]], [[France]], [[Spain]], [[Belgium]], [[Italy]], and [[Luxembourg]].<ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA63|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=63–}}</ref> DHT is available in formulations including topical gel, buccal or sublingual tablets, and as esters in oil for intramuscular injection.<ref name="HydeGengenbach2007">{{cite book|author1=Thomas E. Hyde|author2=Marianne S. Gengenbach|title=Conservative Management of Sports Injuries|url=https://books.google.com/books?id=uzPwfNYyjjUC&pg=PA1100|year=2007|publisher=Jones & Bartlett Learning|isbn=978-0-7637-3252-3|pages=1100–}}</ref> Relative to testosterone, and similarly to many synthetic AAS, DHT has the potential advantages of not being locally potentiated in so-called androgenic tissues that express 5α-reductase (as DHT is already 5α-reduced) and of not being aromatized into an estrogen (it is not a substrate for aromatase).

Young people stop growing after their bones go through a change called epiphyseal closure. Complete fusion happens on average between ages 12–18 for cisgender girls (with the most common being 15-16 years) and 14–19 for cisgender boys (with the most common being 18-19 years).<ref>{{cite journal |pmid=16225203 |title=Age ranges of epiphyseal fusion in the distal tibia and fibula of contemporary males and females |journal=Journal of Forensic Sciences |volume=50 |issue=5 |pages=1001–7 |date=September 2005  |quote=complete fusion in females occurs as early as 12 years in the distal tibia and fibula. All females demonstrated complete fusion by 18 years with no significant differences between ancestral groups. Complete fusion in males occurs as early as 14 years in both epiphyses. All males demonstrated complete fusion by 19 years|last1=Crowder |first1=C |last2=Austin |first2=D |doi=10.1520/JFS2004542 }}</ref><ref>{{cite web |last1=Barrell |first1=Amanda |title=At what age do girls stop growing? |url=https://www.medicalnewstoday.com/articles/320668 |website=MedicalNewsToday |accessdate=9 June 2020}}</ref><ref>{{cite web |last1=Jarret |first1=Robert R. |title=Puberty: Tanner Stages – Boys |url=http://pediatric-house-calls.djmed.net/puberty-tanner-stages-boys/ |website=Pediatric HOUSECALLS |accessdate=9 June 2020}}</ref><ref>{{cite web |last1=Jarret |first1=Robert R. |title=Puberty: Tanner Stages – Girls |url=http://pediatric-house-calls.djmed.net/puberty-tanner-stages-girls/ |website=Pediatric HOUSECALLS |accessdate=9 June 2020}}</ref><ref>{{cite web |title="When do most males' growth plates close?" |url=https://answers.zocdoc.com/details/21489/when-do-most-males-growth-plates-close |website=Zoodoc |accessdate=9 June 2020}}</ref> Once that happens, a person's bones cannot grow anymore, so they can't get any taller. For young people who have not yet started or completed epiphyseal closure, they can take [[growth hormone]], potentially together with an aromatase inhibitor or a GnRH analogue, to increase final height.

The World Professional Association for Transgender Health (WPATH) ''Standards of Care'', 7th edition, sets the standard used in all countries for what doctors see as the requirements for a trans person to be allowed to go on HRT. The WPATH says that these are the four criteria for HRT:<ref name="soc 34">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 34. https://wpath.org/publications/soc</ref>  

Masculinizing HRT largely switches a person's health risks to be the same as if they had been [[sexes#assigned male at birth|assigned male at birth]]. This means that very few conditions would make it impossible or less safe for a person to take masculinizing HRT. The WPATH says HRT is only contraindicated in rare cases, due to serious health conditions.<ref name="soc 35">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 34. https://wpath.org/publications/soc</ref> There are a few conditions that have been seen as contraindications to masculinizing HRT.<ref>{{cite web|last=Hembree, W.C.|url=http://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/Endocrine-Treatment-of-Transsexual-Persons.pdf|archive-url=https://web.archive.org/web/20140313131201/http://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/Endocrine-Treatment-of-Transsexual-Persons.pdf|url-status=dead|archive-date=2014-03-13|title=Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline|date=September 2009|publisher=Journal of Clinical Endocrinology & Metabolism|page=18|accessdate=March 13, 2014|display-authors=etal}}</ref>The only absolute medical contraindications currently recognized by the WPATH are pregnancy, and unstable coronary artery disease and untreated polycythemia with a hematocrit of 55% or higher, as further described below. Even in situations where going on masculinizing HRT could have an effect on someone's risk factors for certain conditions, usually this is not a reason to not go on HRT, and all that is needed is a conversation with a doctor to make sure the patient is aware of those risks, and knows how to mitigate the risks, such as through other healthy lifestyle choices.  

The WPATH considers pregnancy an absolute medical contraindication, based on a 2004 study.<ref name="soc 45">World Professional Association for Transgender Health. ''The Standards of Care,'' version 7. 2012. Page 45. https://wpath.org/publications/soc</ref><ref name="carnegie 2004">Carnegie, C. (2004). "Diagnosis of hypogonadism: Clinical asessments and laboratory tests." ''Reviews in urology'', 6 (Suppl 6), S3-8.</ref> Masculinizing HRT can affect the developing fetus.<ref name="soc 45" /> It is still possible for someone to get pregnant while on HRT, and after having been on HRT, because HRT does not prevent pregnancy. People on masculinizing HRT need highly effective birth control to prevent getting pregnant while on HRT.<ref name="soc 45" /> People on masculinizing HRT should temporarily stop taking that HRT while pregnant or trying to get pregnant.

Clinicians differ in any additional conditions that they consider to be contraindications.<ref name="gorton 16">R. Nick Gorton, Jamie Buth, and Dean Spade. ''Medical Therapy and Health Maintenance for Transgender Men: A Guide for Health Care Providers.'' San Francisco, CA: Lyon-Martin Women's Health Services, 2005. Page 16-17. https://www.nickgorton.org</ref> Additional conditions that some clinicians may consider to be contraindications may include breast feeding, active known androgen sensitive breast cancer, or active endometrial cancer.<ref name="gorton 16" /> Conditions that some clinicians may consider to be relative contraindications may include androgen sensitive epilepsy, severe obstructive sleep apnea, severe hypertension due to the salt retaining effects of testosterone, active substance abuse, personal or significant family history of androgen sensitive breast cancer, history of uterine cancer, or bleeding disorders (for injected testosterone only).<ref name="gorton 16" /> Many of these conditions are believed to worsen in response to a normal male level of testosterone, which is sometimes only conjecture based on limited evidence.