As previously mentioned MTF transitions require a number of different hormones in order to start a feminising process on the male body:
Oestrogen (Estrogen) is the main feminizing hormone you can take. It will cause your skin to get softer, fat to accumulate lower on your body, make you accumulate more fat in general, induce breast growth, cause penis atrophy, Shrinkage of the penis due to the effects of hormones. reduce body hair, make your nails more brittle, increase blood clotting factors, and make you moody. Prolonged usage of estrogen will cause permanent infertility in about 9 months. (If you plan on taking estrogen strongly consider sperm banking.) Estrogen comes in many formats from plant-based, to synthetic, to extracted from horse urine. The natural plant estradiol versions seem to be better for you.
Progesterones are primarily used to induce breast ductal growth as well as to stabilize mood. Synthetic progesterones have a bad rap for causing depression---beware! If you experience any sort of prolonged depression definitely talk to your doctor.
You can get progesterones in pill format but one of the most popular pills uses a peanut oil suspension. For those allergeic to nuts and nut oils this means you wll have to find alternatives. If you do have a known nuts allergy ensure you inform both your doctor and endocrinologist.
Antiandrogens are used to reduce or eliminate testosterone. This helps reduce or reverse male pattern baldness, oiliness of your skin, reduces sperm count, reduces muscle mass, and can make you more mellow.
One of the more popular drugs is spironolactone or Aldactone. This drug is a potassium-sparing diuretic which is often used to treat high blood pressure and to curb the aggressive tendencies of its users. This means it makes you go to the bathroom a lot more and you have to begin watching out for taking in too much potassium (e.g. bananas, smoothies, power drinks) otherwise you could suffer heart failure. You'll also be a lot more thirsty. Spironolactone works to block the testosterone receptors as well as inhibit conversion of testosterone to dihydrotestosterone---the hormone primarily responsible for hair loss.
If you are questionning i.e. unsure if you are GID, you might want to request getting an antiandrogen because the effects of antiandrogens are generally completely reversible and will help stave off further masculinization indefinitely. Plus they help to reduce your blood pressure.
If you plan on sperm banking, definitely bank before using antiandrogens. They will greatly reduce the quantity and quality of your sperm.
Female to Male transitions require just one:
Testosterone is the masculinising hormone and is a steroid hormone from the androgen group. Testosterone effects can be classified as virilising and anabolic effect. Anabolic effects include muscle mass growth and strength. Increased bone density and stimulation of linear growth and bone maturation. Virilising effects, for FTM's, can include a deepening of the voice, facial hair growth and auxiliary hair. The clitoris can also be stimulated due to testosterone and may increase in size.
Below is a list of the different forms that each of the hormones are produced:
Table of contents:
Oestrogens
Oestrogens are responsible for the development of female secondary sex characteristics, so the main component of any hormone regime for a GID patient will be some form of oestrogen. Typically this is obtained either from combined oral contraceptives or oestrogen tablets intended for HRT in postmenopausal women.
The principal natural oestrogen produced by the ovaries in a natural-born premenopausal female is 17 beta-oestradiol. Numerous derivatives and metabolites exist and play specific roles in the female body. While some of the metabolites (e.g. oestrone, oestriol) may be used successfully in treating menopause symptoms in postmenopausal women, they are not suitable for GID patients; it is necessary to supply 17 beta-oestradiol or a synthetic replacement for it.
Oestrogen therapy must be continued for life in a post-operative subject, otherwise numerous problems can occur. In particular, several very severe cases of osteoporosis have been reported in post-ops who have discontinued their oestrogen treatment. 'Menopause-like' symptoms also occur if oestrogen is discontinued.
Oestradiol Valerate
This drug is equivalent to natural 17 beta-oestradiol. It is generally well-tolerated, and clinical data from postmenopausal women suggest it is safer than ethinyloestradiol for long-term use, with less risk of breast cancer, thromboembolic events or liver problems. It is not certain whether this improved safety applies in the high doses necessary for pre-op patients.
