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: estrogen, progesterone, and testosterone. A small quantity of testosterone is also produced by the adrenal gland. Proportionally, females have more estrogen and progesterone than males; males have more testosterone.

Estrogens include natural and synthetic estradiols, estrones and estriols. They excite estrogenic receptors, causing the body to differentiate into female form and function. Natural and synthetic estrogens are hereafter referred to simply as estrogens.

Progestins/progestagens/gestagens (synonyms) are synthetic progesterone analogues. Progesterone and progestins excite progesteronic receptors, which in cooperation with estrogenic activity, cause the body to further differentiate into female form and function.

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. The basic mechanisms are:

Aggressive exogenous hormone therapy indirectly reduces endogenous (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 genitals opposite those of birth. However, postnatal contrasexual hormone therapy does cause development of secondary sex characteristics as subsequently described in this document. 

What Are Normal Endogenous Androgen and Estrogen Levels?

The normal endogenous androgen range in a male is 300-1100 nanograms per deciliter. Estrogen is generally below 50 picograms per milliliter.

The normal endogenous androgen range in a female is 10-100 nanograms per deciliter. (Within this range lower numbers are not necessarily considered better; remember, free-circulating androgens cannot bind to receptors very well, and therefore cannot cause much harm, if an androgen blocker is being used. Note, also, that if the androgens are at the bottom end of the scale, then libido and overall energy will likely be lacking as well.)

There are dramatic cyclic and individual variations of estrogen (simple sum of estradiol and estrone) in females, with 100-400 picograms per milliliter being the most usual, with 25-700 being possible depending on the individual. 400 is considered a nominal "mid-peak" (ovulation) level. 200-250 is considered a reasonable target for exogenous estrogen treatment. Note that only natural estrogens can be meaningfully measured, so it you take any estrogen besides estradiol valerate or estradiol, you will not be able to accurately judge the results of a blood test.

Unfortunately, serum hormone levels cannot be used as a foolproof device for titrating exogenous hormone dosage, because there is no widely available test for sensitivity to the hormones, which varies considerably between individuals. Levels should be considered a means rather than a goal. After all, M2Fs undergo hormone therapy for transformation of secondary sexual characteristics, and do not have ovaries or a uterus which would impose obvious limitations on hormone levels; non-male-to-female women have entirely different reasons for undergoing hormone replacement therapy which generally requires only a low (endogenous) level. 

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 yecount 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. However, this should not be counted on for birth control, because a miniscule sperm count might remain until the testes are surgically removed. Estrogens, progesterone, progestins, 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.

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 2 to 4 months, start becoming irreversible within 6 to 12 months, start leveling off somewhat within 2 years, and be mostly done within 5 years. The leveling generally takes longer if the testes are not removed. These timelines are generalizations based on what many people have reported, but do not necessarily mean that everyone will find development (or reversibility) to be within these limits. 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 ar 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.

• Male sex drive decreases. Directly stimulated erections can become infrequent and difficult to maintain. Spontaneous erections usually stop. Semen secretion decreases, usually resulting in less intense ejeculatory orgasms (however, the ability to achieve a satisfying orgasm--even with little or no semen--is determined more by psychological factors and frequent practice than anything else). The testes and prostate atrophy. The penile skin also shrinks if erections are not regularly encouraged.

• Breast size increases. Typical growth is one to two cup sizes below closely related females (mother, sisters). The growth is not always symmetrical--neither is it for females. Sometimes the areoles 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 migrate away from the waist and toward the hips and buttocks.

• Body hair growth (not including head, face, or pubic area) generally slows, becomes less dense, and may lighten in color.

• Blotches (cloasma) appear on the skin of some people during hormone therapy. This is the same effect as the "mask of pregnancy" and probably related to other dermal changes as noted below.

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 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. Sometimes, tear glands also become less active, resulting in dryer eyes, which can cause some discomfort for those who wear contact lenses. Dermal gland activity trends can generalized with the formula (A+P)/E where A = androgens, P = progesterone and progestins, and E = estrogens. Synthetic estrogens seem to be especially likely to reduce activity.

• 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.

• Fingernails become thinner and more brittle.

• Body odors (skin and urine) change. They become less "tangy" or "metallic" and more "sweet" or "musky".

• If exercise is not increased, some muscle tone is lost.

• 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.

• Some middle-aged and older transsexuals who start or resume hormone therapy report improved memory and overall mental faculty.

• 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-ejeculatory orgasms become more likely for those with the predisposition to have them, if for no other reason than the fact that ejeculatory orgasms are difficult or impossible to achieve, and the need for sexual release forces a rewiring of perceptions and responses.

• It has been occasionally reported that sensitivity to air-born allergens decreases.

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 change the bone density slightly.

What Are the Popular Treatment Philosophies?

The following estrogen dosage philosophies are popular for treatment of male-to-female transsexuals:

Table 1: Estrogen dosage philosophies

		Dosage	Reasoning
1	A	Adjust estrogen to achieve a serum estrogen level in the normal range of a female; more or less ignore the serum androgen level	The body cannot make good use of more estrogen than a female would naturally generate	Androgens do not directly compete with estrogens for estrogen receptor sites	A higher level of exogenous estrogen might cause adverse effects
	B	Administer consistently low dosage of estrogens
2		Adjust estrogen for gross empirical results while paying extra attention to health	See discussion below
3	A	Adjust estrogen to achieve a serum androgen level in the normal range of a female; more or less ignore the serum estrogen level	The body might be able to make good use of more estrogen than a female would naturally generate	Androgens might compete with estrogen for estrogen receptor sites	High levels of exogenous estrogen over a limited period, i.e., less than 3 years, do not usually cause adverse effects in a person with a very healthy liver.
	B	Administer consistently high dosage of estrogens

Clearly, philosophy 1 and 3 reasonings flatly contradict each other. There are good endocrinologists in each camp, which demonstrates that we still really do not know exactly how hormones work. However, there is more compelling evidence for the reasoning of philosophy 1. In some people philosophy 1 might have a not have quite as steep of a ramp of results as philosophy 3--but, with patience, the results are often just as good. The A philosophies adjust to the body's assimilation of the estrogens, whereas the B philosophies assume "one size fits all."

Philosophy 2 occupies an awkward but extremely important space in between, where we acknowledge that in some cases neither endogenous nor exogenous hormone levels are great indicators, because the levels in "typical" post-pubescent non-transsexual bodies do not always relate well to the plethora of absorption and response factors in a given post-pubescent transsexual body, especially when anti-hormones are added to the mix. If there is unusually little development after, say, 6 months of hormone therapy, then consider using gross empirical results, e.g., breast growth and fat redistribution, as the primary rather than secondary indicator, provided ones health (especially blood clotting and liver function) is not compromised. Finally, note that the endogenous level of estrogen in females (F2M) seems to be a less important factor for development than the endogenous level of androgens in males (M2F) anyway.

The following estrogen coadministration philosophies are popular for treatment of male-to-female transsexuals:

Table 2: Coadministration philosophies

1	Add anti-androgen	The remaining endogenous androgens (including those from the adrenal gland) can be more safely and effectively fought with an anti-androgen than by mega-dosing with estrogen. Spironolactone and finasteride are recommended. Post-ops rarely find any antiandrogen useful except for finasteride. Of transsexuals taking estrogen, those who are older than 25 or so seem to find the anti-androgen much more important than those who are younger.
2	Add progesterone or progestin	Progesterone administered with estrogen helps promote breast growth: estrogen stimulates cell mitosis and growth of the ductal system, while lobular development and differentiation seems to be dependent on progesterone (breast fat accretion seems to require both). Progesterone consistently administered with estrogen seems to reduce the risk of fibrosis, cysts, and cancer from administration of estrogen alone. On the other hand, synthetic progesterone (progestins) can partly reverse the lipid (cardiovascular) benefits of estrogen. Moreover, progestins have a slightly androgenic effect in some people, and apparently can even antagonize estrogen absorption. Non-synthetic progesterone (as opposed to a progestin) is very rarely reported to have any adverse effect, and seems to provide a healthier balance for an aggressive estrogen dosage, as well as improving libido and overall energy level.
3	Add another estrogen	This may cause faster results for some people, but generally not better results in the long run.

