Hormone specific FAQs for primary care clinicians

Hormone therapy is often used in patients with gender incongruence to alleviate gender dysphoria and produce either masculinising or feminizing effects.

Indigo Gender Service is commissioned by NHS England to assess, diagnose and recommend treatment plans including hormone therapy.

Shared care protocols via the Greater Manchester Medicines Management Group have been produced to support primary care clinicians across Greater Manchester with initiation, monitoring and titration of hormone therapy following an individualised and personalised care plan. These can be found here: http://gmmmg.nhs.uk/html/gmmmg_app_scgs.php

These FAQs and the embedded links to further information will hopefully answer many of the questions around the commonly used hormones in trans and non-binary healthcare. For further clinical advice please contact indigo.advice@nhs.net


Testosterone

Testosterone is the most commonly used hormone to achieve masculinising effects. It is given as either a topical gel or intramuscular injection.

Gels can take longer than injections to achieve masculinizing effects but they are easily stopped if there are any significant side effects or if it is not tolerated by the patient. Lower doses can be given and dose adjustments can also be made easily. In some patients it may be better to start with a gel before considering transfer over to injectable testosterone. Gels may be preferable for some patients who have needle phobias or do not want injections. Gels can be difficult to apply especially if multiple pumps are needed.

The most commonly testosterone preparations are:
Gels

  • Testogel® pump (1 pump = 20.25mg) 2 – 5 pumps daily usually applied in the morning.
  • Bloods taken 4 – 6 hours after application aiming for upper ½ of local male reference range.
  • Tostran® pump (1 pump = 10mg) 5 – 10 pumps daily usually applied in the morning.
  • Bloods taken 4 -6 hours after application aiming for upper ½ of local male reference range.

Injections

  • Sustanon® 250mg/1ml given IM every 2 – 4 weeks aiming for a trough level in the lower 1/3 of the local male reference range.
  • Nebido® 1g/4ml given by deep IM injection every 10 – 14 weeks (after loading dose) aiming for a trough level in lower 1/3 of the local male reference range.
  • Trough levels should be taken just before the next injection is given and doses adjusted according to results.

Many people self-inject Sustanon® usually into the anterolateral thigh. Preference should be discussed with each patient and they should be shown how to safely self-inject by a primary care clinician. Indigo has a specialist nurse who can show patients how to self inject and we can give needles and syringes, but we ask that their primary care clinican prescribe a sharps bin.

Nebido® is not suitable for self-injection due to the volume and requirement of a deep IM injection, this should be administered by a primary care clinician, usually a practice nurse.

For the majority of people on testosterone cessation of menses will occur. However, testosterone can cause virilisation of a foetus so contraception should be discussed if there is penis in vagina intercourse. Suitable options include the progesterone only pill, implant or coil. Oestrogen based contraception is often not wanted by trans men.

If testosterone alone does not stop periods and this is causing distress or dysphoria then other additional options include the progesterone only pill, cyclical medroxyprogesterone or GnRH analogues if there is no underlying gynaecological pathology.

It is important to monitor for polycythaemia. This is more common with injectable forms of testosterone especially Nebido®. Haemoglobin of >18.5 g/dl and / or haematocrit > 0.52 L/L require either dose or route modification. Some patients require venesection to lower their haemoglobin or haematocrit to prevent thrombosis.
Cardiovascular risk factors should also be monitored annually including BMI, blood pressure, lipid profile and QRisk where appropriate. Primary prevention advice and treatment should be given as per standard NICE guidance https://www.nice.org.uk/guidance/cg181

Testosterone will reduce fertility and gamete storage should be discussed prior to treatment. Referral for gamete storage is done via the patient’s own primary care clinician with no need for an IFR if the patient is under 42. Further information can be found at - https://gmeurnhs.co.uk/Docs/CCG%20Manchester/Manchester%20Assisted%20Conception%20Policy.pdf

Fertility can return on stopping testosterone but this is variable and more research is needed. Trans men have become pregnant after stopping testosterone therapy.

Further information on gamete storage for trans and non-binary people can be found at - https://www.hfea.gov.uk/treatments/fertility-preservation/information-for-trans-and-non-binary-people-seeking-fertility-treatment/

No, it is usually recommended that a patient is on testosterone for 6 - 12 months prior to chest reconstruction or ‘top’ surgery as it is commonly known. Testosterone does not have to be stopped prior to any other types of surgery.

