Hormone Replacement Therapy

Contents

There are three main components to hormone therapy for women with Benjamin's Syndrome. The first is an anti-androgen. This acts against the excess testosterone produced by the body, to prevent further masculinisation and allow the estrogen to work freely. It also tends to cause a reduction in libido and male sexual function (not usually considered a drawback). Higher doses of estrogen on its own can be used instead, as the body's feedback mechanism for testosterone levels is affected by estrogen, but this is not as effective as taking a seperate anti-androgen. Anti-androgens work by reducing the production of testosterone by the body, and preventing the testosterone that is produced from working. After surgery, they are usually no longer necessary. Unlike estrogen and progesterone, which occur naturally in the human body and help the body work the way it's supposed to, anti-androgens are drugs that interfere with the body's normal functioning, and should be treated very carefully.

The second and most important component is estrogen (aka oestrogen), which is responsible for feminisation of the body. It causes breast growth, redistribution of body fat in female patterns, softening of the skin, etc. It may result in (positive) mental changes as well. It can also reduce muscle mass, and weaken scalp hair undoing some of positive effect of anti-androgens. There are three main types of human estrogen (estradiol, estriol, and estrone), but it is not necessary to take all of them. Estradiol has the strongest effect, and the body has some ability convert between the different estrogens. Some doctors recommend cycling estrogen (and progesterone) to mimic the hormonal variations produced by the ovaries. This is probably not neccessary, as the main reason for the cycle is to regulate fertility and menstruation (obviously not relevant to women with Benjamin's Syndrome), and it can result in unpleasant mood swings. However, it has been suggested that cycling hormones prevents the body from becoming desensitised to them, and consequently better long term results... I don't know how much truth there is in that theory, but it could explain the breast growth spurt sometimes experienced after sugery (a few weeks without hormones is recommended before surgery).

Progesterone is the final and most controversial component, and is often left out. There have been no medical studies to show that it has any effect on women with transsexuality, but there is a great deal of annecdotal evidence, and I strongly encourage using it. It can help with the development of the nipples and milk ducts, though this is only likely to improve appearance and not to increase the size of the breasts significantly, and can boost libido. In women with uteri, progesterone regulates the lining of the uterus. It can also counteract some of the negative effects of high estrogen levels. Cycling is more common than with estrogen.

There's no standard way to go about hormone therapy, but it is best to add just one new drug at a time, and wait a while to see how it's affecting you before adding another. I started with an anti-androgen to reduce my testosterone so the estrogen wouldn't be competing with it, added estrogen a few months later, and a progesterone substitute after a couple of years, which seems to be a logical progression (though there's no need to wait two years before taking progesterone). The dosages needed to achieve the desired hormone levels vary from person to person, so you should start low and gradually work your way up until you find what's right for you. Which hormones work best can also depend on the individual, and sometimes a combination is most effective (eg taking two different types of estrogen simultaneously). Some people find oral hormones are ineffective for them, and have to use transdermal patches or regular injections. And it's important to have regular blood tests to monitor hormone levels, liver function, etc, especially while you're still figuring out the hormone regime that works best for you. The effectiveness of HRT is a highly individual matter, and decreases with age.

The most effective anti-androgen is Androcur (cyproterone acetate). I started my hormone therapy with one white 50mg Androcur tablet daily, and it took effect very quickly. I noticed a rapid drop in sex drive, and an immediate reduction in hair loss (not that I was at any risk of going bald, but it was nice not to have to unblock the plug hole in the shower every couple of days). It also caused me to wake up at night needing to use the toilet quite frequently, which wasn't quite so much fun. I later reduced my dose to 25mg daily (half a tablet) which was still enough to keep my testosterone below the normal female range and seems to put less strain on my bladder. Temporarily stopping androcur entirely resulted in a very obvious increase in testosterone levels, so even that low dosage is having a significant effect. Androcur is a powerful drug with potentially dangerous side effects, and should be taken with care at the lowest effective dose. It is not available in the USA, and it's very expensive if you have to pay for it yourself. It has a long half life.

An alternative to Androcur is spironolactone (brand name Aldactone). It doesn't work as well as Androcur, and is primarily intended as a diurectic which may be an undesirable side effect for anyone using it as an anti-androgen (considering the diuretic effect even Androcur has on me, I'm not going anywhere near this stuff). It is potassium sparing, so it's important to watch your potassium intake while taking spiro, and get plenty of salt. However, it is somewhat safer than Androcur. Typical dosages are around 100mg to 200mg daily.

