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Masculinizing hormone therapy, also known as transmasculine hormone therapy or female-to-male (or FTM) hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of transgender people from feminine or androgynous to masculine.^[1][2][3] It is a common type of transgender hormone therapy (another being feminizing hormone therapy), and is predominantly used to treat transgender men and other transmasculine individuals who were assigned female at birth. Some intersex people also receive this form of therapy, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect.

The purpose of this form of therapy is to cause the development of the secondary sex characteristics of the desired sex, such as voice deepening and a masculine pattern of hair, fat, and muscle distribution. It cannot undo many of the changes produced by naturally occurring puberty, which may necessitate surgery and other treatments to reverse. The medications used for FTM therapy include, mainly, androgens (namely testosterone) and GnRH analogues.

While the therapy cannot undo the effects of a person's first puberty, developing secondary sex characteristics associated with a different sex can relieve some or all of the distress and discomfort associated with gender dysphoria, and can help the person to "pass" or be seen as their gender identity. Introducing exogenous (not internally produced) hormones into the body impacts it at every level and many patients report changes in energy levels, mood, appetite, etc. The goal of the therapy, and indeed all somatic treatments, is to provide patients with a more satisfying body that is more congruent with their gender identity.

Masculinizing hormone therapy has been shown to likely reduce the distress and discomfort associated with gender dysphoria.^[4]

Medical uses

• Testosterone replacement therapy (TRT):

Utilized to address hypogonadism or low testosterone levels in assigned female at birth (AFAB) individuals, fostering the development of masculine secondary sexual characteristics.

• Gender affirmation in transgender men:

Administered as part of gender transition to align the physical appearance with the affirmed gender, inducing changes such as facial hair growth and deepening of the voice.

• Puberty suppression in gender diverse youth:

In certain cases, hormonal interventions are employed to delay puberty, offering individuals more time to explore their gender identity before undergoing permanent physical changes.

• Treatment of polycystic ovary syndrome (PCOS):

Testosterone may be prescribed to manage symptoms of PCOS in AFAB individuals, addressing issues like irregular menstruation and hirsutism.

These medical uses of masculinizing hormone therapy are subject to individual health considerations and are typically administered under the supervision of healthcare professionals.^[5]

History

Requirements and accessibility

This section needs expansion. You can help by adding to it. (January 2019)

Contraindications

Several contraindications to androgen therapy exist.^[6] An absolute medical contraindication is pregnancy.

Relative medical contraindications are:

• Androgen-sensitive epilepsy
• Migraines
• Sleep apnea
• Polycythemia (elevated red blood cell count)
• Cardiac failure, renal failure, or severe hypertension susceptible to sodium retention and fluid overload
• Significant liver disease
• Coronary artery disease or risk factors for this condition
• History of uterine cancer
• Bleeding disorders (for injected testosterone)
• Significant history of violent behavior
• History of breast cancer (testosterone has antiproliferative effects on most but not all breast cancers)
• Acne (mild to severe)

Safety

Due to insufficient comprehensive research, there is no consensus on the full range of risks of lengthy testosterone administration, especially as it is difficult to achieve a sufficient number of participants for results to be meaningful.Two 2019 studies indicate the potential for elevated risk of cardiovascular events. One study found that transgender men taking testosterone had an increased risk of cardiovascular events compared to cisgender women, with 11 vs. 3 cardiovascular events per 100,000 person-years, though the risk was less than that of cisgender men. Researchers were not able to control for smoking status or stressors.^[7] The other study found elevated risk of heart attacks among self-identified transgender men—which persisted even after adjusting for age, diabetes mellitus, chronic kidney disease, smoking, hypertension, hypercholesterolemia, and exercise—though the study did not include data about whether the subjects were undergoing hormone therapy and did not control for stressors. The study found that transgender men have a >4-fold and 2-fold increased odds of having a myocardial infarction when compared with cisgender women and cisgender men, respectively.^[8] Though it is not always the case,^[2][9] testosterone for transmasculine people is often intended to be used long-term.

A 2022 review entitled The efficacy, safety, and outcomes of testosterone use among transgender men patients: A review of the literature,^[10] while pointing out that more research is needed for newer therapies, concludes that:

More conventional therapies, including intramuscular injections, subcutaneous injections, and transdermal gels, have been extensively studied and show promising efficacy and outcomes with limited safety concerns.

Interactions

Testosterone is metabolized by the cytochrome P450 enzyme system (specifically CYP3A isoforms) in the liver. There are certain drugs that increase or decrease the activity of cytochrome P450 enzymes and may cause increased or decreased levels of testosterone:

• Enzyme inducers – May cause decreased levels of testosterone (and other sex steroid) levels: Phenobarbital and phenytoin (seizure medicines), rifampin (antibiotic), and alcohol.
• Enzyme inhibitors – May cause increased levels of testosterone: Nefazodone, fluoxetine, paroxetine (antidepressants), itraconazole, fluconazole, and other azole antifungals, cimetidine (an anti-ulcer agent that can cause gynecomastia in men because of this effect). Clarithromycin and other macrolide antibiotics, and protease inhibitors (HIV treatment).

