Smile. And if you did not already have a headache... trying to read what I am about to write probably will give you one. LOL.

More seriously... there are many possible reasons for what you are describing -- and there are way too many details about your health that I do not know to even attempt to make a diagnosis over the internet. But that said... there is some general advice I can give you, which may (or may not) be useful to you. By all means, listen to those others who have recommended seeing a doctor in person. But until you do... some suggestions.

Giving you anything resembling a "real" answer is going to be a very long reply, though... so first I will give you my "best guess". The short answer is: Mild "cerebral discomfort" is probably not a cause for concern. Most likely the symptoms will abate in time (a month or so), as your body adjusts to the new chemical balance. But... and this is important... I am making a lot of assumptions about your general health in saying that. So... here comes the "long answer", that may give you a better idea as to whether or not my "short answer" applies in your particular case...

Do an internet search using the phrases "drug fact sheet", and what ever the name is of your particular medication. "Estradiol" is sort of a generic name... it merely describes the active ingredient -- it could come in several different specific formulations. Lacking knowledge of which specific brand you are taking, I can still make a few comments. The following, for example, comes from the drug fact sheet for "Estrace", which is estradiol-17-beta (micronized).

Shrug. Before I get to that, though... I sort of get the impression (perhaps mistaken) from others comments that you are a "do it yourself" patient. If so... the more you know about what, exactly, you are taking into your body, the better. So... a short aside, first. Just some general information about hormones... which you may or may not want to read. In case you decide to skip this, I will block quote this section -- ignore it if you want. The only really important thing to take away from this is that Estradiol is also known as "E2" -- and that is only important as you will likely see that used as shorthand for Estradiol-17-beta in various articles on the web...

The "estrogen", or 'oestrogen" if you are from the UK, molecule has several different chemical structures... but they are all closely related. The basic form is that of three "hexagonal rings" of carbon atoms (where the central ring shares one edge with each of its neighbours) and a four "pentagonal" ring (known as the "D ring) sharing an edge with the third hexagonal ring. In total there are 18 carbon in any estrogen molecule (17 in the four rings, plus an extra one in a "branch" at atom 13), each of which is given a number -- starting with "1" in the "A ring", and working its way up the chain. The missing atom from that last ring makes it somewhat more chemically active than its neighbours... which is why the 17th carbon atom in the chain is of special interest -- and why "estradiol-17-beta" has a 17 in it. The "beta" part refers to which of four possible "linking sites" on the carbon atom that the hydroxyl group is attached. Smile. Which is what the chemical difference is between the various types of estrogen. All estrogens have a single hydroxyl group (a hydroxyl group is just an oxygen and a hydrogen atom, linked together} attached to the "A ring" at carbon atom "number 3" of the chain. Estrone, sometimes called "E1" on blood tests, has only that single hydroxyl group... with a single oxygen atom at 17-beta. Estradiol, also known as "E2" on blood tests, has two hydroxyl groups -- with the second one attached at 17-beta. Estriol, "E3" on blood tests, has three hydroxyl groups -- the same two as Estradiol, plus another one attached to the 16th carbon atom.

So... what has all this got to do with anything? Well, the thing to know about all these estrogen molecules -- as well as all "sex hormone" molecules -- is that they are all closely chemically related. The evil "Testosterone" molecule, for example, is nearly identical to the three human estrogens -- take an estradiol-17-beta molecule, remove the hydrogen atom from the hydroxyl group at C5... then add an extra carbon group at C10... and viola -- you have a "19 carbon" testosterone molecule. Add an extra hydrogen at C5 (using something called the 5-alpha-reductase enzyme, if you care) to testosterone, and you have Dihydrotestosterone -- also known as "DHT", the other "evil" hormone that is best known for causing baldness. Or take a testosterone and lop off the "hydroxyl tail" at 17-beta, replacing it with "alternate tail" of two carbons and an oxygen... and you have the "21 carbon" progesterone molecule.

Actually... it works the other way around. All sex hormones start life as cholesterol, with 27 carbons. Various enzymes whittle that molecule down in various ways... from cholesterol, to progesterone (via an intermediate molecule)... to various other things of no interest at the moment... to either testosterone or estrone (via a couple other molecules). The testosterone can then either convert to DHT or estradiol, and the estradiol can be converted to estriol. The estrone can convert to estradiol, or directly to estriol.

Shrug. The general pattern in all this is that you start with a long chain of carbon atoms, and you slowly knock bits and pieces off. But once you knock a carbon off the chain... it is (biochemically speaking) easier to start over with a "fresh" cholesterol molecule, than it is to try to re-attach a carbon to the chain.

Or in other words... if you have too much testosterone in your system, some of it can become estrogen -- but the reverse is not true. And note that progesterone is a possible "precursor" chemical for either estrogen OR testosterone -- which is why some people *sometimes* experience "androgen-like" side-effects with that HRT medication. [Hair growth, etc].

