Hormones

1. What are hormones, and how do they work?

Hormones are long-range chemical messengers of the body, manufactured and controlled by the endocrine system, hence the title of endocrinologist for hormone doctors.

The hypothalamus produces gonadotropin-releasing hormone (GnRH). This signals the anterior pituitary gland to synthesize and release luteinizing hormone (LH). To a lesser degree, GnRH also triggers the synthesis and release of follicle stimulating hormone (FSH). Subsequently, LH and FSH signal the gonads (ovaries in females, testes in males) to synthesize and release hormones that cause differentiation of the body tissue into female or male form: estrogens, progesterones, and testosterones. A small quantity of testosterones are also produced by the adrenal gland. Proportionally, females have more estrogens and progesterones than males. Males have more testosterones.

Estradiols are synthetic estrogen analogues. Estrogens and estradiols excite estrogenic receptors, causing the body to differentiate into female form and function. Natural and synthetic estrogens are hereafter referred to simply as estrogens.

Progestogens (or progestins) are synthetic progesterone analogues. Progesterones and progestogens excite progesteronic receptors, which in cooperation with estrogenic activity, cause the body to further differentiate into female form and function. Natural and synthetic progesterones are hereafter referred to simply as progesterones.

Various testosterones are collectively known as androgens. They excite androgenic receptors, causing the body to differentiate into male form and function. Natural and synthetic testosterones are hereafter referred to simply as androgens.

Anti-hormones can be useful in transsexual hormone therapy because they block hormone action or production. There are several mechanisms:

• Androgen receptor antagonist: blocks the action of androgens at certain receptor sites.
• Androgen conversion inhibitor: blocks the conversion of one type of androgen to another.
• Estrogen receptor antagonist: blocks the action of estrogens at certain receptor sites.
• GnRH agonist: Briefly over stimulates then effectively suppresses pituitary LH and FSH production.

Aggressive hormone therapy indirectly reduces natural gonadal hormone production by fooling the pituitary into thinking that there are plenty of hormones already in the body; consequently, the pituitary reduces the LH and FSH signals that stimulate the gonads.

Postnatally administered hormones do not cause development of primary sex organs (uterus, ovaries, vagina, testes, or penis) that are opposite those born with. However, postnatal contrasexual hormone therapy does cause development of secondary sex characteristics as described below.

2. What effect does female hormone therapy have on a male, and how soon?

The longer after puberty hormone therapy is started the less effective it is--but not a linear scale, e.g., results are considerably more dramatic in an 18 year old than a 28 year old, but results are not on the average dramatically different between a 38 year old and a 48 year old.

The following effects have been observed in varying degrees--anywhere from little to moderate--with extended treatment. With effective and continuous dosages, most of the changes that a particular body is genetically prone to start within 1 to 4 months, start becoming irreversible within 6 to 9 months, start leveling off somewhat within 18 months, and be mostly done within 3 years. The leveling may take longer if the testes are not removed. High levels of estrogen will cause faster development up to a point, but not better results in the long term than moderate levels of estrogen.

Fertility decreases. Sperm count drops rapidly. Sometimes it returns to almost normal if hormonal treatment is discontinued within the first couple of months, but permanent sterility can occur in as little as six months. This should not be counted on for birth control, because a miniscule sperm count might remain until the testes are surgically removed. Estrogens, progesterones, and gonadal androgen production inhibitors are the chemicals responsible for lowering fertility. It appears to the author that the other types of anti-androgens do not necessarily effect fertility--but one would be wise to take frequent fertility tests if one chooses to employ only the other types of anti-androgens with the intent of maintaining fertility.

Male sex drive and enjoyment decreases. Directly stimulated erections become infrequent and difficult to maintain. Spontaneous erections eventually stop. Semen secretion decreases, resulting in less intense or unobtainable ejeculatory orgasms. The testes and prostrate atrophy. The penile skin also shrinks if erections are not regularly encouraged.

