NGICNS Endocrine Management of Adult Transgender Patients v.17 October 2018 1

National Gender Identity Clinical Network for Scotland (NGICNS) Endocrine Management of Adult Transgender Patients (Revised October 2018 (First published 11 August 2015))

This guidance is based on the Scottish Government gender reassignment protocol 2012. See www.sehd.scot.nhs.uk/mels/CEL2012_26.pdf. The groups convened by NGICNS (Appendix A) took into account all relevant guidelines, published evidence and clinical experience in formulating this guidance. It was accepted by the group that there is limited evidence in this area of practice and a wide variation in practice exists across services. The aims of this guidance are to set standards of endocrine care for transgender patients across Scotland thus enabling all clinicians who encounter this patient group to provide acceptable, safe and effective treatment.

The Role of the GICs GICs will carry out initial assessments, and most patients will be followed up regularly by the GIC until a stable medication regimen is established at which point primary care are asked to continue the prescribing and monitoring requirements.

The Role of Primary Care Primary Care practitioners are asked to prescribe hormonal therapy on the advice of the GIC or Endocrinology specialist and to take over monitoring of patients after a stable medication regimen is established.

Outline Assessment Process For further detail, please refer to NGICNS Scottish Gender Protocol Explanatory Notes on NGICNS website (http://www.ngicns.scot.nhs.uk/wp-content/uploads/2016/04/NGICNS-Explanatory-Notes-for-GRP-v1-0-2.pdf ). Adult patients (17 or 18+) presenting with Gender Dysphoria1/ Transsexualism2 are initially seen and assessed at their local Gender Identity Clinic (GIC). This assessment includes a detailed history and a physical and mental health assessment prior to the initiation of hormonal treatment if required. Most patients will be followed up regularly by the GIC until a stable medication regimen is established at which point primary care should continue the monitoring requirements.

1 The term Gender Dysphoria refers to discomfort or distress that is caused by a discrepancy between a person’s gender identity and

that person’s sex assigned at birth (and the associated gender role and / or primary and secondary sex characteristic). This includes situations where a person has a non-binary gender identity and describes themselves as other than a man or a woman. It should be noted that ICD 11 classification is likely to be scheduled for international adoption in 2022

2 The term Transsexualism is more specific than the term Gender Dysphoria and refers to the desire to live and be accepted as a

member of the opposite sex, usually accompanied by the wish to make his or her body as congruent as possible with the preferred sex through surgery and hormone treatment.

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Where significant medical co-morbidities exist, patients should be referred to local Endocrinology services for assessment and treatment. Co-location of endocrine services in a GIC is recommended. Adult patients already on established hormonal treatment (i.e. treatment elsewhere, self medicating) should be made aware of this guidance should they wish to change or amend their prescription. Patients are assessed according to the World Professional Association of Transgender Health (WPATH) Standards of Care, 2011 Criteria for the initiation of hormonal treatment as follows: 1. Persistent, well-documented gender dysphoria;3 2. Capacity to make a fully informed decision and to consent for treatment; 3. Age of majority4 4. If significant medical or mental health concerns are present, they must be reasonably well

controlled. In selected circumstances, it can be acceptable practice to provide hormones to patients who have not fulfilled these criteria. Examples include facilitating the provision of monitored therapy using hormones of known quality as an alternative to illicit or unsupervised hormone use or to patients who have already established themselves in their affirmed gender and who have a history of prior hormone use. For further information about managing such circumstances refer to NGICNS Scottish Gender Protocol Explanatory Notes. Patients are encouraged to stop smoking, take regular exercise, have a good balanced diet, maintain a healthy body weight, and consume no more than 14 units of alcohol per week. Informed consent is essential when initiating hormonal therapy and all prescribers should ensure that this has been documented. This consent is required at the initial prescribing decision and is not required for every recurring prescription. The impact of endocrine treatment on fertility should be discussed with the patient prior to initiating treatment. For further information about fertility preservation options refer to NGICNS Scottish Gender Protocol Explanatory Notes (See http://www.ngicns.scot.nhs.uk/grp/).

