The condition of gender dysphoria (GD) is one of self-diagnosis, but ratified by a mental health professional experienced in matters of gender fluidity. Transition treatment is followed by maintenance treatment, perhaps after removal of the testes. The testes are powerful engines of hormone production, much more so than the ovaries.
In the treatment of the trans woman, there is the need to employ testosterone blockade in addition to the feminising oestrogens; this all in contrast to the simpler treatment of trans men. There is little comparison between oestrogen replacement in menopausal hormone therapy and transitional oestrogen. In using oestrogen for gender transition, it should be understood that the therapist is trying to effect a feminising change as opposed to replacement. I generally like to escalate the dose gradually, doubling the dose every three weeks, until I reach an arbitrary maximum. I usually prescribe oestradiol valerate (Progynova) in an initial dose of 2mg daily up to a maximum of 8mg at three-week intervals. At the three-month stage, I estimate levels to ensure what we are achieving objectively. Other oral oestrogens may be used, but ethinyloestradiol, although very cheap as an oral contraceptive and powerful, is best avoided in terms of the increased thrombotic risk.1 In fact, I see all oral preparations as having increased risk and so, at the six-month stage, when initial oestrogenisation and the testosterone blockade have been completed, I offer an oestrogen implant with which I may include 2–4mg of Progynova as a top-up, for a while at least. Not all practitioners are comfortable with implant therapy, but it works well in my practice at 50mg given every 5–6 months. The cheaper, but less potent, mode d’emploi is that of transdermal oestrogen.
Some patients like to access their own preparations from the internet. Progynon injections were popular, but have been discontinued in this country at least; in any event, the absorption curve of this injectable oestrogen is short and sharp and the irregular absorption is adverse. Some older women and those who are attempting partial transition may choose transdermal preparations, such as the patch (Estradot/Climara) or gels (Sandrena), that are readily available on the PBS. These may be used in ‘at risk’ patients (previous deep vein thrombosis, pulmonary embolism, or at risk for these) or in those who are simply older.
Feminising oestrogen is one side of the therapeutic approach, with the other side being suppression of testosterone by blockers, or in the vernacular, ‘T blockers’. In contrast to the function of ovaries producing oestrogen, the power of the testes to produce testosterone is extraordinary. While administered oestrogen may to some extent be effective, it will not achieve the required full suppression in conventional doses. There is some advantage in using tablet oestrogen, which is why I may continue oral together with implant therapy. Oral oestrogen exerts the so-called ‘first pass effect’, that is, direct stimulation of sex hormone-binding globulin within the liver. This decreases the concentration of free testosterone available to continue its masculinising effects. Strangely, not many endocrinologists seem to support or recognise the importance of this and it may be recognised in the PBS authority criteria for androgen scripts, which is a source of continuing frustration.
Oral oestrogen in excessive doses must be regarded as potentially thrombogenic and this should be clearly understood before commencing transition. It becomes quite difficult when a thrombosis or, even worse, a pulmonary embolus eventuates, to decide what hormone regime to choose. This can be one situation where premature castration can assist. Oral oestrogen may provoke gall bladder problems due to the increase in biliary viscosity. Other troublesome side effects, such as nausea and headache, are best managed by returning the dose to a minimum and then escalating gently.