It is possible to vary the hormone dosages on a monthly basis so as to roughly mimic a female menstrual cycle.

Cycling hormones before removal of the testes is not recommended. The gonadotropin axis (feedback mechanism) is already precarious in a pre-op under hormone therapy; small fluctuations in the hormone regimen can translate into large variations in the endogenous androgen level, causing significant physical and emotional discomfort.

Cycling in post-ops is a more interesting topic. Unfortunately, therapy results are even more difficult to evaluate than the usual non-cycling hormone therapy, due to the increase in variables and decrease in objective data.

There is mounting anecdotal evidence, and the theory put forth by at least one reputable endocrinologist, that estrogen receptors can become saturated, temporarily reducing the sensitivity and/or quantity of available receptors. If that is the case, then giving the receptors a rest would improve hormone therapy results. For example, many people have reported a significant surge in breast development when estrogen dosage is sharply increased after months or even years of a very conservative dosage. In some cases, the surge in development continues for quite a few months if the estrogen is cycled. Development often trails off again after 3-6 months, after which, it seems that another, or longer, rest is called for.

Cycling is worth trying for those post-ops who have not achieved significant breast development (sub-A cup). If the estrogen boosts are administered via intramuscular injection or transdermal film, and the patient has no history of adverse reactions to hormones (e.g., blood clotting or prolactin problems), it is generally considered to be a safe experiment.

If one is going to cycle, given the current lack of data to suggest otherwise, one may as well more or less mimic a 28 day female cycle, rather than picking another cycle out of the air. This can be roughly achieved by intramuscular injection of estrogen in oil on day 1, then taking another shot of 1/2 dosage on day 13. Some people will experience menopausal symptoms (hot flashes, night sweats, severe mood swings, etc.) in the days proceeding each shot; if the discomfort is unacceptable, a small, constant dosage of oral or transdermal estrogen can be used to provide a "floor" serum estrogen level. If progesterone is part of the regimen, it can be cycled by intramuscular injection in oil on day 8, or by ramping it orally from days 1-14 with the peak on day 8. Some say that cycling the progesterone is more important than cycling the estrogen; other say that the progesterone must be constant to best avoid breast cancer. Of course, many variations are possible. There is no formula better for a transsexual than "do what works." If enough people report that a different cycle is more appropriate, that will be reflected here in the future.

Estradiol cypionate probably has a longer half-life than estradiol valerate. If ev is not available but ec is, consider eliminating the oral/transdermal floor, as it might not be necessary.

Cycling in this manner usually results in at least some noticable development for 1-3 months, then the rate of improvement generally trails off in an asymptotic curve. In any case, one should revert to a very conservative regimen for 3-6 months (whether it be either low-dosage non-cycling or low-dosage cycling) before trying again. If one does not achieve any result whatsoever from cycling within a few months of starting, it will likely not help to continue the cycling.

Aggressive cycling is meant to facilitate bursts in development, and is not appropriate for pre-ops or lifetime maintenance. However, lifetime post-op cycling can be done safely with more conservative dosages.

For reference--endogenous androgens in genetic women generally peak just before ovulation and again just before menstruation--that is, on roughly days 13 and 27 of the cycle as defined in this document.

How Are Hormones Delivered?

Table 3: Delivery methods

	Advantages	Disadvantages
Injection	Less liver stress than oral delivery. Inexpensive.	Less steady hormone level. Pain and slight infection risk from hypodermic needle usage.
Oral	Convenience. Possibly more beneficial for blood cholesterol levels than other methods.	Increased stress on the liver since it has to process the hormones multiple times, resulting in an increase in clotting factors
Transdermal film	Less liver stress than oral delivery. Hormone level more steady than injections.	Inconvenience and skin irritation. Multiple simultaneous patches required for pre-op dosage. Expensive.
Sublingual/Bucosal	Uncoated tablets can be placed under the tongue or between the cheek and gum. Consider this a blend of transdermal and oral methods: if most of the drug is absorbed sublingually/bucosally, then one gains the same benefit to the liver as transdermal delivery; however, some is also dissolved in the saliva and swallowed. In any case, it is certainly not any worse than immediately swallowing a full oral dose, so try this if you can stand the taste of the tablet.
Cream, Suppositories, and Pessaries	Less liver stress than oral delivery.	Absorption through a mucosal membrane is best; absorption through through scrotal skin is not as good as mucosal, but better than through other skin (need more data about typical doses and absorption). Beware non-prescription creams from "transformation" stores: if the cream is not strong enough to require licensing, it is not strong enough to have significant effect on development.

Note that the absorption of oral preparations varies greatly among individuals. With some the absorption is poor; in that case, another delivery method is indicated.

Sustained-release intramuscular injectable hormones are suspended in oil. This is the usual procedure for administration:

1. If you are very sensitive to pain, obtain 2 new needles for each administration: 1 to fill the syringe (18-22 gauge), and another for the injection (22 gauge). That way the injection needle will be entirely sharp. Be careful not to drag the injection needle across anything, even skin, before the injection, because that will dull it.

2. If you are fairly tolerant of pain, or cannot afford 2 needles for each injection, then use the same new needle (22 gauge) to fill the syringe as to make the injection. Do not under any circumstances reuse needles between injection periods, or between different people.

3. Warm the vial (ampule) between your hands for a moment to help the oil flow more freely.

4. Cleanse the top of the vial and the area for injection with a swipe of povidone-iodine (10%), or if you cannot obtain that, use rubbing alcohol (95-99%) or hydrogen peroxide (3-5%).

5. The best intramuscular injection sites are the upper outer quadrant of the buttock, or upper outer thigh. Either is fine, as long as you are hitting at least two inches of fat and muscle, not bone or an artery.

6. Securely mount the drawing needle on the syringe, then if you are using a rubber-corked vial, pull back the plunger about 1/4-1/3 cc farther than the intended injection amount (e.g., if you intend to inject 1 cc, then draw back 1 1/4 - 1 1/3 cc of air).

7. With the vial right-side-up, insert the needle in the top, such that the needle end is in the bottle air, but not the oil. Inject all of the air from the syringe into the vial.

8. Be sure the needle end is in oil (not air, and not bumping against the glass), then slowly but firmly draw back the plunger until you have a bit more than the injection amount. You will probably see some small air bubbles; that is normal. Inject the extra solution, along with the top bubble, back into the vial. If you have a rubber-corked vial, this is easiest if the vial is upside-down.

9. Withdraw the needle (still needle up), then set the vial down. If you are using a second needle for the injection, swap needles now. Make sure the injection needle is securely fastened (usually a twist-on).

10. With the injection needle pointed up, tap the syringe and very slowly squeeze out the final bubbles. You might lose a bit of the solution, but it is important to be patient amount removing all of the significant bubbles (however, you need not worry about the suspended bubbles which are so tiny as to be nearly invisible).

11. If you need to change position to make the injection, put the protective cover on over the needle so you can set it down. Some people find it easiest to stand; others prefer to lay on their stomach if the buttock is target. If possible, have someone you trust make the actual injection; it is much easier that way.

12. Uncover the needle, grasp the outside of the syringe firmly (finger off the plunger), place the needle against your skin, perpendicular, then bravely push straight in (no bending at all) to a depth of roughly 2 1/2 - 3 1/2 cm , (1 - 1 1/3 inches). There should not be much pain past the initial prick. Once the needle is in, try not to shift your weight around or flinch such that the muscles there would move.