Consent Forms are found in Appendix B.

The forms can usefully be combined with detailed information contained within WPATH Standards of Care; pages 33 to 40: https://www.wpath.org/publications/soc A further source of information is A Guide to Hormone Therapy for Trans People produced by the NHS Department of Health: http://www.gires.org.uk/assets/DOH-Assets/pdf/doh-hormone-therapy.pdf

Individualised Treatment Treatment is individualised according to patient presentation and preference. Non–binary identifying patients, in particular, will require an individualised treatment package agreed with an

3 It is not necessary for a patient to change their name or the gender role in which they live prior to starting hormone treatment.

4 Age of legal majority in Scotland is 16 years

NGICNS Endocrine Management of Adult Transgender Patients v.17 October 2018 3

experienced clinician. Once an individualised treatment plan has been agreed with the patient, the GIC will write to the patient’s GP to request that medication is prescribed. Initial monitoring is undertaken by the GIC until the patient is well established on treatment (typically 6-12 months). Monitoring should continue in primary care once the patient is discharged. GICs will always be available to discuss any issues arising through ongoing monitoring.

Endocrine treatment The individual Feminising and Masculinising Endocrine Treatments are outlined below.

FEMINISING ENDOCRINE TREATMENT

This section relates to patients originally assigned male at birth, identifying as trans women, trans feminine or non-binary. Baseline assessment: Responsibility of GIC

Medical, family and sexual histories; particular concerns are hypertension, thromboembolic disease, migraine, breast disease, liver disease and prostate disease. Patients with significant co-morbidities should be referred for an endocrinological opinion at a service local to the patient.

Assess cardiovascular risk status (BNF or http://www.qrisk.org/).

Glucose, U and E, and lipid profile (preferably fasting).

LFT

Prolactin.

Consider PSA if age is greater than 50yrs or symptomatic.

Consider HIV, Hepatitis B core Antibody, Hepatitis C Antibody, and sexual health screen. Consider Hepatitis A and B and HPV vaccination if sexual history indicates higher risk.

BMI on its own should not be a contraindication of hormone treatment. However, people with higher BMI/BMI deemed within the unhealthy range should be counselled re. additional risks of taking hormones, offered weight-loss assistance and informed in clear terms that BMI limits for surgery exist and surgery may not be possible for patients with a high BMI.

Monitoring of patients on established hormonal therapy: Responsibility of Primary Care

Hormone blood tests as below on a 3-4 monthly basis for the first year (this would usually be undertaken by GIC until patient is on a stable medication regime) and 12 monthly thereafter.

Monitor cardiovascular risk including blood pressure, height, weight and lipid profile annually if risk factors present.

LFT annually.

Serum estradiol (aiming for levels not higher than 600pmol/L; if greater than 600pmol/L seek advice from GIC).

Prolactin (if greater than 1000mU/L seek advice from endocrinology).

If on spironolactone: U+E annually.

Maintain awareness of prostatic disease and institute appropriate investigations should lower urinary tract symptoms occur. PSA monitoring is not required.

Breast cancer screening as for natal female guidelines.

DEXA scanning is only recommended for patients who cannot take estrogen or testosterone and who have been on a GnRH analogue treatment alone for more than 12 months. Refer to local Board guidance on management of osteoporosis.

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Patients migrating to Scotland on established, stable hormone therapy should be allowed to continue without re-undergoing assessment, but in the case of any concerns, referral to GIC or endocrinology should take place.

Exclusion from cervical screening recall should be actioned using the ‘no cervix’ code. Medication Patients will usually attend regular GIC appointments for review while hormone dosages are adjusted. The GIC will liaise closely with the patient’s Primary Care Provider until a stable hormonal regimen is established. Estrogen doses are gradually increased e.g. 1-2mg oral estradiol increased by 1-2 mg increments until therapeutic range and clinical efficacy appropriate.

