Mechanics of using the transbuccal route for HRT

When taking one's HRT via the transbuccal route, there are really only two things you have to master. One is physically keeping it in place long enough for it to be fully dissolved without swallowing it all in saliva (which is the same as swallowing it as a pill). The other is picking the right place for this in your mouth.

Where?

In choosing where to put your HRT, you can use any place in your mouth, since the micronized estradiol in Estrace or its generics (or compounded troches) can move right through any part of the entire oral mucous lining. But the optimal location will be the one that causes the fewest associated symptoms due to its uptake, and that's likely to be a personal situation that can be determined only by experience.

Dissolving your pill or troche under the tongue seems pretty straightforward and controllable, and indeed is the direction provided with many compounded HRTs. But some women may find that they get a headache almost instantly, one that can take an hour or more to clear. The suspicion is that when this happens it's going zinging from under the tongue straight into the circulation through one's head to run full tilt into the brain with a mighty SLAM. Ouch.

When some women put it between gum and upper lip (back halfway between the pointy eyeteeth and the last molar--if you feel up there with your tongue, there's usually space "on top of" the roots of your teeth where it can be tucked and not slide back down), it stays up well and absorbs fully, but it can make one's nose/sinuses fill with mucous. Now, estrogen is given to chickens to make them retain water and weigh more once they are butchered, so speculation we've read on this response was that either this was a reaction to the estrogen as a sinus irritant or it was causing local fluid retention, hence the snotting-up.

A third option is in front, between the lower gum and lip, all the way down at the bottom "below" the roots of those teeth. For women troubled by the above problems (and there are plenty of women who aren't, so don't assume that you will be if you prefer to start with one over another), this one may be a viable alternative and we've not read any other problems with this location except for the need for some dexterity in maintaining it in position.

How?

The other aspect, then, involves getting it to actually stay put and dissolve. That's almost more of a motor skill than anything else, and you can expect a few failures at first. You may want to practice in privacy lest you grin too many good morning smiles with lavender-smeared teeth. Here's what we've found helps.

Before putting the tablet (or partial tab, if you're customizing your dose) in your mouth, try to sort of suck up all the excess saliva so the location is fairly dry. Then pop the tab into place without a lot of lingering to get wet on the way. This seems to help make the tab stick where it's put. Get too much saliva in there between skin and tab and you run a risk of having it pop back out: we've heard of them actually being sneezed them across the room on mornings when the timing was off, and we really don't want to be envisioning you scrabbling around on the floor on your hands and knees trying to get it before the cat does.

Okay, so you have it tucked out of the way and fairly adhered. Now, practice leaving it alone. That means stop touching it with your tongue every 30 seconds to see if it's still there! Sure, it's nearly irresistible, but resist anyway. Every time you let your tongue sneak in there, you're bringing in a little saliva to float some loose and raising the amount you lose by swallowing.

This doesn't mean you can't swallow—you'll just have to learn to not let saliva float around the tab and then swallow. Yeah, saliva traffic management is the key (we are rolling our eyes to think that, yes, this is what taking hrt comes down to). With time and practice,you may learn such advanced tricks as drinking coffee without disturbing your tab (yes, we're talking very hardcore, here, plus years of practice). You will probably find that you cannot, however, swim laps with it in place or shower—even we will admit that there are limits.

What happens is that the tab moistens pretty rapidly into a sticky sludge, and that sludge is gradually absorbed into the skin until it is all gone. Then you're done. This generally takes about 20-30 minutes for complete absorption. If you taste a sweet taste, you've got it floating in saliva—you shouldn't be tasting it, because what you're tasting, you're losing down your throat and the digestive first pass effect will get rid of almost all of that for you.

In terms of dose dynamics, this route fits someplace between oral and other transdermal deliveries. You do get a single dose peaking and then falling, but because this effect is slower than when HRTs are swallowed, you don't lose a lot to first pass and trigger the demanding liver loads that seem to be correlated with the worst oral effects (clotting, cardiovascular, gall bladder).

But because it's not a trickle-type dose that enters your system continuously, like a patch, you do get peaks and dips. Some women are highly sensitive to this; others aren't bothered by it. One factor in women's ability to manage hormone levels through the day on a single dose seems to be related to how long postop/into menopause they are, suggesting that it takes some time for our bodies to accommodate to this new mode of managing hormone levels. According to one research study we've found on this (and it's a very small study, so should only be considered a hint, not irrefutable demonstration) and some further discussion of it on a site covering transgender use, sublingual estradiol created a higher, faster peak in blood estrogen levels than oral doses of the same compounds, and this level is predominantly estradiol for the initial two hours and then is mostly estrone (note that the discussion site focuses on just the estradiol dynamic). This represents the expected pattern of estrogen management, converting the surplus amount of active estradiol into estrone, the inactive form, for later use. In contrast, oral doses of estradiol are primarily estrone by the time they reach general circulation after processing in the liver. This suggests that women who find oral estradiol somewhat lacking might also get more active coverage from the transbuccal route, even leaving aside the first pass losses.

And it's very important to keep that increased activity and quantity of estrogen from the transbuccal delivery in mind when picking a starting dose. There is no table of bioequivalency, no conversion formula that states that if you are using so much of an oral dose than you need this much in transbuccal form. Alas. In fact, there is little general consensus on what this conversion should be in even rough terms, and we've seen recommendations for everything from 50% of the oral dose to only 20% of it. While the latter figure is somewhat borne out by typical progesterone doses, we're tending to see with estrogen that most women who have switched from oral to transbuccal Estrace find that around 50% seems to be a reasonable starting point. We tend to see women in surgical menopause using 0.5-0.75 mg per day, although the range has been from 0.25mg to 2 mg, (although we can hardly claim to have seen a definitive cross section of the population). This goes along with what few recommendations we've seen elsewhere as well.

Cautions

About the only peril you need to watch out for specific to this route is if you should develop some persistent oral irritation where you place your pill. We've not heard of problems related to this use, but you are subjecting your oral lining to something a little concentrated and unusual, so it's good to keep an eye on the area for potential trouble. You might  have your dentist or oral hygienist take a look during your next dental exam as well. For the same reason, it's good to switch sides regularly and not to use a particular location if it has a canker sore or other injury nearby.

This is an off-label use, and as such may make your doctor, pharmacist, and/or insurance company nervous. Some women have their prescriptions written as though they're using it orally, just to avoid having to explain things, and that's something for you and your doctor to work out between yourselves; we're just pointing out potential stumbling blocks.

As with oral use of the Estrace generics, there can be a fair amount of difference in the dissolving/uptake times of the generics when taken transbuccally. This can affect both dose needs and uptake dynamics, although the most obvious impact is on dose absorption time and difficulty. In general, women's experience has been that brand name Estrace is the harder tablet with the slowest dissolution time, while the generics vary from one brand to the next with Watson of medium density and Barr towards the softer/more rapidly dissolved end of the range. Your pharmacist can help you keep track of the actual brand name you are using, so that you can keep track of which generic suits you best.

The good points

We've never heard of this route failing to deliver hormones to a woman's system. Sometimes the delivery dynamic doesn't suit a particular woman and she gives it up for that reason, but it does seem remarkably effective in getting hormones into us. It can also be used when we're sick, which is a problem with orals if we have a gastrointestinal virus. It's not likely that it will contaminate others around us when we use it, as some other transdermal forms might. It gets around whatever it is in some women's skin that makes uptake poor when using patches, creams and gels.

