Mechanical difficulties
First of all, some women do not adequately absorb hormones by some routes. There are women for whom a hormone cream might as well be the cheapest sort of hand lotion for all the hormonal benefit that makes its way through their skin. For others, they could as well be swallowing after dinner mints as hormones. Or, as a charming waitress in Tennessee once put it, "Darlin' you might as well just open up your mouth and let the moon shine in." Some of us just can't get hormones into our bodies by one specific route or another. For every route, there's someone it just doesn't work for. And, obviously, a great many for whom it does.
For other women, it's a more complicated situation of the absorption dynamic not suiting our metabolic needs. A pill meant to be taken once a day may peak too hard and fast; a patch may get used up days before it's due to be changed; a troche may rush into the system so fast that life is a boom-or-bust hormone rollercoaster.
How are we to know? The only way to find this stuff out is to try it on an individual basis, and if one approach doesn't work, move on to another. This can push the limits of some doctors, in that having read research that says a given hormone works, they may find it more appealing to blame you (I'm giving you hormones, so if they don't work, you must be depressed) than revise their understanding.
In fact, some women spend years, literally, trying every possible combination of hormones, routes and doses in order to find the right one for their body. We don't mean that this is going to happen to everyone—many more women happily hit on the right thing on their first or second attempt. But you should know that there are lots of variables, and while it gets mighty aggravating, it's not hopeless. This is a true TANSTAAFL situation where you have to pick out what may be the least of evils based on your own preferences and needs.
Route-related effects
Oral HRTs
Unfortunately, when this happens with a whole pill's worth of important medication that is meant to last out the day, most of it can be disposed of by the liver before it can do its work. This is called the first pass effect.
Because of this liver action, hormone pills must contain a very high dose of hormones so that enough of the dose gets past the liver to have some systemic activity. Obviously, this can be hard on the stomach, and so nausea and stomach irritation are sometimes associated with this route. This heavy processing binge can also be hard on the liver, and in fact oral hormones are associated with a higher incidence (two- to three-fold) of gallbladder disease and liver problems than hormones taken by other routes.
On the other hand, oral estrogens have a greater beneficial effect on cholesterol and blood lipids than estrogens given by other routes. Oral progesterone is believed to have more sedating metabolites than transdermal progesterone.
Oral dosing is associated with a higher blood level of binding globulins, special proteins in our circulation which can in turn decrease the bioavailability of some other circulating hormones (sex hormone binding globulin, for example, inactivates testosterone and thyroid binding globulin inactivates thyroid hormone). There is also some feeling that oral progesterone and estrogen are more likely to be linked to fluid retention than when taken by other dose routes.
Oral HRTs are associated with higher levels of inflammatory factors such as c-reactive protein. These, in turn, may be the reasons why blood clots, cardiovascular disease and autoimmune disorders are more negatively impacted by oral than other routes. This is a current topic of research, so this picture may grow clearer in the next few years, but research is generally firming up on this interpretation.
Finally, oral estrogens metabolize into different proportions of the three estrogen forms (generally, more estrone) than the same estrogen taken by another route.
In terms of adjusting doses, pills allow you to adjust only in multiples of pills, for the most part. A few can be divided, but they are in the minority. Compounded pills can be made to any dose, but a new order must be made up to change doses. All three hormones may be delivered by the oral route although progesterone must be made up into an oil-filled gelcap to do so.
Transdermal HRTs
Because transdermal hormones bypass the liver's first pass effect, they may be preferred by women with clotting problems, smokers, and drinkers as well as those who have liver or gallbladder disease. According to other studies, they may be a better choice for those with or at risk for hypertension and other cardiovascular diseases. Transdermal estrogens seem to be associated with a higher circulating level of a protein associated with a lower cardiovascular risk profile.
Some women find the application of creams or gels to the skin time-consuming and messy. Care is needed to apply them, to prevent them from being removed by clothing or other people before they have been fully absorbed. The rule of thumb pharmacists have often given women is that it takes about half an hour until enough cream dose is absorbed that it's okay to shower or sweat heavily. Gel manufacturers often note that clothing may be worn over an application site as soon as the product has dried fully.
But that may not be an accurate measure of transfer risk. The makers of Estrasorb, a creamy lotion, report that levels high enough to alter a partner's estrogen levels may persist as long as eight hours after application (interestingly, this is in the prescribing information, not the patient instruction sheet).