Facial and body hair growth, scalp hair loss, voice deepening and clitoral enlargement are irreversible effects of testosterone therapy.

Some effects of testosterone such as increased muscle mass, body fat redistribution, acne and vaginal atrophy are reversible on stopping treatment.

Yes, if a patient decides they want to continue lifelong then they should be able to. Monitoring is important and dose or interval adjustments may be needed on an individualised basis. Cardiovascular health should be monitored and treated accordingly.

There are some potential drug interactions with testosterone including:

  • Warfarin – anticoagulant effect may be increased
  • Insulin and antidiabetic drugs – testosterone may improve glucose tolerance and reduce the need for diabetes medications.
  • Corticosteroids or ACTH – testosterone may enhance oedema formation and caution is needed in cardiac and hepatic disease.

This list is not exhaustive and the BNF should be checked for comprehensive information.

Potential contraindications include:

  • Known hypersensitivity to testosterone or any of its excipients
  • History of breast or endometrial cancer
  • Liver tumours
  • Unstable coronary heart disease

Testosterone should also not be given in pregnancy or breastfeeding.

Once stable on a dose and formulation, the patient should have bloods twice a year. Every 6 months for testosterone and annually for FBC, LFTs, lipid profile. Monitoring may need to be more frequent if a patient has underlying comorbidities. Indigo will be able to give advice and support regarding monitoring.

Further information on doses and monitoring can be found on the prescribing policy for hormone therapy between primary care prescribing clinicians and Indigo Gender Service.


Oestrogen

Oestrogen is the mostly commonly used hormone to achieve feminising effects. It is given as a gel, tablet or patches. It is not given in combination with progesterone as this does not have any additional feminizing effects and may increase side effects.

Oestradiol not ethinyloestradiol is used to lower the risk of VTE.

Patients may have a preference for a particular formulation or there may be a medical reason to use a certain mode of administration. Patches are often used if there is a higher risk of VTE as the risk of clot formation is lower than with tablets. Side effects such as nausea may make tablets difficult for some patients.

The most commonly used preparations are –

  • Progynova® or Elleste Solo® tablets 2 – 8mg daily (dose can be divided) aiming for levels of 400-600 pmol/l. Blood samples to be taken before morning dose.
  • Sandrena® or Oestragel® starting at 0.5 – 6mg daily aiming for levels of 400 – 600pmol/l. Blood samples taken 4 – 6 hours after gel application.
  • Everol® or Progynova® patches 50 – 400mcg / 24 hours aiming for levels of 400 -600 pmol/l. Blood samples taken before dose titrations or the next patch is due.

Thromboembolic and cardiovascular disease are potential risks especially if there are additional risk factors. The VTE risk is four times higher than women not taking oestrogen and most occur within the first 2 years of treatment.

Cardiovascular risk factors should also be monitored annually including BMI, blood pressure, lipid profile and QRisk where appropriate. Primary prevention advice and treatment should be given as per standard NICE guidance https://www.nice.org.uk/guidance/cg181

Changes in lipid profiles and liver function tests can also occur and monitoring is important. There is a higher incidence of gallstones.

Oestrogen will reduce fertility and gamete storage should be discussed prior to treatment. Referral for gamete storage is done via the patient’s own primary care clinician with no need for an IFR if the patient is under 42. Further information can be found at - https://gmeurnhs.co.uk/Docs/CCG%20Manchester/Manchester%20Assisted%20Conception%20Policy.pdf

Further information on gamete storage for trans and non-binary people can be found at - https://www.hfea.gov.uk/treatments/fertility-preservation/information-for-trans-and-non-binary-people-seeking-fertility-treatment/

Due to the increased risk of VTE oestrogen is often stopped prior to surgery and for a short time afterwards. This reduces the risk of VTE. Practice varies internationally and there is no universally agreed guidance regarding this. Risks and benefits must be discussed with the patient. More research is needed in this area to develop best practice guidelines.

Breast growth is irreversible. Reduced testicular volume, sperm production, erectile dysfunction and spontaneous erections have variable amounts of reversibility.

Some effects such as softening of the skin, body fat redistribution, reduced muscle mass and slowed growth of facial and body hair are reversible on stopping oestrogen.