In terms of bang for the buck, transbuccal use of generic estradiol tabs (generic Estrace) is probably the cheapest HRT as delivered to the system. Please don't tell your neighborhood drug reps this—we'd hate to see these products taken off the market in favor of something more profitable expensive. As of this writing, 100 generic 1mg tabs are selling at major online chain pharmacies and such places as Costco for $10-20. If one were taking 0.5mg day, then, this would be 200 days' worth. And that can be a real boon for a woman with no insurance, little cash, and a burning hormone deficit.

Transbuccal use of Estrace: support for the efficacy of this delivery method

There are a fair number of women about the world today taking their HRT by the transbuccal route. Nonetheless, there are still doctors who do not believe that this is a viable route, especially for retail drugs like Estrace or Elleste Solo (available in the UK), since this is not listed as an approved delivery route on the medicine data sheet. Since the manufacturers have never bothered to test and obtain licensing approval for the use of this route, it can't be listed.

But that's not the same thing as not working. So when you ask your doctor about taking transbuccal hrt, you may have to prove your case. Here's what has helped some women in this situation.

It's a problem finding explicit references for this—the original ones that first suggested the idea to us are long gone from the internet and they were, in fact, barely more than passing mentions which we seized on as clues. As we recall, the premise was that compounded estradiol troches were a valid use because they were the same ingredient as Estrace, and that had been demonstrated to be effective when taken sublingually. We also know that nasal spray estradiol has long been used in research studies because it's such a reliable delivery. That kind of product is not offered commercially, alas, but because oral and nasal linings are structurally the same, that again argues for the physical possibility of uptake.

What we need to do is reason in the other direction, now, by analogy, and while that sounds iffy, it's really pretty straightforward. It goes like this:
The compounding pharmacies are using micronized estradiol to formulate their troches and oils that are made up for transbuccal use. There is adequate documentation in the professional literature that this route does deliver adequate circulating levels of hormonal agents when prepared in micronized form (that only refers to the size of the molecule, but that's what makes it capable of penetrating the skin and that's why things in larger molecular size, like premarin and CEEs, cannot be delivered by this route). Estradiol is micronized estradiol in brand name form; numerous generics exist as well. Estrace (and its generics) and Elleste Solo are readily soluble and those solubility figures can be provided by a pharmacy getting in touch with a particular manufacturer.

That estradiol is deliverable transbuccally is demonstrable (even though these particular studies were not specifically to test its efficacy as a delivery route, the fact that they caused measurable increase in serum estrogen levels does support the premise that this is a valid delivery route for estradiol) and you may provide your physician with this list of references; more are undoubtedly searchable at PubMed:

• "Sublingual administration of micronized estradiol and progesterone, with and without micronized testosterone: effect on biochemical markers of bone metabolism and bone mineral density"
• "Ação do estradiol sublingual na vasomotilidade coronária dependente e independente do endptélio em mulheres menopausadas portadoras de síndrome X" (scroll down to #014; abstract is in Portugese)
• "The acute effects of sublingual estradiol on left ventricular diastolic function in normotensive and hypertensive postmenopausal women"
• "The acute effects of sublingual 17beta-estradiol on the cardiovascular system"
• "Bioequivalence of a 17 beta-estradiol hydroxypropyl-beta-cyclodextrin complex in postmenopausal women"
• "Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women"
• Sublingual Mucosa as a Route For Systemic Drug Delivery

One woman we know reported the conversation with her doctor on this topic as initially producing considerable skepticism. He looked over the info she emailed him, though, and talked to some pharmacists, and eventually told her that while he liked the sound of Estrace and thought it a great hrt, he wasn't totally convinced of how much got absorbed transbuccally (as opposed to swallowed). He ultimately said, she reported, that he was fully convinced it was going to get into her system one way or another if she put it in her mouth, so as long as she was happy with the coverage she was getting from her dose amount, he didn't see any reason to quibble with what she chose to do with it between bottle and circulatory system.

And then there is a body of anecdotal evidence from women using it this way who have had enough experience with various HRTs and menopausal symptoms to distinguish effective from ineffective, but of course, we know that this is highly unscientific and unreliable since we are *ahem* easily misled by treatment that successfully alleviates our symptoms.

Of course there's another approach to taking transbuccal hrts, and that's to take home a prescription for oral Estrace or Elleste Solo, adjust the dose for the change in route, and simply take it transbuccally. We wouldn't tell you to do that. But we can tell you it works.

Ovaries or not: is your only choice one between ovarian cancer and surgical menopause?

While most of us have the time to be fairly well convinced of our need (or not) for a hysterectomy, doctors often don't bring up the question of the future of our ovaries till we get down to the final pre-op appointment and signing the operative permit. In fact, it may never be discussed at all but just lumped in with the other indigestible terminology in the permit itself. Women who ask about keeping their ovaries when they are not aware of any particular disease affecting them have been told things like "most ovaries fail within three years and the rate for ovarian cancer is well over 50% in those that do fail" (actual post from our discussion forum) or simply "you'll require another separate operation once they go bad later." As the woman whose doctor is quoted above went on to say, "I have not researched those statistics but I would not want to take any chances."

Most of us don't want to take any chances, either, but this is a case where we need to do some thinking of our own. Dorie, over on HysterList's blog, has spelled out the basic situation pretty succinctly: many doctors see no need for hormones in menopause and don't acknowledge that post-menopausal ovaries contribute to health, but unless you would consider having a separate surgery to remove your healthy ovaries to reduce your risk of cancer, it's worth giving some though to why you're so anxious to go for a "two-fer."

But we were a little alarmed at the stats that poster passed along from her doctor and decided to do a little extra research on the risks and benefits.

First of all, the ovarian function rate is better expressed as: 50% of the women who retain ovaries at the time of a hyst experience natural menopause (with some variable degree of continued hormonal support) within the following five years. That's quite a bit different from this particular doctor's figure, and we can only wonder at the population pool he practices within if his experience deviates so radically from what research has shown.

The question of cancer is a more complex one, since that is not the only risk we face. Balanced risk management is trickier, but more realistic if we are talking overall survival: cancer is not necessarily what we are going to die from and in fact is statistically less likely to kill us than a number of other things. Let's look at what we could find in the research.

The main issue is the balance between the risks of ovarian cancer as compared to other disorders that relate to lower levels of estrogen:

For women at average risk of ovarian cancer, heart disease, osteoporosis, breast cancer and stroke, the probability of survival to age 80 after hysterectomy at ages 50 to 54 ranged from 62 percent for those who kept their ovaries but didn't take estrogen, to 53 percent for those who had their ovaries removed but didn't take estrogen. 

Keeping the ovaries without estrogen therapy reduced the percent of women dying by age 80 of heart disease from 15 percent to 7 percent, and those dying of hip fractures from nearly 5 percent to 3 percent. 

The reductions in those two diseases, Parker said, far outweigh the increase in ovarian cancer deaths by age 80. (source)

And from another, stating the numbers more graphically:

For a hypothetical cohort of 10,000 women undergoing hysterectomy who chose oophorectomy between the ages of 50 and 54 without estrogen therapy, our analyses predict that, by the time they reach age 80, 838 more women will have died from CHD than in a similar cohort of women who chose ovarian preservation; 158 more will have died from hip fracture; 47 fewer women will have died from ovarian cancer. In the base case analyses, oophorectomy in women ages 50–54 leads to an overall excess mortality of 858 per 10,000 women subjected to surgery. (source)

In fact, the incidence of ovarian cancer seems to reduced by the hyst:

The incidence rate of ovarian cancer was 0.27 per 1000 person-years in the group that had undergone hysterectomy and 0.34 per 1000 person-years in the general population (age-standardised). The extrapolated lifetime risk of developing ovarian cancer was 2.1% after hysterectomy and 2.7% in the general population. (source)

The opinion of gynecologist/researcher William H. Parker, M.D. in his book A Gynecologist's Second Opinion brings the estrogen back into the situation:

Thus, the risk of a woman developing ovarian cancer after hysterectomy is probably closer to 1 in 300 rather than 1 in 80 for women who have not had a hysterectomy. The benefit of removing ovaries for ovarian cancer prevention has been overstated in the medical literature and is, therefore, misunderstood by most physicians. 

