Surgical menopause, hrts, and headaches

Headaches aren't special to menopause or even the surgical variety, but for those prone to them, hrt can involve some special concerns.

Headaches due to low estrogen

This may be one of the earliest symptoms to hit us after we have a hysterectomy—once the headache from not being able to have coffee before surgery wears off! Some folks develop a lingering, grinding headache that they just can't shake until their hrt is properly adjusted to their needs. For them, headaches become a tuning symptom, something we know has a specific meaning for our own body.

If we've not immediately gone onto hrt after surgery, doctors are sometimes worried that a headache during the recovery period means we're having or are at high risk for a stroke and shouldn't have hrt. While there is validity to ruling stroke out, especially when we've just had surgery, and while there is a slightly higher risk of stroke in the first year of using an oral hrt, some women are left with their doctors' refusal to prescribe just because they are still afraid of that risk. That says something rather sad about their faith in their own diagnostic capabilities and it says something terrible about a woman being able to get the care she needs. Shopping for a new doctor can, sadly, be about the only way out of this trap.

Generally speaking, headaches due to low estrogen tend to abate pretty well once our estrogen levels are meeting our needs.

Headaches from high estrogen

Yes, this happens too.

Decreasing the dose is the right answer for risk and for this kind of headache. How can we tell which is which, high vs low? By the other symptoms that appear with the headaches, just as with any other aspect of hrt tuning.

In general, the tactic of adding a diuretic (water pill) to hrt with the goal of reducing fluid retention from excessive estrogen is not an effective strategy for dealing with this kind of headache, let alone the risks posed by excessive estrogen exposure. It's a common medical response, however, to see each new symptom of imbalance as a separate disease that requires separate medication. We need to be alert to the state of our hrt balance and, if our doctor wants to prescribe diuretics when we think we're in hormone overload, we should be prepared to advocate for our own preferences. Suggesting a trial of dose reduction before adding a new drug is not an inappropriate proposal and a doctor willing to work with us should prove amenable to this kind of trial.

If going down in dose of an hrt doesn't cover our overall hormone needs but that previous dose being the next increment up presents excess, then we can understand that to mean that this isn't the best hrt for our bodies and that we could make more progress by moving along to a new hrt. While we always advocate adjusting dose before giving up on an hrt that appears to be delivering, there's only so far we can adjust things. If we're bracketing our needs without being able to find an acceptable middle ground, we're there. Moving along is likely to be more satisfying sooner.

Headaches upon taking an HRT dose

Some of us don't consider ourselves prone to headaches but then when we begin taking hrt, BLAM. These are often those who had semi-regular headaches during their former menstrual cycle, and if so, that's a great clue we can use in tuning our hrt.

In the situation of menstrual cycle headaches or right-after-taking-hrt headaches, the culprit often seems to be the rapid rise of estrogen levels; once a woman is a few hours or days into a dose, it abates. Because every dose of hrt takes us from a lower level to a higher one, especially early in our adjustment period, we're simply recreating the hormonal setting of those earlier cyclical headaches.

For these women, the key seems to be getting onto a stable level of hormonal support and a dependable delivery, so that they're not swinging up and down with each dose. While there will always be an uptake curve at one end of an hrt dose and a wash-out curve at the other end, once we stack several days' doses on top of each other, we reach a background level of hormonal supply that keeps us supported between doses. Some women, alas, take this sort of situation to mean they need to overlap their hrt doses or take them in tiny increments under the impression that a perfectly even and continuous delivery is necessary. In fact, however, this is something our bodies can sort out for themselves if those doses are adequate to permit us that background leveling between doses. While it's still the case that some hrts will be more comfortable than others for a woman sensitive to this dynamic, there's no single answer as to which those hrts will be.

Headaches with HRT

This is a bit different from the above situation in that a person on a poorly-fitting hrt may have frequent headaches as part of a picture of poor coverage: jangly nerves, anxiety, poor sleep, mood instability, and a general sense that they're walking a knife edge of disaster, not at ease in their skin. This situation tends to persist through dose adjustments up and down and even with a change of hrts. Often, these folks come to our forums summarizing their experience as "I can't tolerate hrt."

