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ANTIANDROGENS, GnRH AGONISTS AND ORCHIDECTOMY

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ANTIANDROGENS, GnRH AGONISTS AND ORCHIDECTOMY

הודעה  Other life style on 15/12/2007, 7:22 pm

HRT - Transgender Hormone Replacement Therapy

http://www.transgenderzone.com/research/hrt.htm
ANTIANDROGENS, GnRH AGONISTS AND ORCHIDECTOMY


Hormone treatment in pre-operative male-to-female subjects is normally supplemented by some form of antiandrogen treatment. While oestrogens and progestogens are to some extent antiandrogenic in themselves, a number of other methods exists to suppress the effects of androgens and make the feminising hormones more effective without having to administer the latter in unreasonably high doses. These treatments also, of course, cause a significant reduction in male sex drive (and indeed sexual function), which is generally considered highly desirable by transsexual subjects. There are three approaches to antiandrogen treatment:
1. Antiandrogen drugs.
2. GnRN (Gonadotropin-releasing-hormone) agonists. 3. Bilateral orchidectomy (castration).
These treatments are not applicable to patients who are post-operative, as their bodies will, by definition, be incapable of producing gonadal androgens. Adrenal androgens are produced in small amounts by both sexes, and no attempt should be made to suppress them unless a serum androgen test has indicated significant overproduction, as in cases of adrenal hyperplasia. In general it is considered unwise to administer antiandrogens to post-operative subjects (and indeed to severely hypogonadal subjects such as certain intersexed patients), as the small amount of adrenal androgens remaining in such subjects are necessary for normal functioning.
Antiandrogen Drugs
These drugs either inhibit gonadal androgen production, interfere with androgen receptor sites, or both. Most are likely to produce some side effects in effective doses; some patients cannot tolerate some or all antiandrogen drugs, in which case bilateral orchidectomy is likely to be a preferable treatment. The effect of these drugs on fertility and male sexual function is reversible to an extent, however (like feminising hormones) irreversible infertility may ensue after some months of treatment. All antiandrogen drugs, like feminising hormones, must be withdrawn prior to major surgery This may lead to a degree of reversion towards masculinity, which may be pronounced and disturbing in some patients.
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Androcur Cyproterone Acetate

הודעה  Other life style on 15/12/2007, 7:24 pm

Androcur Cyproterone Acetate
This drug (brand names Androcur, Cyprostat) is widely regarded as the antiandrogen of choice by practitioners in Europe (it is not approved in the USA). It is an androgen receptor antagonist and weak gonadal androgen production inhibitor;
normal dose is 50mg daily, which may be increased to 100 or in exceptional cases 150mg daily if required. In these doses there are some risks associated with the drug, particularly a heightened risk of thromboembolic disease or liver damage.
Carbohydrate metabolism changes are also reported; patients should receive regular blood tests (LFT and fasting glucose) and BP checks. Possible side effects include severe lassitude, loss of concentration and depression, also weight gain and nausea. Anecdotal reports suggest that the side effects can be lessened by taking the drug after meals; opinions differ as to the best time of day to take a single dose to minimise the tiredness effect: patients are best advised to experiment for themselves, though after lunch or after the evening meal seem to be the usual choices.
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Flutamide

הודעה  Other life style on 15/12/2007, 7:26 pm

Flutamide
This is a relatively new drug which has been used with success in some transsexual patients, particularly those who have experienced unacceptable side effects with cyproterone. There is relatively little clinical data available for this drug in transsexual patients. It is a strong androgen receptor antagonist. Like cyproterone it can be hepatotoxic, it can also have significant adverse haematological effects (reduced platelet, leukocyte or erythrocyte count) or cause hypertension, and it can also produce less serious side effects such as fluid retention. Regular LFTs and blood checks are advisable when using this drug. This drug also produces psychological side effects which can be severe in some patients. Depression, anxiety or nervousness can be extreme, and patients should be made aware of this possibility Lassitude, insomnia and gastrointestinal disturbances have also been reported. Typical dose is 250mg to 750mg daily (one to three 250mg tablets).
Spironolactone
This drug was originally developed as an antihypertensive/diuretic; it is also a weak androgen receptor antagonist. It is much less effective as an antiandrogen than cyproterone or flutamide, but can find use in patients who have hypertension or severe fluid retention, either pre-existing or as a result of hormone treatment. Side effects may include lassitude, loss of concentration, and various gastrointestinal problems. There is a risk of potassium retention. Doses range typically from 100 to 400mg daily.
GnRH Agonists
These drugs take a different approach to antiandrogens: they act on the pituitary, initially overstimulating it and then rapidly desensitising it to GnRH. The effect of this is that over a period of weeks, gonadal androgen production is greatly reduced. Their principal advantages are that they are generally fullly reversible in their effects, which makes them a useful treatment in adolescent subjects where it is desired to stall the changes of puberty but not desired to induce permanent feminisation until the subject is older; and that they do not carry the risks of thromboembolic disease associated with antiandrogens. This can be particularly useful when hormones/antiandrogens are withdrawn prior to surgery - GnRH agonist treatment can be used to minimise the reversion to male biochemistry that many transsexual subjects find deeply disturbing. GnRH agonists do carry risks of significant side effects and should be used with great caution. There is as yet relatively little clinical data on the use of these substances in transsexual subjects, particularly in long-term use.
Nafarelin
Acetate Normally administered as a nasal spray (typical dosage 1600l.tg daily). May cause depression, insomnia. skin problems and other side effects. Being administered daily, the drug can easily be withdrawn should side effects occur.
Goserelin Acetate
Administered as a depot (i.e. time-release) injection (typically 3.6mg monthly). Reported adverse effects include heart failure, obstructive pulmonary disease and severe allergic reactions as well as more minor side effects such as lethargy and nausea. In view of the fact that it is a depot injection, this drug should be treated with caution as it cannot be rapidly withdrawn should problems occur.
Leunrorelin Acetate
Similar to Goserelin Acetate, with a typical dose of 3.75mg every 4 weeks. This drug has been used to good effect in adolescent subjects. Allergic reactions and other side effects have been reported.
Bilateral Orchidectomy
Orchidectomy offers several advantages over antiandrogen or GnRH-agonist therapy: After orchidectomy, the patient is endocrinologically equivalent to a post-operative subject. This has clear safety advantages especially in patients thought to be at elevated risk of thromboembolic events. Some patients report transient lethargy as their body adapts to the loss of androgens, but all the side effects associated with antiandrogens or GnRH agonists are eliminated. There are some disadvantages to orchidectomy such as irreversibility and shrinkage of scrotal tissue. Bilateral orchidectomy normally requires a referral from a psychiatrist; some surgeons may require a second opinion from an independent psychiatrist.
http://www.transgenderzone.com/research/hrt.htm
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