Significantly, the ovaries produce hormones long after menopause. Estrogen continues to be produced in small amounts, about 25 percent of normal pre-menopausal levels. Blood levels of estrogen in some post-menopausal women are equivalent to the levels attained by low-dose estrogen patches used for estrogen replacement in menopause. (source)

Even the North American Menopause Society, which doesn't advocate the use of HRT for more than a few months, states in their position "Women Undergoing Hysterectomy Before Age 65 Derive Survival Benefit From Ovarian Conservation":

after menopause, the ovaries continue to produce significant amounts of testosterone and androstenedione, which are converted to estrogen peripherally. Although younger women with BRCA1 or BRCA2 mutations who have significant risk for breast or ovarian cancer may derive a survival benefit from oophorectomy, women at average risk for these cancers experience increased risk of osteoporotic fracture and coronary heart disease. The study found that women younger than age 65 clearly benefit from ovarian conservation, and at no age is there a clear benefit from oophorectomy. (source)

If low estrogen raises risk for other problems, what does HRT use do for ovarian cancer risk? One older study, which was based on higher doses than currently used, found:

Ovarian cancer risk was associated with use of hormone replacement therapy both for women who had had a hysterectomy and for those who had not. Among those who had had a hysterectomy before entering the study, the risk increased by a significant 8% with each year of estrogen-only use, and 20 or more years of use was associated with a tripling of risk (rate ratio, 3.4). Women who had used only combined hormone replacement therapy did not have a significantly higher risk of ovarian cancer than women who had never used replacement hormones; however, only 18 such women developed ovarian cancer, so the analysis was limited. The duration of use of this type of therapy (which averaged only 5.6 years among long-term users) was not significantly associated with the risk of ovarian cancer. Women who switched from estrogen-only to combined hormone therapy had a marginal increase in risk of ovarian cancer, which the researchers hypothesize reflected their prior use of estrogen-only therapy. Commenting on the findings, the investigators observe that many women who had used estrogen-only formulations were likely exposed to higher daily doses of hormone than are used today; the study could not determine the independent effects of dose and duration. Therefore, they conclude that it remains uncertain if long-term use of lower doses of estrogen is associated with an elevated risk of ovarian cancer. (source)

On the other hand, for those who develop ovarian cancer, the logic is inarguable that they would presumably not have done so had they had their ovaries removed. The reason for that qualifying "presumably" is that existing cancer at the time of surgery may subsequently develop elsewhere despite ovarian removal.

The literature has recorded elective oophorectomy rates of between 50% and 66% in women 40-64 years of age undergoing hysterectomy. Data from the Centers for Disease Control and Prevention collected between 1988 and 1993 concur that ovarian retention occurs in approximately 40-50% of patients undergoing hysterectomy at 40 years of age or older. It has been suggested that, in the United States, approximately 1,000 cases of ovarian cancer can be prevented if prophylactic oophorectomy is practiced in all women older than 40 years of age who undergo hysterectomy. This assumes an annual incidence of 24,000 new ovarian cancer cases and does not take into account the incidence of peritoneal carcinoma. The dilemma for the patient and the clinician is whether the estimated number of cancer cases prevented is worth the number of oophorectomies performed (approximately 300,000). The benefit of prophylactic oophorectomy may be offset by the consequence of estrogen loss early in life. (source, now no longer available)

In one study that is a literature review of previous work, the authors could not find that the retention of ovaries was more of a liability than an asset:

I asked how often do women get ovarian cancer? And is there any relationship between a non cancer condition in the uterus, and the likelihood of subsequently developing ovarian cancer? Dr. Garcia had been taught that there was evidence to suggest that women were better off having healthy ovaries removed while a surgeon had easy access to them during a hysterectomy. 

We decided to investigate and our search of published papers led us to conclude that the "evidence" had been based on a grammatical error. The literature had been misquoted.
Our research further suggested that the studies recommending ovariectomy were erroneous. We concluded that the ovary does contribute to the hormonal well-being of women past their reproductive years and should be left intact especially during hysterectomy if possible. (source)

Elsewhere in the above discussion they go on to explain:

For example, Annegers et al. Reported a 5 % prior hysterectomy rate in ovarian cancer patients, compared with a 23% hysterectomy rate in age-matched women who had not undergone prior ovariectomy. Two other studies published in the 1950s showed a similarly low 4% and 4.5%30 rate of prior hysterectomy among the ovarian cancer patients. Unfortunately, even though these data are quiet clear in showing that hysterectomy in ovarian cancer patients is disproportionately lower, misleading logic has been applied for the reverse conclusion, i.e., that ovaries should be removed at hysterectomy. This incorrect conclusion has been widely cited and, thereby, a false premise perpetuate. 

Another line of investigation also supports the safety of retaining the ovaries at hysterectomy. Prospective rates of ovarian cancer in ovaries retained after hysterectomy also support the absence of a risk. A cohort study following 900 hysterectomized women for 20 years showed an overall rate of subsequent ovarian cancer at 0.2% in the sample. The women who had both ovaries preserved showed a much lower rate (0.01%) of subsequent cancer than those who had only one ovary preserved (0.3%). (source)

And we could go on, or you can, using a simple google search. What this all indicates, however, is that risks continue to need to be considered not in isolation but as part of an individual's total risk profile. That ovarian removal does not protect from cancer in high risk individuals or in those cases where complexity of anatomy/scarring or surgeon incompetance promotes retention of some ovarian tissue fragments is well demonstrated. That ovarian removal increases the risk of other problems associated with higher levels of mortality is also demonstrated. Use of HRT adds another layer of individualized risk. There is no risk-free option and no single option is without its associated risks. While the fears that cancer raises in us, especially ovarian cancer, are real, whether or not we choose to make them the driving force in our decision is a personal decision regardless of whether that decision is driven by fear or research and statistics. Those who are seeking a broader evaluation of risks and benefits of either option for their ovaries, however, would be better served by looking at (and perhaps getting specialized medical evaluation of) their personal risk factors in order to make a reasoned, nuanced choice. Because no matter what your doctor may tell you, "most" women who have a hyst and retain their ovaries don't go on to develop ovarian cancer.

Troubleshooting patches: Are all patches the same?

Since all patches currently on the market in the US and elsewhere all contain the same bioidentical estradiol, it would seem obvious that they would be, essentially, interchangeable. Aside from matters of adhesion, they ought to be so equivalent in function that if one fails to work out well for a woman, she might as well give up on the idea. Right?

No. In fact, the adhesive, which is the distinct and patented part of the patch (because the estradiol itself can't be patented), can have a significant impact on the delivery dynamic itself. For that reason, some women may change brands and find that while they had this or that symptom on one patch, their experience is completely different on another brand. In fact, there are two basic adhesive formulations, and these are what drive the differences. Because they are the major sellers of the two types, we'll look at the differences between Climara and Vivelle Dot.

