Hormone Therapy - Feminising

Management of Gender Clients

Hormone therapy for “Male-to-Female” (MtF) clients:

A Resource for General Practice

Hormone therapy (when client has testes)

General Principles

The goal of cross sex hormone therapy is twofold: to reduce endogenous hormone levels and hence the secondary sexual characteristics of the individual’s assigned (birth) gender, and to induce characteristics of the new gender by direct stimulation of target receptors. Medical conditions that can be exacerbated by hormone depletion or cross-sex hormone treatment should be evaluated prior to initiation of treatment. The cross-sex hormone level should be maintained as close as possible to the physiological range of the desired gender.

Oestrogen therapy

A. Principles

Oestrogen works by direct stimulation of target receptors. It also provides some suppression of LH.

The level should ideally be in the follicular range. Only oestradiol formulations can be assayed for oestradiol level. Note that ethinyloestradiol and conjugated equine oestrogens are not measured in the lab. The adequacy of their doses is assessed indirectly by checking the suppression of testosterone.

B. Formulations

  1. HRT oestrogen-alone preparations are a good option. They avoid the unwanted side effects of progesterones while being available on the PBS. A typical dose would be Progynova or Zumenon 2mg, two to four daily, or Climara patches 100ug, one or two per week, or Sandrena Gel one or two sachets daily. The correct dose is the lowest dose that suppresses testosterone into or just above the female range, gives a normal follicular level of oestradiol and some suppression of LH. Transdermal oestradiol carries the lowest risk of thromboembolic disease, and may pose less cardiovascular risk for older clients.

  2. Contraceptive pills on the PBS such as Levlen ED, one daily, are cheap and potent. However, the Levonorgestrel may exacerbate facial hair in some people. Pills containing an anti-androgen are not PBS e.g. Diane-35, one daily. Ethinyloestradiol is the most thrombotic form of oestrogen, and should not be used in biological males over 40, or those with any thrombotic risk factor such as smoking or obesity. Many gender clinics do not use COCs at all for cross-sex therapy, due to safety concerns.

  3. Injectables are available from compounding pharmacies, have a short shelf life and may have variable efficacy.

C. Contraindications and Precautions

These are similar to the contraceptive pill.

A past history of thromboembolic disease carries a high risk. Cyproterone and progesterones may not be free of vascular risk either, but Spironolactone is considered safe. If the DVT/PE history is not clear, confirmation of the history and quantification of the risk should be sought from a vascular specialist. In the case of known DVT or PE, it can be appropriate to proceed with transdermal oestrogen if the burden of gender dysphoria is greater than the iatrogenic risk.

Known Thrombophilias, or a family history of clots, are a relative contraindication. This risk is highest in the first year of use, but it also increases with age. Again, use transdermals.

All clients on oestrogen should be taught to recognise a possible DVT.

A history of male breast cancer would carry a high risk.

Other medical conditions which have a moderate-high risk of adverse outcomes include macroprolactinoma, coronary artery disease, cerebrovascular disease, severe liver dysfunction, focal migraine.

Conditions which should be treated before commencing oestrogen include hypertension and morbid obesity.

Pre-treatment bloods should include baseline Testosterone, fasting BSL and lipids, LFTs.

Abnormal LFTs should be investigated. If the cause is known, e.g. Hepatitis C, and the enzymes are less than 3 times the upper limit of normal, oestrogen therapy is safe. Favour transdermals. Oral oestrogen has been implicated as a cause of non-steatotic hepatitis.

Diabetes is not a contraindication, but monitor carefully, and favour transdermals.

D. Other side-effects

Symptomatic side effects are not a big problem in this highly motivated population. The occasional patient cannot take oral oestrogen because of nausea. Oestrogen may cause a bit of weight gain; address lifestyle factors.

Oestrogen may amplify feelings but it does not create them. If the client reports “mood swings” this is probably related to their situation, and may indicate depression.

Anti-androgens

A. Principles

Most hormone regimes include an anti-androgen with an oestrogen. Anti-androgens work by:

  1. interfering with binding of testosterone to receptors in targets organs e.g. facial hair (Spironolactone, Cyproterone)

  2. interfering with the production of testosterone (Spironolactone, Cyproterone)

  3. interfering with the metabolism of testosterone (Finasteride in male hair areas)

  4. suppressing LH (Cyproterone)

Anti-androgens are used primarily to manage facial and body hair; Cyproterone is also useful for those clients distressed by erections. As anti-androgens are reversible, they can be useful alone for clients having counselling prior to commencing oestrogen.

B. Formulations

  1. Spironolactone at a dose of 100mg bd is cheap and effective. The maximum effect plateaus at 9 months. The principal side effect is cramping due to losing salt and water. Those experiencing cramps need to increase their salt and water intake, take Calcium and Magnesium, do more stretches, or reduce their dose. Urinary frequency can also limit the use of Spironolactone.