Finasteride is a slightly different type of antiandrogen. Rather than blocking testosterone itself, it prevents its conversion to DHT (dihydrotestosterone) which strongly promotes male hair patterns. Reducing DHT is desirable, but this leaves more standard testosterone in the body, so it should generally be used in conjuction with another anti-androgen. Only a small dose is needed - about a quarter of a tablet daily is plenty. The brand names are Proscar and Procepia; Proscar is more highly concentrated and cheaper per mg, so it is most cost-effective to use Proscar and split the tablets into several pieces. Finasteride can cause birth defects, even in tiny quantities such a dust from splitting a tablet, so if must be kept away from pregnant women.

Typical Dose of Androcur	50mg daily
Typical Dose of Spironolactone	100mg twice daily
Typical Dose of Finasteride	1mg daily

My estrogen of choice is oral estradiol (brand names Estrofem or Estrace), a synthetic chemical identical to one of the main estrogens naturally occuring in the human body. I initally took 4mg daily (two small blue 2mg tablets, one in the morning and another in the evening), and was happy with the results, but my blood levels of estrogen were on the low side so I increased the dose to 6mg daily. That helped a little, but as my levels were still lower than I would have liked I decided to try taking it sublingually, ie dissolving the tablet under the tongue so it's absorbed directly into the blood stream and bypasses processing by the liver (good for both the effectiveness of the estradiol and the health of the liver). That made a dramatic difference, and I strongly recommend taking estradiol sublingually. After surgery I switched back to 4mg sublingual daily. Though the effects of oral estradiol haven't been as dramatic as from my initial prescription of transdermal estradiol, it is continuing to gradually improving my appearance, and it's definitely working for my mental wellbeing. Estrofem comes in a nice little plastic disk dispenser marked with the days of the week to make it easy to keep track of when you're supposed to take it. Estradiol is the only form of estrogen that gives meaningful blood test results.

Premarin is the most well know estrogen, but I strongly recommend avoiding it. I didn't achieve any further noticeable feminization in the year I was taking it (previously I'd only had three months on transdermal estradiol). It is a mixture of estrogens which are not found naturally in the human body. Furthermore, it is derived from pregnant mare urine, and there is a lot of concern over possible inhumane treatment of the horses used to produce it. I also experienced significant depression while on Premarin, which stopped shortly after I switched to oral estradiol... I'm not certain there's a connection (I was falling in love about the same time I stopped being depressed :-) but I'm very suspicious. Initially I was on one yellow 1.25mg pill per day, and after three months increased the dose to two pills daily. 5mg is more common in the US, but that is without Androcur to help counteract the effects of testosterone.

Patches and injections are the most effective and safest way to obtain estrogen, because they are absorbed directly into the blood stream instead of being filtered through the liver (and so require a much lower dosage), but personally I find them too impractical. For my first three months on estrogen I used Femtran patches (containing 7.8mg estradiol) changed weekly. I obtained very good results from these, but they irritate the skin, can come loose or wrinkle, and are there 24 hours a day 7 days a week. I find it much less hassle just to swallow a little pill a couple of times a day and not have to worry about it the rest of the time. I believe they are also quite expensive. It's also possible to inject yourself every week or two (with estradiol valerate or others), which doesn't have the problem of skin irritation or the constant presence, but it's not an idea that appeals to me. Taking oral estrogens sublingually works on the same principal, but some will always be swallowed rather than absorbed.

The other most common oral estrogen is ethinyl estradiol (Estinyl), a synthetic hormone slightly different from anything naturally ocurring in the human body. Estinyl has a very long half life, so it takes a number of days to reach full effectiveness, or to get out of your system once you stop taking it. I don't have any experience of it myself, but a typical dosage would be about 0.1mg daily.

Normal Female Estrogen Range	100-400 pmol/l*
Typical Dose of Estradiol	4mg daily
Typical Dose of Premarin	5mg daily
Typical Dose of Ethinyl Estradiol	0.1mg daily

* the actual range is much wider due to the fluctuations of the menstrual cycle, but this is probably a reasonable average to aim for.