Breast size increases. Typical growth is to one to two cup sizes below closely related females (mother, sisters). The growth is not always symmetrical--neither is it for females. Sometimes the aureoles and nipples swell, but generally not significantly, unless the body is less than a decade past puberty. Fat is redistributed. The face becomes more typically female in shape. Fat tends to move away from the waist and toward the hips and buttocks. Body hair growth (not including head, face, or pubic area) slows, becomes less dense, and may lighten in color. Many people also report the following effects, but they are not verified in any medical literature that the author has read:

• If exercise is not increased, some muscle tone is lost--especially from muscles that were not well-developed before hormone therapy. Outer skin layer becomes thinner, lending a finer translucent appearance and increased susceptibility to scratching and bruising. Tactile sensation becomes more intense.
• Oil and sweat glands become less active, resulting in dryer skin, scalp, and hair.
• Scalp hair becomes thicker, and male pattern baldness generally stops advancing. In some cases, a fine fuzz may grow back along the line of where scalp hair was recently lost--but only from the living follicles, not dead ones.
• Metabolism decreases. Given a caloric intake and exercise regimen consistent with pre-hormonal treatment, one tends to gain weight, lose energy, need more sleep, and become cold more easily. Fingernails become thinner and more brittle.
• Body odors (skin and urine) change. They become less "tangy" or "metallic" and more "sweet" or "musky".
• Internal emotions are amplified, becoming more apparent, distinguishable, and influential. Some people report reduced anxiety and increased sense of well-being. This could be a placebo effect.
• Changing the hormone therapy (adjusting dosages up or down in the regimen) sometimes causes a week or two of depression and otherwise unexplainable emotional angst.
• "Female" sex drive and enjoyment increase. This observation is obviously completely subjective since males have no way to directly compare the experience. Non-ejaculatory orgasms become more likely for those with the predisposition to have them, if for no other reason than the fact that ejaculatory orgasms are difficult or impossible to achieve, and the need for sexual release forces a rewiring of perceptions and responses.

Female hormones do not:

• Cause the voice to increase in pitch.
• Dramatically reduce facial hair growth in most people. There are some exceptions with people who have the proper genetic predisposition and/or are less than a decade past puberty.
• Change the shape or size of bone structure. However, they may decrease the bone density slightly.

3. What effect does male hormone therapy have on a female, and how soon?

The longer after puberty hormone therapy is started, the less effective it is--but not a linear scale, e.g., results are considerably more dramatic in an 18 year old than a 28 year old, but results are not on the average dramatically different between a 38 year old and a 48 year old.

The following effects have been observed in varying degrees--anywhere from little to moderate--with extended treatment. With effective and continuous dosages, most of the changes that a particular body is genetically prone to will start with the very first administration of androgens, start becoming irreversible (only the vocal cord thickening) almost immediately, start leveling off somewhat within 2 years, and be mostly done within 3 years. The leveling may take longer if the ovaries are not removed.

• The vocal cords thicken, deepening the voice--although not necessarily all the way down to an average male frequency. Fertility decreases. Menstrual cycle becomes irregular then stops.
• Sex drive increases. Sexual enjoyment may also increase, but the clitoris may become so sensitive as to make direct stimulation painful.
• Clitoris elongates, eventually reaching 3-8 cm.
• Body and facial hair growth speeds up, becomes much thicker, and may darken.
• Male pattern baldness may set in.
• Muscle mass increases with exercise. It may even increase slightly with no exercise.

Many people also report the following effects, but they are not verified in any medical literature that the author has read:

• Outer skin layer becomes rougher in feeling and appearance.
• Oil and sweat glands become more active. This may result in acne.
• Fat is redistributed. The face becomes more typically male in shape.
• Fat tends to move away from the hips and toward the waist.

Metabolism increases. Given a caloric intake and exercise regimen consistent with pre-hormonal treatment, one tends to lose weight, gain energy, need less sleep, become hot more easily, and feel generally more alert. However, appetite usually increases, so one may gain weight because of increased caloric intake and increased muscle mass.