Combination with an ACE inhibitor can cause hyperkalaemia and should be avoided.

  1. Cyproterone Acetate is a little more potent as it also suppresses LH, but it can cause depression or low energy. It has not been adequately studied in this population, but there is a theoretical risk of DVT. There have been occasional reports of hepatic failure from Cyproterone Acetate in patients taking it for prostate cancer. In practice, it does not seem to cause liver problems but it would be prudent to do periodic LFTs.

  2. Finasteride can be used as in other natal males, to treat male-pattern baldness; presumably there is a little testosterone still circulating in the presence of another anti-androgen.

 

Progesterones

Their use is controversial. They function as anti-androgens and can be used to suppress the gonadal axis. Some clinicians use them to help increase breast size, but this does not always work. Unknown genetic factors are at work in the response. If used, they can be pulsed, e.g. Medroxyprogesterone Acetate 10 mg daily for 2 weeks on, then 2 weeks off, as progesterone best acts as a breast stimulant when first started, rather than in continuous use.

Side effects of progesterones depend on the progesterone, and can be extrapolated from the COC literature.

The long-term vascular effects of progesterones are unknown, but the HRT data suggests caution, and they are best avoided in clients over 40. Compounded Micronised progesterone (eg from Stenlake) may be safer.

 

Typical MtF Regime

The client commences Spironolactone 100mg one daily for a week. This can be commenced at any time in the exploration/assessment/transition process. If there are minimal side effects, increase to 100mg bd. Check electrolytes on this dose.

If the client is ready for hormone therapy, commence Oestradiol tablets (Progynova, Zumenon) 2mg bd. Alternatively, commence Sandrena Gel one daily or a 100ug patch.

If an increase in oestrogen dose is required, this may be in the form of Progynova 2mg, three or four daily. Another effective strategy: leave the oral dose at 4 mg daily and add a topical such as Sandrena one daily, or a 100ug patch. Alternatively, if using a topical alone, double the dose.

Monitoring hormone therapy in MtF

Expected timeline

The rate and degree of change depend on the dosage, the age of the client, and the client’s intrinsic responsiveness. The latter is probably genetically determined.

Typically within the first 1-6 months there is a redistribution of body fat, decrease in muscle mass, softening of skin and decreased oiliness, breast growth, decreased testicular volume, decreased libido and decreased spontaneous erections.

Breast growth and redistribution of body fat attain their maximum at 3 years.

Decreased terminal hair growth is noticeable at 6-12 months and continues over several years, but cannot be eliminated by hormones alone.

Many changes are reversible if hormones are ceased. However breast tissue remains.

It is not known when sperm production ceases, and when this may become irreversible.

Bloods

After 3-4 weeks check serum oestradiol, LH, testosterone and FAI (or calculated free Testosterone).

These should ideally be in the physiological range. If so, clinical effects will happen over time.

If results are nearly physiological, bloods again in 3 months may confirm that the client is on an adequate dose. If hormone levels are somewhere between male and female ranges, increase the oestrogen.

If there is not full suppression of testosterone but the patient is completely happy with the clinical result, leave well alone unless this is a teenager in whom puberty may not be complete.

If there is good clinical effect but the oestradiol level is very low, suspect the type of assay, and check with the lab.

LFTs, BSL and lipids are usually measured annually, but this depends on the patient’s general risk factors. Some clinics measure 6 monthly.

Prolactin should be measured annually in early transition but the mild elevations usually found are benign. Levels several times normal require investigation.

 

General Surveillance

Breast screening should follow female guidelines, especially in clients who have been on therapy for decades, as breast cancer risk appears to be related to length of time on therapy. It is also higher in 47, XXY males, some of whom will be found in the transgender population.

A very small number of cases of prostate cancer in MtFs have been reported in the world literature. They have been older patients who have been on oestrogen for decades; it is not known why the prostate cancer “escaped”. The prostate is usually very small in clients on long-term oestrogen.

Consider doing a PSA and rectal exam in older natal males before commencing hormones, consistent with your screening policy.

Oestrogen lowers the PSA but it can still be tracked for increases.

 

Speech Therapy

  • In Brisbane Ms Kerry Ann Thornber ph: 07 3252 2383 has been helpful with voice training.

  • On line training is also available.

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Support

 

Follow-up

Follow-up appointments involve an awareness of the issues below, although not all will be addressed at once.

1. Hormone therapy

    a. positive effects

    b. side-effects or problems

    c. dose and timing

 2. Family situation

 3. Sexual relationships

 4. Work and training

 5. Symptoms of mood disorder/suicidal risk

 6. Substance use including smoking

 7. Management of lifestyle cardiovascular risk factors

 8. Transition issues such as

   a. facial hair management

   b. voice training

   c. cosmetic surgery

   d. change of gender marker on identity documents

Significant dates such as when the client commenced hormone therapy and when the client changed their identity documents should be clearly noted in the file.