Monitor estradiol level at clinic visits (3-4 monthly during first year, then annually) and increase dose of estradiol aiming to achieve estradiol levels in range 200-600pmol/L.

Androgen suppression is recommended for all patients who do not suppress androgen levels with estrogen alone. This occurs in approximately 1 in 3 patients after 3-6 months.

Should androgen suppression not occur, anti-androgen therapy can be offered. Typical medication regimes may include

Transdermal estradiol patches (initially 40-50mcg changed twice weekly but increase to up to 160-200mcg changed twice weekly) recommended for use in patients over 40 and in patients with cardiovascular risk factors, high BMI, liver disease or patient preference OR

Oral estradiol 1mg to 6mg daily OR

Estradiol gel 1-3mg daily

Estradiol level in the range 200-600pmol/L is appropriate.

If there are availability issues, it is acceptable to switch to other equivalent prescriptions. Generic prescribing is recommended.

PROGESTERONE (or synthetic progestogens) is of no proven benefit in this patient group and is not recommended Androgen suppression

Leuprorelin/Triptorelin 3.75mg 4 weekly or 11.25mg 12 weekly by IM injection* OR Goserelin 3.6mg implant subcutaneously 4 weekly or 10.8 mg implant 12 weekly*

OR

Cyproterone Acetate (25-100 mg daily: 6 monthly checks of LFTs are necessary as serious hepatotoxicity has been reported)

Finasteride 5mg daily and Spironolactone (50 -100mg daily) are not recommended as they are less effective in androgen suppression although may help with hirsutism (NB: ensure normal renal function with spironolactone and monitor for possible hyperkalaemia).

*If prescribing GnRH analogues a short term prescription of Cyproterone Acetate 100mg daily for 10 days only may be useful at the time of first GnRH administration to prevent the effects of a short-lived increase in testosterone levels.

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Surgery Individual guidance regarding cessation and restarting of hormone therapy should always be sought from the surgical team. For gender related surgery, surgeons currently recommend that estrogen therapy should be ceased 6 weeks prior to surgery, and resumed 3 weeks after surgery if there are no complications. The surgeon will usually communicate directly with GPs before and after surgery. Androgen suppression is not required after orchidectomy. Gender related surgery could include: Orchidectomy, penectomy, vaginoplasty, clitoroplasty, labiaplasty, breast augmentation, facial feminisation surgery and tracheal shave. It should be noted that there are strict cut-offs with regard to BMI for surgery as set by the surgical providers, and commencement of hormones does not mean that a patient has a BMI which is suitable for surgery. Post operative care The estrogen dose should continue to be monitored post operatively with circulating estradiol levels maintained below 600pmol/L.

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MASCULINISING ENDOCRINE TREATMENT

This section relates to patients originally assigned female at birth, identifying as men, trans masculine or non-binary. Baseline assessment (GIC)

Medical, family, sexual histories and menstrual histories are taken; particular concerns are hypertension, breast disease, heavy menstrual bleeding and haematological disease. Patients with significant co-morbidities should be referred for an endocrinological opinion at a local service.

Assess cardiovascular risk (BNF or http://www.qrisk.org/).

FBC, LFT, glucose and lipid profile (preferably fasting).

Consider hormonal profile if history of irregular menses (LH, FSH, estradiol, testosterone, prolactin).

Consider HIV, Hepatitis B core Antibody, Hepatitis C Antibody, and sexual health screen.

Consider Hepatitis A and B vaccination if sexual history indicates higher risk. Consider HPV vaccination if at risk and missed school vaccination programme.

BMI on its own should not be a contraindication for hormone treatment. However, people with high BMI/BMI deemed within the unhealthy range should be should be counselled re the additional risk of taking hormones with a higher BMI, offered weight-loss assistance and clearly informed that strict BMI limits for surgery exist and surgery may not be possible for patients with a high BMI.

Monitoring (GIC OR Primary Care) On a 3-4 monthly basis for the first year and 12 monthly thereafter.