Both of these are "matrix" patches (the hormone is spread through the adhesive and the adhesive is the delivery medium) as opposed to "reservoir" patches (the hormone is in a puddle confined and dispensed by a semipermeable membrane that lies between skin and puddle).

The difference between these two matrix patches, however, lies in the specific adhesive used and the way the hormone is mixed into it. With Climara (or the regular Vivelle or Esclim), the hormone is evenly mixed into (and dilutes, to some extent) an acrylic adhesive. This dilution effect (more hormone = less sticky) is why the Climara has to have a larger area per hormone quantity delivered. The manufacturer has hit on what seems to be an acceptable middle ground between these two demands, but it may not work out that way for any given woman.

With the Vivelle Dot, however, there are actually two adhesive agents. One is that same acrylic adhesive with the hormone mixed into it. The other is a silicon adhesive that is undiluted and thus can devote its entire strength to sticking. The two adhesives actually chemically repel each other rather than wanting to combine, which results in micro-puddles of the hormone-containing adhesive distributed throughout the (stickier) non-hormonal adhesive. This provides for a better adhesion although it may affect the allergic properties to do with the specific adhesives.

This is also cited as justification for the assertion that cutting the patch alters its dose delivery, on the premise that many of the micropuddles are cut and "open" along the new edge. We can't imagine that the scale of this could be of any functional implications, however, and the suggestion that one powder the cut edges to prevent lifting of the patch due to adhesive exposure along the sides would go a long way towards reducing this again.

There's not necessarily any predictive value in knowing this. Where it is useful is when a woman is having difficulties getting the coverage she wants from a particular patch but wants to continue with the patch form rather than giving it up to try another type of HRT. In these cases, then, switching from one sort of matrix patch to the other may provide a different enough performance. By the same token, women who change brands won't necessarily find them fully interchangeable and this is why.

Troubleshooting patches: "runs out early" or, how patches actually function to deliver hormones

One of the complaints we see voiced quite frequently is that "my patch runs out early." Women experience symptoms of falling estrogen or hormonal fluctuation a day or more before they are due, according to their prescription instructions, to change the patch out for a new one.

Now, we've discussed elsewhere that it's normal for the effects of our HRTs to rise, plateau, and fall again in the lifespan of a single dose. In the case of patches, that lifespan is spread over a half to a full week, depending upon the brand. But the intent of the manufacturer is that the decline should be happening just when it will cross the upward curve of the next dose, providing fairly steady hormone levels despite the changeover. So what is going wrong when it doesn't last the full specified amount of time? The clue we need is revealed when we look at just how patches work to deliver hormones to our body.

Patches (or cream or gel or ring, for that matter) work by a simple diffusion mechanism. All substances move from an area of high concentration to one of low concentration to equalize their distribution (assuming they are in a medium that allows them to move—which patch adhesive, skin, body fat and your circulatory system all do).

So you have a patch that has X amount of hormone distributed in the adhesive matrix. You have your body in which you have a lesser amount of hormone (and this is why you have to rotate patch sites, to get them on an area that is less-saturated from the last dose). The rate at which the hormone moves is related to the relative difference in levels between the supply and deficit sides. That is, the steeper the gradient, the stronger the pull and the faster it moves. Or, if this is easier to picture, the lower the level on the one side relative to the (supply) other, the faster it flows downhill.

Another variable in this movement is how rapidly it clears the recipient area—if the circulation is carrying it away quickly, the local concentration will stay low and suck the supply down more rapidly. This is why you look for consistency of fatty tissue, not muscle or bone, to put the patch on. If you place it on circulation-rich muscle one time and on circulation-poor fat the next, you'll get a very different level of clearing from the recipient site and hence experience a different dose delivery curve in the body.

Patch doses, in terms of "life of the patch," are calculated (and licensed) by the manufacturer on an average amount of deficit in a well-balanced user placing the patch on an average bit of fatty tissue with an average amount of circulation so that the amount of hormone it contains is transferred over to the tissue in the average planned lifetime of the patch.

If, however, you place it on a more efficient (in terms of clearing it through into your system) tissue or if your underlying deficit is higher than those calculated averages, you will exhaust the supply in the patch sooner than that planned lifetime between changes.

Now, remember how we said above that in the normal patch dosing curve, hormone release will rise sharply after the patch is put on, hold a peaking curve through most of the patch lifespan, and fall off towards the end? That falloff is due to this same mechanism of diffusion. At the end of the patch lifespan, the recipient site is becoming more saturated and can't clear the hormone on its way as rapidly, and the patch itself is drawing down and hormone has to be gathered from all through the matrix instead of that right up against your skin. This is all the normal physics of this delivery system, not it going awry in any way. The timing of the dose delivery curve, then, relates to the dose in the patch and the amount of hormones in the delivery area and the overall system, not some actual timing mechanism built into the patch itself.

For most women, once their systemic levels are high enough that they don't immediately suck all the hormone out of the patch, the lull towards the end is offset by the higher onset of the new patch and the reserves that remain, undiffused but slowly clearing, from the old site. If their overall supply is enough for their system to be meeting their needs, this amount of fluctuation should not be troubling (slightly noticeable, perhaps, but disabling, no).

Where women seem to be running into difficulty is when they are running in such borderline deficit all the time that they are sucking the patch dry too soon and then having more of a lull than they can cope with during that period when their needs are then going unmet. Again, it's not a matter of the patch misperforming for them—it's working fine. What the problem is more likely to be is that it's not an adequate dose for their needs and their demand is higher than that particular patch dose is calibrated to deliver.

Thus, the first response in troubleshooting "running out too soon" should probably be to question the overall dose, not the patch timing per se. Were that same woman using a slightly higher dose, one that meets her needs more fully, she might not find that she is exhausting the patch "too soon."

Does it matter whether she does this or just changes the patch more often? If she's fooling herself and her doctor by thinking that she's using a lower dose, then yes, this may be harmful in that it can cause undervaluation of risks. For example, if she is using a nominal 0.25mg weekly-change patch to limit her hormone exposure due to some hormone-related risk but she is changing it twice a week (and exhausting it fully on that interval) instead, she's in fact getting 0.5mg. That's a big difference and perhaps enough to totally rewrite her true exposure risk. If she and her doctor fail to understand this, they may even misinterpret the situation to be that she's better off using "only" the 0.25mg and changing it more often than if she were to increase to a 0.5mg. Remember: nominal patch dose is not a delivery throttle: it's only the "average" draw an "average" woman puts on it. If you're using more than that, it doesn't matter whether you get it by more dose per patch or more patches per time, you're still using more.

While some women have suggested that waiting till the patch wanes to change it provides a sort of self-regulating optimal dose, we're not sure but that keeping the body on that sort of edge may ultimately be the most stress-free level of balance. The idea of correctly-functioning patch delivery is, remember, that the end-patch dip is covered by the new-patch ramp up, maintaining a fairly steady supply. By relying on dip before changeout, then, a woman is putting herself back into fluctuation and insufficiency on a regular basis, without ever getting into a cycle, such as women on daily dosing experience, in which the body's innate caching and conversion mechanisms can cover her needs between doses. While we've seen some women invent all sorts of complicated systems of patch change, requiring cutting the patch into multiple pieces and then changing them out on a more frequent schedule in an attempt to avoid any dips, we have to question the ultimate viability of that kind of scheme. Not only is it excessively fussy (and easily confused) a system, but if they are on such a knife-edge of imbalance that they can't get a decent overlap of wax and wane, perhaps they should ask whether they might be using the wrong delivery system altogether.