Backing up for a moment, purely because of a question I saw asked over on a Yahoo group recently... from progesterone you can also synthesize cortisol and corticosterone hormones. Not important... other than if you are taking other medications containing those, it can do strange things to your HRT. Also on the "not on the warning labels" list is a possible side effect of *stopping* HRT... which can occasionally cause weight gain. Why? Because of the chemical link to cortisol, which is used by the body to regulate many things related to weight control. [Some people, not all, also experience some weight gain from being on HRT for much the same reason. Basically, keep in mind that all of these hormones are chemically similar, and hence are made in the same places in the body -- the gonads, and the adrenal glands. They all use similar enzyme chemistry to convert common precursor molecules... and therefore, if you "mess with" the levels of any of these hormones, it can side-effect the bodies manufacture of other hormones in this class.

Okay, enough with the biochemistry already. The short version is... there can be side effects from taking HRT, possibly with body systems that you might not expect to have effected -- that was what all that chemistry stuff was about. The link between HRT and other, chemically similar, hormone molecules... which control other systems in the body, and hence HRT can possibly side-effect those other systems.

Keep in mind... that is what the "hormone" part of "Hormone Replacement Therapy" is all about. Hormones are simply chemical messengers -- the signalling system that the body uses to turn on and off various other things in the body. When you alter the balance of those chemical messengers... you send signals that can make some substantial changes to other systems in the body -- changes that are completely out of proportion to the amount of medication taken, since hormones are simply used to turn other processes on or off, they are not "fuel" used up in the processes themselves.

Shrug. I am sorry, "tels"... but I can not agree with you. Brain chemistry (as well as other chemistry all throughout the body) actually *is* altered by HRT -- it is not a "myth". That said... I think I understand what you were trying to get at, and I can agree with that. Hormones will alter the chemistry, but they will *not* alter the physical structure of the brain. (Well... there is some controversy about that in the long run... so let's just say, not for many years, and not significantly). So... what "tels" said about the "can not be changed" is more or less right, even if "tels" is a little off in the details...

Back to the "drug fact sheet" that I started all this with... there are (rather obviously) some parts of it that you can ignore. I rather doubt you need to worry about being pregnant... uterine cancer... other uterine possible problems... breastfeeding... and undiagnosed vaginal bleeding. Smile. But that still leaves a bunch of reasons for NOT taking estrogens:

• Allergies to "non-medicinal ingredients". Shrug. Read the fact sheet carefully for those -- I am "lactose intolerant", for example... and Estrace contains some lactose. Not a whole lot... so more or less got away with taking oral estrogens back when I took them -- but it did bother me a bit. [I use injection HRT now, so it is not an issue for me any more... but that is something to watch for -- and such allergic reactions are one of many possible sources of your headaches...
• Thrombosis history. Blood clot problems... whether heart related (coronary thrombosis) or brain related (previous stroke)... or just general "diseases of circulation or clotting". Shrug. Estrogens interact with blood clotting factors, meaning that if you have any kind of history of blood clotting problems -- HRT is something to only consider under direct medical supervision, if then. This is not something to play around with -- this can kill you, and quickly. If you do have such a history... and are experiencing headaches with HRT -- get your ass to your doctor or the emergency department of the nearest hospital, as soon as you read this!
• A previous history of migraines. Shrug. Probably not the case with you, since otherwise you would not be really noticing new headaches. If it applies... it is sort of like the thrombosis history, but not quite so serious. Generally, there is always a suspicion of circulation problems when there is a history of migraines... and hence a worry about thrombosis issues. But it is "less" of a concern... and I do know folks with migraines that have successfully been on HRT. Medical supervision is strongly recommended, though.
• Liver impairment (obstructive), or "has had partial or complete loss of vision or double-vision from eye disease related to circulation problems". Shrug. See my comments with migraines. Either of these indicates problems with your blood that are likely to get worse with HRT -- and the liver one is especially a "red flag", as oral HRT tends to put extra strain on your liver. HRT may still be possible... under doctor supervision... but transdermal ("patches") or injection HRT would be my recommendation in either case -- not oral.

If you are following along on whatever drug fact sheet applies to your particular medication... you will probably also see a section on "Side effects". Shrug. All forms of estrogens tend to have very similar side effect sections... so I am going to continue making comments based on Estrace. Even if you are actually taking something else, odds are what you are reading is extremely similar to this. Again, there are some that can be ignored -- I doubt you will experience vaginal bleeding, for example...

The following are considered "mild side effects", meaning... see your doctor if they really bug you, but they are "probably" not life threatening. Ignore them, and see if they will go away on their own after a few weeks (when your body has fully adjusted to the new chemical balance), if you want... or go see either your pharmacist or doctor for advice on managing these symptoms, if they persist longer than that.