Similarly, the manufacturers of testosterone gels go to considerable length on transfer minimization (for example, in this Testogel data sheet, check out the "Potential testosterone transfer" subsection, partway down the page) and suggest "a long interval between Testogel application and sexual intercourse." Unfortunately, they don't specify just what they mean by "long," leaving us wondering what order of magnitude they have in mind: minutes? hours? days?
We haven't come up with good answers on this one, but users of transdermal HRTs might be well advised to ask their pharmacists about their specific brand/formulation if exposure of a partner or children is a concern for them.
Because hormones are fat soluble, they can be locked up by indigestible oils used in cosmetics, such as mineral oil. It's important, if you use transdermal hormones, to read the labels on your body moisturizers, bath oils and other potions to make sure you are not binding your hormones up beyond use.
On the other hand, hormones delivered by this method are readily adjustable in quantity and timing. If you are just getting started in the HRT tuning process or find that you need to adjust your dose on a regular basis, a cream/gel may be the easiest vehicle for doing so. Hormone creams are best applied on thin skin over fat—which means inner thighs, upper arms, chest (not breasts) and belly; gel application areas are generally specified by the manufacturer. You should rotate locations so that your hormones are released evenly rather than clumped in one area of the body.
Unfortunately, since many hormone creams come in a jar or tube, it's seductively easy to just use a glob, eyeballing the quantity. But because our bodies are sensitive to small variations in hormone dose, rewarding us with hot flashes if we allow our levels to fluctuate too much, it is actually pretty important to be accurate in measuring quantity. While a measuring spoon can be helpful, greatest accuracy is achieved by using a syringe. Syringes without needles can be obtained from the pharmacist who fills your prescription or from veterinary supply catalogs; some pharmacists will provide your prescription in pre-filled syringes upon request. Especially when you are getting balanced on a hormone dose, accuracy can make a big difference in how you feel from day to day. When we are talking about measuring 1/4 teaspoon doses, just having it mounded a little high can be a 25% increase in the hormone dose delivered—and that's a lot as HRTs go.
Hormone patches are another transdermal delivery route. They are attractive for many women because they have to be messed with only once or twice a week. Their delivery is supposedly totally steady from the time it hits the skin till it's removed. That "supposedly" is in there because, in practice, hormone delivery will decline a bit before the patch is due to be changed and lag a bit before release really kicks in from a new patch.
Patches come in doses, which means they meter out the hormone in different amounts such that your total hormone quantity is different over time. This is generally achieved by area: the size of the patch is proportional to the size of the dose (to go to a higher dose, you cover that much more of your skin with it). To adjust a dose of a patch, you may need to switch to another patch size or even wear two patches at once. Some patches can be cut to modify the dose downwards; in others, the delivery system is destroyed by cutting. This is important to know about your particular patch brand, and is be included in our discussions of each HRT brand.
The rate of hormone absorption (and hence your dose) is also affected by where on your body you place the patch. Patches can be worn on the belly, flanks, buttocks, thigh, chest (not breasts) and upper arms. Not all patch manufacturers have determined the release rate on all these locations, so it's a good idea to read the fine print on the brochure that comes with your patch. As a general rule, delivery is higher by 17%-25% when a patch is placed on the buttocks rather than the belly. Which one you use doesn't really matter, once you are balanced on your dose, so long as you are consistent in the general area you use from one application to the next. It doesn't mean, however, that you replace a patch on the very same place every time. It's important to rotate patch locations to give maximum time for each area to clear the last dose thoroughly.
The skin to which a patch is applied is important as well. Patches should not be applied immediately after a shower or bath, when the pores are open—this can sting, a lot. Wait a few moments till the skin is cooler and dryer, and you'll be a lot more comfortable. Also on the list of patch peculiarities is the sticky ring of glue left after some patches are removed. The most benign things to remove the glue with are oily skin lotion or oily makeup removers, smeared on and left for a few moments to soften the glue before scrubbing with soap in the shower. Harsher things such as acetone or glue-removers or citrus degreasers shouldn't be necessary if you are patient in working with this, and avoid having more chemicals absorbed through your skin to stress your liver.
All transdermal hrts may be affected by temperature, both yours and the temperature in which they are transported and stored. Check the data sheet that comes with your hrt or ask your pharmacist about this. Some women in hot climates have experienced reduced hrt strength when their mail-order hrts spend time being carried about by the mailman and placed in a hot mailbox; other hrts can be "cracked" or damaged by freezing, as can happen with mail delivery in cold climates.