13. Still holding the outside of the syringe, pull back the plunger to be sure you did not hit a significant blood vessel. If you see no blood in the syringe, then very slowly but firmly depress the plunger. If you do see blood, then withdraw the needle, apply pressure to the site for a minute, then [optionally install a new needle and] try again a few centimeters away, or on the opposite side of your body.

14. Remove the needle from your body, replace the protective cover, and dispose of that part into a sharps container, or at least a container of strong composition that cannot be punctured by the used needles.

15. It is normal for there to be slight oozing of blood and/or oil from the injection site (and a small bruise later), given the large needle gauge. If it oozes for more than a few seconds, apply pressure for a minute. If you are the extraordinarily tidy type, you can also place a dot bandaid over it, but it is not really necessary.

Congratulations!

How Can the Intended Effects of Hormone Therapy Be Maximized and the Dangers Minimized?

Exams

• Before starting hormone therapy, take a full physical exam, and have blood drawn to check liver function (enzymes) and clotting factors. If you can possibly afford it, also take tests for thyroid, kidney, electrolyte, lipid (cholesterol), prolactin, sugar, estrogen, and androgen levels. It is also interesting to monitor the skeletal health via the calcium and phosphorus levels, especially if you are more than 40 years old (better yet, with a bone densitometer).

• If you take oral estrogen or progestin (synthetic progesterone), repeat the liver and clotting tests a few months after each significant increase of dosage. At the very minimum, recheck them 6 months and 12 months after starting. Even after achieving a stable long-term (> 2yr) oral regimen, it is not a bad idea to recheck the liver and clotting again every couple of years. If you are only on injectible or transdermal hormones, a single recheck 9-12 months after starting should be sufficient, if you are otherwise healthy.

• If you take spironolactone, have an electrolyte test about a month after each significant increase of dosage, especially if you have any known problems with potassium levels.

• There may be a dramatic spike in the prolactin level, causing significant discharge from the nipples (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. However, if nipple discharge is noted when there has not been a significant estrogen dosage change for several months, take a serum prolactin test: >100 ng/ml is cause for concern; pituitary gland monitoring and a reduction in estrogen dosage is probably indicated.

• 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 monthly breast self-exams, anyway; take mammograms every 2 years before age 40, 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.

• Hypothyroidism will partially or completely block development, so if there is family history or any other signs of that disorder, take the appropriate tests. Correct this before attempting cross-sexual hormone therapy.

•  

Dosage

• Do not start taking the maximum planned dosage of all hormones at once. Start with a low dosage of one, and carefully watch for negative vital signs and symptoms. If there are no problems after 1-2 months, increase the dosage to the planned level. Wait another 1-2 months before adding the next hormone or anti-hormone (2 months is better). 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 are surgically removed. It is not recommended to take pre-operative dosages of hormones for more than about 3 years. Reduce the dosage to a conservative level after surgery, especially after you are reasonably satisfied with breast and other secondary sex characteristic development (keep in mind that this development is almost always less pronounced than in females; you must adjust your expectations accordingly). The lower the level you can stand for lifetime maintenance (consistent with skeletal and mental health, of course), the better.

• Divide oral preparations into twice-daily takings, if practical.

General

• Be constantly aware of your body so that adjustments can be made if any new problems develop during therapy.

• Have regular medical checkups (minimally every year; more often if you have any significant health problem); 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. It might be worth paying special attention to the B vitamens: it has been reported by some that 1-2mg/day folic acid seems to help increase estrogen assimilation, and that, more generally, the entire B-complex (hello

• Estrogens delivered orally burden the liver, and excite it to produce extra blood clotting factors, more than other delivery methods. However, orals are not generally considered highly dangerous unless a pre-op dosage is administered for more than 3 years, or the liver is already weakened by alcohol, drug use, or infection, or you or your immediate family have a history of blood clotting disorder. In any case, it is a good idea to reduce alcohol and other drug intake.

• 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 (especially with oral estrogens). Stop smoking, reduce stress, and increase aerobic exercise. Investigate persistent calf pain or an increase of calf diameter 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). Stop oral estrogens and progestins at least one month before having major surgery that would keep you in bed for more than 1 full day without any walking (to reduce the risk of thrombosis). If you take a significant oral estrogen dosage, consider adding 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 (note that aspirin seems to affect a separate and unrelated clotting mechanism, so the protection is incomplete).

• Since spironolactone 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.

Results

A hormone therapy regimen that works well for one person may not for another. If development is not well under way in, say, 6 months, some experimentation may be in order; try different hormone types and/or combinations. However, if you change the regimen very often, it will be difficult to tell which one was working best. Be patient. The obvious exception is if you have a strong adverse effect that you or your physician deem dangerous; in that case you obviously must stop taking the hormone (or anti-hormone) in question.

It is unusual for the therapy to not work; the most common cause is the choice of oral preparations since the absorbtion varies among individuals. Since the endocrine system is a complex self-balancing mechanism, there are several disorders that can effect cross-sexual hormone therapy, including hypothyroidism. If there is family history or any other signs of such disorders, do not hesitate to check for them. 

How Can One Obtain Hormones?

In the U.S., most reputable therapists and medical doctors who regularly work with transsexuals follow the

If a sympathetic endocrinologist is not available, try local gynecologists; they are sometimes more understanding, and are used to prescribing estrogens and progesterone/progestins.

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.

It is possible to have a health insurance company to cover hormones just like any other prescription drugs, especially if the doctor prescribes them for a "hormone imbalance" or "hormone replacement" 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.

Some people in the U.S. have reportedly taken advantage of the 

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 dosage of a progestin, with or without a tiny dosage of estrogen--less than one-tenth the strength required for an effective course of treatment for a pre-op transsexual. If one is absolutely determined to use a particular birth-control pill, then one should carefully study the PDR to understand the dosages of the component hormones of the pill in question, compared to the typical dosages of the same hormones in this FAQ.

Exactly what hormones are available? What Are the Details On Popularity, Dosage, Availability, 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:

Table 4: Popular estrogens

Name	Safety and Efficacy	Source
Estradiol Valerate	Excellent	Synthetic (plant-based?)
Estradiol Cypionate	Good	Synthetic (plant-based?)
Estradiol	Good	Synthetic (plant-based)
Ethinyl Estradiol	Fair	Synthetic
Quinestrol	Fair	?
Estropipate	Fair	Synthetic (plant-based)
Esterified Estrogens	Fair	Synthetic (plant-based)
Conjugated Estrogens	Fair	Live animals

Estradiol Valerate

Brand Name Manufacturers	Delestrogen by B.M. Squibb Dimenformon Prolongatum? Progynova by Schering Progynon-Depot by Schering, Germany
Generic Manufacturers	Goldline Gynogen by Forest Major Schein Steris Valergen by Hyrex
Pharmacology	Ester 17b of estradiol with same effect as endogenous estrogen
Delivery	1, 2mg oral tablets. Sustained release intramuscular injection.
Typical dosage	Pre-op 15-40mg/2wks or 7-20mg/1wk injection Pre-op 6-12mg/day oral Post-op 10-30mg/2-4wks injection Post-op 2-6mg/day oral
Availability	Injection approved by U.S. FDA. Oral tablets may be approved but do not seem to be available in U.S.
Indications	Estrogen replacement therapy in females
Contraindications	Active blood clotting disorders. Estrogen-dependent tumors. History of blood clotting disorders associated with estrogen use. History of sensitivity to estradiol or any part of the preparation. Known or suspected breast cancer except in appropriately selected patients.
Adverse reactions	CNS Convulsions. Dizziness. Headache. Migraine. Mental depression. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blotchy skin pigmentation. Localized skin irritation. Loss of scalp hair. Increase of body hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Elevated blood pressure. Fluid retention. Glucose intolerance. Increased serum calcium level. Increased sensitivity to light. Liver tumors.
Comments	Note that "Progynon-Depot" by Schering, Germany is estradiol valerate, but "Progynon-Depot 100" by the very same company is an entirely different substance, estradiol undecylate. Estradiol undecylate has a longer chain length than estradiol valerate; its action is therefore prolonged, and smaller dosages are probably appropriate. The author does not have enough information to make any other comments about estradiol undecylate except that it will reportedly go out of production soon due to the side effect of "excessive feminization" for its only labeled usage, prostate cancer. If you are allergic to any nut oil, be sure to ask your pharmacist about the base, especially for the generic form of this drug. Castor oil is most often employed, which few people are sensitive to, but a few pharmacies employ other oils such as sesame, because it is less viscous and easier to run through their equipment.