Body odors (skin and urine) change. They become less "sweet" or "musky" and become more "tingly" or "metallic." Emotions change. Aggressive and dominant feelings may increase.

Male hormones do not:

Significantly decrease the size of the breasts. However, they may soften somewhat.

Change the shape or size of bone structure. However, they may decrease the bone density slightly.

4. How are hormones administered?

ADMINISTRATION OF FEMALE HORMONES

The popular treatment combinations are:

Estrogen alone

Adding an anti-androgen. An anti-androgen fights the androgens remaining in the body. This may enable one to reduce the estrogen dosage and still obtain acceptable development speed, and very similar results in the long run. However, the author is not aware of any one person who has tried the two regimens (high estrogen dosage vs. moderate estrogen dosage plus anti-androgen) for long enough to be able to objectively compare their performance.

Adding a progesterone. Progesterone administered with estrogen promotes extra breast growth by increasing the volume of the lactation and ducting tissue. Some studies of birth control pills in females seem to show that progesterone's administered with estrogens reduce the risk of cancer from administration of estrogens alone. Adding another type of estrogen. This may cause faster results for some people, but not necessarily better results in the long run. Some endocrinologists mimic a female cycle by decreasing or eliminating estrogen for one week of the month and/or adding or increasing progesterone for the same week. The author is not aware of solid evidence that this is either beneficial or harmful, although a recent study in females seemed to show that cycling progesterone's may decrease the beneficial effect of estrogen on cardiovascular health. The primary effect of cycling is the invocation of extreme mood swings similar to PMS in females.

ADMINISTRATION OF MALE HORMONES

The popular treatment combinations are:

Single androgen

HORMONES ARE DELIVERED BY THE FOLLOWING METHODS:

Oral (estrogens, progesterone's, androgens): This is the popular delivery method for estrogens and progesterone's. The main advantage is convenience. The main disadvantage is increased stress on the liver since it has to process the hormones twice instead of just once.

Injection (estrogens, progesterones, androgens): This is the popular delivery method for androgens. The main disadvantages are unsteady hormone levels (except for sustained-release preparations in oil or microscopic beads), and pain and infection risk from hypodermic needle usage.

Dermal patch (estrogens, androgens): The main disadvantage is skin irritation. Androgen patches are meant to be applied to a post-surgical genital site.

Cream (estrogens): The main disadvantage is the low transfer rate into the body, too low to be effective unless it is very frequently rubbed on very large skin surfaces. Application to just the breast area does not limit the distribution to that area; the little estrogen absorbed is distributed throughout the body and in insufficient quantity to make the breasts grow significantly. The only obvious effect is moister and healthier skin.

RESULTS

A hormone therapy regimen that works well for one person may not for another. If development is not well under way in, say, 4 months, some experimentation may be in order; try different hormone types and/or combinations.

Hormone dosage can usually be reduced to a nominal maintenance level after the testes or ovaries are surgically removed.

5. How can the intended effects of hormone therapy be maximized and the dangers minimized?

IN GENERAL:

Before starting hormone therapy, take a physical exam and the following blood tests:

Minimum: liver, thyroid, kidney and lipid (cholesterol)profiles; serum prolactin and sugar levels; blood clotting time.