And of course your insurance may be a problem even if your doctor specifies an accelerated change schedule. The fact of medication pricing is that the same dose in one vs two units has a different cost. The cost of two patchs of, say, 0.25mg is higher than the cost for one 0.5mg patch because of the additional backing, other ingredients, packaging and handling. For some women, then, this might be a make-or-break factor, and it can be useful to know that they can address the "runs out too soon" problem with a different dose rather than more patch expense.

Demystifying the mechanics of patch delivery can go a long way in troubleshooting balance problems you may be experiencing with them. Whatever solution you ultimately take is your own responsibility, but we hope that it's one that is based on fact rather than fooling yourself about the mechanisms involved.

Troubleshooting patches: location

There are two factors that affect patch performance that involve location.

The first is the purely mechanical. It doesn't matter how much the patch is capable of delivering if you can't keep it flat and adhered fully. This means that folds, rumples, areas of high clothing friction, and places with thick fine body hair are just not going to work well no matter where they are. Upper arm and thigh are some off-label locations that some women have reported satisfactory results with when they don't have enough suitable real estate in the mid-body areas.

As a rule, though, best results are obtained in the outer half of each body half, but not so far "around the edge" that there's a lot of curve to the location and not directly over an area where there is little padding over the bone or over large muscles.

The other location factor is that studies by manufacturers have shown that patch delivery (same patch, same dose, same degree of adhesion, different location) varies by 17-25% depending on whether it's on the front of your body or back. That is, locations on your butt deliver more to your system, from the same patch, than if it were placed on the front of your body.

Our speculation on this—and that's all that it is because it's not elucidated by the manufacturers—is that the large muscles in the butt (the same ones that make it a good location for shots) cause more circulation to the area when you move around, leading to the hormone being pumped away from the patch location at a more rapid pace. On the belly, unless we're seriously into muscle-building, that's less likely to be the case. This would correspond to the experiences women with little body fat or women who undergo a lot of weight/fat loss see, where they find that their patch dynamics are changed such that they may not be able to use patches satisfactorily any longer.

Now it's true that not every manufacturer includes this dosing variability in their product information, and that some state that the patch can only be used in one particular location. These cautions have more to do with the testing and approval process than actual patch dynamics, however. If the manufacturer does not go to the expense and time of specifically testing their product in multiple locations, they can't claim those results—only the ones they actually demonstrated in their FDA application can show up in their licensing. And because they can only claim those specific results, it's obvious that they can tell you that only that location works as specified. It's not that other variations don't work, won't work or have been determined not to work: it's just that they don't have the legal right to allow even that they might work without demonstrating this through specific testing.

There is nothing in the physiology of hormone uptake or the mechanical delivery of hormones from patches that would make one work in a specific location and not the other. In practical terms, it is entirely reasonable to generalize from the specific test data to general patch performance, leaving aside delivery variations due to specific patch qualities.

Further, this can be expanded to general considerations in patch placement. Aside from on or within the immediate circulatory feeders of breast tissue, there's virtually nowhere that is an absolute contraindication to patch placement. We'd have second thoughts about over some moles (for the same reasons as avoiding breast tissue), but otherwise, if the bottom of your foot is the only available real estate and you want to use a patch, there's not an obvious reason beyond the mechanical why that won't work. We have no idea what the delivery efficiency would be, but that can be deduced in practice.

The point is, then, that different underlying tissue types seem to affect your uptake (and provide a subtle way of manipulating that intake) for any two locations where the mechanics of sticking are equivalent. But because delivery is first and foremost dependent upon patch adhesion, locations where a patch won't stick just aren't in the running.

For more information on alternate locations and their dose delivery, plus more documentation on the importance of the tissue type underlying a patch, check out this other post looking at what we can learn from contraceptive patches. For help doing the math on how much difference location makes to a specific patch dose, please join us on our discussion forums.

Troubleshooting patches: adhesion

Because of the way it physically delivers hormones to our bodies, a patch must be 100% adhered to our skin 100% of the time in order to deliver the nominal patch dose. If it's not, even by a bit, the effectiveness of the patch is diminished by that amount. This means that getting a patch stuck down and keeping it that way is absolutely critical to using patch HRTs.

Skin prep

The first part of sticking a patch down involves preparing the skin for the patch. The most effective strategy seems to be washing the site thoroughly with a mild and pure soap—not something loaded with moisturizing oils but rather a something more like a glycerin cake or castile soap, for example.

Then dry it thoroughly. A hair dryer set on low is good for this, so that the site's not picking up lint from a towel.

Since putting a fresh patch on skin with dilated blood vessels from a hot shower can give us a nice little zap from the enhanced uptake, it's important to let the skin cool thoroughly.

Then it's time to apply the patch. Another session with a slightly warm hair dryer or holding a warm hand firmly on the patch for several minutes after it's applied, pressing it down fully and evenly, will help make the seal fully seat onto the skin.

As a final measure, a light dusting of powder (on top of the applied patch, not underneath or before applying it!) will reduce the sticky along the edges and help prevent peeling from sticking to clothing. You may need to renew the powder daily if the adhesive tends to extrude a bit with time.

Do not use benzoin or the skin prep pads sold to people with ostomies to help their appliances stick to the their skin—those will make the patch stick, perhaps, but interfere with hormone transfer from the patch into your body, which sort of negates the whole effort.

Don't use things like acetone or industrial solvents to clean the area before application—that's going to alter the skin's uptake and expose you to risks from those agents. If you have to resort to heavy chemicals, you're not a good candidate for a patch.

If you want to be extra-sure you've cleaned the skin of all oils, one patch manufacturer suggests wiping the area down well with an alcohol wipe. Rubbing alcohol on a tissue or cotton ball will work equally well—you don't need to buy the expensive packets of individual wipes (although they're handy for travel use). Be sure to fan the area (or give it another whoosh with the hair dryer) to be sure all of the alcohol has evaporated and the skin is fully dry before you apply the patch.

Last, do make sure that the skin is well smoothed out before putting the patch onto it. One of our discussion group members shared a tip she got from her patch manufacturer: when applying a patch to the butt, sit down to apply it. This obviously will stretch things out and help assure that when you sit down later, you're not ripping it loose as your skin stretches. Clever, eh? That won't, of course, help with patches in other locations, but we can take a lesson from this and make sure we do smooth and even stretch out the skin if it's an area where there normally is considerable stretch in the course of our daily activities.

Problems

Some women find that they have a lot of body hair and this presents them with adhesion problems. For them, careful shaving may be necessary—careful because nicking or scraping the skin will also alter the uptake of the patch and then provide a risk of infection when sealed beneath the patch for that many days. This isn't something to undertake unless patches spring up obviously standing away from the skin on hair—women who have a history of bandaid failures know what we're talking about here. Don't get into this unless you absolutely have to, and even then, it's a good reason to consider another HRT form.

If that doesn't do it for you, then you need to look at the actual mechanics of the problem. If it's just edges rolling up from clothing, perhaps more careful selection of application location would help. If the powder trick doesn't work, perhaps taping down the edges would—that's okay, so long as the edges are well-sealed to begin with and you're just protecting them, not sticking failed portions of the patch back down. If you tape edges and the patch remains fully stuck down right up until the time when you peel it off to change it, you're okay; anything less than that total adhesion and you're fooling yourself (and not your body) with the tape. Don't take the tape off and replace it if it starts to curl, though—that's just going to lift the patch with it.