Estradiol Cypionate

Brand Name Manufacturers	Depo-Estradiol by Pharmacia/Upjohn
Generic Manufacturers	Depogen by Hyrex Dep-gynogen by Forest Estro-cyp by Keene Goldline Moore Rugby Steris
Pharmacology	Ester with estradiol same effect as endogenous estrogen
Delivery	Sustained release intramuscular injection, 5mg/ml
Typical dosage	Pre-op 1.5-4mg/2wks injection Post-op 1-3mg/2-4wks injection
Availability	Approved by U.S. FDA
Indications	Estrogen replacement therapy in females
Contraindications	Active blood clotting disorders. Estrogen-dependent tumors. History of blood clotting disorders associated with estrogen use. History of sensitivity to estradiol or any part of the preparation. Known or suspected breast cancer except in appropriately selected patients.
Adverse reactions	CNS Convulsions. Dizziness. Headache. Migraine. Mental depression. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blotchy skin pigmentation. Localized skin irritation. Loss of scalp hair. Increase of body hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Elevated blood pressure. Fluid retention. Glucose intolerance. Increased serum calcium level. Increased sensitivity to light. Liver tumors.
Comments	The 1997 pdr generics book shows a 1:10 ratio of cypionate:valerate ovarian failure replacement dosages. This has been roughly confirmed in the limited anecdotal evidence gathered from transsexuals.

Estradiol

Brand Name Manufacturers	Almedion by ? Aquadiol by ? Climara by Berlex Labs (film) Dermestril by ? in Italy Estraderm by Ciba (film) Estrace by B/M Squibb (oral) Estrafem by Novo Nordisk in Denmark Estrovite by ? Follicyclin by ? Gynoestryl by ? Menorest by ? Oestrogel by ? Ovociclina by ? in Italy Ovocyclin by ? Profoliol B by ? in Switzerland Vagifem by ? Vivelle by Ciba (film) Zumenon by Solvay
Generic Manufacturers	Apothecon Geneva Goldline Major Moore Qualitest Rugby Watson
Pharmacology	17b estradiol with same effect as endogenous estrogen
Delivery	Oral tablets 0.5, 1, 2mg Extended release film 0.0375, 0.05, 0.075, 0.1mg/24hrs Vaginal cream and suppositories.
Typical dosage	Pre-op oral 4-8mg/day, 2-4 film patches 0.1 changed twice weekly Post-op oral 1-4mg/day, film 0.05 or 0.1 changed twice weekly - weekly Need more data about typical cream and suppository dosage and absorption.
Availability	Approved by U.S. FDA
Indications	Estrogen replacement therapy in females
Contraindications	Active blood clotting disorders. Estrogen-dependent tumors. History of blood clotting disorders associated with estrogen use. History of sensitivity to estradiol or any part of the preparation. Known or suspected breast cancer except in appropriately selected patients.
Adverse reactions	CNS Convulsions. Dizziness. Headache. Migraine. Mental depression. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blotchy skin pigmentation. Localized skin irritation. Loss of scalp hair. Increase of body hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Elevated blood pressure. Fluid retention. Glucose intolerance. Increased serum calcium level. Increased sensitivity to light. Liver tumors.
Comments	The Climara and Vivelle films reportedly lasts longer, and probably deliver more, than the Estraderm brand.

Quinestrol

Brand Name Manufacturers	Estrovis by Parke-Davis
Generic Manufacturers	None
Pharmacology	3-cyclopentylether of ethinyl estradiol. Acts on receptors apparently the same as endogenous estrogen.
Delivery	Oral 0.1mg tablets
Typical dosage	Pre-op ? Post-op 0.1-0.2mg/wk
Availability	Approved by U.S. FDA
Average Wholesale Price	$141.70/100
Indications	Estrogen replacement therapy in females
Contraindications	Active blood clotting disorders. History of blood clotting disorder in association with estrogen therapy. Known or suspected breast cancer. Known or suspected estrogen-dependent tumors.
Adverse reactions	CNS Dizziness. Headache. Mental depression. Migraine. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blood eruptions from skin. Blotchy skin pigmentation. Increase of body and facial hair. Loss of scalp hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Breast and liver tumors. Elevated blood pressure. Fluid retention. Gall bladder disease. Increased calcium level in blood. Increased sensitivity to light. Reduced carbohydrate and glucose tolerance.
Comments

Estropipate

Brand Name Manufacturers	Ogen by Pharmacia/Upjohn
Generic Manufacturers	Caremark Duramed Goldline Ortho-est by Ortho Pharm Qualitest Rugby Schein URL Warner Chilcott Watson
Pharmacology	Sulfate of estrone, stabilized with piperazine. Apparently acts on receptors the same as endogenous estrogen.
Delivery	Oral 0.75, 1.5, 3mg tablets
Typical dosage	Pre-op ? Post-op Oral 1.5-9mg/day
Availability	Approved by U.S. FDA
Indications	Estrogen replacement therapy in females
Contraindications	Active blood clotting disorders. Known or suspected breast cancer, unless that is the target. Known or suspected estrogen dependent tumors.
Adverse reactions	CNS Dizziness. Headache. Mental depression. Migraine. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blood eruptions from skin. Blotchy skin pigmentation. Increase of body and facial hair. Loss of scalp hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Breast tumors. Elevated blood pressure. Fluid retention. Gall bladder disease. Increased calcium level in blood. Increased sensitivity to light. Reduced carbohydrate tolerance.
Comments	Since estropipate is a quot;natural estrogenic substance prepared from purified crystalline estrone", the source is likely to be pregnant mares, the same as for conjugated and esterified estrogens. Refuting or confirming evidence would be appreciated.

Esterified Estrogens

Brand Name Manufacturers	Menest by SK Beecham Pharm Estratab by Solvay
Generic Manufacturers	Cheshire
Pharmacology	Esterified estrogens are a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone. They seem to act on estrogenic receptors the same as endogenous estrogen.
Delivery	Oral 0.3, 0.625, 1.25, 2.5mg tablets
Typical dosage	Pre-op 2.5-10mg/day Post-op 0.625-5mg/day
Availability	Approved by U.S. FDA
Indications	Estrogen replacement therapy in females. Inoperable progressing breast or prostate cancer.
Contraindications	Active blood clotting disorders. Estrogen-dependent tumors. History of blood clotting disorders associated with estrogen use. History of sensitivity to estradiol or any part of the preparation. Known or suspected breast cancer except in appropriately selected patients.
Adverse reactions	CNS Dizziness. Headache. Mental depression. Migraine. Spasms of limb and facial muscles. Eyes Intolerance to contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blood eruptions from skin. Blotchy skin pigmentation. Increase of body and facial hair. Loss of scalp hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Breast and liver tumors. Elevated blood pressure. Fluid retention. Gall bladder disease. Increased sensitivity to light. Increased serum calcium level. Reduced glucose tolerance.
Comments