• Interesting: calcium and phosphorus (skeletal health); serum androgen levels.
• The androgen test is rather expensive, and not necessary if one is using clinical results (visible body changes and, for male-to-female transsexuals, cessation of spontaneous erections) for feedback of therapy effectiveness. Particularly in female-to-male transsexuals, androgen therapy creates such dramatic clinical results that there is usually little reason to pay for the test except to satisfy curiosity, or if the clinical results are unsatisfactory.
• Be constantly aware of the body so that adjustments can be made if any new problems develop during therapy.
• Have regular medical checkups (every 2-3 months); pay close attention to vital signs.
• Eat well, and take a good multi-vitamin/mineral supplement to help be sure the body has everything it needs for new development.
• Do not start taking the maximum planned dosage of all hormones at once. Start with a low dose of one, and carefully watch for negative vital signs and symptoms. If there are no problems after one month, increase the dosage to the planned level. Wait another month before adding the next hormone or anti-hormone. Do not change the regimen radically or more often than once per month. Give the body time to adjust.
• Use the lowest hormone dosage that affords the desired changes. Not everyone needs the same dosage, because of differences in body weight and genetically-disposed sensitivity to the hormones. Hormone dosage can usually be reduced to a nominal maintenance level after the testes or ovaries are surgically removed. It is not recommended to take pre-operative dosages of hormones for more than about 3 years.
• Have bone density checked once every few years.
• Try the daily dosage of a hormone before moving to a sustained-release version, e.g., make sure you are not allergic to Provera tablets before you use Depo-Provera (the sustained release intra-muscular injection).

MALE TO FEMALE

Use the lowest hormone dosage that affords the desired changes. Even without an expensive blood serum androgen level test, one can tell when their androgen level is being pushed to the minimum possible level by noting that spontaneous erections become very infrequent or cease entirely, and that body development is as expected. Estrogens delivered orally strain the liver more than other delivery methods. However, it is not highly dangerous unless the liver is already weakened by alcohol, drug use, or infection. It is a good idea to reduce alcohol and other drug intake. Monitor liver stress with a liver profile blood test every 6-12 months. Susceptibility to hardening of the arteries decreases somewhat, but susceptibility to blood clots, phlebitis (inflammation of lower extremity and pelvic veins), varicose veins, elevated high blood pressure increases somewhat. Stop smoking, reduce stress, and increase aerobic exercise. Investigate severe leg pain by x-ray or ultrasound to determine if it is caused by a blood clot before massaging it. Leg and foot cramping not caused by a blood clot might be reduced with potassium and vitamin E supplements (but one should not take potassium concurrently with spironolactone). Monitor blood clotting time with a test every 6-12 months. Stop or drastically reduce estrogen dosage at least one month before having major surgery. Take about 80mg/day aspirin to reduce the risk of blood clots; take it with food and liquid to reduce the risk of stomach ulcer--or, better yet, use the enteric safety-coated variety.

Significant discharge from the nipples (more than would cause about a 2cm diameter stain on the bra) may be a sign of a dangerously elevated prolactin level due to intolerance of the estrogen dosage. Immediately take a test to measure the serum prolactin level; otherwise, take the test every 6-12 months anyway. Note that there may be a dramatic spike in the prolactin level, causing significant lactation for up to a week, if a high estrogen dosage is suddenly stopped; this is similar to the process in a female who has just bore her child.

Since spironolactone (Aldactone) is a diuretic, anyone taking it should drink plenty of water, especially before and after exercise, and may need to reduce dietary intake of potassium--especially if the kidneys are already stressed. Take a blood electrolyte balance test every 6-12 months.

Breast cancer risk seem to be low in comparison to females receiving estrogen replacement therapy. Certain studies in females seem to show that the cancer risk is lowered by consistently administering progesterone with the estrogen. Perform regular breast self-exams, anyway; take mammograms every 2 years before age 35, every year thereafter. Prostate cancer risk is significantly reduced in comparison to males not receiving estrogen therapy. Have the prostate examined once a year if possible, anyway.

FEMALE TO MALE

There is an increased risk of arterial hardening (particularly in the heart) due to increased serum cholesterol levels. Change the diet to reduce cholesterol.

Androgens can stimulate various kinds of liver tumors and cysts, especially if the liver is already weakened by alcohol, drug use, or infection. Reduce alcohol and other drug intake. Monitor liver stress with a liver profile blood test every 6 months. If the menstrual cycle has not ceased within about 5 months of a steady androgen regimen, take a blood test to check the serum androgen level.