It's also possible to sweat patches and cream/gels off to an extent that affects their delivery. In climates where a woman is exposed to a lot of sun, a need to use sunscreen may interfere with hrt adhesion or uptake, and sunscreen itself may contain estrogenic ingredients (free signup required to read).
Estrogens and progestins (not progesterone) are available in patches, creams and gels; testosterone is available in gel or ointment.
Transbuccal HRTs
These are dissolved between gum and cheek or under the tongue, passing through the skin that lines the mouth. This route has the same advantages as transdermal (it's a special subdivision of transdermal, actually) in terms of bypassing the liver's first pass effect. This route may also be referred to as "sublingual" although that's actually a subset of transbuccal, since it literally means "under the tongue" as opposed to generally anywhere in the mouth.
Because of the greater efficiency of transbuccal delivery, a woman generally will take a lower overall dose (as compared to oral) to achieve the same effective circulating hormone level. A transbuccal HRT may come as a standard tablet or as a troche, a gummy square prepared by a compounding pharmacist, or as an oil to be measured out by drops.
It is very important that you not swallow while the pill or troche or oil is dissolving and being absorbed—the objective is for the hormone to enter your system through your oral mucosa (skin) rather than being swallowed, which would make it just another oral hormone instead. It usually takes about half an hour for a dose to be fully absorbed, and things go better if you can resist sticking your tongue on it every few minutes to see if it's all gone yet. This gets easier with practice. At first, doing this in private may prevent embarrassment from having it stick to your teeth and pop up, drooling, or other less attractive activities.
Some women find they absorb a hormone from under the tongue so rapidly it gives them a headache; others find that the upper lip/gum location leads to sinus congestion. As with so many other aspects of HRT, the only way to work out the best approach for yourself is to experiment and listen to your body.
All three ovarian hormones can be taken this way, and dose adjustments are similar to pills: some cutting of pills or troches is possible and the total number of oil drops can be modified. Note, however, that not all hrt pills designed for oral use can be used transbuccally: the molecular size of the hormone compound itself is at issue here and some are just too big to get through. We discuss on the hrts pages which particular ones are suitable for transbuccal use.
Vaginal HRTs
Finally, vaginal delivery also is considered a transdermal method. Hormones are readily absorbed through the vaginal mucosa (skin).
Typically, vaginal methods are used when you want to concentrate hormone delivery in the vicinity: to the vagina, genitalia, or urinary tract. Because of this concentration in local tissues, vaginal estrogens are not considered a safe choice if one is avoiding estrogen use to suppress endometriosis. For women who cannot take systemic hormones, however, low vaginal dosing may help prevent vaginal atrophy without incurring the risks of elevating systemic levels.
Systemic hormones may also be delivered by this route, although this practice seems more typical outside the US. When given for systemic use, the doses are typically higher and may be in a form that has to be converted to active in the blood stream so that local tissues are not overwhelmed. When active forms are used, especially when hrts prescribed for oral use are instead used vaginally, there are some concerns to do with concentrating the dose in pelvic circulation.
Vaginal delivery methods include creams, ointments, gels, rings, and tablets, and can used for the delivery of all three ovarian hormones. Because rings areavailable in both local and systemic doses, it's very important to doublecheck your prescriptions (when they are written by your doctor and when you pick them up from a pharmacy) to be sure you have the correct one for your intended use. When using most vaginal hormones, it is important to space your dose times so as not to deliver the dose to your sexual partner as well.
Subdermal HRTs
This delivery methods include shots and implanted pellets. Both of these are timed-release formulations that slowly release an (ostensibly) even dose over periods of from one to three months.
For some women, these are the only methods that effectively deliver hormones to their systems. For others, this is pure hell. The normal absorption pattern is in fact not a straight line but a curve, with a somewhat higher level initially followed by an ever-steepening decline as the end of a dose's life is approached. Women who fail to tolerate this dosing method often object to the way they feel as their hormones decline before the next shot or implant is due.
Another drawback of a delivery method that is so long-lasting is that if the dose is wrong, you have to live with it for a considerable amount of time. Obviously, you can't take a shot or even implanted pellets (they go just below the skin) back out if the dose isn't right: you just have to wait it out. For some women, the long-interval dosing schedule and the fact that they are reliant on their doctor for administration is a benefit in that they don't have to "bother" with hormones at all. For others, being dependent on someone else's scheduling and availability—not to mention the expense of repeated office visits—is distasteful if not demeaning.
Estrogen and progesterone are most typically given by this route, but there is no functional reason why testosterone cannot be given this way as well.
