According to the recommendations reported in the bibliography section, people who match the following criteria can undergo gender affirming hormonal therapy:

• marked and sustained gender incongruence;

• meets diagnostic criteria for gender incongruence prior to gender-affirming hormone treatment in regions where a diagnosis is necessary to access health care;

• demonstrates capacity to consent for the specific gender-affirming hormone 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, with risks and benefits discussed;

• taking charge of any physical and/or psychological health problems potentially interfering with the outcome of the treatment

• understands the effect of gender-affirming hormone treatment on reproduction and they have explored reproductive options

In Italy, the following criteria have also to be matched:

• 18 years of age (for people under 18 years of age, both parents or legal tutors have to sign written consent to treatment)
• To access the free supply of medicines through the NHS, a diagnosis of gender dysphoria/gender incongruence, according to the DSM-5 (APA, 2013) or ICD-11 (WHO, 2018) criteria, is required and has to be confirmed by a multidisciplinary team of specialists.

In order to start hormonal therapy, a minimum timeframe of evaluation and psychological support or of social transitioning is not necessary. Nonetheless, the physician who prescribes hormonal therapy (generally an endocrinologist) takes the responsibility of ensuring this is the most adequate path to accommodate the person’s needs and reduce the related incongruence and/or suffering, without leading to health issues. For example, hormonal therapy in people with a breast cancer can lead to very negative consequences. In other cases, a person can become aware, also thanks to psychological support, that s/he can reach psychological well-being, living and being recognized in the desired gender role, without necessarily initiating the gender affirming medical path with hormones. This can also include legal gender change. For these reasons it is important that the physician works within a multidisciplinary team with experts in different skills (e.g., psychologist, psychotherapist, psychiatrist, endocrinologist, surgeon) who have adequate expertise in this field and can offer a global support to the person.
Hormonal therapy is tailored taking into account individual needs, risk factors and health status of the person. Naturally, this implies a detailed analysis of people expectations in regards to hormonal therapy outcomes so they are realistic and in line with individual needs. Again, this underlines the importance of a multidisciplinary support.

Finally, in Italy, hormonal therapy can be prescribed for free  if criteria given by Agenzia Italiana del Farmaco (AIFA) are met, as described by AIFA document n. 104272/2020 e n. 104273/2020 del 23 settembre 2020 (GU Serie generale n.242 del 30-09-2020).

References

Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-42.

Coleman E,  Radix AE, Bouman W,  et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. Int J Transgend Health. 2022; Sep 6;23(Suppl 1):S1-S259.

Fisher AD, Castellini G, Ristori J, et al. Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data. J Clin Endocrinol Metab. 2016;101(11):4260-69.

Fisher AD, Gooren L. Encyclopedia of Endocrine Diseases (2nd Edition), edited by Ilpo Huhtaniemi and Luciano Martini, 2018 Elsevier Inc.

Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-03. Erratum in: J Clin Endocrinol Metab. 2018; 103(2): 699. J Clin Endocrinol Metab. 2018; 103(7): 2758-59.

T'Sjoen G, Arcelus J, De Vries ALC et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med. 2020;17(4):570-584.

T'Sjoen G, Arcelus J, Gooren L, et al. Endocrinology of Transgender Medicine. Endocr Rev. 2019;40(1):97-117.

The aim of masculinizing hormonal therapy is to reduce female sexual characteristics and induce masculine ones. Masculinizing therapy is based on the administration of testosterone through intramuscular injections or through transdermal application.
First body changes occur after 3-6 months and include: menstrual bleeding cessation, deepening of voice, facial and body hair growth, breast reduction (mammal tissue hypotrophy), increased sebum production from skin glands (seborrhea) and acne, clitoris increase (clitoral hypertrophy), libido increase, muscle mass increase and in some cases androgenetic alopecia (hair loss due to testosterone action).

FREQUENT QUESTIONS:

DO TESTOSTERONE INJECTIONS WORK BETTER THAN TESTOSTERONE GEL?
Like oestrogens in feminizing therapy, no studies demonstrate that injections are more effective than transdermal application or vice versa.

IS HORMONAL AFFIRMING THERAPY SAFE?
Data are available in literature related to safety of gender affirming hormonal treatment in the short-medium term; these data show a satisfying safety profile in healthy people regularly undergoing medical checks. As of today, few data are available regarding long term treatments or extended to the whole person’s lifetime. For these reasons, before starting hormonal treatment, it is crucial to undergo medical checks to assess personal health condition, as well as to receive a deep counselling regarding risk and benefit profiles of the therapy and regarding expected outcomes in order to reduce adverse events risks and dissatisfaction. 
It is furthermore recommended to undergo regular screening with blood and radiological checks as per the referring endocrinologist recommendation (generally every three months during the first year of therapy and less frequently after). A healthy lifestyle during the therapy is also recommended. Smoke, for example, could further increase thrombotic risk (risk of thrombosis) associated to feminizing therapy with oestrogens and to the masculinizing one with testosterone, resulting in thicker blood. For further information on what “thrombosis” is or how to stop smoking it’s possible visiting ISSsalute.it at sections "Coagulo, trombo, embolo" or "Telefono Verde contro il Fumo (TVF)". 