This is widely regarded as the oestrogen of choice for long-term maintenance in post-op patients due to its good safety record.
Oestradiol valerate appears to be less effective at inducing feminisation in pre-op subjects than ethinyloestradiol, probably due to its short serum half-life --- particularly, it appears to fare poorly when 'in competition' with endogenous male hormones; adequate results have been obtained with oestradiol valerate combined with an effective antiandrogen. Iif 'menopause-type' symptoms appear (hot flushes, night sweats etc) this can often be a sign that the dose is not sufficient to overcome the endogenous male hormones and a switch to ethinyloestradiol would probably be advisable.
Ethinyloestradiol
This drug is a synthetically-produced modification of natural 17 beta-oestradiol. The modified molecule is eliminated only slowly by the liver, giving it a far greater potency and much longer half-life than other oestrogens. It is generally well-tolerated, but appears to be less safe in very long-term use than oestradiol valerate.
Ethinyloestradiol is widely regarded as the oestrogen of choice in pre-operative subjects.
In post-op patients, this drug may still be used, especially for patients whose feminisation has not completed by the time they have GRS. . For long-term post-op use, oestradiol valerate is probably preferable.
It should be noted here that oestrogen overdosage may paradoxically cause vasomotor symptoms similar to those produced by insufficient oestrogen dosage. This is sometimes seen in post-op patients who are still on pre-op dosage, and if this effect is suspected then the oestrogen dosage should immediately be reduced to a typical post-op level. This effect is more likely with ethinyloestradiol than with other oestrogens due to its high potency, and consideration may be given to an early switch to oestradiol valerate if the problem persists.
Conjugated Natural Oestrogens (Premarin)
This drug is a mixture of various oestrogenic substances extracted from the urine of pregnant mares. It lacks the potency of ethinyloestradiol, and there is no evidence that it has any advantages over oestradiol valerate. Many patients dislike this drug because of ethical concerns over the manner in which it is produced. It is increasingly regarded as an outmoded treatment for patients. It is also more expensive than the synthetically-manufactured drugs.
Other Oestrogens
A number of other oestrogenic drugs exist, many of which have been tried in the past in patients. It has already been mentioned that metabolites such as oestrone and oestriol are not suitable for use in patients; other oestrogen derivatives exist but have no advantages over the three oestrogens listed above. Diethylstilboestrol has been used in the past, and while it certainly produces worthwhile feminising effects, its safety record contraindicates its use in subjects: many serious problems, including fatalities, have been reported.
Progestogens
Progestogens administered alone do not produce feminisation in a phenotypic male. However, progestogens are generally quite antiandrogenic and will often provide a useful degree of testosterone suppression in a pre-op patient, and more importantly when administered in conjunction with oestrogen, improve the feminisation attained compared to oestrogen-only therapy, particularly in terms of breast weight and texture.
One UK endocrinologist has claimed that progestogens have no effect in GID patients, however numerous studies both in the UK and elsewhere have demonstrated that this claim is false. Progestogens are now very widely used in conjunction with oestrogens in the treatment of male-to-female GID patients.
Progestogens may also lessen the risk of cancer associated with long-term oestrogen treatment, according to some studies in natural-born females. In addition, some patients report that progestogens affect them psychologically, particularly in terms of maintaining the libido. For all these reasons, it may well be desirable to continue with a low dose of progestogen post-operatively, even though there is no absolute need for it.
No reliable data exists regarding the incidence of breast cancer in GID individuals. Many are lost to followup and conceal their past after completing their treatment, and any instances of breast cancer in this group are likely to be recorded as occurring in normal women rather than post-op GID individuals. One researcher has claimed to find a significant excess of breast cancers among certain chromosomally-intersexed patients who have been reassigned to female.
A few patients experience androgenic effects from some progestogens, possibly including an increase in body hair. If this occurs, a different progrestogen should be tried. Similarly, if fluid retention occurs, a switch to an alternative drug will probably resolve it.
Types of Progestogens:
Medroxyprogesterone Acetate
This progestogen (trade name Provera) is normally used for treating irregular menstrual bleeding or endometriosis, and its safety record is good.