Some recent studies seem to show that tobacco or marijuana smoking reduces the efficiency of androgen uptake. Even if most of the breast tissue is removed by a masectomy, there is enough tissue left to place female-to-male transsexuals at approximately the same risk for breast cancer as genetic males.

Perform regular breast self-exams; have any unusual lumps checked immediately.

6. How can one obtain hormones?

In the U.S., most reputable therapists and medical doctors who regularly work with transsexuals follow the Harry Benjamin Standards of Care, a plan that specifies that one must undergo a minimum of 3 months of psychotherapy to obtain a letter of recommendation to an endocrinologist. One can choose to work with doctors who do not follow the Benjamin Standards, but, in any case, it is a very good idea to meditate and cogitate on the implications for at least 3 months before starting hormone therapy. Some transsexuals find the Benjamin Standards too constrictive--even insulting; others find it worth the trouble to go through the hoop in order to be referred to an endocrinologist who is particularly knowledgeable in the treatment of transsexuals. Choose carefully.

Male-to-female transsexuals: if a sympathetic endocrinologist is not available, try local gynecologists; they are sometimes more understanding, and are used to prescribing estrogens and progesterones.

One should only take hormones that were obtained directly from a licensed pharmaceutical distributor; the quality of drugs obtained through other channels is not only suspect, but likely dangerous-- especially those in injectable form.

Some people are able to get their health insurance company to cover hormones just like any other prescription drug, especially if the doctor prescribes them for a "hormone imbalance" rather than "transsexual hormone therapy." When a health insurance company subcontracts out prescription drug coverage to another company, benefits for hormones are not generally questioned since there is little communication between the two companies.

7. Are birth-control pills a good source of estrogen?

No. Although early birth-control pills contained significant quantities of estrogen, modern ones do not. A typical birth-control pill now contains a tiny dose of progesterone, with or without a tiny dose of estrogen--less than one-tenth the strength required for an effective course of treatment for a male-to-female transsexual. If one is absolutely determined to use a particular birth-control pill, then one should carefully study the PDR to understand the doses of the component hormones of the pill in question, compared to the typical dosages of the same hormones in this FAQ.

8. How can lactation be induced?

This section is provided for curiosity only; the author has no medical references--only anecdotes from other transsexuals and mothers, popular media, and some experience with bovines--to substantiate the answer.

One must maintain a high level of estrogen for quite a while--probably a minimum of 6 months--then suddenly drop it. That is apparently enough in some males to kick the pituitary into releasing enough prolactin (milk-producing hormone) to make it possible to start some lactation.

Along with estrogen, progesterone plays a significant role in the development of lactating tissue (glands and ducts), so maintaining a moderate to high level of progesterone for probably at least 6 months previous would also help.

Finally, assuming the lactating tissue is developed and the milk comes in, one would need to frequently stimulate the milk "let-down" secretion reflex with oxytocin, by either artificially administrating it, or naturally generating it with practice with similar environmental stimuli that nursing females use (relaxing, hearing or thinking of the baby being hungry, direct sucking stimulation of the nipples and immediately surrounding tissue, orgasm, etc.). Not a lot of milk is produced unless suckling (or expressing) is frequent and consistent, say every 2-3 hours. Less stimulation than that, say, once every 5-8 hours, will result in dramatically less milk production. Less than that will result in complete cessation of milk production within 1-3 weeks after it starts. In summary, one has to be committed to the notion of actively and consistently nursing and/or expressing; it is quite a project.

If the milk is to be used for feeding a baby, one should consult the PDR for warnings about usage of hormones and other drugs while nursing.

For more information, try contacting your local chapter of the La Leche Society. They specialize in issues of breast-feeding.