Conjugated Estrogens

Brand Name Manufacturers	Premarin by Wyeth-Ayerst
Generic Manufacturers	None
Pharmacology	Sodium salts of estrogen sulfates. Apparently acts on receptors the same as endogenous estrogen.
Delivery	0.3mg, 0.625, 0.9, 1.25, 2.5mg tablets
Typical dosage	Pre-op Oral 1.25-7.5mg/day Post-op Oral 0.625-3.75mg/day
Availability	Approved by U.S. FDA
Indications	Estrogen replacement therapy in females. Treatment of selected breast and prostate cancers.
Contraindications	Active blood clotting disorders. Known or suspected breast cancer, unless that is the intended target. Known or suspected estrogen dependent tumors.
Adverse reactions	CNS Dizziness. Headache. Mental depression. Migraine. Spasms of limb and facial muscles. Eyes Intolerance of contact lenses. Steepening of corneal curvature. Gastrointestinal Abdominal cramps. Bloating. Cholestatic jaundice. Nausea. Vomiting. Skin Blood eruptions from skin. Blotchy skin pigmentation. Increase of facial and body hair. Loss of scalp hair. Red skin patches from capillary congestion. Other Blood clotting disorders. Breast tumors. Elevated blood pressure. Fluid retention. Gall bladder disease. Increased calcium level in blood. Increased sensitivity to light. Reduced carbohydrate tolerance.
Comments	Conjugated estrogens are derived from pregnant mare urine under cruel conditions including continual confinement, continual standing with no option to lay down or turn around, restriction of drinking water, inadequate veterinary oversight, killing of the newborn or young foals, then immediate reimpregnation. The pregnancies are repeated until the mare becomes infertile or sick, at which time she is killed. This treatment has not been directly witnessed by the author. However, Redwings Horse Sanctuary, World Society for the Protection of Animals, and others have researched this issue, interviewed Wyeth-Ayerst representatives, and directly inspected the farms in question. Furthermore, Wyeth-Ayerst has aggressively blocked every attempt other drug companies have made to obtain FDA approval to sell a synthetic generic equivalent, based on the argument that those generics cannot possibly be equivalent--because they do not contain the same organic impurities.

Other prescription estrogens are available; however, they are mixed with other drugs, or are intended only for treatment of inoperable cancer, and are therefore not as suitable for treatment of transsexuals.

The reason this document specifies estradiol cypionate as potentially less safe than estradiol valerate is that ec is much stronger and longer-lived, putting the author in mind of the stimulation of liver-based enzyme/clotting factors--and attendant thrombosis risk--when recirculated many times like ethinyl estradiol. Plain (natural) estradiol is also be considered excellent in safety if delivered via a non-oral method.

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 advertized to contain "raw ovaries" from any animal have not been proven to be effective.

Progesterone and Progestins

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

Table 5: Popular progesteronic compounds

Name	Safety	Efficacy	Source
Progesterone	Excellent	Highly variable	Yams or Soy Beans
Hydroxyprogesterone Caproate	Good	Variable	Synthetic
Dydrogesterone	Good	Variable	Synthetic
Medroxyprogesterone Acetate	Fair	Variable	Synthetic
Norethindrone Acetate	Fair	Variable	Synthetic

Progesterone

Brand Name Manufacturers	Cyclogest by LD Collins in the U.K. Gestone by ? in the U.K.? Prometrium by Schering in Canada Prometrium by Solvay Pharmaceuticals Utrogestan by Besins-Iscovesco in France Progesteronum by ? in Poland
Generic Manufacturers	Compound pharmacies advertising unbranded progesterone on the web include Bajamar Women's Healthcare Pharmacy and Women's International Pharmacy.
Pharmacology	Suspension of progesterone in oil. This is the same molecule as produced endogenously in females, not a progestin.
Delivery	Capsules. Vaginal cream and suppositories.
Typical dosage	Pre-op 100-400mg/day capsules in conjunction with estrogens. Post-op 50-400mg/day capsules in conjunction with estrogens. Need more data about typical cream and suppository dosage and absorption.
Availability	Approved by U.S. FDA
Indications	Menopausal discomfort
Contraindications	Active or past blood clotting disorders. Liver dysfunction or disease.
Adverse reactions	Generally mild and transient.
Comments	Those allergic to peanuts, beware: Prometrium uses a peanut oil medium. Compounding pharmacies supplying non-branded progesterone may also use peanut oil; ask them if you need to know. Some people call this drug progesterone USP/PharEu/BP (according to the local regulatory commission), to differentiate from progestins. In some countries the drug is simply referred to as progesterone. The largest fraction progesterone taken orally is destroyed in the digestive tract, which, along with the very short half-life, accounts for the high dosage in comparison to synthetics, and may also account for some of the variability in efficacy.

Hydroxyprogesterone Caproate

Brand Name Manufacturers	Caposten by ? Capton by ? Caprosteron by ? Hormofort by ? Delalutin by ? Depolut by ? Estralutin by ? Neolutin by ? Primolut-Depot by ? Progesteron-retard by ? Prolutin-Depot by ? Syngynon by ?
Generic Manufacturers	Hylutin by Hyrex Moore, H.L. Rugby Schein Steris
Pharmacology	Progestogen (progesterone derivative)
Delivery	125 and 250mg/ml sustained-release intramuscular injection
Typical dosage	125mg-250/2-4wks intramuscular injection
Availability	Approved by U.S. FDA
Indications	Unusual menstrual bleeding. Endometriosis.
Contraindications	Active or past blood clotting disorders. Cerebral clotting or haemorrhage.
Adverse reactions	CNS Headache. Insomnia. Loss of coordination. Mental depression. Sleepiness. Slurred speech. Weakness, numbness, or pain in extremeties. Eyes Change of vision. Retinal blood clots. Inflamed optic nerves. Gastrointestinal Cholestatic jaundice. Nausea. Skin Skin discoloration, rash, itching, and other allergic reactions. Other Blood clotting disorders. Chest pain. Decreased glucose tolerance. Fever. Fluid retention. Shortness of breath.
Comments

Dydrogesterone

Brand Name Manufacturers	Duphaston by Solvay
Generic Manufacturers
Pharmacology	Progestin (progesterone derivative)
Delivery	5, 10, 20mg tablets
Typical dosage	Pre-op 5-20mg/day Post-op 2.5-10mg/day
Availability	Approved in the U.K. Rejected by U.S. FDA.
Indications	Endogenous progesterone deficiency. Unopposed estrogen replacement therapy. Premenstrual syndrome. Menstrual abnormalities. Endometriosis. Infertility. Undesired spontaneous abortions.
Contraindications	None.
Adverse reactions	Nausea. Breast tenderness. Headache. Bloated feeling. Transient dizziness. Skin reactions.
Comments