It is widely regarded as the preferred progestogen, at least when the patient is not using combined contraceptive pills as a low-cost source of oestrogen and progestogens. Some patients, however, report slight virilising effects including, occasionally, a return of some degree of male sexual function even in post-orchidectomy subjects, which can be found disturbing; it appears that a proportion of the drug may be metabolised into testosterone in some patients. Medroxyprogesterone acetate is generally less virilising than the testosterone-derived synthetic progestogens (e.g. norethisterone and levonorgestrel), but more virilising than dydrogesterone. If a patient experiences virilising effects with medroxyprogesterone acetate then a switch to dydrogesterone should be considered.
Dydrogesterone
This progestogen (trade name Duphaston) may be used as an alternative to medroxyprogesterone acetate. It is not metabolised into testosterone within the body, and is therefore free of the virilising effects which some patients experience from other progesterones. Conversely it may be less effective in maintaining libido than medroxyprogesterone acetate.
Dydrogesterone is regarded as the progestogen of choice when patients have experienced virilising effects from other progestogens.
Natural Progesterone USP
This drug, which is probably unavailable in the UK , has a small but vocal group of GID adherents in the USA , who claim that it is superior to other progestogens. The present authors have been unable to find any clinical data to support this claim; while it appears to be free of virilising effects, first-pass effects are liable to make it relatively ineffective relative to dydrogesterone, which is also non-virilising.
The main problem with 'Natural Progesterone' is that it is largely destroyed by the digestive tract and liver upon ingestion, so very large doses (hundreds of milligrams) are used. Since the precise percentage of the drug metabolised in this way is variable and unknown, the actual serum levels obtained are unpredictable.
Synthetic Progestogens
This heading covers substances such as levonorgestrel and norethisterone, which are usually found in combined contraceptive tablets, usually with ethinyloestradiol.
Contraceptive pills provide a useful low-cost source of feminising hormones for patients who have to pay for their own medications, but of course the patient is limited to the combinations of substances available, and cannot 'mix and match' as one can with separate oestrogen and progestogen drugs.
Care should be taken with some preparations (for example, Brevinor) as they contain too high a ratio of progestogen to oestrogen, so that taking enough tablets to obtain a suitable dose of oestrogen would result in a dangerously high intake of progestogen.
One combined tablet that has been used widely in the treatment of GID patients is Ovran. Most patients tolerate this well, and it generally produces satisfactory feminisation, but levonorgestrel appears (anecdotally) to give more frequent problems with water retention, hypertension and weight gain than medroxyprogesterone acetate. Safety fears have also been raised in the past about levonorgestrel-based contraceptive implants.
Some patients experience virilising effects with norethisterone or levonorgestrel, which may impair the feminising effects of oestrogen. If this is suspected then an alternative progestogen should be tried.
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.
Type of Antiandrogens:
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.
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.
Flutamide
This is a relatively new drug which has been used with success in some GID patients, particularly those who have experienced unacceptable side effects with cyproterone. There is relatively little clinical data available for this drug in GID 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.
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.
Finasteride
This drug is not suitable as a general antiandrogen, but is mentioned here as it can be useful in countering male-pattern baldness in GID subjects. Classed as an androgen conversion inhibitor, it blocks the conversion of testosterone to DHT.
It is generally free from significant side effects, but does not appear to affect male sex drive.
Testosterone
'Depot' drug formulations are created by mixing a substance with the drug that slows its release and prolongs the action of the drug. The two primarily used forms in the US are the testosterone esters testosterone cypionate (Depo-Testosterone) and testosterone enanthate (Delatestryl) which are almost interchangeable. Enanthate is purported to be slightly better with respect to even testosterone release, but this is probably more of a concern for body-builders who use the drugs at higher doses (250-1000 mg/week) than the replacement doses used by transgender men (50-100mg/week.) They are mixed with different oils, so some individuals may tolerate one better than the other. Enanthate costs more than cypionate and is more typically the one prescribed for hypogonadal males in the US. Cypionate is more popular in the US than elsewhere (especially amongst bodybuilders.) Other formulations exist but are more difficult to come by in the US. Sustanon is a formulation that mixes shorter acting and longer acting testosterone preparations that gives more even levels of testosterone with injections given every three weeks. A newly marketed formulation of injected testosterone available in Europe, Nebido (testosterone undecanoate in oil) provides significantly improved testosterone delivery with far less variation outside the eugonadal range than other formulations with injections required only four times yearly. However, each quarterly dose requires injection of 4ml which may require multiple simultaneous injections.
