Hormone management of trans men

Blog Managing trans people within a health service Join the discussion: www./blog Hormone management of trans men Jonny Coxon, GP and Clinical Assistant, Endocrinology; Leighton Seal, Consultant Endocrinologist, Gender and Identity Clinic, The Tavistock and Portman NHS Foundation Trust, London In this article the authors describe how hormonal treatments are used in trans men undergoing transition. The hormone regimens are explained and the vital role of primary care in managing ongoing prescribing and monitoring of treatment is also discussed. In healthcare, as in all spheres of life, we are all meeting more trans people. While more progress needs to be made, in some societies much more than others, many of those who in the past have battled in silence feel freer to live the lives they wish to and need to. As a result, increasing numbers of trans people will present to healthcare professionals in various stages of their transition. This is illustrated by the fact that referrals to gender identity clinics in the UK have doubled every five years since the late 1960s. Gender dysphoria is a recognised condition defined in DSM-V as a persisting difference between a person s expressed or experienced gender and the gender others would assign to him or her, with resultant significant distress or impaired functioning. 1 Of notable significance, the draft ICD-11 classification places gender incongruence outside the mental health section, replacing the current ICD-10 diagnosis of transexualism. 2 As practising clinicians, there are some aspects of care for trans people that may be unfamiliar. That said, the Facial hair growth following testosterone treatment may take up to six months to become apparent. Other changes like skin oiliness occur more quickly majority of general medical management for the trans population should, of course, not differ in any way from other patients. There have already been two excellent articles on transgender issues in this publication, one looking at general support for trans people in our practice, 3 and another looking at male-to-female genital reconstruction. 4 While the latter touched briefly on hormonal therapy, we will explore this subject in more depth in this and a subsequent article. We aim to clearly summarise some of the important considerations relevant to providing the optimal hormonal milieu for people to commence and maintain their physical transition. Hormonal treatment For trans men and women, the aim of hormone treatment is to suppress production of the sex hormones of a person s assigned gender, and replace them with those of the experienced gender. Thorough multidisciplinary assessment should precede the initiation of hormone treatment to evaluate an individual s biopsychosocial health, and baseline blood tests are an integral part of this. Science Photo Library 8 Trends in Urology & Men s Health September/October 2018

Transgender health It is also important to identify any intersex states or medical conditions that could have a bearing on the safety of hormone prescribing. Cross-sex hormone treatment is usually continued throughout a patient s lifetime, including after any genital reconstructive surgery, to prevent long-term complications such as heart disease or osteoporosis. As the various national contracts in the UK stand, GPs play an invaluable role in helping their patients travel along their transition journey, as the prescribing of hormone therapy is continued in primary care. Clear shared care agreements should be made available to support this process. The General Medical Council (GMC) has published succinct guidance which can be viewed online. 5 Its recommendations for co-operating with gender identity clinics include prescribing medicines recommended by a gender specialist for the treatment of gender dysphoria and following recommendations for safety and treatment monitoring. The GMC statement on prescribing for gender dysphoria is given in Box 1. The goal of hormonal therapy in trans men is to simulate natural male puberty, a process which can take two to five years to complete. 6 As expected, the mainstay of hormonal management here is testosterone therapy. In the majority of cases, the testosterone doses used are sufficient to suppress ovarian production, thereby achieving the dual aim of suppressing and replacing assignedgender hormones to aid transition. Physical and behavioural changes The various physical changes seen with testosterone therapy, along with expected timeframes, are summarised in Table 1. One of the most distressing features for trans men before treatment (menstrual bleeding) will usually cease early on through negative feedback on the pituitary. This most commonly occurs within two or three cycles. 6 There are, of course, implications for fertility. Trans men who think they may wish to have children should seek gamete storage before starting testosterone. Uncommonly, cessation of menses may take longer. In some individuals additional therapy may be required if bleeding continues after testosterone levels are confirmed in the target ranges. Our preferred options then are to recommend either medroxyprogesterone 10mg three times daily (probably associated with less clot risk than norethisterone) or a gonadotropin-releasing hormone (GnRH) analogue, such as threemonthly injections of 11.25mg triptorelin (Decapeptyl). These medicines should be stopped if the patient undergoes hysterectomy and oophorectomy. Another early change will be an increase in clitoral size. This is usually seen from around three to four months and stabilises around one year, reaching a typical length of 4 5cm. 7 This is usually not sufficient for penetrative intercourse. Vaginal atrophy develops over a similar time scale. Also developing quite soon after testosterone initiation are skin changes in the form of increased oiliness and acne. This can appear Box 1. GMC statement on prescribing for gender dysphoria in general practice 5 Once the patient has been discharged by a gender identity clinic or gender specialist, the prescribing and monitoring of hormone therapy can be carried out in primary care without further specialist input. From the patient s perspective, management in primary care is far easier, and there is no specific expertise necessary to prescribe for and monitor patients on hormone therapy. within a few months and will stabilise at around one to two years. A little later, from approximately six to twelve months, deepening of the voice will become noticeable, again becoming maximal over one to two years. 8 This move to a more masculine sound is irreversible. Some men find additional speech therapy helpful to consolidate the change. Facial and body hair will develop in a male pattern, with changes again seen from around six months, taking four to five years to complete. In genetically susceptible trans men, male pattern baldness may develop. Over a similar time scale, a more masculine body shape can also be expected. There will be an increase in lean mass with increased strength and muscle definition, and Effect Onset (months) Maximum (years) Skin oiliness/acne 1 6 1 2 Cessation of menses 2 6 - Clitoral enlargement 3 6 1 2 Vaginal atrophy 3 6 1 2 Fat redistribution 1 6 2 5 Increased muscle mass/ strength 6 12 2 5 Deepening of voice 6 12 1 2 Facial/body hair growth 6 12 4 5 Scalp hair loss 6 12 - Table 1. Physical effects seen with testosterone therapy, and expected timings Trends in Urology & Men s Health September/October 2018 9