Some women who develop rashes under patches like to use an over-the-counter steroid ointment to facilitate that healing. We're not sure that any degree of irritation that takes drugs to recover from is being all that kind to our bodies in the long run, but in the overall scheme of balancing risks and benefits, we'll have to leave that one up to you. Remember, though, that different brands of patch have different chemical constituents in the adhesive, and so a rash from one brand will not necessarily happen with another.

After bathing

If you use body moisturizer after your showers, be sure to skip the place where you're going to put your fresh patch. It's fine to use a regular moisturizer, if it doesn't sting, where the old patch was. After all, that area is probably going to see another patch in a couple weeks, so making sure it's healthy and recovered is just right.

The dreaded goo-and-lint aftermath

Once you've removed the patch, you may be left with that unattractive lint-and-goo ring. This is also not the time to reach for heavy industrial solvents that aren't meant for use on skin that's just spent days underneath an airtight barrier. Instead, try a light coating of vegetable or nut oil or body butter. Let it sit on the goo for a few minutes, then shower. You should be able to wash the now-softened goo off with your usual soap and washcloth.

It still doesn't work

Finally, keep in mind that each patch adhesive is by definition (and patent) different. If one brand doesn't stick for you but you love patches as a concept, for goodness sake try the rest of the brands to see if another might provide better results for you. That's what samples are for.

HRTs and dose dynamics

We tend to think of HRTs as being divided according along such lines as bioidentical vs synthetic or based on route of delivery, and certainly these characteristics have a great deal to do with how a given HRT may "fit" any given woman. But there's another factor that can be important in how we experience an HRT, and that's the uptake dynamic. What do we mean by that? It's the timing and speed with which the hormone enters, resides in, and departs our systems.

For example, an oral HRT that dissolves well, such as Estrace, will hit the stomach and very rapidly be completely absorbed into the circulation and just as rapidly greatly diminished in concentration by the "first pass effect" in the liver. An HRT of that same estradiol compounded in an oil base will be more slowly absorbed and less rapidly eliminated from circulation. By the same token, a new patch on a new location will be taken up much more rapidly by the body than an older patch on a more fully saturated location that's been in use for some days. A gel or cream HRT that is rubbed into a small area will be taken up more slowly than one spread widely, and all things being equal, a gel is more likely to be taken up more rapidly than a cream.

Going beyond the initial uptake of a dose, the curve of concentration of hormone delivered by any HRT to the body will be different over time. For example, a dose taken once daily will peak shortly after administration and then gradually fall during the day to a low point before the next dose is due. A dose take weekly, on the other hand, will describe that same curve but it will be spread over days instead of hours. For HRTs given on even longer intervals, such as rings that last three months or implants that last up to six months, a corresponding lengthening in time of those portions of the dose curve will obviously be experienced.

What difference does this all make? Different women have different levels of tolerance for hormonal fluctuations. For some women, their bodies seem to be overwhelmed by too much coming in too quickly, and the sharp rise of a quick-uptake HRT causes symptoms that don't exist once the hormone is more stably in their system. One case where women seem to run into this is where taking their HRT causes headaches that last only during the uptake period or the downward turn when a dose is wearing off. Here the culprit may not be the hormone itself, but rather the rise and fall of that particular HRT. Sometimes when these women can switch to a form with a slower period, these symptoms will abate.

Another related effect is the contrast between women who seem to do well with once-a-day dosing and those who seem to need a continuous trickle. Now, premenopausally we all experienced a daily rise and fall in our hormone levels in addition to our monthly cycle. We could call up more ovarian output when we needed it, and we could convert between active and inactive forms of estrogen as our physical demands dictated. Once in surgical meno, though, our supply is suddenly more limited. This in itself provides for a period of shock and adjustment. It's been our observation that women early in postop recovery seem to be less able to manage their hormone needs over time and tend to do better with a more constantly available trickle of intake. It's as though their bodies haven't quite had the time yet to master relying on the tricks of shuffling those hormones around between the different forms, as though their bodies put hormones away in the storage form and then misplace them, or forget how to get them back. We're anthropomorphizing here, we know, but nonetheless there seems to be a greater fragility in early postop hormone management. Once some time goes by and women get stabilized on an acceptable level of hormonal support, dose intervals become less critical for many women. In fact, the constant trickle of "just enough" doesn't provide for that caching and management that we're prepared to use in menopause, and they may increasingly have a sense that their early HRT choice is leaving them edgy and unfulfilled. At that point, in revisiting their HRT choices, many find that they are now able to move to a daily dose and their bodies can cope more gracefully with a more intermittant supply. This then, is where the dose dynamic that pertains to how long HRTs stay active in our system comes into play.

The downward side of the dose dynamic curve, the waning dose, can be anything from a minor annoyance to disabling. For some women on especially long-lived HRTs, the lag between when one dose is running out and when they can get another inserted can be most unpleasant unless they have things calculated very finely. For other women, the nighttime dip in hormones provides a few breakthrough hot flashes that tells them that their morning-scheduled daily hormone dose is just enough but no more than the minumum they need, and that nighttime flash serves as a gauge of just where they are in meeting their needs.

Dose dynamics are not necessarily something we need to fuss over when choosing an HRT, but they can become a neglected but critical element when we are troubleshooting our HRTs. Many times, when we are looking for what about an HRT is letting us down, if we consider what the delivery dynamic is providing our systems, we can gain important clues that may help us make choices that better suit our bodies. It's not something we can predict in advance, but it can be one more useful tool when we get to the tweaking, tuning and troubleshooting parts of the process.

Are generics okay for HRT?

That's a good question. Our insurance companies think so, but then they are the ones who think we should get our medical care from JimBob's House of Automotive Painting and Gynecology because he'd cut them a reduced-price deal, too.

So long as the active ingredient(s) is the same, the FDA considers HRT generics to be fully equivalent to brand name products. And in that regard they are indeed: 17-B estradiol is going to be the same hormone no matter what it's delivered by; conjugated equine estrogens aren't the same as conjugated plant estrogens, so they aren't considered interchangeable generics for each other even when delivered exactly the same way.

But if you've hung in here reading with us for some time, you may be getting the idea that even within the same route of delivery, the peculiarities of which we've already discussed elsewhere, the individual HRT dose dynamics can make a difference. And this is where the real keen eye of fine tuning can come into play.

In patches, for example, all of the major brands contain human-identical 17-B estradiol. All of them are different (so that they can be patented) in the adhesive composition and characteristics, however, and those different adhesives affect the delivery of the hormone in ways that make one patch brand perform quite differently from another brand. The same is true for the generic patch, since it cannot infringe upon any of the brand names' patents. And because it's different (and I use the singular, but generic brands come and go, so on any given day there may be more than one), it can indeed be enough different from a brand name version that it will deliver differently when applied to your body.

And in the case of some generic patches, part of the different construction includes a much larger, thicker, stiffer form. We have read numerous reports from women complaining of the great difficulty, if not impossibility, they encountered getting generic patches to stick because of these characteristics. And, alas, because they don't necessarily understand that a patch must be adhered to deliver and that these patches do not predict the performance of all patches, many women (or their doctors) give up on patches just because of these mechanical problems. For these women, then, a generic isn't good enough. Does this apply to all women and all generic patches? We doubt it: there must be someone out there who buys the generic more than once or the company wouldn't find it profitable enough to keep in production. Will this be your experience? There's really no way to tell without a trial. Our point, however, is that if you experience unsatisfactory performance from a generic patch, it may be mechanical difficulties with that particular patch, and neither the hormone nor patches as a class of HRTs need to be ruled out solely based upon that one trial.

