Gender-affirming hormone therapy

多くの国際的なガイドラインや機関は、性別適合療法を開始するための前提条件として、持続的で十分に文書化された性別違和を求めている。性別違和とは、出生時に割り当てられた性別が本人の性自認と一致しない場合に個人が経験する心理的な不快感や苦痛を指す。^{[ 7 ]}性別違和の兆候には、うつ病、不安、自尊心の低下、社会的孤立などの併存する精神的ストレス要因が含まれることがある。^{[ 8 ]}性別不適合者 全員が性別違和を経験するわけではなく、性別不適合に対する医療介入を検討する際には、個人の性別違和を測定することが重要である。^{[ 9 ]}

For transgender youth, the Dutch protocol existed as among the earlier guidelines for hormone therapy by delaying puberty until age 16.^[10][11] The World Professional Association for Transgender Health (WPATH) and the Endocrine Society later formulated guidelines that created a foundation for health care providers to care for transgender patients.^[12][13]UCSF guidelines are also sometimes used.^[4] There is no generally agreed-upon set of guidelines, however.^[14]

National and regional guidance also exists in several countries. In Canada, Rainbow Health Ontario publishes primary-care guidelines for gender-affirming care with trans and non-binary patients.^[15] In Australia, the Australian Informed Consent Standards of Care for Gender Affirming Hormone Therapy are recognised as an Accepted Clinical Resource by the Royal Australian College of General Practitioners.^[16] In New Zealand, adult primary-care initiation guidelines for gender-affirming hormone therapy were released in 2023 and endorsed by the Royal New Zealand College of General Practitioners.^[17] France's Haute Autorité de santé has published practice guidelines for the care of transgender adults.^[18] In German-speaking countries, adult care may refer to the AWMF S3 guideline on gender incongruence, gender dysphoria and trans health.^[19] In Japan, the Japanese Society of Psychiatry and Neurology issues guidelines on the diagnosis and treatment of gender incongruence.^[20]

性別違和感を抱える思春期の若者は、思春期の開始時に思春期抑制ホルモン療法を受けることを選択する場合があります。WPATHが定めたケア基準では、思春期抑制ホルモン療法を受ける人は、少なくともタナー段階2の思春期発達を経験するまで待つことを推奨しています。^{[ 7 ]}タナー段階2は、陰毛がわずかに生え、乳房の芽が発達し、睾丸がわずかに成長している状態と定義されます。^{[ 21 ]} WPATHは、思春期抑制ホルモン療法を「完全に可逆的な」介入として分類しています。思春期を遅らせることで、個人はより永続的な介入を決定する前に性同一性を探求する時間をより多く得ることができ、思春期に伴う身体的変化を防ぐことができます。^{[ 7 ]}

出生時に男性と割り当てられた人と出生時に女性と割り当てられた人の両方にとって好ましい思春期抑制剤はGnRHアナログである。^{[ 7 ]}この方法は、思春期に二次性徴の発達を引き起こすホルモン（エストロゲン、テストステロン）の産生を担う視床下部-下垂体-性腺（HPG）軸を一時的に停止させる。^{[ 22 ]}

2025年1月にJAMA Pediatricsに掲載された研究によると、米国の民間医療保険に加入している青少年のうち、性別違和を治療するために性別適合薬を服用しているのは0.1%未満である。^{[ 23 ]}

女性化ホルモン療法は、通常、女性的な二次性徴の発達を望むトランスジェンダー女性によって用いられます。ノンバイナリーを自認する人も、自分の望む性表現に身体をより近づけるために、女性化ホルモン療法を選択することがあります。^{[ 24 ]}女性化ホルモン療法には、通常、テストステロン産生を抑制し、女性化を誘発する薬が含まれます。薬の種類には、エストロゲン、抗アンドロゲン（テストステロンブロッカー）、プロゲステロンなどがあります。^{[ 25 ]}最も一般的には、エストロゲンと抗アンドロゲンを組み合わせてテストステロンを抑制および遮断します。^{[ 26 ]}これにより、脱男性化と女性化および乳房の発達の促進が可能になります。エストロゲンは、注射、経皮パッチ、経口錠剤など、さまざまな方法で投与されます。^{[ 26 ]}

The desired effects of feminizing hormone therapy focus on the development of feminine secondary sex characteristics. These desired effects include: breast tissue development, redistribution of body fat, decreased body hair, reduction of muscle mass, and more.^[26] The table below summarizes some of the effects of feminizing hormone therapy in transgender women:

Masculinizing hormone therapy is typically used by transgender men, who desire the development of masculine secondary sex characteristics. Masculinizing hormone therapy usually includes testosterone to produce masculinization and suppress the production of estrogen.^[40] Treatment options include oral, subcutaneous injections or implant, and transdermal (patches, gels). Dosing is patient-specific, depending on the patient's rate of metabolism, and is discussed with the physician.^[41] The most commonly prescribed methods are intramuscular and subcutaneous injections. This dosing can be daily, weekly or biweekly depending on the route of administration and the individual patient.^[41]