But frequently that's not the full story. Often these users, even when they've explored dose adjustments, have pretty much stuck to the estradiol hrts. And that's understandable because most of the hrts on the market today are estradiol hrts. We tend to divide the hrt market into human-identical estradiol and Premarin, and Premarin's reputation is a difficult one for many women to embrace. Routinely, more doctors seem to be offering estradiol than Premarin (or the other conjugated estrogens), and people are choosing estradiol hrts on their own.

But estradiol is the active form of estrogen and it seems that some of us don't want that much activity dumped into our system at once. These users seem to do better whwith an hrt that is comprised of some or all estrone rather than 100% estradiol. Estrone is a much less active form of estrogen, even a storage form, and it can be much gentler in its impact.

It feels, watching what the surgical menopause community is discussing, as though this problem is showing up more today than it did, say, a decade or two ago. But that was when we more freely used progesterone to take the edge off of a poorly-fitting estrogen hrt (a practice that's waning today due to better understanding of progestogens' risks) and that was when there were more estrone hrts on the market. These have mostly disappeared, now, and we think that this has left those who prefer them more adrift in what seems to be an all-estradiol world.

If an individual has tried various routes of estradiol hrt and still doesn't feel comfortable, they may want to explore the remaining non-estradiol hrts. These include:

• compounded hrts with all estrone or a blend of just a bit of estradiol with mostly estrone;
• Menest, which contains mostly estrone with a bit of equilin estrone (synthetic horse estrogen, similar to some of the compounds in Premarin);
• Enjuvia or Cenestin or a generic for them, which contain various blends of synthetic estrogenic compounds that are mostly estrone-ish in action plus a few that are estradiol-ish (no longer on the market); or
• Premarin, which contains a blend of synthetic estrogenic, androgenic and progestogenic compounds that are mostly estrone-ish in action.

With the exception of the compounded hrts, these are all oral deliveries, which may not be our first choice these days. Those who experience this particular problem often find, however, that they are willing to accept that profile in the interests of a better hrt fit. It really can make an astounding difference from the impact of estradiol hrts.

Migraine headaches and HRT

Migraines are a miserable affliction and for those who hoped that removal of their ovaries would put an end to a monthly brain implosion, they, disappointingly, can continue right on thanks to the efforts of our menopausal hrts.

The primary migraine triggers seem to be much like the general headache causes: hormonal fluctuations and the type of estrogen used (by which we mean, the activity of the form of estrogen the hrt contains). So when troubleshooting hrts around migraines, those are some of the considerations to work with.

Sadly, hrt alone isn't always enough to control migraines, and some women end up finding that a combination of hrt plus other drugs that are specific to migraines ends up working the best for them. Still, these hrt adjustments do give us a place to begin that can be more helpful than simply being told we can't take hrt if we get migraines.

Vaginal delivery of systemic estrogen HRT

We've been following discussions of this topic for some time now in a number of locations on the internet and it's come up on our forums as well.

There is, of course, one vaginal-delivery systemic estrogen hrt on the market already, Femring. But we're also seeing some individuals report exploring the use of Estrace and its generics (micronized estradiol) vaginally for systemic support. And that raises some distinct concerns.

Vaginal micronized estradiol: will it work?

First of all, yes, absorption through vaginal tissues will function as a delivery route for this hrt. Oral mucosa is very similar to vaginal and it is indeed permeable to this molecular form of estrogen. In fact, it's been quite some years now since we first heard of using a tiny bit of the dust leftover from cutting tabs for transbuccal or oral use for local vaginal supplementation. We had some concerns initially that either the colorant or the base might prove problematic since neither are designed for the vaginal environment, but that has not been the case for those who've shared their experiences with us. We've also run this past a few doctors who have said there doesn't seem to be any obvious peril beyond the issue of making sure the dose is appropriate. So that seems to be both effective and reasonable as a means of local supplementation. But that's not the same thing as using this delivery for systemic support.

Risks: concentration in pelvic circulation

Our greatest concern with using this route for systemic vaginal dosing, however, is where that estrogen goes immediately after it is absorbed.

With transbuccal use, many users see distinct local effects according to where in their mouths the tablet is placed. Those seem primarily to do with fluid retention (such as sinus stuffiness, ear fullness or transient headache) and we have speculated that they represent higher local concentrations in the part of the circulation to which they are initially delivered, before they are well-diluted. Most of those reporting this effect have had success in switching to other locations in the mouth where this is less problematic, although the non-problematic location varies (of course it does) from individual to individual.