Preparation Dose Frequency Monitoring method Target range, testosterone Maximum dose How to adjust, if needed Testosterone injections (short-acting) Sustanon or testosterone enantate Starting dose: 250mg (1ml vial) Dose range:150 250mg, 0.6 1ml 2 4 weekly Trough: just before an injection (same day) P eak: 7 days later Trough level: 8 12 nmol/l Peak level: less than 30 nmol/l 250mg every 10 days F ocus on trough level first and adjust dosing interval as needed to achieve target (usually by a week up or down). I f trough is in range but peak is high, reduce dose in 50mg steps Longer-acting injection Nebido (testosterone undecanoate) (has a loading phase) 1000mg (4ml vial) 6 15 weekly Trough: just before an injection (same day) 15 20nmol/L 1000mg every 6 weeks Adjust dosing interval as required (usually by a week up or down). Dose is not usually adjusted Testosterone gel (topical) Sachets:Testogel 50mg/5g Pump: Testogel 16.2mg/g (20mg per squirt) or Tostran (10mg per squirt) Starting dose: 40 50mg Dose range:20 100mg Daily, applied in the morning B loods taken 4 6 hours after gel application (ensure no gel on arms) 15 20nmol/L 100mg daily (2 sachets; 5 squirts of Testogel pump; 10 squirts of Tostran) A djust dose as required. Adjustments usually as steps of ½ sachets, or 1 2 squirts of pump Table 2. Testosterone therapy as used by the authors clinic a decrease in fat mass and hip to waist ratio. Common behavioural changes include increased libido, energy levels and general drive/motivation. Some trans men will also report an increase in aggressive behaviour, though this is not usually excessive. This mirrors changes seen with testosterone therapy in cis (non-trans) men. 9 Trans men usually describe feeling more settled as the various physical changes help to confirm their experienced gender role. Potential adverse effects of testosterone therapy Lipid profile and cardiovascular risk A recent meta-analysis of 29 studies concluded that there were small but significant aberrant changes in the lipid profile with testosterone treatment in trans men, with mean changes of: LDL-cholesterol + 0.46mmol/L, HDL-cholesterol - 0.22mmol/L and triglycerides + 0.24mmol/L. 10 It found minimal reports of myocardial infarction (MI), stroke, venous thromboembolism, and death events. It has previously been reported that MI rates in trans men are only about one third of the expected rate in cis men. 11 However, cardiovascular risk should be assessed and managed just as it would for any other patient. Polycythaemia Testosterone is well known to increase haematocrit through increased levels of erythropoietin. The resultant polycythaemia is not usually significant, but must be monitored for due to the increased thrombosis risk. We recommend seeking advice if the haematocrit rises above 0.54, when testosterone therapy may need adjusting. We advise halting therapy (temporarily) with results of 0.6 or higher. Cancer risk There is a theoretical risk of endometrial hyperplasia and potentially subsequent cancer through the action of low levels of oestradiol (converted from testosterone via aromatase) unopposed by progesterone. While current recommendations advise on a hysterectomy after two years, 6 or scanning every two years to assess endometrial thickness, the 10 Trends in Urology & Men s Health September/October 2018