With oral HRTs, the same thing can happen. Take the example of Estrace, a tablet of human-identical micronized estradiol that can also be taken transbuccally. It's a fairly inexpensive HRT, being simple and rather old, but a prescription for the brand name may cost $70-$90 whereas the generic may be available for $10-15. Even without insurance restrictions, many women wonder whether this is a case where brand makes a difference.

The answer lies, as it does with all tablets, in the inert ingredients that make up the rest of the tablet. Leaving aside things like allergies to some coloring agents (which are always listed, along with all of the other inert ingredients, on the brand data sheet and, when we can find them, on our website HRTs pages), which will be distinct and special contraindications for some brands, there are many factors that can individualize our reactions to "equivalent" formulations. Some generics—and in the case of Estrace there are a number of generic manufacturers—are rather hard; some cut cleanly if the pill must be divided; others crumble and dissolve almost before you can swallow them. In turn, these different mechanical behaviors affect how rapidly the hormone may enter our system and, further, how the dose uptake curve affects us and how quickly the hormone may be eliminated from our systems. A slower uptake from a less soluble tablet may preserve more of the dose in the system (sneaking it past the first pass effect) and prevent things like headaches that may be caused by more rapidly-rising hormone levels. On the other hand, a more rapid uptake may prevent a woman who is taking it transbuccally from swallowing (and losing) as much of the dose. There are lots of variations on this, the exact details of which aren't necessarily important. What's important is knowing that variations can occur. We've been told by one woman who has surveyed the generic market for Estrace that she sees actual in-body dose equivalency variations of up to 0.5mg. That is, she has found that she can take 1.5mg of one generic brand and get the same effect as 2.0mg of another generic brand. But those numbers don't matter—what matters, again, is understanding that there can be this variation and if one generic performs slightly off, adjustments or changing brand may solve the problem without moving to a different HRT entirely.

So will a generic be okay for you? Maybe; maybe not. But it's worth trying out first, because if the delivery dynamic of the generic works, the hormone equivalancy means that it can be just as good an HRT as the brand name. And if it doesn't, then it's worth considering whether you want to push for the brand name or a different generic (your pharmacist is your best resource for finding out what generic brand you're using and whether other generic options exist for you) to stick with the overall type of HRT you've chosen. It's a little outside our scope to get into how you manipulate your insurance company's coverage for these things—sometimes a responsive company will permit a brand name if a doctor attests in a letter or in the prescription that the brand name is the only one that provides the desired effect; sometimes a higher copay is required; sometimes one has to simply bite the bullet and buy out of pocket. These things are determined by individual plan and the attitudes and policies of the company you're working with, and you'll have to do the research on that.

One thing that we've found helpful, when considering a switch from a brand to a generic, is talking about it beforehand with the pharmacist. If your doctor writes the prescription specifying that the choice of generic or brand be left up to patient preference, your pharmacist may be willing to sell you a very small test refill—say a week or so's worth—to try out the new variation before purchasing a whole three months' or whatever your refill quantity normally is. This lets you audition the new version without spending much money and without ending up with three months' worth of something that is suboptimal but you're stuck with it. We can often audition new options in brand names, especially the newer, more heavily-promoted ones, using samples our doctor's office receives from drug reps, but this mechanism doesn't exist for generics. But a mini-refill can let us test the waters without jumping in all the way, something that can be reassuring when dealing with something as personal and individual as HRT.

And, finally, do be sure, when reporting back to your doctor on an HRT, that you distinguish clearly between generic and brand in your discussions. A doctor who hears "well, this one didn't work," is going to hear "I want a different HRT," not "I like this type of HRT but I don't think this is the best brand for me and I want to experiment around and by the way do you have any samples of Brand X or Brand Y in my dose?"

Researching it yourself

There's a lot of silly, erroneous, malicious and otherwise untrustworthy and unrecommendable stuff out there. You may remember our mentioning when we introduced ourselves that while we work hard on making this site as scientifically accurate and unbiased as we can, we still don't think you should just take our word for it; you need to do enough research for yourself to make sure you should believe us. That, though, is just the perfect setup for the question "and how should I do that, then?" Well, we're glad you asked.

There are really two aspects to this question: how do I find credible sources and where do I go to do it? We're going to take a look at both of them.

Evaluating what you read

Maybe this seems out of order, discussing your search results before you do the searching, but on the other hand, you can eliminate a lot of sources without even reading them if you know what you're looking for in terms of reliable, credible information.

The first, most important quality of information you read relates not to who is saying it but how they got it. The truism goes that on the internet, nobody knows you're a dog. Huh? Well, just because you say you're an expert that doesn't make you one. Subvarieties of this include people who title themselves "doctor." There are many types of doctors, and only some of them have any legitimate, clinically-earned credentials within the health practice field. We have all kinds of respect for anyone who can earn a PhD. or, really, anyone who can get themselves and their funds together to order a PhD. from a mailorder vendor. But that's the rub: we can't tell them apart and we can't tell a PhD. in 16th century Estonian literature from an M.D. when they simply refer to themselves as doctor. If all we see cited is Dr. Jane Somebody as the source of information, we don't have a reliable source or at least, it's not credible on those grounds alone.

But that doesn't mean a site attributed to Jane Somebody, MD is any more credible. There are lots of doctors who have lots of opinions, but just because they've earned (or lied about) a medical degree doesn't mean they're licensed, legitimate, or even sane. If it's one doctor speaking, you still only have one person's opinion. That may be an educated opinion and their synthesis of the available medical knowledge may be impeccable, but you can't tell just from their name and title. We won't necessarily rule them out, but we'll hold their comments aside to see if additional research validates at least the information upon which their opinions are based.

As for other titles, the same thing applies if we even recognize the title: we have a fair idea of what a nurse's nominal background and licensing involve; ditto a Registered Pharmacist. But how about a Certified Lab Manager, Biomedical Researcher, or Joe Sombody, M.S.J.L.? Since we just made all of those nice-sounding credentials up, maybe they're not a good source of authority. A title needs to be verifiable, not just impressive-sounding when it's spelled out with capital letters.

If an individual is suspect, how about an institution? Now we're making progress. Reputable, major institutions may also be expressing opinions in how they summarize and present information, but at least they are opinions held by a group and subjected to the personnel selection/affiliation guidelines of that institution. On the list of fairly trustworthy institutions we would include most government agencies, professional medical groups, and major educational institutions. While their information may be biased, it will typically lead you astray only in the direction of being excessively conservative, not, generally speaking, wholly delusional.

One of the most important research reading skills is reading not only what is said, but what is not said. After the above paragraph, you could be wondering: what is a disreputable institution? Who should I not believe? First of all, if you haven't heard of them before, they may not be first-tier. Reading names carefully is important, here. The American Heart Association is a well-known and credible, if conservative, source of information. The American Heart Research Association, which only gets one google hit, probably doesn't exist and they should not be confused with the AHA. It takes some careful reading into the "about us" pages and some secondary searching to sort out just who is behind many groups, which is why they have a higher index of suspicion.

But first and foremost, an institution or group immediately puts us off if it's selling something, whether a specific product or simply the promotion of a class of products (think: National Institute for Hormone Health, American Society of Radish Fanciers). If we so much as sniff a profit motive, we're taking everything they say with a grain of salt. They may be telling the truth so far as it goes, but it may not be the whole truth because, by definition, they want you to buy what they're selling and if it needs selling, there's more to the story. That's why we look not at drug company publicity pages or ads, but at the licensed prescribing information (which is still subject to politics, but you have to draw the line somewhere). This means that pharmaceutical companies, vitamin mailorder houses, individual medical clinics, and testing labs are all on our "I'll believe this only if it's corroborated elsewhere" list. As soon as a profit motive comes into it, our faith in them as an unbiased source goes out of it. Harsh, but we're very suspicious of being led astray.