References
Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-42.

Coleman E,  Radix AE, Bouman W,  et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. Int J Transgend Health. 2022; Sep 6;23(Suppl 1):S1-S259.

Fisher AD, Castellini G, Ristori J, et al. Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data. J Clin Endocrinol Metab. 2016;101(11):4260-69.

Fisher AD, Gooren L. Encyclopedia of Endocrine Diseases (2nd Edition), edited by Ilpo Huhtaniemi and Luciano Martini, 2018 Elsevier Inc.

Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-03. Erratum in: J Clin Endocrinol Metab. 2018; 103(2): 699. J Clin Endocrinol Metab. 2018; 103(7): 2758-59.

T'Sjoen G, Arcelus J, De Vries ALC et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med. 2020;17(4):570-584.

T'Sjoen G, Arcelus J, Gooren L, et al. Endocrinology of Transgender Medicine. Endocr Rev. 2019;40(1):97-117.

De-masculinizing therapy’s aim is to reduce male sexual characteristics. Therapy is based on the use of antiandrogens (in order to inhibit effects of testosterone), among which, cyproterone acetate is the one more widely used in Europe (and the one which is therefore more known in terms of efficacy and risks). Spironolactone can be a suitable alternative but, as it reduces arterial pressure, is generally less utilized. Also administration of medicines called gonadotropin releasing hormone (GnRH) analogs (GnRHa), which suppress sexual hormones production, could theoretically be utilized, anyway they are uncomfortable because they can be administered only through injections.

De-masculinizing therapy is able to reduce hair growth and beard growth and excessive skin sebum production. It is important to be aware this therapy requires many months to induce a significant reduction of hair and often it is anyway necessary to divert to alternative procedures (for example electrolysis). Antiandrogens cause also sexual function worsening (with frequent loss of spontaneous erections and difficulty in maintaining erections during sexual intercourse), effects that can be desired by some people but not by others. Furthermore, they determine libido reduction. De-masculinizing therapy, if done as adults, is not able to modify tone of voice and make it more feminine.

FREQUENT QUESTIONS:

IS HORMONAL GENDER AFFIRMING THERAPY SAFE? 
Data are available in literature related to safety of gender affirming hormonal treatment in the short-medium term; these data show a satisfying safety profile in healthy people regularly undergoing medical checks. As of today, few data are available regarding long term treatments or extended to the whole person’s lifetime. For these reasons, before starting hormonal treatment, it is crucial to undergo medical checks to assess personal health condition, as well as to receive a deep counselling regarding risk and benefit profiles of the therapy and regarding expected outcomes in order to reduce adverse events risks and dissatisfaction. 
It is furthermore recommended to undergo regular screening with blood and radiological checks as per the referring endocrinologist recommendation (generally every three months during the first year of therapy and less frequently after). A healthy lifestyle during the therapy is also recommended. Smoke, for example, could further increase thrombotic risk (risk of thrombosis) associated to feminizing therapy with oestrogens and to the masculinizing one with testosterone, resulting in thicker blood. For further information on what “thrombosis” is or how to stop smoking it’s possible visiting ISSsalute.it at sections "Coagulo, trombo, embolo" or "Telefono Verde contro il Fumo (TVF)". 

References
Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-42.

Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. Int J Transgend. 2012;13(4):165-232.

Fisher AD, Castellini G, Ristori J, et al. Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data. J Clin Endocrinol Metab. 2016;101(11):4260-69.

Fisher AD, Gooren L. Encyclopedia of Endocrine Diseases (2nd Edition), edited by Ilpo Huhtaniemi and Luciano Martini, 2018 Elsevier Inc.

Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-03. Erratum in: J Clin Endocrinol Metab. 2018; 103(2): 699. J Clin Endocrinol Metab. 2018; 103(7): 2758-59.

T'Sjoen G, Arcelus J, De Vries ALC et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med. 2020;17(4):570-584.

T'Sjoen G, Arcelus J, Gooren L, et al. Endocrinology of Transgender Medicine. Endocr Rev. 2019;40(1):97-117.