Testosterone can also alter the effects of other drugs:

• Increases the blood thinning effect of warfarin;
• Decreases the effectiveness of propranolol, a nonselective beta blocker used in the management of cardiovascular conditions;
• Increases the effect of some oral medicines for diabetes and can cause dangerously low blood sugar levels.

Because of these interactions, it is advised that trans men make their healthcare providers aware of their hormone therapy when this is relevant to their treatment for other medical issues.

Medications

Medications used in hormone therapy for transgender men include androgens and anabolic steroids like testosterone (by injection and other routes) to produce masculinization, suppress estrogen and progesterone levels, and prevent/reverse feminization; GnRH agonists and antagonists to suppress estrogen and progesterone levels; progestins like medroxyprogesterone acetate to suppress menses; and 5α-reductase inhibitors to prevent/reverse scalp hair loss.

Testosterone

The elimination half-life of testosterone in the blood is about 70 minutes, so it is necessary to have a continuous supply of the hormone for masculinization.

A study of 45 FtM individuals randomly assigned to receive testoviron depot (intramuscular, 100 mg/10 days), testosterone gel (50 mg/day), or testosterone undecanoate (intramuscular, 1000 mg) found increased lean body mass, decreased fat mass, decreased high-density plasma lipoprotein levels, increased low-density lipoprotein levels, and increased prothrombin time. No differences were found between the different formulations of testosterone, and at week 54 all subjects were amenorrheic (no longer experiencing menstrual periods).

1 year after treatment, general life satisfaction was increased in all subjects.^[21]

Injected

'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 or Xyosted) 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 mg/week) than the replacement doses used by transgender men (50–100 mg/week). These testosterone esters are mixed with different oils, 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 US. Testosterone cypionate is more popular in the US than elsewhere (especially amongst bodybuilders). Other formulations exist but are more difficult to come by in the US. A formulation of injected testosterone available in Europe and the US, testosterone undecanoate (Nebido, Aveed)^[22][23] 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 an injection of 4 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 US, Canada, and Europe, but it is very short-acting compared to the other testosterone esters and must be administered once every 2 or 3 days, and for this reason, is rarely used.

The adverse side effects of injected testosterone esters are generally associated with high peak levels in the first few days after an injection. Some side effects may be ameliorated by using a shorter dosing interval (weekly or every ten days instead of twice monthly with testosterone enanthate or testosterone cypionate). 100 mg weekly gives a much lower peak level of testosterone than does 200 mg every two weeks, while still maintaining the same total dose of androgen. This benefit must be weighed against the discomfort and inconvenience of doubling the number of injections.

Injectable forms of testosterone can cause a lung problem called pulmonary oil microembolism (POME). Symptoms of POME include cough, shortness of breath, tightening of the throat, chest pain, sweating, dizziness, and fainting.^[24][25] A postmarketing analysis by the manufacturer of Aveed (testosterone undeconate injection) found that POME occurred at a rate of less than 1% per injection per year for Aveed.^[26]

Injected testosterone esters should be started at a low dose and titrated upwards based on trough levels (blood levels drawn just before your next shot). A trough level of 500 ng/dL is sought. (Normal range for a cisgender man is 290 to 900 ng/dL).

Transdermal

Testosterone patches, creams, and gels are available. Both approximate normal physiological levels of testosterone better than the higher peaks associated with injection. Both can cause local skin irritation (more so with the patches).

Patches slowly diffuse testosterone through the skin and are replaced daily. The cost varies, as with all medication, from country to country, it is about $150/month in the US, and about €60 in Germany. Transdermal testosterone has the advantage of delivering a consistent supply of hormones over a given period and having a simple method of diffusion.^[28]

Transdermal testosterone is available throughout the world under the brand names Andromen Forte, Androgel, Testogel and Testim. They are absorbed quickly when applied and produce a temporary drug depot in the skin which diffuses into the circulation, peaking at 4 hours and decreasing slowly over the rest of the day. The cost varies, as with all medication, from country to country, from as little as $50/month to about $280/month.

Transdermal testosterone poses a risk of inadvertent exposure to others who come in contact with the patient's skin. This is most important for patients whose intimate partners are pregnant or those who are parents of young children as both of these groups are more vulnerable to the masculinizing effects of androgens. Case reports of significant virilization of young children after exposure to topical androgen preparations (both prescription and 'supplement' products) used by their caregivers demonstrates this very real risk, the same principle also applies to estrogens.^[29]

Implants

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.

Oral

Oral testosterone is provided exclusively as testosterone undecanoate. It is available in Europe and Canada, but not in the US. Once absorbed from the gastrointestinal tract, testosterone is shunted (at very high blood levels) to the liver where it can cause liver damage (albeit very rarely) and worsens some of the adverse effects of testosterone, like lower HDL cholesterol. In addition, the first-pass metabolism of the liver also may result in testosterone levels too low to provide satisfactory masculinization and suppress menses. Because of the short terminal half-life of testosterone, oral testosterone undecanoate must be administered two to four times per day, preferably with food (which improves its absorption). Zdroj:https://en.wikipedia.org?pojem=Masculinizing_hormone_therapy
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