Well then, how about books? If someone's a published author or entertainment celebrity, we can believe them, right? Uh, no. In fact, there are all sorts of rubbish published every day in books, and it's important to remember that publishers are in the making-money-from-selling-books trade, not the publishing-truth trade. We could say that we've published a book, too—give us a moment and we can work up a nifty cover graphic and a few enthusiastic fake review quotes as well. Just because it's a familiar face you've seen "everywhere" doesn't mean that they have any greater insight or well-researched knowledge than you do: they just have a better publicist and are selling that familiarity in every market they can.

Sometimes it's really hard to evaluate what you're seeing, though. If you don't know the right answers when you begin, how will you recognize them when you see them. There is an excellent presentation of The Seven Warning Signs of Bogus Science that may help you out with this.

So what is it that we do like for information sources? Hard scientific research. Research that conforms to standard practices, uses blind controls, and is statistically analyzed, replicable, and published in peer-reviewed format. Discussion based on research, comparisons of research, summaries of research, speculations (where clearly identified as such) taking off from research-demonstrated premises—all of these are good things when they cite their sources and justify their science. Why does it matter what their sources are if there are a lot of them? Because not all sources are equally valid. To take a broad example, a study of 20,000 women over 20 years has one kind of predictive weight for human science while a study done in 20 rats over 2 days has another. Where a discussion follows primarily from small, obscure, animal-only research, we're less inclined to give them quite as much weight as a well-designed human study with a large population, a long timeline and good controls (note that last one, though—it can sink a lot of otherwise good-looking results).

But what about all of the anecdotal information we've presented on this website? What about the reports by women like us who are actually experiencing these things? What about what we can read every day on the message lists and forums all over the internet? Surely we can believe the women themselves? Sorry, no. Where we've presented comments on things women have told us, we've specifically identified that as the source of that information just because we know that this is less reliable. The level of simple physiological misunderstanding and lack of knowledge we women have about our bodies and how they work is astounding (the same is true of men, so don't think there's a sexist aspect to this). Further, we are all bad reporters; we miss things; we misrepresent things; we have biases we don't even know about; and worst of all, we are individuals. Nothing that happens to one person ever constitutes science that can be extended to a population, especially when something as hideously complex as hormones is involved. A lot of women talking about the same thing may mean there's a common thread, but it doesn't sort out correlation from causation. And any forum is inevitably going to be biased towards the negative: those who would express the positive, those without problems, those presenting the "typical" are vastly under-represented because they're not online talking about it; they've gone on about their lives. Even if "everyone" online is talking about how the latest hrt made their left legs fell off, we have to remember that this is incomplete data because we're not hearing from the whole user group and we don't have any way to get in touch with those whose left leg didn't fall off.

One other point we'd like to make: look at the dates. The whole field of menopausal health and HRTs is rapidly changing. There are sites that were put up five to eight years ago that reflect prevailing opinions at the time that have become totally outmoded by subsequent developments. That doesn't mean we have to reject everything more than a few years old, but it does mean that we need to make sure that it hasn't been negated by more recent work.

For a different look at evaluating online information, including some technical details to do with really looking at where a website comes from, we found this from the library at the University of California at Berkeley.

Where to look

Moving on, then, what are some worthwhile sources for turning up information? While there are many online sources of advice for writing good searches, from simple to detailed, we have to know where to look.

Google is pretty much the default search engine these days, and it's a fine one to use. For many initial searches, the basic page is fine although the advanced search may be needed to home in on some more complex concepts with greater discrimination. Be advised that the links in the righthand column and those at the top with the colored background on all Google search results pages are sponsored (paid) links and thus are not likely to meet our non-commercial test. Google Scholar is a separate service that "provides a search of scholarly literature across many disciplines and sources, including theses, books, abstracts and articles" and may return a usefully different set of search results because it . Try a basic search on something like "estrogen" on Google Scholar and compare it with the same term on Google Search: you'll be surprised at how different the results are.

Depending upon how you write your search, you may find that the first few pages of hits are almost exclusively sales-related. For example, if you are searching for a particular hrt, you are likely to find the manufacturer's site up in the colored results at the top of the list. The first page of hits is also likely to contain a number of hits for overseas drug sources, and domestic mail order pharmacies, and nutraceutical vendors. In with them may be some useful sites, however, like drugs.com and rxlist, which are reference sites that republish the information in the prescribing information sheets that the FDA requires for all prescription drugs.

As you plumb deeper into the results (or rewrite your search to eliminate these sorts of hits), you'll begin to come across mentions of your topic in discussions or in forums. Depending upon whether you are looking for discussion or research, you may want to explore some of the most reliable-looking (look at the url, not the topic title or summary, to tell who has posted the information) discussions as you go. Often, though, if you are looking for research, you will have to go pages and pages into the hit results. Don't despair, though—you're skimming the available topic range while you do so, and sometimes that can be helpful in itself: you're getting acquainted with the general body of knowledge while you're on your way to the specific. And sometimes we've picked up better ways of wording our searches, just from looking at how the hits we did get turn out to be phrased.

Once you get down to the research, you may find that you're up against the wall of proprietary, subscription-based content. Before you shell out your hard-earned cash for articles that might not be what you hope, you should know that in many cases free abstracts, or executive summaries, of articles are available for free. When you click on a "full version" link and it takes you to a login for subscribers, back up and try the "abstract" link, which is often free. With time, you may notice that this link often takes you to a different site. This is the PubMed database, and you can in fact go there and search directly (either simple search or advanced) courtesy of the National Institutes of Health. We've had good luck searching not only on topics or specific terms, but by research article title or even journal date and name.

Do make sure that when you are reading study results or summaries that you're at PubMed or a real medical journal site. Just the other day one of us was researching and found a very interesting statement that seemed just what was being looked for in a quote from a study that was part of a set of references on a sales site. Hoping to find out more detail on that statement, she went looking for the original study, which turned out to be online in a full copy from the original publisher. And, lo and behold, that single statement that brought the study into support of the sales site's premise was nowhere to be found in the original study, even though the rest of the quote was valid. See: it pays to be suspicious.

Some other sites we have found useful not just for research but for generally keeping current are:

1. Medscape: This medical news and continuing education site is aimed at health care professionals but subscription is free once you sign up and we have never been spammed by them. They have specialized pages for women's health, which is where they cover menopausal topics, but there are other special sections for things like osteoporosis and cardiovascular disease and cancers. You can also sign up for a free emailed summary that comes out on a weekly basis or subscribe to an RSS feed of news items. This is the source of many useful summary articles as well as pointers to medical journals, and their archive links are good longer than those of the news services.
2. Reuters: Although limited to press notices and coverage, this service will provide good pointers for further research. You can also subscribe to it in RSS format.
3. Eurekalert: Another medical news service, they don't have a breakout for women's health they way they do some mens' topics (hrmph) but they too offer an RSS feed.

So that's the brief overview. It still takes work to read smart, getting the most out of study results (and recognizing their limitations). But finding them is the first step, and this should get you started with that part of it. We're always ready to discuss research and poke at information sources or the latest news in the media on our forums, too. Don't forget that we have a publicly-available bookmark collection where we flag a lot of the latest news and commentary on menopausal topics, too.