Medroxyprogesterone Acetate

Brand Name Manufacturers	Amen by Carnrick Curretab by Solvay Provera and Depo-Provera by Pharmacia/Upjohn
Generic Manufacturers	Cycrin by Esi Lederle Generics Geneva Goldline Greenstone Intl Labs Major Martec Moore Parmed PD-RX Qualitest RID Rosemont Rugby Schein URL Warner Chilcott
Pharmacology	Progestin (progesterone derivative)
Delivery	2.5, 5, 10mg tablets 400mg/ml sustained-release intramuscular injection (brand-name only)
Typical dosage	Pre-op 2.5-10mg/day tablets in conjunction with estrogens Pre-op 50mg/2weeks injectible in conjunction with estrogens Pre-op ? for neutering without estrogens Post-op ?
Availability	Approved by U.S. FDA
Indications	Endometrial and kidney cancer. Unusual menstrual bleeding.
Contraindications	Active or past blood clotting disorders. Known or suspected breast or gonadal tumors. Known sensitivity to medroxyprogesterone acetate. Liver dysfunction or disease.
Adverse reactions	CNS Headache. Insomnia. Loss of coordination. Mental depression. Sleepiness. Slurred speech. Weakness, numbness, or pain in extremeties. Eyes Change of vision. Retinal blood clots. Inflamed optic nerves. Gastrointestinal Cholestatic jaundice. Nausea. Skin Skin discoloration, rash, itching, and other allergic reactions. Other Blood clotting disorders. Chest pain. Decreased glucose tolerance. Fever. Fluid retention. Shortness of breath.
Comments	There are many anecdotal reports of inexplicable or exacerbated depression while taking this drug. In that case, progesterone is indicated. Upjohn claims that the bioavailability of Provera is higher than generic formulations. The article "Gender Dysphoria Update" by Blaine R. Beemer (originally published in Journal of Psychosocial Nursing and Mental Health Services, 1996: 34(4), 12-19) reports that clients at Vancouver (BC) "routine receive the progestin medroxyprogesterone acetate (Provera)" and asserts that apart "from its effect as an antiandrogen, medroxyprogesterone has been shown to promote bone formation, and may counter the bone loss that might occur with the bllockade of male hormones," citing as a reference: Prior, JC, Vigna, YM, Barr, SI, Rexworthy, C, & Lentle, BC (1994), "Cyclic medroxyprogesterone treatment increases bone density: A controlled trial in active women with menstrual cycle disturbances. American Journal of Medicine, 96, 521-530. A question to consider: does the medroxyprogesterone administration have to be cyclic to have the bone density effect?

Norethindrone Acetate

Brand Name Manufacturers	None
Generic Manufacturers	Aygestin by Esi Lederle Generics
Pharmacology	Progestin
Delivery	Oral 5mg tablets
Typical dosage	Pre-op 2.5-15mg/day Post-op ?
Availability	Approved by U.S. FDA
Indications	Endometriosis. Unusual menstrual bleeding.
Contraindications	Blood clotting disorders. Known or suspected breast or gonadal cancer. Known sensitivity to norethindrone acetate. Liver dysfunction or disease.
Adverse reactions	CNS Insomnia. Mental depression. Sleepiness. Eyes Retinal blood clots. Inflamed optic nerves. Gastrointestinal Cholestatic jaundice. Nausea. Skin Acne. Increase of body and facial hair. Loss of scalp hair. Other Blood clotting disorders. Fever. Fluid retention. Mild to severe allergic reactions.
Comments

Dydrogesterone and hydroxyprogesterone caproate are both synthetic analogues of progesterone. This makes them less objectional than other progestins on the market, which seem to be more closely analogued to testosterone.

The following natural sources of phytoprogesterones (progesterone-like compounds) have been identified, but the author is not aware of an effective course of treatment using them. Since phytoprogesterones are not nearly as efficacious as true progesterone, huge and potentially toxic amounts of these unrefined items would have to be consumed. They are presented in alphabetical order: Suma, Vitex, Wild or Mexican Yam.

Anti-androgens

The following anti-androgens are popular for treatment of pre-operative male-to-female transsexuals. They are presented in descending order of preference in the humble opinion of the author:

Table 6: Popular anti-androgens

Name	Safety	Efficacy
Spironolactone	Excellent	Good
Finasteride	Excellent	*
Cyproterone Acetate	Fair	Excellent

Spironolactone

Brand Name Manufacturers	Aldactone by Searle Spironolacton by ? in Bulgaria Uractone by ? in Italy Verospiron by ? in Hungary
Generic Manufacturers	Caremark Cheshire Geneva Goldline Heartland Major Moore, H.L. Mutual Mylan Parmed PD-RX Purepac Qualitest Raway Rugby UDL URL Vanguard
Pharmacology	Mostly inhibits production of testosterone at the stage of 17-hydroxylation, and competes with DHT (dihydrotestosterone) for bonding at peripheral receptors. It is also said to intensify catabolism of androgens, and activate conversion of testosterone into estrogens.
Delivery	25, 50, 100mg oral tablets
Typical dosage	Pre-op 100-400mg/day Post-op 50mg/day
Availability	Approved by U.S. FDA
Indications	Congestive heart failure. Elevated blood pressure. Fluid retention. Hyperaldasteronism. Inadequate pottasium retention. Liver cirrhosis.
Contraindications	Elevated potassium levels. Inadequate urine production. Kidney disfunction.
Adverse reactions	CNS Confusion. Dizziness. Drowsiness. Headache. Lethargy. Loss of precise motor control. Gastrointestinal Cramping. Diarrhea. Dry mouth. Gastric ulceration and other stomach inflammation. Vomiting. Skin Acne. Itchy, fluid-filled patches of skin. Increase of body and facial hair. Red skin patches from capillary congestion. Other Deepening of the voice. Drug fever. Pottasium retention. Severe decrease of blood granulocytes. Sodium loss.
Comments	One person reported suicidal depression as an adverse effect. The brand-name formulation tastes awful; the generic formulation is much less offensive.

Finasteride

Brand Name Manufacturers	Proscar by Merck Propecia by Merck
Generic Manufacturers	None
Pharmacology	Androgen conversion inhibitor. Inhibits the production of dihydrotestosterone (DHT) from testosterone by inhibiting the binding of 5a-reductase, which is the enzyme responsible for converting testosterone to DHT. DHT is the active androgen found in the skin and prostate gland, and is associated with the development of male pattern baldness, excess body hair, and benign prostatic hypertrophy. Not suitable as a general anti-androgen since it only affects DHT production. However, it seems to be more helpful in counteracting male-pattern baldness and excess body hair than general anti-androgens.
Delivery	5mg oral tablets (Proscar) 1mg oral tablets (Propecia)
Typical dosage	Pre-op 0.05-1mg/day Post-op 0.05-1mg/day (See comments below)
Availability	Approved by U.S. FDA
Indications	Benign prostate enlargement
Contraindications	Hypersensitivity to any component of the product.
Adverse reactions	Generally mild and transient
Comments	Anecdotal evidence strongly suggests that pill fragments (say, 4-12 from each pill) taken daily are just as effective as taking the entire pill. There might issues with oxidation, so avoid handling the unused fragments, and keep them in a small, air-tight container. Pre-ops who take finasteride should consider coadministration of a more general anti-androgen such as spironolactone (since finasteride only blocks conversion of testosterone to DHT, the body sometimes boosts the testosterone level in response.) On the subject of scalp hair regrowth: In addition to finasteride therapy, it is customary to apply minoxidil 5% (topical) daily to the balding scalp area in order to achieve maximum results. Some people also add tretionin (retinois acid) creme 0.05%, but it is not yet clear whether that always helps (and speaking of minoxidil: note that a few people have reported that it seemed to have a systemic effect, in that it increased body hair even though it was applied only to the scalp). Do not let a female who is pregnant, or might be pregnant, anywhere near finasteride fragments or powder. It is a strong teratogen, known to cause intersexed genital expression in the male fetus. Based on rabbit and rat studies, there may be a slight effect on male fertility that would reverse within 6 weeks of discontinuing.