The adverse side effects of injected testosterone esters are generally associated with high peak levels in the first few days after an injection. Some side effects may be ameliorated by using a shorter dosing interval (weekly or every ten days instead of twice monthly with enanthate or cypionate.) 100 mg weekly gives a much lower peak level of testosterone than does 200 mg every two weeks, while still maintaining the same total dose of androgen. This benefit must be weighed against the discomfort and inconvenience of doubling the number of injections.
Injected testosterone esters should be started at a low dose and titrated upwards based on trough levels (blood levels drawn just before your next shot.) A trough level of 500 ng/dl is sought. (Normal range for a biological male is 290 to 900 ng/dl.)
A newer form of injected testosterone, Nebido (testosterone undecanoate in oil) provides better testosterone delivery with much less variation outside the normal male range, with injections required only every twelve weeks. However, each quarterly dose requires injection of 4ml which may require multiple simultaneous injections. Nebido is also much more expensive and currently unavailable in the United States.
Transdermal
Both testosterone patches and gels are available. Both approximate normal physiological levels of testosterone better than the higher peaks associated with injection. Both can cause local skin irritation (more so with the patches.)
Patches slowly diffuse testosterone through the skin and are replaced daily. The cost varies, as with all medication, from country to country, it is about $150/month in the US, and about 60 Euros in Germany.
Transdermal testosterone is available in the United States under the brand names Androgel and Testim. Both are absorbed quickly when applied and produce a temporary drug depot in the skin which diffuses into the circulation, peaking at 4 hours and decreasing slowly over the rest of the day. The cost varies, as with all medication, from country to country, it is about $150/month in the US for either brand name drug. However, certain pharmacies are able to compound the drug more cheaply.
Transdermal testosterone poses a risk of inadvertent exposure to others who come in contact with the patient's skin. This is most important for patients whose intimate partners are pregnant or those who are parents of young children as both of these groups are more vulnerable to the masculinizing effects of androgens. Case reports of significant virilization of young children after exposure to topical androgen preparations (both prescription and 'supplement' products) used by their caregivers demonstrates this very real risk.
Testosterone pellets
6-12 pellets are inserted under the skin every three months. This must be done in a physicians office, but is a relatively minor procedure done under local anesthetic. Pellets cost about $20 each, so the cost is greater than injected testosterone when the cost of the physician visit and procedure are included. The primary advantages of Testopel are that it gives a much more constant blood level of testosterone yet requires attention only four times yearly.
Oral
Not frequently used in the US, sometimes used in Europe. Once absorbed from the GI tract testosterone is shunted (at very high blood levels) to the liver where it can cause liver damage and worsens some of the adverse effects of testosterone - lower SHBG levels, lower HDL (good) cholesterol. In addition, the ‘first pass’ metabolism of the liver also may result in testosterone levels too low to provide satisfactory masculinization and suppress menses. The safest of the oral formulations is Andriol (testosterone undecanoate) which is not available in the US.
Sublingual/Buccal
In 2003 the FDA approved a buccal form of testosterone (Striant®.) Sublingual testosterone can also be made by some compounding pharmacies. Cost for Striant® is greater than other formulations ($180-210/month.) Testosterone is absorbed through the oral mucosa and avoids the 'first pass metabolism' in the liver which is cause of many of the adverse effect with oral testosterone. The lozenges can cause gum irritation, taste changes, and headache but most side effects diminish after two weeks. The lozenge is 'mucoadhesive' and but be applied twice daily.
