What We (Don’t) Know About Estrogens
In my Trans-Health articles over the last year I have explored testosterone a few times. Now let’s try estrogens.
I won’t bore you with the details of basic physiology, organic chemistry and biochemistry. If you would like to be bored by those topics, I suggest reading the sections in my article Androgens: Under the Hood that cover these subjects. I’ll wait until you finish… and wake up.
We seem to know quite a bit more about androgens than we do about estrogens. Chemically, the classes of molecules are quite similar; the difference is significant enough, though, that a different receptor is required for estrogen to do its thang. There are actually two distinct estrogen receptors; the second was discovered within the last few years and seems to have been greeted in the research community with the same enthusiasm expressed by fans of N’Sync when the boys roll up on the tour bus. (Not that research biochemists are running around screaming, mind you, though that would be pretty hysterical….)
ER-ß (Estrogen Receptor Alpha) is found in greater numbers in the kidneys, pituitary gland and adrenal gland and has been implicated as a possible contributor to breast cancer; ER-ß (“Estrogen Receptor Beta”) is found in larger numbers in the brain and lungs. Both receptors are found in the reprouctive systems (testis, ovaries, uterus) and in breast tissue.
Estradiol, Estrone and Estriol
Estrogens are a class of molecules, much like steroids, androgens and progestins. The three molecules shown in Figures 1, 2 and 3 are the estrogens produced naturally in our bodies. There are several metabolic pathways to the creation of these estrogens, including, interestingly enough, from androgens via enzymatic conversions. They are also produced in the adrenal glands, and in the ovaries in bodies that have them.
Figure 1: Estradiol
Figure 2: Estrone
Figure 2: Estriol
The various estrogens have different avidities and affinities for the estrogen receptors. Compared to the other two, estradiol produces the most dramatic effects in the body. This is why trans women who have chosen to use hormones often use injectable versions of the hormone. The most commonly used injectable estradiol in North America is estradiol valerate.
For ease of use, the majority of trans women choose an oral version of estrogens. By far the most popular is Premarin, more generically known as conjugated estrogens. Premarin is a mixture of several different kinds of naturally occurring estrogens, some of which are not produced by the human body. (Premarin is extracted from horse urine: the story is that the brand name of the drug is shortened from the descriptive phrase “PREgnant MARe urINe,” though I cannot vouch for the veracity of that story.) I am not one of the people who thinks that Premarin is bad for you simply because it contains estrogens that the human body does not produce. I would be more concerned about using Premarin simply because it is taken orally.
Which brings me to a relevant point about taking estrogens: Estrogens have long been tied to problems with circulation and blood clots. Studies have shown that estrogen encourages the production of blood clotting factors in the liver. THIS IS IMPORTANT. If you are a woman, trans or non-trans, taking estrogen replacement, please pay attention to the symptoms of blood clotting that your physician should have warned you about when s/he prescribed them to you. Blood clots can be very dangerous, even fatal.
What does this have to do with oral drugs? Drugs that are consumed orally undergo an initial pass through the liver. As I mentioned above, the liver is the place in which the clotting factors in question are produced. Injectable preparations do not pass through the liver in the same way, and therefore they do not have the same degree of risk for clotting.
(My argumentative Type A readers will note that I did not state that injectable estrogens carry zero risk of side effects related to clotting, only that they likely do not carry the same degree of risk as oral preparations.)
How much do I take?
If you have been reading my articles for a while, you should know better than to ask me this question. Shame on you! I am not going to tell you how much to take. Only a licensed and experienced physician should make those recommendations. The most important thing to keep in mind is that supraphysiological levels of estrogen have been linked to health problems in the population that has been most thoroughly studied— menopausal and post-menopausal chromosomally XX women. I would not recommend increasing your dosage just because you can.
The two most common hormone replacement therapies for trans women in North America are injectable estradiol valerate and the oral Premarin. Therapeutic doses range from 2.5mg-10mg/day of Premarin, and 10-40mg/fortnight (two week) of estradiol valerate. Doses can be reduced significantly if the testicles are removed in surgery, either orchidectomy or GRS.
Personally, I was prescribed 10mg (1mL) of estradiol valerate, to be injected once every two weeks. I have been using it for almost 18 months and am 11 months post-orchidectomy. I am happy with the changes I have experienced on that dosage. However, one change I did make was to inject 5mg (1/2mL) once a week instead of 10mg every two weeks. I was experiencing mood swings at the end of each two week period. Switching my injections to weekly injections have cleared up that problem and now I am back to my constantly (some would say “annoyingly”) chipper self. Ask Your Doctor or Pharmacist.
There has been much more research done on hormone replacement for trans women than on hormone replacement for trans men. As such, there is a wealth of information available online and in print. Not all of it is good. Don’t take anybody’s word (including mine or your physician or endocrinologist) for anything. I have heard stupid and inaccurate statements regarding estrogen replacement therapy from a GP physician and even from an endocrinologist, both of whom had extensive experience with trans patients. If I had not done my own research, I would not have known any better.
Stay safe! And stay tuned for more technical and practical articles about hormone therapies for trans folk.
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