Looking at that same aspect in terms of vaginal delivery, then, we have a concentration of estradiol—which is the active form of estrogen—delivered to local pelvic circulation. We know from research done with vaginal progesterone that this kind of concentration in the pelvic area does happen with vaginal delivery of that hormone supplement and there is no reason at all to expect that estradiol could escape a similar distribution pattern.

Now, when that happens with progesterone, that represents a desirable situation in terms of delivering a therapeutic concentration of that hormone to pelvic organs without causing a corresponding systemic concentration—and heightened systemic effects. But with estrogen, there's no real reason that this concentration would be desirable and in many situations, we're quite concerned that it isn't. Anyone with endometriosis, for example, would hardly want higher estrogen concentrations flowing directly to their endo implants. Anyone with a risk of ovarian cancer retains that risk even when their ovaries are removed because there is a (low but present) risk that before oophorectomy, micro-tumors may have escaped their ovaries to later be stimulated by that higher level of estrogen in the circulation that feeds them. This is recognized in the specific warnings for current vaginal systemic hrt, that caution high risk users about precisely this.

We know from users of the systemic vaginal ring that some find this route of supplementation to be highly uncomfortable, citing symptoms of pelvic bloating or congestion as well as stimulation of irritable bowel syndrome or bowel cramping. There is also a mixed body of evidence suggesting that higher levels of estrogen may add to incontinence. So not only do we have the progesterone model to shape our expectations but we have experience with vaginal delivery and pelvic symptoms to suggest that it most certainly does happen and we have FDA concurrence that this represents an undesirable level of risk for at least some users.

It is worth noting that Femring, the vaginally-delivered systemic hrt, uses a form of estradiol that, although human-identical, is inactive until it has been further processed in the bloodstream. This means that it is well on its way to being diluted and distributed before it becomes fully active as estrogen. It seems likely that this is deliberately done to reduce estradiol activity exposure at systemic levels to those pelvic tissues. In other words, there may be significant negative concerns with vaginal delivery of systemic estrogen that led the pharmaceutical companies to put additional funding into working around that problem rather than, more economically, just repurposing an existing product they already had on the shelf. While we may not know what led them to do so, the simple fact that they spent money on this raises the warning flag that it was probably not done without substantive reason.

Risks: estrogen activity and vaginal tissue health

Were an individual to elect to try vaginal estradiol systemic hrt notwithstanding the above risks, we would also think that a regular, detailed and careful exam of vaginal tissues by a knowledgeable practioner would be important. While the low-dose vaginal hrts are documented to have a fairly light effect on the tissues they directly contact, all that systemic-dose estrogen going through a relatively small location (even though the tab breaks up quickly, it's still not going to be distributed over a wide area of mucosa in the fairly static vagina) may have disturbing effects upon the mucosal cells in that area.

This is a concern raised by some doctors when users discuss transbuccal use, based upon similar issues seen with some sublingual and nasal drugs. Those using this route need to be careful to switch locations around frequently, visually check their oral mucosa regularly, and also ask their dentists and oral hygienists to do so as a backup. We see no reason why similar precautions with vaginal use would not be a good idea (only, of course, probably not asking your dentist to be the one do it) to make sure that we are not stimulating some sort of cellular changes that could become problematic. Remember: the reason why estrogen is carcinogenic is that it fosters growth of tumors, and that's not something we want going on out of sight in our vaginas.

Would this work with any of the oral estrones?

That's a good thought that came from our discussion of vaginal systemics on our discussion forums. We don't really know, but it seems as though since there was an Ogen vaginal cream made for local use, the oral estrones Ogen or Ortho-Est would seem to be usable transbuccally or vaginally since they contain the same compounds.

That said, many of the same concerns with respect to vaginal systemic dosing would still apply. Although estrone is an inactive form of estrogen, the conversion of estrone to estradiol occurs in cells throughout the body. A higher-than-normal local concentration of estrone might well still result in higher-than-desirable estradiol exposure to vaginal and pelvic tissues. We certainly don't see any reason why switching out estrone for estradiol would moderate risk adequately that those with specific risk factors such as endo or ovarian cancer could be confident that this would safer for them, however much the systemic impact might be gentler than all-estradiol dosing.

So should we use oral hrts vaginally or not?