Progesterone is an important part of HRT that has often been overlooked. It works with estrogen to promote breast growth, in particular the nipples and milk ducts. It can also boost the libido, counteracting the neutering effects of a low testosterone level to some extent. It may also have other beneficial effects, but medical knowledge about hormones in general is limited, and progesterone has recieved less attention than others. Its most obvious role is the regulation of the menstrual cycle, which is why doctors may consider it to be unnecessary for women without uteri. But it also appears to balance estrogen in some way - it is possible that many of the problems associated with menopause are due to an imbalance of estrogen and progesterone rather than a lack of estrogen (progesterone levels drop much more severly than estrogen levels at menopause). Progesterone is known as Micronized Progesterone, Progesterone USP, Progesterone BP, Prometrium, and Utrogestan. It comes in spherical white 100mg capsules, and should be taken twice daily as the body processes it very quickly.

Stopping progesterone may result in unpleasant emotional effects while the body adapts, eg mild depression or irritability. Women with uteri experience a drop in progesterone levels before menstruation. This could be taken as an argument against cycling of hormones, or a desirable replication of natural emotional cycles, depending on your point of view.

Progesterone cream and other over-the-counter preparations claiming to contain progesterone or progesterone-like substances are generally not effective. If they contained enough progesterone to be effective, they would require prescriptions.

There are alternatives to progesterone, known as progestins or progestogens, but they are a Very Bad Thing. Do not take them under any circumstances if you can get hold of real progesterone, and be very cautious if you have no option. Though they are chemically similar to progesterone, and are generally effective as a substitute, they also tend to have unpleasant side effects that genuine progesterone does not have. These side effects may include depression and masculinisation amongst other things. In my case, Provera seems to have caused darkening of my facial hair, and worsening of my previously sub-clinical asthma. However, I'm not yet sure whether the asthma is an progestin side effect or something progesterone can also do. Provera (medroxyprogesterone acetate) is the most commonly prescribed drug in this category. Many doctors and endocrinologists are unaware of the distinction between progesterone and progestins, and may even claim that Provera is progesterone.

Normal Female Progesterone Range	20-100 nmol/L
Typical Dose of Prometrium/Utrogestan	100mg twice daily
Typical Dose of Provera	5mg daily

Testosterone is not an evil poison which should be eliminated at any cost, despite what may be suggested by the attitudes of many women with Benjamin's Syndrome. Women are supposed to have a healthy level of testosterone (which is produced by the ovaries and adrenal glands), just a lot less than men. Before surgery it is necessary to suppress testosterone (but not usually to eliminate it entirely), but afterwards it may even be a good idea to take a testosterone supplement to bring your levels up to within the normal female range.

Methyltestosterone is one option for post-GRS testosterone supplementation. Estratest is a combination of 1.25mg esterified estrogens and 2.5mg methyltestosterone. It is also available in a half-strength version, which is probably more suitable. Even lower doses may be preferable if possible (maybe 0.5mg daily). Unwanted side effects are possible, so treat it with care.

Normal Female Testosterone Range	1-3 nmol/l
Typical Dose of Methyltestosterone After Surgery	1.25mg daily

Hormone treatment can undo very little of the damage caused by testosterone, only prevent further damage, which is why it should be started as early as possible. It is unlikely to significantly affect your voice; once it's broken, it stays broken (men with Benjamin's Syndrome are much luckier in this regard). It does not reduce the size of the adams apple, though contrary to popular belief women do have this structure, it's just much less prominent on average than in male bodies. It will not have any significant effect on facial hair, though it might cause a reduction in thickness, darkness, and density of body hair if you're lucky. It may reverse male pattern baldness to some extent, but this effect is limited, and if you've lost enough hair for it to be a serious problem for you, hormones probably won't be enough to fix it. Although it does cause any subsequent bone growth to occur along female lines if you haven't stopped growing yet, it can't undo growth which has already occurred, so your height, build, and the size of your hands and feet won't get any more delicate than they already are. Fortunately testosterone doesn't seem to have any serious permanent negative effects on the brain; a decent supply of estrogen is enough to get it working properly.

• Hormone FAQ - information on HRT for women with Benjamin's Syndrome.
• Hormones (TS>F) - HRT section at Kathleen's Korner.
• Hormone Treatment in Transsexuals