9. How can a male be neutered without causing feminization?

One can cause the gonads to dramatically reduce androgen production by shutting down the output of LH and FSH from the pituitary gland. This can be done one of two ways:

Introducing consistently large quantities of any estrogen or progesterone. Progesterone does not have a feminizing effect, so one could use medroxyprogesterone acetate (Provera). This has been demonstrated to work on males with severe behavioral disorders exacerbated by androgens (read: serial rapists), who were given the choice of taking periodic Depo-Provera shots or remaining in prison. The sustained-release injectable preparation is easier on the liver than orally delivered tablets, but one should first try the tablets for a month or two to be sure there is not an allergic reaction. Be aware that there are annoying and dangerous adverse effects with progesterones, ranging from severe mood swings to blood clotting disorders.

Alternatively, one can use a GnRH agonist. This is a more elegant solution, and has fewer adverse affects than progesterones. However, it might be more difficult to get a doctor to prescribe one. Note that neither of these methods can be used for reliable birth control; some small amount of sperm may still be produced, even if the androgen levels are forced to be very low.

Stopping the administration of progesterone or GnRH agonist will result in the gonads resuming androgen (and sperm) production within a few months. The degree to which production is restored depends on how long the progesterone or GnRH agonist was used; the author's guess is that treatment of more than a few months will result in some degree of atrophy of the gonads; more than six months may result in permanent sterility. There has been little research on the reversibility of this treatment.

10. Exactly what hormones are available?

What are the details on popularity, dosage, availability, price, contraindications, adverse effects, etc.?

ESTROGENS

The following estrogens are popular for treatment of male-to-female transsexuals, and are presented in descending order of preference in the humble opinion of the author:

Estinyl, Estigyn, Etivex (ethinyl estradiol)

Estrad Val (estradiol valerate, 17 beta estradiol)

Estraderm (17 beta estradiol)

Estrace (17 beta estradiol)

Premarin (conjugated natural estrogens)

Menest

The following estrogens have been suggested for treatment of male-to-female transsexuals, but the author does not have information about how effective they are. Since their primary indication is for replacement therapy in females, they are probably suitable and relatively safe. They are presented in alphabetical order:

Estratab

Estrovis (quinestrol)

Ogen (estropipate)

Ortho-Est (estropipate)

The following estrogens have been suggested for treatment of treatment of male-to-female transsexuals, but the author does not have information about how suitable, effective, or safe they are. They are presented in alphabetical order:

Delestrogen

Estradurin (polyestradiol phosphate)

Estrone

Menrium

TACE (clorotrianazine)

The following estrogens have been suggested for the treatment of transsexuals, but, in opinion of the author, the adverse effects strongly outweigh the potential benefits. They are included here for the sake of warning, and are presented in alphabetical order:

Diethylstilbestrol, DES

The following natural sources of phytoestrogens (estrogen-like compounds) have been identified, but the author is not aware of an effective course of treatment using them. They work by weakly binding to estrogen receptors. In males, this may result in a mild feminizing effect (in females, it may give the opposite result, that is, a mild androgenic effect, since the phytoestrogens are competing with endogenous true estrogens for the estrogen receptors). Since phytoestrogens are not nearly as efficacious as true estrogens, huge and potentially toxic amounts of these items would have to be consumed. They are presented in alphabetical order:

• Black Cohosh (Cimicifuga racemosa)
• Blue Cohosh
• Borrage
• Butterfly Weed
• Caraway
• Chaste Tree or Vitex (Verbenaceae species)
• Dates
• Dill
• Dong Quai (Angelica sinensis)
• False Unicorn root
• Fennel seed
• Fenugreek
• Ginseng
• Goats Rue
• Gotu Kola
• Licorice root
• Linseed or Flaxseed
• Milk thistle
• Motherwort
• Pennyroyal (Hedeoma pulegioides)
• Pleurisy root
• Pomegranates
• Red Clover Sprouts
• Red Raspberry leaf
• Southernwood
• Soya Flour
• Tansy

Preparations advertised to contain "raw ovaries" from any animal have not been proven to be effective

Author: Unknown

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