We have really mixed feelings about this whole premise. That it would work to deliver estrogen to our systems, there is little doubt. It is likely that in reaching the circulation through pelvic rather than head/upper body dilution, the specific local effects that are problematic for some women with transbuccal use might be avoided.

We can't, however, see that it in any way alters the way the dose is processed by the body other than that initial concentrated absorption uptick, so the premise that it somehow is delivered more evenly than transbuccal is likely a subjective impression that is not supported by physiology. It may be different from other transdermal (general body skin) deliveries, just as transbuccal is, because it represents a different uptake dynamic and the skin/fat reservoir and transmission effects are taken out of the mix. Like the transdermals, however, it also represents a risk of transfer to a partner than is unquantifed but certainly real.

We've taken up elsewhere the issues of whether not estradiol needs to be dosed multiple times per day and whether "even" is ever a state that can be achieved (spoiler: no, it's a myth), so we won't reference those concerns here other than to say that there is nothing in pelvic delivery that would lead us to feel they are not applicable here as well. Anyone whose body is not capable of using a daily dose via this route, as with any other, is not utilizing that particular hrt well. Whether or not other hrts would better suit them is the issue here, not just the route and timing; multiple-dose dosing is a stopgap measure to try to force a fit with a deficient hrt, not a good or sustainable strategy in itself (although it's true that in some instances where trying other things is truly not feasible, stopgaps may be the best thing we have within our reach). The ability to divide a vaginal dose into micro-doses given at extremely short intervals is thus not a compelling argument that in any way offsets the risks, let alone makes this route somehow unique.

So the bottom line on this is that there's just no reason to be really comfortable with the risks that this concentration provides in this location. That doesn't mean it mightn't be the more practical option for some women, but it would require special precautions that make it nothing to be taken lightly. One of the dangers of discussion forums that focus on support rather than information is that women can advocate for use of a particular hrt strategy without any corresponding exploration—or even awareness—of the risks it poses.

We do think this notional hrt use is worthy of exploration, but that exploration should be done knowledgeably and with great care to monitor for negative outcomes. Given the widespread lack of understanding of hrt and hormone effects, though, we're afraid that users will be injured by and later regret decisions made without fully understanding those risks. Individuals with hormonal concerns may distrust their doctors because that relationship is so formulaic, paternalistic, and illness-based, ill-suiting their menopausal health needs. Yet when they engage in risks without that backup of medically sophisticated knowledge, they've lost an important safety net. Maybe it looks as though we're being too conservative in this case, but with things we can't get back from without great cost, yeah, conservative does have positive benefits.

But then what about compounded hrt to be used this way?

Are compounded vaginal estrogen hrts being prepared for systemic use? What are compounders doing about these issues? We're not seeing direct-to-consumer advertising of this type of hrt, so we don't really know if this market niche currently exists and we haven't yet encountered anyone who does.

Because there is no substantive difference between retail human-identical and compounded bioidentical hrts in terms of this risk situation, our concerns would definitely extend to those hrts as well. While doctors in theory vet the prescriptions suggested by compounders, in practice many of them tend to just pass them on as suggested by a fully qualified professional and happily pocket their share of the business income so generated. So there's a questionable safety net right there.

In fact, if they are doing so, this would be exactly where we tend to think that the FDA has a reasonable ground to be critical of compounding. This would be a major departure from what is known and tested and generalizable from other tested and licensed retail hrts. This is where their current practice model might indeed overstep their training and licensure and, of course, constitute the legal vulnerability that is being exploited by the pharmaceutical companies in response to what is actually a perceived marketing threat rather than the nominal concern for patient safety in which it is couched.

So we're going to hand this part of the question back to you. What do compounding pharmacists you are working with have to say about direct systemic vaginal estradiol hrts? And estrone used that way? Are they making and selling it? What precautionary screenings are they doing or what counseling are they doing on risks specific to this delivery? We'd be very interested to know what the compounders' take on this is. If you have any information, please do share the results of your inquiry with us.

This is an idea we need to explore just because there are indeed individuals out there claiming to be using this route and promoting it on discussion forums. The more concrete the information we have, the more useful it becomes to us, whether it's to give us the go-ahead to experiment more freely or to convince us that it's really not such a good idea after all. We're not at all opposed to exploring and pushing the envelope in search of alternative ways to use the available hrts, but we're always going to be taking a firm hard look at the risks along the way.