Transgender health recent evidence in fact indicates endometrial thinning. 12 For cervical screening, the recommendation is to follow the same programme as for all those assigned as female at birth (while the cervix remains). It is important to remember that IT systems will not find these individuals for invitation purposes once their gender is changed. Patients therefore often have to present themselves for screening, unless practices have set their own internal recalls for them. Breast cancer risk seems to be very low, comparable to cis men. 13 Self-examination is still advised, including for those who have had chest reconstruction surgery, which is often not a full mastectomy. Bone density A reassuring recent meta-analysis found no significant impact of testosterone therapy on bone mineral density at any site in trans men. 14 Liver function While there have been historical concerns with high rates of liver. Recommended blood tests for monitoring dysfunction due to anabolic steroid use, modern protocols of testosterone therapy are associated with mild changes in liver function in only 4 7% of patients. 11 Testosterone therapy regimes and monitoring Prescribing of testosterone for trans men is, in many ways, similar to that for cis men treated for testosterone deficiency. Whilst Sustanon (a blend of four testosterone esters) is licensed for use in this transgender setting, the off-licence use of other medicines is very well established. We will usually recommend starting trans men on Sustanon to provide a quick and reliable onset of action that can be easily reversed should the need arise. Once stabilised, other options include using gels or the longer-acting testosterone undecanoate injection (Nebido). This choice often comes down to patient preference, although the latter two options tend to give more stable levels of testosterone, avoiding the potentially symptomatic fluctuations seen with Sustanon. In addition, gels Timing of blood tests: Sustanon / testosterone enantate: i) on the day of injection, just before injecting (trough): request testosterone, full blood count (FBC), fasting lipids, liver function tests (LFTs). ii) seven days later (peak): request testosterone only Nebido: on the day of injection, just before injecting (trough): request testosterone, FBC, fasting lipids, LFTs. No peak level needed Gels: four six hours after gel application: request testosterone, FBC, fasting lipids, LFTs. Remember to ensure no gel was applied to the arm from which blood is taken (or very high levels may result) When the dosing regimen of a preparation is changed, repeat blood tests (as above) need to be arranged: Sustanon / testosterone enantate: trough and peak around the time of the fourth injection after the adjustment Nebido: a trough level at the time of the third injection after the adjustment Gel: eight weeks after the adjustment Monitoring frequency: Once stabilised, bloods should be taken six-monthly for two years, then annually if still stable and with no concerns raised appear to be associated with lower rates of polycythaemia than injections. It is crucial that patients are regularly monitored, both clinically and biochemically, through blood tests. This should be continued after discharge from a gender identity clinic, usually on an annual basis once stabilised. While the risk of adverse effects is low, as outlined above, it is important that safety blood tests are included alongside monitoring of testosterone levels. Table 2 shows the forms of testosterone therapy recommended by our clinic, with outlining the advised monitoring. Conclusion Through a multidisciplinary approach, including a vital ongoing role for primary care practitioners, trans people can be safely and effectively medically managed through the early and later phases of their transition. Hormonal treatment for trans men will in most cases be straightforward and is often achieved with testosterone alone. There are low rates of adverse effects, provided simple monitoring is adhered to. Declaration of interests: none declared. References 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association, 2013. 2. World Health Organisation. ICD-11 (Mortality and Morbidity Statistics) Draft (https://icd.who.int/dev11/l-m/en; accessed 25 April 2018). 3. Wylie K, Wylie R. Supporting trans people in clinical practice. Trends in Urology & Men s Health 2016;8(6):9 13. 4. Rashid T. Mike to Michaela: male-tofemale genital reconstruction. Trends in Urology & Men s Health 2018;9(1):7 10. 5. General Medical Council. Trans healthcare (https://www.gmc-uk. org/ethical-guidance/ethical-guidance/ trans-healthcare; accessed 7 August 2018). Trends in Urology & Men s Health September/October 2018 11

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