Cyproterone Acetate

Brand Name Manufacturers	Androcur by Schering AG, Farma (Germany) Cyproteron by NM Pharma (England)
Generic Manufacturers	?
Pharmacology	Androgen receptor antagonist. Weak gonadal androgen production inhibitor. Weak progestin.
Delivery	10mg, 50mg oral tablets
Typical dosage	Pre-op 10mg/wk-100mg/day (See comment below) Post-op not recommended
Availability	Not approved by U.S. FDA
Indications	Acne and/or overactive oil glands. Androgen dependent loss of scalp hair. Hirsutism. Inoperable prostate tumors.
Contraindications	Lactation. Dubin-Johnson syndrome. Liver disease or tumor. Previous or existing blood clotting disorder. Rotor syndrome. Severe chronic-depression. Severe diabetes with vascular changes. Sickle-cell anaemia. Wasting diseases (with the exception of prostate tumor).
Adverse reactions	CNS Headache. Lessened ability to concentrate. Mental depression. Tiredness. Gastrointestinal Nausea. Other Blood clotting disorders. Elevated prolactin level. Pituitary size increase. Carbohydrate metabolism changes. Liver dysfunction or tumors. Shortness of breath.
Comments	The extreme range of dosage comes from input that some people find 10mg/wk sufficient to induce total impotence, and yet others take as much as 200mg/day with no obvious short-term adverse effects. Given this range, it would seem prudent to start on the low side and work your way up only if necessary. More than 100mg/day is generally considered excessive. There are some reports of depression when the dosage is too high for a given individual. There appears to be a causal relationship because the depression evidently disappeared as soon as the dosage was reduced, according to those reports.

*Although it is not a general anti-androgen, finasteride coadministered with estrogen, topical minoxidil 5%, and topical Retin-A, is very helpful to halt--and in some cases, partly reverse--male-pattern baldness. Many people report that finasteride also helps to reduce excess body hair.

Cyproterone acetate is a very strong anti-androgen but also causes strong adverse effects in some people.

Nilutamide and flutamide have been suggested, but are not entirely suitable for transsexuals, especially as monotherapy: because of the way they interfere with normal negative feed-back action of androgens, they stimulate gonadotropin production and subsequently androgen production.

Prescription adrenal androgen production inhibitors are available but not listed because adrenal androgen production is insignificant (i.e., about the same as in females) in comparison to gonadal adrenal production. Adrenal androgens are best ignored, or if absolutely necessary, countered with finasteride.

Other prescription anti-androgens are available but not listed because their primary indication is not as an anti-androgen, and/or because the adverse effects are dangerous when weighed against the possible benefit.

The following natural sources of phytoantiandrogens (anti-androgen-like compounds) have been identified, but the author is not aware of an effective course of treatment using them. Since phytoantiandrogens are not nearly as efficacious as true antiandrogens, huge and potentially toxic amounts of these items would have to be consumed. They are presented in alphabetical order: Saw Palmetto.

Other Anti-Hormones (GnRH Agonists)

These pharmaceuticals can be used to dramatically reduce gonadal hormone production in both males and females. They are used mainly by pediatricians to reduce precocious puberty, so it might be difficult to persuade a doctor to prescribe them for an adult. Also, they are very expensive. None the less, this type of chemical castration is worth investigating for those cases when the pre-operative male-to-female cannot take the hormones of choice because of other health problems (e.g., hormone dependent tumors or blood clotting disorders), and cannot yet have the surgery performed (note that such a problem is quite rare). They are presented in descending order of preference in the humble opinion of the author:

Table 7: Anti-hormones

Name	Safety and Efficacy
Goserelin Acetate	Excellent
Nafarelin Acetate	Excellent
Leuprolide Acetate	Fair

Goserelin Acetate

Brand Name Manufacturers	Zoladex by Zeneca
Generic Manufacturers	None
Pharmacology	GnRH agonist. After an initial stimulating phase, the pituitary is desensitized to GnRH, which causes it to stop producing LH, which in turn dramatically decreases gonadal production of hormones within a month.
Delivery	Sustained release subcutaneous injection 3.6, 10.8mg
Typical dosage	Pre-op 3.6mg/month (3.6mg implant is for 1 month; 10.8 mg implant is for 3 months)
Availability	Approved by U.S. FDA
Indications	Androgen-sensitive prostate cancer
Contraindications	Known hypersensitivity to GnRH, GnRH analogues, or any of the components of the product
Adverse reactions	CNS Dizziness. Insomnia. Lethargy. Gastrointestinal Anorexia. Nausea. Skin Sweating. Other Congestive heart failure. Fluid retention. Hot flashes. Increased calcium level in blood. Mild to severe allergic reactions. Obstructive pulmonary disease. Ureteral and spinal compression.
Comments

Nafarelin Acetate

Brand Name Manufacturers	Synarel by Searle
Generic Manufacturers	None
Pharmacology	GnRH agonist. After an initial stimulating phase, The pituitary is desensitized to GnRH, which causes it to stop producing LH, which in turn dramatically decreases gonadal production of hormones within one month.
Delivery	Nasal spray
Typical dosage	Pre-op 1600mcg/day (2 sprays into each nostril twice a day)
Availability	Approved by U.S. FDA
Indications	Central precocious puberty. Endometriosis.
Contraindications	Hypersensitivity to GnRH, GnRH agonists analogs or any component of the product
Adverse reactions	CNS Headache. Insomnia. Mental depression. Skin Acne. Body odor. Increase of body and facial hair. Itchiness. Itchy, fluid-filled patches of skin. Oily skin. Rash. Vaginal dryness. Other Chest pain. Fluid retention. Hot flashes. Muscle pain. Nasal irritation. Ovarian cysts. Shortness of breath. Vaginal bleeding.
Comments

Leuprolide Acetate

Brand Name Manufacturers	Lupron by Tap
Generic Manufacturers	None company
Pharmacology	GnRH agonist. After an initial stimulating phase, the pituitary is desensitized to GnRH, which causes it to stop producing LH, which in turn dramatically decreases gonadal production of hormones within one month.
Delivery	5, 7.5, 11.25, 15, 22.5mg sustained-release intramuscular injection
Typical dosage	Pre-op 3.75-7.5mg/month
Availability	Approved by U.S. FDA
Indications	Advanced prostate cancer. Endometriosis.
Contraindications	Hypersensitivity to GnRH or GnRH analogs.
Adverse reactions	CNS Anxiety. Delusions. Dizziness. Headache. Hearing disorders. Insomnia. Memory disorder. Nerve disorders. Personality disorder. Eyes Eye disorders. Gastrointestinal Anorexia. Constipation. Coughing up blood. Dry mouth. Nausea. Thirst. Vomiting. Skin Change of facial and body hair. Skin rash. Other Ankylosing spondylosis. Blood in the urine. Bone and muscle pain. Change in heart electrical activity. Congestive heart failure. Decrease of bone density. Decreased tolerance of protein. Decreased red blood cell count. Decreased white blood cell count. Difficulty urinating. Elevated blood pressure. Elevated LDH. Elevated phosphorus. Escape of blood into the tissues from ruptured blood vessels. Fluid retention. Hair loss. Hot flashes. Increased heart beat rate. Increased uric acid. Increased urination frequency or urgency. Lactation. Liver disorder. Loss of strength. Low blood pressure. Lymphadenopathy. Mild to extreme allergic reaction. Palpitations. Pelvic fibrosis. Penile swelling. Prostate pain. Pulmonary disorders. Respiratory disorders. Temporary increase of hormone production. Temporary suspension of respiration and circulation.
Comments

The point of this faq is to be a reference for the popular range of transsexual hormone therapies. Specific recommendations are not easy to make, because individual responses and constraints are so variable. As such, this faq seems too vague for many readers, who produce the remaining most frequent question:

"All of this is quite interesting, but I am a healthy individual, and would really appreciate a specific suggestion. Understanding that adjustments for my situation can be made as I go, what is a good guideline?"