Yes, if a patient decides they want to continue lifelong then they should be able to. Monitoring is important and dose or interval adjustments may be needed on an individualised basis.

Cardiovascular health should be monitored and treated accordingly.

There are some potential drug interactions with testosterone including:

  • Enzyme inducing medications - the metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (e.g. barbiturates, phenytoin, primidone, carbamazepine) and anti-infectives (e.g. rifampicin, rifabutin, nevirapine, efavirenz) and possibly also felbamate, griseofulvin, oxcarbazepine, topiramate and products containing the herbal remedy St. John's Wort (Hypericum perforatum).
  • HIV medications - when co-administered with sex hormones, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors , including combinations with HCV inhibitors, can increase or decrease plasma concentrations of oestrogen. The net effect of these changes may be clinically relevant in some cases. Therefore, the prescribing information of concomitant HIV/HCV medications should be consulted to identify potential interactions and any related recommendations.
  • Strong and moderate CYP3A4 inhibitors - such as azole antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of oestrogen.

This list is not exhaustive and the BNF should be checked for comprehensive information.

Potential contraindications include:

  • Active or recent arterial thromboembolic disease including angina or myocardial infarction
  • History of breast cancer
  • History of venous thromboembolism
  • Active or recent arterial thromboembolic disease
  • Oestrogen dependent cancer
  • Thrombophilic disorders
  • Acute or active liver disease

Once stable on a dose and formulation patients should have bloods annually for FBC, LFTs, lipid profile. Monitoring may need to be more frequent if a patient has underlying comorbidities. Indigo will be able to give advice and support regarding monitoring.

Further information on doses and monitoring can be found on the prescribing policy for hormone therapy between primary care prescribing clinicians and Indigo Gender Service.

 


GnRH Analogues (Hormone Blockers)

In adults GnRH analogues are mainly given to trans women or non-binary people where oestrogen alone does not suppress testosterone levels in to the female reference range usually < 3. They can also be used in trans men if testosterone alone does not stop menstrual bleeding or cyclical cramping.

They are given by injection and initially usually given monthly for 2 months and if well tolerated 3 monthly long term or until genital reconstructive surgery where the testes are removed.

The most commonly used in trans health due to its side effect profile and cost effectiveness is Decapeptyl® but all of the GnRH analogues are effective.

  • Triptorelin (Decapeptyl® SR) - intramuscular injection
  • Goserelin (Zoladex®) - intramuscular injection
  • Leuprorelin (Prostap®) - subcutaneous or intramuscular injection

These are best administered by a trained healthcare professional such as a practice nurse.

They are normally very well tolerated and the effects are reversible on stopping treatment. A significant testosterone flare does not usually occur as the patient will already be taking oestrogen and have a partially suppressed testosterone level. Changes in mood and worsening of depression can happen. Rarely GnRH analogues may unmask a previously unknown pituitary adenoma presenting with headaches, vomiting and visual change.

Reversible infertility will occur with GnRH analogues alone but as these are given alongside hormone therapy which can lead to irreversible changes to fertility gamete storage should be discussed as above prior to starting treatment.

No, for genital reconstruction or ‘bottom’ surgery as it is commonly known it is important to keep testosterone suppressed. Oestrogen is often stopped to reduce the risk of VTE but GnRH analogues can be continued. Once the testes have been removed there is no need to continue GnRH analogues.

There are some potential drug interactions to be aware of:

  • Drugs which raise prolactin levels should not be prescribed concomitantly as they reduce the level of GnRH receptors in the pituitary
  • Co-administration with drugs affecting pituitary secretion of gonadotropins, caution should be exercised and it is recommended that the patient's hormonal status be supervised.

This list is not exhaustive and the BNF should be checked for comprehensive information.

Hypersensitivity to GnRH (gonadotropin releasing hormone), its analogues or to any of the excipients is the only contraindication.

Caution should be given in:

  • History of depression
  • Metabolic bone disease
  • Diabetes (particularly leuprorelin and goserelin)
  • Risk of osteoporosis (leuprorelin)
  • Hypertension (Goserelin)

No additional blood monitoring is needed over the investigations that are being undertaken for either oestrogen or testosterone. Blood pressure and BMI should be checked every 6 months.