Cardiovascular risk assessment, including blood pressure, height, weight and lipid profile annually.

FBC (Hb and haematocrit).

For parenteral treatment monitor testosterone trough level (Ideal 9-15 nmol/L), if more than 20nmol/L discuss with GIC).

For transdermal preparations monitor testosterone level (should be within normal male range; beware taking blood from the arm to which testosterone is applied)

Cervical screening should continue as for female guidelines if cervical tissue is present, however, sensitive discussion of this should take into account the patient’s dysphoria.

Breast screening should also follow female guidelines if mastectomy has not been performed.

Monitoring for osteoporosis if high risk for osteoporotic fracture or prolonged periods of hypogonadism. DEXA scanning is only routinely recommended for gender patients who cannot take estrogen or testosterone and who have been on a GnRH analogue treatment alone for more than 12 months. Refer to local guidance on management of osteoporosis.

Medication Patients will usually attend regular GIC appointments for review while hormone dosages are adjusted. The GIC will liaise closely with the patient’s Primary Care Provider until a stable hormonal regimen is established. Testosterone is introduced gradually and slowly titrated to avoid adverse reactions e.g. affective changes, amongst others. Initiation phase (GIC)

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Gradual introduction of testosterone:

Transdermal testosterone 1% (eg Testogel or Testim sachets) 50mg on alternate days for 2 months, increasing to 50mg-100mg daily thereafter

Transdermal testosterone pump dispensers: o Tostran 2%; 10mg/press. 20mg per day for 2 months, increasing to 40-60mg

daily thereafter, ie 2 presses increasing to 4-6 presses. o Testogel 16.2mg/g; 20.25mg/press. 20.25mg per per day for 2 months,

increasing to 40.5 mg daily thereafter, ie 1 press increasing to 2 presses OR

Sustanon or testosterone enantate, 125mg three weekly for 2-3 months, increase to 250mg 3 weekly if well tolerated and testosterone levels subtherapeutic

After 6 months patients either continue on the treatment they are on or can be offered the maintenance treatments below.

Note that topical DHT for clitoral growth is not recommended.

Please note that administration differs by topical testosterone product, please see Summary of Product Characteristics for detailed administration information when prescribing (links below).

Tostran 2% gel product information: https://www.medicines.org.uk/emc/product/332

Testogel 16.2mg/g gel product information: https://www.medicines.org.uk/emc/product/8919/smpc

Testim 50mg gel product information: https://www.medicines.org.uk/emc/product/6614 GnRH analogues can be prescribed for cessation of menses. These should be stopped once patient is established on testosterone, typically after 6 months.

Goserelin 3.6mg implant subcutaneously 4 weekly or 10.8 mg implant 12 weekly OR

Leuprorelin/Triptorelin 3.75mg 4 weekly or 11.25mg 12 weekly by IM injection. Maintenance treatments

Testosterone undecanoate (Nebido) 1000mg intramuscular injections 10-14 weekly OR

Testosterone (Sustanon or Enantate) intramuscular injections 125-250 mg 2-3 weekly OR

Transdermal testosterone (Testogel, Testim, Tostran) 40-100mg daily.

Sustanon results in very large variation of serum testosterone levels over the 3 week cycle of administration, and is therefore less preferred to longer acting injectable treatment.

If there are availability issues, it is acceptable to switch to other prescriptions of the closest equivalent dose. Generic prescribing is recommended.

Testosterone oral preparations are not recommended

Surgery Individual guidance regarding cessation and restarting of hormone therapy should always be sought from the surgical team. Gender related surgery could include:

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Chest reconstruction, mastectomy, yysterectomy, salpingo-oophorectomy, vaginectomy, metoidioplasty, phalloplasty, urethroplasty, scrotoplasty, testicular prostheses.

It should be noted that there are strict cut-offs with regard to BMI for surgery, and commencement of hormones does not mean that a patient has a BMI which is suitable for surgery. Post operative care The testosterone dose should continue to be monitored post operatively aiming for circulating concentrations as described above under ‘monitoring’.