Feminizing therapy’s aim is to induce feminine sexual characteristics. Therapy is based on use of oestrogens (to promote femininization).
Oestrogens exist either in pills (oestradiol valerate) or as gel or patch (oestradiol o oestradiol hemihydrate). Oestrogens allow to redistribute body fat in feminine sense (more on hips and less on belly), to induce breast growth and together with antiandrogens to make skin more smooth and less seborrheic. Breast development with hormonal therapy is extremely variable and unpredictable and it doesn’t seem to depends on the type of oestrogens taken. Approximately 70% of transwomen applies for addictive mastectomy (surgical intervention which provides application of prothesis to breast) due to unsatisfaction of breast obtained with hormonal therapy. Anyway, as breast can continue to grow for at least two years from the beginning of hormonal therapy, it is recommended to proceed with breast augmentation surgery not before this timeframe has passed. Hormonal therapy with oestrogens and antiandrogens, if undergone in the adult age, is not able to modify tone of voice and make it more feminine.

FREQUENT QUESTIONS:

DO INJECTIONS WORK BETTER THAN PILLS AND DO PILLS WORK BETTER THAN GEL OR PATCHES? 

There are no studies that show one administration is better or more effective than another. The endocrinologist has to check that blood levels of oestrogens are appropriate and to modify, if it wasn’t the case, the dosage of pills, gel or patches. Therapy with gel or patches and the one with injections can be preferred in people with a higher risk of thrombosis (for example in cases of strong smokers, advanced age, previous thrombosis in the past). Anyway, injective oestrogens are not available in Italy. For further information on what “thrombosis” is it is possible to visit ISSsalute at section "Coagulo, trombo, embolo".

WHY IS IT BETTER NOT TO USE ETHINYL-ESTRADIOL FOR HORMONAL THERAPY?

Ethinyl-oestradiol (usually embedded in contraceptive pills), often requested for a supposed major efficacy, is a semisynthetic hormone (a partially modified in laboratory hormone) which acts like oestrogens. Its administration can increase risk of mortality for pulmonary embolism or hearth attack and, for this reason, the use of this medicine is not recommended. For further information regarding embolism or stroke it’s possible to visit ISSalute.it at sections "Embolismo" o "Infarto del miocardio".

CAN PROGESTERON HELP IN BREAST GROWTH?

It’s not demonstrated that progesterone is helpful in increasing breast growth, but it seems it increases risk of thromboembolism and stroke. Furthermore, progestins can increase breast cancer risk. Therefore, even if progestins is often requested by transgender women, risks linked to assumption of this medicine and lack of advantages do not justify its use. For further information related to stroke please visit ISSalute.it at section "Stroke".

IS HORMONAL GENDER AFFIRMING THERAPY SAFE? 

Data are available in literature related to safety of gender affirming hormonal treatment in the short-medium term; these data show a satisfying safety profile in healthy people regularly undergoing medical checks. As of today, few data are available regarding long term treatments or extended to the whole person’s lifetime. For these reasons, before starting hormonal treatment, it is crucial to undergo medical checks to assess personal health condition, as well as to receive a deep counselling regarding risk and benefit profiles of the therapy and regarding expected outcomes in order to reduce adverse events risks and dissatisfaction. 
Its is furthermore recommended to undergo regular screening with blood and radiological checks as per the referring endocrinologist recommendation (generally every three months during the first year of therapy and less frequently after). A healthy lifestyle during the therapy is also recommended. Smoke, for example, could further increase thrombotic risk (risk of thrombosis) associated to feminizing therapy with oestrogens and to the masculinizing one with testosterone, resulting in thicker blood. For further information on what “thrombosis” is or how to stop smoking it’s possible visiting ISSsalute.it at sections "Coagulo, trombo, embolo" or "Telefono Verde contro il Fumo (TVF)". 

References
Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635-42.

Coleman E,  Radix AE, Bouman W,  et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. Int J Transgend Health. 2022; Sep 6;23(Suppl 1):S1-S259.

Fisher AD, Castellini G, Ristori J, et al. Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data. J Clin Endocrinol Metab. 2016;101(11):4260-69.

Fisher AD, Gooren L. Encyclopedia of Endocrine Diseases (2nd Edition), edited by Ilpo Huhtaniemi and Luciano Martini, 2018 Elsevier Inc.

Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(11):3869-03. Erratum in: J Clin Endocrinol Metab. 2018; 103(2): 699. J Clin Endocrinol Metab. 2018; 103(7): 2758-59.

T'Sjoen G, Arcelus J, De Vries ALC et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med. 2020;17(4):570-584.

T'Sjoen G, Arcelus J, Gooren L, et al. Endocrinology of Transgender Medicine. Endocr Rev. 2019;40(1):97-117.