The effectiveness of the combined medication is best judged on the criteria of breast soreness and development, together with suppression of penile erectile capacity; the desirability of this is reduced for those seeking ‘partial reassignment’. It is important to clarify that breast development takes time (think of a pubertal girl achieving development over a period of years). A degree of mood variability is to be expected (real girls do cry). After gender affirmation surgery, there is no need to continue T blockers, although some may continue a small dose to maintain suppression of facial hair growth. At this time, the dose of oestrogen may be reduced to a maintenance dose as in hormone replacement. Other T blockers, such as bicalutamide, can be used, but this is usually in conjunction with a gonadotrophic agonist for prostate cancer. Gonadotrophic agonists are used in the younger patient below the age of 18. Finasteride is a 5α-reductase inhibitor preventing the reduction of testosterone to the far more powerful dihydrotestosterone, mainly in the treatment of prostate cancer and the prevention of scalp hair loss in men. Blood testing of hormone levels may be desirable at intervals or when problems arise. It is appropriate to change doses and preparations one at a time so that apparent side effects can be accurately attributed. The choice generally lies between Aldactone (spironolactone or ‘spiro’) and Androcur (cyproterone acetate). Spiro is cheap, but as a diuretic and hypotensive it can have undesirable side effects. Androcur is powerful and may reduce testosterone to a zero status, resulting in a loss of energy and mood upset often misdiagnosed as a depressive state (pseudodepression); this medication requires an authority script using a ‘streamliner’ number. I will usually start with a 100mg dose and then reduce to a more comfortable dose, while maintaining good suppression. Some patients seek a script for progesterone, perhaps to attempt a fuller mimic of the natural female cycle and to encourage breast development. This medication upsets moods needlessly and stimulates breast soreness, but not development.
At times, I will check blood tests for hormone screening, liver function, lipid profile and even glucose tolerance, as the insulin-sensitising effect of testosterone is lost. I am less certain of the need for prolactin estimation and screening mammography; a prostate-specific antigen can be done, but these tests should be symptom-led. I always do a bone density estimation, as bone density is hormone-dependent.
The treatment for trans men, in contrast, is much simpler, as there is no need to suppress ovarian function since this falls victim to the onslaught of the powerful administered testosterone. Initially, injectable testosterone, such as Primoteston (testosterone enanthate), is given in a 250mg dose every three weeks. This can be self-injected into the anterior thigh. While many will continue this indefinitely, as it is cheap, it doesn’t require an authority script and remains largely under the control of the individual. It does suffer the inconvenience of a short burst of the hormone rather than the smoothly maintained level of Reandron (testosterone undecanoate), given in a dose of 1000mg at an interval of 6–10 weeks as a deep injection into the buttock; prescription of Reandron requires an authority script if sought on the PBS. A recent sadness is that the PBS, after advice from andrologists and on the basis that cis men are using too much of the hormone, have made authority scripts far more problematic. It is important ensure a gender change is recorded with Medicare when the grounds for authority can be declared as being absence of testes, but still with certification from the appropriate specialist. Truly, life was not made to be easy.
One criterion of success is that menstruation is entirely suppressed. Any breakthrough bleeding raises the suspicion of inadequate dosage or the possibility of uterine pathology. Breast sensitivity is abolished and that makes breast-binding less uncomfortable. The emergence of beard growth is to be expected and the voice pitch becomes roughened before descending into a deeper male pitch. Side effects include an increase in haematocrit, although the risk of thrombotic events from this is less certain.2 There is a need to check liver function from time to time, as testosterone is potentially hepatotoxic. Oral testosterone (methyl testosterone) is to be avoided, as it is toxic enough to run the rare risk of primary hepatoma. Skin acne may be a problem best treated by a low-level continuous antibiotic, such as tetracycline or doxycycline. The injection sites may be sore for some days. It is important to exclude peanut allergy, as the carrier oils may be distantly related to peanut oil.
Administered testosterone should not be relied upon for effective contraception. If the individual is engaging in penile intercourse, barrier contraception or the use of a Mirena should be encouraged. Cessation of the hormone will permit a return of fertility within months. There is little need to store eggs in advance of transition, in contrast to the situation for trans women, who may elect to store some sperm as ‘straws’.
- Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: Extensive personal experience. Journal of Clinical Endocrinology & Metabolism 2008 Jan;93(1):19-25.
- Schreijer A, Reitsma P, Cannegieter S. High haematocrit as a risk factor for venous thrombosis. Cause or innocent bystander?Haematologica 2010 Feb;95(2):182-184.
Thank you Dr. this info is very helpful and the way you expose how hormones as hrt work in a more detailed and realistic way.
Exactly, what blood analysis îs necesar after starting hrt. I intend to start with bicalutamida and cyclo progynova. 44 years. Thank you