Appendix A Endocrine Management Group Membership (2015) Dr David Gerber, Consultant Psychiatrist Prof Alastair McLellan, Consultant Endocrinologist Prof Richard Anderson, Consultant in Reproductive Medicine Dr Guftar Shaikh, Consultant Paediatric Endocrinologist

Additional Contributors (2015) Dr Sarah Kennedy, Consultant Psychiatrist Dr Gordon McKenna, Consultant GUM Physician Dr John Ewan, Associate Specialist Mr James Morton, Scottish Transgender Alliance

Revision Group Members (2016)

Dr David Gerber, Consultant Psychiatrist Prof Richard Anderson, Consultant in Reproductive Medicine Dr Sarah Kennedy, Consultant Psychiatrist Dr Marie Freel, Consultant Endocrinologist Dr Colin Perry, Clinical Lead and Consultant Endocrinologist Dr Chris Schofield, Physician in Diabetes and Endocrinology/Acute Medicine

Revision Group Members (2018)

Dr David Gerber, Consultant Psychiatrist, NHS Greater Glasgow and Clyde Prof Richard Anderson, Consultant in Reproductive Medicine, University of Edinburgh and NHS Lothian Mr James Morton, Manager, Scottish Transgender Alliance Dr Colin Perry, Consultant Endocrinologist, NHS Greater Glasgow and Clyde Dr Gordon Wilkinson, Consultant Child and Adolescent Psychiatrist, NHS Greater Glasgow and Clyde Dr Anna Lamont, RCGP Representative & Associate Medical Director, NHS24 Dr Louise Melvin, Consultant in Sexual and Reproductive Health, NHS Greater Glasgow and Clyde

Additional Contributors (2018)

David Parker. Gender Nurse Specialist, NHS Lothian

Appendix B - Consent forms

INFORMED CONSENT FOR FEMINISING ENDOCRINE TREATMENT

This form refers to the use of estrogen or anti-androgen treatment by persons who wish to become more feminised as part of a gender transitioning process

To be retained in patient’s notes

Patient details (or pre-printed label)

Patient’s surname / family name: _______________________________________ Patient’s first name: __________________________________________________ Date of birth/CHI no: _________________________________________________

Consent to commencing estrogen and/or anti-androgens

Names of person present (including relationship to patient if relevant):

1.

2.

3.

The information listed in the box below shows potential benefits, risks and side effects associated with estrogen and anti-androgens.

These will have been discussed with you during appointments with your Clinician, as well as in this information leaflet.

BENEFITS

These changes may be permanent

POTENTIAL RISKS / SIDE EFFECTS

Breast development Continued associated long-term health risks associated with those assigned male at birth, e.g. prostate cancer

Reduction in facial and body hair Additional long-term health risks associated with females e.g. breast cancer

Change in distribution of body fat Prevention of sperm production with likely loss of fertility and unknown long-term effects on the testicles

Reduction in erectile function Increased risk of developing blood clots in the leg or lung (deep vein thrombosis or pulmonary embolism)

Reduced sex drive Increased risk of high blood pressure, heart attacks and strokes

Increased levels of energy and drive

Increased risk of Benign Intracranial Hypertension

Changes in mood or affect

Migraine

Abnormal liver function blood tests

In order to progress with prescribing estrogen and/or anti-androgens we require your informed consent.

By signing this consent statement, you are demonstrating: You understand of all the information given to you and all of your questions have been answered to

your satisfaction

You are aware of the physical and psychological changes that will occur with gender affirming

hormones, including associated risks and side effects

That you have adequate knowledge on which to base an informed consent and wish to progress with

treatment on estrogen and/or anti-androgens

Please take the time to read and consider the following points before signing:

1. I have read and understood this information about oestrogen treatment

2. I understand the different ways estrogen and/or anti-androgens can be given

3. I have been informed of the potential benefits of starting estrogen and/or anti-androgen treatment

4. I have been informed of the potential risks and side effects associated with estrogen and/or anti-androgen treatment

5. The option of preservation of my fertility has been discussed with me, and I am aware of the consequences of deciding against this.