Unlike feminizing hormone therapy, individuals undergoing masculinizing hormone therapy do not usually require additional hormone suppression such as estrogen suppression. Therapeutic doses of testosterone are usually sufficient to inhibit the production of estrogen to desired physiologic levels.^[22]

The desired effects of masculinizing hormone therapy focus on the development of masculine secondary sex characteristics. These desired effects include: increased muscle mass, increased bone turnover,^[42] development of facial hair, voice deepening, increase and thickening of body hair, and more.^[43]

The Standards of Care published by the World Professional Association for Transgender Health (WPATH) summarize many of the risks associated with feminizing hormone therapy (outlined below).^[7]

The Standards of Care published by the World Professional Association for Transgender Health (WPATH) summarize many of the risks associated with masculinizing hormone therapy (outlined below).^[7]

GAHT may limit fertility potential.^[57] Should a transgender individual choose to undergo gender-affirming surgery, their fertility potential is lost completely.^[58] Before starting any treatment, individuals may consider fertility issues and fertility preservation. Options include semen cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation.^[57][58]

A study presented at ENDO 2019 (the Endocrine Society's conference) shows that even after one year of treatment with testosterone, a transgender man can preserve his fertility potential.^[59] A 2015 study demonstrated normal spermatogenesis in some transgender women who were long-term estrogen therapy patients.^[60] In other cases, there is some research showing effective restoration of fertility by alternative means than HRT cessation alone. Dr. Will Powers has demonstrated the effectiveness of clomifene in restoring spermatogenesis in trans women.^[61] His study also includes an in-depth description of other methods for fertility restoration.^[61]

Some molecular biology research suggests that GAHT induces a "unique molecular profile" with potential relevance to the recipient's immune system, or (in)susceptibility to certain health conditions (which are sometimes sexually dimorphic in people); one 2022 analysis found that GAHT (both feminizing and masculinizing) influenced gene expression.^[62][63][64] The study's lead author stated that they observed "changes [to] the epigenetic landscape of DNA" in some regions but not others, and that of the observed "epigenetic changes in regions of DNA that were distinct between sexes before hormone therapy, these regions consistently shifted towards the profile of the affirmed gender after 12 months of hormone therapy."^[62] A 2023 molecular study on the breast tissue of transgender men found that adding androgens induced such changes, appearing to silence genes across the breast tissue, including a suppression of genes linked to breast cancer.^[65][66]

Some online scammers have been targeting trans consumers with products that do not contain any hormones or contain ones that are opposite of what is advertised. ^[67]

The WPATH Standards of Care, most recently published in 2022, outlines a series of guidelines which should be met before a patient should be allowed gender-affirming hormone therapy:^[55]

• Gender incongruence is marked and sustained
• Patient meets diagnostic criteria for gender incongruence prior to gender-affirming hormone treatment in regions where a diagnosis is necessary to access health care
• Patient has capacity to consent to hormone therapy treatment
• Other possible causes of apparent gender incongruence have been identified and excluded
• Mental health and physical conditions that could negatively impact the outcome of treatment have been assessed
• Understands the effect of gender-affirming hormone treatment on reproduction and they have explored reproductive options

The WPATH standards of care distinguish between gender-affirming hormone therapy, and hormone replacement therapy, with the latter referring to the replacement of endogenous hormones after a gonadectomy to prevent cardiovascular and musculoskeletal issues.^[55]

Some organizations—but fewer than in the past—require that patients spend a certain period of time living in their desired gender role before starting hormone therapy. This period is sometimes called real-life experience (RLE).

In Sweden, for instance, patients seeking to access gender affirming healthcare must first undergo extended evaluations with psychiatric professionals, during which they must—without any form of medical transition—successfully live for one full year as their desired gender in all professional, social, and personal matters. Gender clinics are recommended to provide patients with wigs and breast prostheses for the endeavor. The evaluation additionally involves, if possible, meetings with family members and/or other individuals close to the patient. Patients may be denied care for any number of "psychosocial dimensions", including their choice of job or their marital status.^[69][70]

ケイト・ボーンスタインなどのトランスジェンダーやジェンダー非適合の活動家は、RLEは心理的に有害であり、「ゲートキーピング」の一形態であり、永久的ではないにしても、可能な限り長く個人が性別移行することを事実上妨げていると主張している。^{[ 71 ]}

2022年9月、世界トランスジェンダー健康専門家協会（WPATH）のトランスジェンダーおよびジェンダー多様性のある人々の健康のためのケア基準（SOC）バージョン8が発表され、性別適合手術を含むすべての性別適合治療に対するRLEの要件が削除されました。^{[ 72 ]}