Obligatory reiteration of disclaimer: The answers in this document are collected from a variety of sources: medical literature, pharmaceutical company advertizement, verbal advice of medical doctors, second-hand anecdotes, and personal experience. Despite the authoritative tone of this document, it is presented for educational interest only, not direct advice. It contains opinions, sweeping generalizations, and at least one mistake. The author is not a medical doctor, and makes no claim or warranty as to the suitability of the information in this document for application to any particular individual. You, the reader, take sole responsibility for interpretation and application of this information. Form your own opinions by doing your own research. May your favorite deity curse you if you seriously consider sueing the author for misinforming you. The endocrine feedback system is intricate, delicate, and poorly understood. Even the experts do not entirely agree on how to best meddle with it. Hormone therapy is fraught with risk as well as promise. Be sure you have fully considered the implications before you start. Work with a medical doctor who is qualified to interpret your signs, symptoms, blood tests, and development in the context of your personal medical history. Do not take hormones that you did not obtain directly from a licensed pharmaceutical distributor; the quality of drugs obtained through other channels is not only suspect, but possibly dangerous--especially those in injectable form.

Subject to the above disclaimer, the context of this entire document (especially the sections on

1. Month 1: Begin twice-monthly injections of 20mg

2. Month 2: Given continued health, add anti-androgens: 100mg/day

3. Month 3: Given continued health, add progesterone or progestin: 200mg/day oral

4. Month 4: If breasts are not yet developing (budding), given continued health, increase estrogen dosage to the following: twice-monthly injections of 40mg estradiol valerate, or 4mg estradiol cypionate. Also, take 1-3mg/day sl-oral estradiol or 2-4mg/day sl-oral estradiol valerate or a single 0.075-0.1mg transdermal estradiol film changed weekly. If these injectables are not available, employ 2 0.1mg transdermal estradiol films changed twice weekly, offset (e.g., change the first film monday morning and thursday evening; change the second film wednesday morning and saturday evening), or 6mg/day sl-oral estradiol, or 9mg/day sl-oral estradiol valerate. Note that injectables or films are much preferable to administration of the entire estrogen therapy orally. Do not increase estrogen at this time if there is currently progress in breast development.

5. Month 5: If androgens are still a problem (continued scalp hair recession, frequent spontaneous erections, etc.), given continued health, increase antiandrogens to the following: 200mg/day spironolactone plus larger fractional tablet (0.1-1mg)/day finasteride. If spironolactone is not available but cyproterone acetate is, employ 25mg/day cyproterone acetate.

6. Month 6: If breasts are not yet developing, given continued health, increase progesterone/progestin dosage to the following: 300-400mg/day oral progesterone, or twice-monthly injections of 125mg hydroxyprogesterone caproate, or 20mg/day sl-oral dydrogesterone.

7. Month 7: If breasts are not yet developing, given continued health, increase estrogen dosage to the following: twice-monthly injections of 60mg estradiol valerate, or 6mg of estradiol cypionate. Also, take 2-4mg/day sl-oral estradiol or 3-6mg/day sl-oral estradiol valerate or a single 0.1mg transdermal estradiol film changed every 4-7 days. If these injectables are not available, employ 3-4 0.1mg transdermal estradiol films each changed twice weekly, offset, or 8mg/day sl-oral estradiol, or 12mg/day sl-oral estradiol valerate (do not attempt to run up the oral doses in the same ramp as other deliveries; if this dose of orals is not doing the job, it is quite unlikely that adding more will help). Do not increase estrogen at this time if there is currently progress in breast development.

8. Month 8: If androgens are still a problem, given continued health, increase antiandrogens to the following: 300-400mg/day spironolactone plus larger fractional tablet (~0.25-2.5mg)/day finasteride. If spironolactone is not available but cyproterone acetate is, employ 50mg/day cyproterone acetate.

9. Given continued health, keep on with this regimen, or adjust as appropriate (titrating downwards, preferrably) for up to 3 years. After that, if one cannot--or does not wish to--obtain orchidectomy or full srs, it is still best to reduce oral estrogen, progestins, and cyproterone acetate after 3 years. Estradiol via injection and film is relatively safe, as is progesterone.

10. Srs minus 1 month: Stop progestins and sl-oral estrogen.

11. At orchidectomy or srs: Stop all estrogens, antiandrogens and progesterone. Beginning 1-2 weeks after, employ a single 0.075mg transdermal estradiol film changed weekly, or 2mg/day sl-oral estradiol, or 3mg/day sl-oral estradiol valerate, or an injection of 15mg estradiol valerate or 1.5mg estradiol cypionate once per 3 weeks. Keep this simple regimen for 3 months to allow time for adjusting to the abrupt reduction of endogenous androgens (unless one was on an effective GnRH agonist course, in which case gonadal androgen production was already shut down).

12. 3 months after testes are removed: If menopausal symptoms are noted just before the injection, either increase the frequency of the shots to twice monthly (reducing the dose of each shot, respectively, to 10mg ev or 1mg ec), or add 1mg/day sl-oral estradiol or 2mg/day sl-oral estradiol valerate. If menopausal symptoms are continual, increase the dosage ~50% each month until the symptoms disappear, or at least are tolerable. An alternative, and perhaps safer way to deal with menopausal symptoms and/or low energy, is to add progesterone or a progestin: 100mg/day progesterone or 5mg/day sl-oral dydrogesterone.

13. If one has not attained significant feminization (still using breast growth as the most obvious measuring device, but keeping in mind the modest expectations which are required in this matter), and no progress whatsoever is noted after the testes have been removed for 6 months, try aggressive cycling for 3 months timed as outlined in the

14. If scalp hair continues to recess, try a fractional tablet (0.05-0.5mg)/day finasteride for several months. If it stalls the recession, continue taking it for a year, then stop for a few months to see what happens. If recession resumes, then restart the finasteride and consider yourself a lifetime customer.

15. For lifetime maintenance, use the lowest dosages consistent with skeletal and mental health. Lifetime cycling feels right for some people, and is safe as long as it is done with conservative dosages, for example, with timing as described in the philosophy section, and the following peak dosages: 0.075mg-0.1 transdermal estradiol film, or 2-4mg/day sl-oral estradiol, or 3-6mg/day sl-oral estradiol valerate, or 10-20mg injectable estradiol valerate or 1-2mg injectible estradiol cypionate. If progesterone or a progestin is included, peak at 200-400mg/day oral progesterone, or 125mg injectable hydroxyprogesterone caproate, or 10mg/day sl-oral dydrogesterone. Only exceed these peaks on a long-term basis if absolutely necessary. Be especially wary of oral estrogens and progestins. Between peaks, if using orals or films, run the troughs down to as close to zero as you can without causing significant emotional or physical discomfort. The effects at post-op levels are subtle; observe yourself closely to determine what is the most healthy for your individual case.

16. If you are post-op more than a couple of years, and find yourself devoid of energy, stamina, motivation, and libido, even when you are on what seems to be the best possible lifetime estrogen/progesterone regimen, consider this: after ruling out purely psychological issues, you might need a subtle boost of testosterone. As perverse as that might sound after spending years fighting the evil T, some post-ops find that residual endogenous androgen production (mainly from the adrenal glands) is just not quite enough to sustain a high level of activity. Some genetic women have the same problem. If this bothers you enough to do something about it, take a tiny daily dose of testosterone. Unfortunately, it can be difficult to find low-dosage preparations, especially to be funded by your national or commercial health plan. 0.25-1.0mg/day of oral fluoxytestosterone or 0.5-2mg/day oral methyltestosterone can do the trick, but tablets are especially difficult to obtain because of laws meant to prevent the abuse of anabolic steroids. Some people cover at least 3/4 of the active surface of a testosterone transdermal film before wearing it (rotating the barrier as needed), or else open the film and apply a small amount of the gel each day. It is also possible to have a compounding pharmacy add 5-10mg of micronized testosterone to a custom estrogen and/or progesterone capsule or pessary. If you prefer to cycle, take into account that endogenous androgens in genetic women generally peak just before ovulation and again just before menstruation--that is, on roughly days 13 and 27 of the cycle described in the