6. I have been given the opportunity to ask questions and participate in discussions about starting estrogen and/or anti-androgens with my Clinician

7. I am aware of the requirement for life-long regular monitoring of estrogen treatment (blood tests and physical monitoring) by medical practitioners, either by gender specialists or my GP

8. My decision to commence estrogen and/or anti-androgens has been made voluntarily

9. I understand I can stop treatment at any time without having to give reasons and that I will not be penalised

10. I am fully aware that starting estrogen and/or anti-androgen treatment will bring about permanent changes to me, and should I wish to stop this treatment later on in my life, the changes that happen may not all reverse

Person consenting: ___________________________ ________ ______________ Signature Date ___________________________ ______________ Name (PRINT) Clinician obtaining consent: ___________________________ ________ ______________ Signature Date ___________________________ ______________ Name (PRINT)

INFORMED CONSENT FOR MASCULINISING ENDOCRINE TREATMENT

This form refers to the use of testosterone treatment by persons who wish to become more masculinised as part of a gender transitioning process

To be retained in patient’s notes

Patient details (or pre-printed label)

Patient’s surname / family name: _______________________________________ Patient’s first name: __________________________________________________ Date of birth/CHI no: _________________________________________________

Consent to commencing testosterone

Names of person present (including relationship to patient if relevant):

1.

2.

3.

The information listed in the box below shows potential benefits, risks and side effects associated with testosterone.

These will have been discussed with you during appointments with your Clinician, as well as in this information leaflet.

BENEFITS

*IRREVERSIBLE changes

POTENTIAL RISKS / SIDE EFFECTS

Periods will stop

Continued health risks associated with female organs e.g. breast, cervical & uterine cancer, until surgery

*Deepening of the voice Additional cardiovascular health risks associated with males e.g. high blood pressure and heart attacks

*Growth of the clitoris Increased red blood cells (Polycythaemia)

Change in distribution of body fat and increased muscle mass

Reduction in ovulation with likely loss of fertility. Long term effects of testosterone on ovaries/eggs unknown

*Growth of facial and body hair *Male pattern hair loss or balding

Increased levels of energy and drive Mood or affective changes and aggression

Increased sex drive Benign Intracranial Hypertension

Increased appetite and potential weight gain

Increased risk of raised cholesterol, abnormal liver function and diabetes

The need for contraception

In order to progress with prescribing testosterone we require your informed consent.

By signing this consent statement, you are demonstrating:

You understand of all the information given to you and all of your questions have been answered to

your satisfaction

You are aware of the physical and psychological changes that will occur with gender affirming

hormones, including associated risks and side effects

That you have adequate knowledge on which to base an informed consent and wish to progress with

treatment on testosterone

Please take the time to read and consider the following points before signing:

1. I have read and understood this information sheet about testosterone

2. I understand the different ways testosterone can be given

3. I have been informed of the potential benefits of starting testosterone treatment

4. I have been informed of the potential risks and side effects associated with testosterone treatment

5. The option of preservation of my fertility has been discussed with me, and I am aware of the consequences of deciding against this

6. I have been given the opportunity to ask questions and participate in discussions above starting testosterone with my Clinician

7. I am aware of the requirement for life-long regular monitoring of testosterone treatment (blood tests and physical monitoring) by medical practitioners, either by gender specialists or my GP

8. My decision to commence testosterone has been made voluntarily

9. I understand I can stop treatment at any time without having to give reasons and that I will not be penalised

10. I am aware that starting testosterone treatment will bring about permanent changes to me. Should I decide to stop this treatment later on, some changes that have happened will not reverse

Person consenting: ___________________________ ________ ______________ Signature Date ___________________________ ______________ Name (PRINT) Clinician obtaining consent: ___________________________ ________ ______________ Signature Date ___________________________ ______________ Name (PRINT)