• Acne; bloating of stomach; cramps of lower stomach; nausea; loss of appetite; hair loss. All of these are possible... but not very relevant at the moment, so I am mostly going to ignore them. Note that the "nausea" symptom also appears in the "serious side effects" section. Basically, if the nausea is "mild", see this part. If it is severe, see the other list.
• Changes in cholesterol levels; increased blood sugar levels; weight changes. Remember all that chemistry stuff I wrote about? This is part of where that comes in. HRT messes with the chemistry of your gonads ("testicles") and adrenal glands... which also produce other hormones that affect all of these. Interestingly, changes in blood sugar levels (caused mostly by side effect on cortisol levels, by the way) can express itself in many ways... including headaches...
• Depression or nervousness; dizziness; headaches (mild). Again, this is the chemistry stuff in action. The "nervousness" is your adrenal glands being "messed with" by HRT -- as you may have guessed from their name, adrenal glands also produce "adrenaline" (also known as "epinephrine")... and an increase in adrenal levels can cause headaches and "nerves". Blood sugar levels (cortisol) may also be a factor in these symptoms -- see above.
• Breast pain or swelling. Smile. Okay, I am just listing this one for completeness sake -- I assume this "side effect" is what you actually *want* to have happen... Grin.

The following are considered "serious side effects" -- see your doctor immediately if you have any of these. Shrug. What can I say about these -- I am mostly just going to repeat them verbatim from a fact sheet, in case you have not actually looked them up yourself... but I will group them together, and add a few comments to them...

• Crushing pain or chest heaviness; shortness of breath (sudden and unexplained); weakness or numbness in arm or leg. Can you say, "Heart attack"? Blood clots, big time... in your heart or lungs. Hospital. Go. Now!
• Loss of coordination; loss of vision or change of vision (sudden); slurring of speech (sudden); headache (sudden or severe). Blood clots again, this time in the brain. Stroke is very possible. Go. Now.
• Pains of chest, groin, or leg, especially in the calf of leg. Blood clots... and if the pain is in your chest, see my "heart attack" comment above. I mostly just gave this a separate entry due to the calf muscle pains... which *might* be due to blood clots -- or might not. Many folks on transgendered HRT are taking both an estrogen, and an androgen blocker such as spironolactone. If you are also taking Spiro... be aware that Spiro is a potassium sparing diuretic -- which means that in addition to blocking the testosterone, if can also screw around with your blood potassium levels. And one of the side effects of *that* can also be leg cramps... which are a whole lot less serious if they are due to Spiro, than if they are due to estrogen. So... take a moment to figure out which one is the problem, before you panic due to this symptom. By the way... the need to figure out *which* medication is causing a side effect is why it is *strongly* recommended that those starting HRT start only one medication at a time, then wait a month or two before starting the next one. Otherwise, if something goes wrong, you have not a clue as where the source of the problem is -- or possibly how serious the problem may be...
• Stomach pains, nausea, and vomiting. "Severe nausea", rather than mild. There are several possible reasons for this... severe allergic reaction... digestive problems resulting from hormonal changes to liver, gall bladder, or pancreas function... assorted organ failures due to reactions to HRT or blood clot issues... to name a few. A rather long list, the more I think about it. The short version is: none of these are good, and many of them are life-threatening. See a doctor, the sooner the better.

Sigh. Medicine is a complicated field... and I could babble mindlessly on for pages, listing possible reasons why you might be having headaches, and what it means. Which is why some others are simply suggesting that you do this under medical supervision. That is ALWAYS good advice, and I highly recommend it. But... that said... I remember "borrowing" birth control pills from a female friend back when I was a teenager -- and I do know how strong the motivation can be to start "fixing" your body, regardless of the consequences. How big the fears can be, that may keep you from talking with a doctor. How tempting just "doing it yourself" can be. Which is why I sometimes write things like this. Not because I recommend "DIY" HRT -- I do not -- but simply because I understand... and since I *know* folks will do it, regardless of whether they have any clue what they are doing, or not (as I was totally clueless in my youth). So I try to "minimize the risk", with articles like this...

But please... see a doctor. Some people can take HRT without supervision, and never have a problem. Some can not. Everyone's body is different... everyone responds slightly differently to medications. You (obviously) are already experiencing complications. Mild ones, most likely... but complications. In your case, I would really strongly recommend that you do this "the right way", as your risk is probably higher than average -- based on what has already happened.

Good luck.

Disclaimer: Although I am a licensed medical professional, I am only licensed in the area that I live in... which is more than likely not where you live. I am also writing this quickly, without proof reading it, after midnight (my time zone)... which is to say, it is entirely possible there may be factual errors in this article. This should therefore not be treated as anything other than "general education" advice... and you should always rely on what your own doctor tells you.

Copyright (c) 2012 by S.L.Hawke, all rights reserved. Do not re-post or quote this article elsewhere on the web without prior written permission.