Primary Prevention of Cardiovascular Disease With HRT

We've just bookmarked an important new article that we think really brings home the post-Women's Heath Initiative Study (WHI) thinking on the flaws of that study and what we really need to know about the cardiovascular risks of hrt. Why should we care when cancer terrifies us? More of us will die from cardiovascular disease than breast cancer. It lacks the drama and publicity, but that doesn't mean we shouldn't pay very serious attention indeed to this aspect of our health.

Primary Prevention of Cardiovascular Disease With HRT (free signup required to read)
Kate Maclaran; John C Stevenson
01/03/2012; Women's Health. 2012;8(1):63-74

Abstract 

Prevention of cardiovascular disease has increasingly important health implications as our population ages. Menopause is associated with the development of cardiovascular risk factors and there are many plausible biological mechanisms through which estrogen may confer cardiovascular protection. Despite a wealth of observational data to support the use of estrogen, large randomized controlled trials failed to demonstrate a benefit. It is now becoming clearer that the beneficial cardiovascular effects of estrogen are greatest in younger women and those closest to menopause. This has led to the development of the timing hypothesis. Use of age-appropriate estrogen doses is crucial to maximize cardiovascular benefits while minimizing risk of adverse effects such as venous thromboembolism and stroke.

Article summary

The article gives an excellent overview of the current thinking on how hrt use relates to cardiovascular disease, taking into account WHI data, the "critical timing" hypothesis, as well as the combination and route of hrts, both conventional hormones and those that have been modified (SERMs).

It starts out by spending some time going through the various cardioprotective mechanisms of estrogen, including metabolic ones related to lipid levels and fat distribution, insulin resistance, and actions on blood vessels themselves. It then introduces a review of the data from the disastrous Women's Health Initiative Study and looks closely at why this was in such contradiction to a substantial body of sound other evidence.

Crucial differences in the study populations are likely to help explain many of the discordant findings. The observational studies generally involved women who started HRT around the time of the menopause for symptomatic relief. Subjects tended to continue treatment consistently and were followed-up for a long duration, often 10–15 years. By contrast, women in the WHI studies were started on HRT at an advanced age (average 63 years), often with a significant delay following menopause. Furthermore, subjects had elevated BMI, were not using HRT for symptom relief (only 12–17% had moderate-to-severe vasomotor symptoms) and generally had much shorter duration of treatment and follow-up

While research studies cannot assume any reason for observations, the article notes that

The presence or absence of vasomotor symptoms in study populations is important as hot flushes are increasingly being recognized as a determinant of vascular health.

That means, in research terms, that they must now state that hot flashes cause cardiovascular disease. But because we're not researchers, we can read into that the premise that this more likely reflects an underlying commonality, and quite likely demonstrates the difference between women who are not meeting their hormone needs or are fluctuating a lot, vs those who are hormonally adequate and stable. For now, though, this implied causality results in the conclusion that

further evidence is needed to help fully understand the mechanisms by which vasomotor symptoms may influence cardiovascular risk.

One of the important aspects of hrt use and cardiovascular disease is that the payout time is quite long.

This theory is supported by further analysis of the WHI estrogen-only arm, which demonstrated that lower cardiovascular event rates in women receiving estrogen compared with placebo only appeared to emerge from 7 years onwards...Similarly, data from the WHI estrogen plus progestogen arm showed that CVD benefit only appears in younger women after at least 6 years

Why is this important for us? Too many women are given hrt briefly after surgery and told they will be discontinuing it in a few months when their menopause "goes away."

Other women run up against the pretty generally accepted current guidelines that state that

HRT should be used for the shortest possible duration, often interpreted as less than 5 years.

That magical 5-year figure actually is another bit of fallout from WHI, in that it was after five years of study progression that the cancer figures for the combined hrt arm (not for the estrogen-alone arm—and this is a critical difference often missed in the panic) crossed the arbitrary threshold for study cancellation. So, nothing about cardiovascular disease is in that limit, even though it's cardiovascular disease that kills more women than breast cancer.

The article goes on to note that these kinds of time limitations may need to be re-evaluated in the light of the long pay-out on hrt when measured against cardiovascular disease, and this is likely an important and valid issue for all of us in surgical meno.

Next up: the "timing hypothesis." Succinctly stated, this holds that

there is a window of opportunity where HRT may be beneficial for prevention of CVD in younger women, but that in older women, it does not appear to have the same benefits.

But what about the bad cardiovascular outcomes in WHI? The article reviews the potential negative effects of estrogen, but then brings things into a context that is rarely seen in these discussions: need and dose and combination of hormones.

Although these potentially adverse effects of estrogen have been identified, it has been suggested they are not harmful except when inappropriately high doses of estrogen are used, or in the presence of certain progestogens, particularly MPA, which acts to negate the beneficial effects of estrogen and may cause vasospasm.

Ah, here we have the "new" thinking on hrts and this brings things much much closer to what we as women using hrt have found: dose, combination, and route all make a difference; hrts are not a single monolithic entity in which giving any random one stands for the effects of all. Seriously—please consider standing up and cheering at this point: it's that radical a departure from traditional thinking on hrts.

Is there firm data that these things really make a difference? No, the article notes that this is the direction thinking is going and that studies being conducted now should be clarifying this relationship as they are completed.

The article then looks at specific forms of cardiovascular disease that are worrisome based upon WHI results. In terms of stroke, which is what caused the ending of the estrogen-alone arm with a 32% increased risk, the authors provide supporting data from more recent studies that find that route and dose are critical to these outcomes and, not surprisingly, lower doses and non-oral hrts reduce this rate to "extremely low."

Similar insight is found into the issue of venous thromboembolism (blood clots): route and dose and specific hormones make a big difference.

oral, but not transdermal, therapy was associated with increased risk of VTE and also that the thrombotic risk differed depending on the progestogen used. There was no increased risk with micronized progesterone, pregnane or nortestosterone derivatives, but significantly increased risk with norpregnane derivatives.

Overall, there is still not a good solid body of research evidence that pits one hrt against another for route and dose. It's well enough demonstrated that different hrt types and routes have different specific effects, and it's worthwhile, as we make our own hrt selections, to review these—the article does a decent job of listing them and providing citations for the actual research. At the moment, based upon their overview, their conclusion is that

the dose of estrogen is probably more important than the route of administration on the risk of CHD, whereas both route and estrogen dose can influence stroke and VTE risk.

Estrogen, we've long emphasized here, does not act in a vacuum. While the use of progestogens (progesterone-like hormonal agents) in surgical menopause is probably declining, it remains a critical element for the prevention of endometrial cancer and endometriosis growth and continues to be popularly pitched to women by hormone marketing, especially in the compounding realm. The article takes a look at the existing data on different protestogens, noting that it's "the androgenicity of progestogens [that] influences their metabolic effects." Any woman who requires a progestogen as part of her hrt should read this section as she considers the overall effects she both wants and must avoid.

Tibolone and the selective estrogen receptor modulators (SERMs) are often offered to women as being "safer" than actual hormones while still holding benefits of other types. There's not a lot of data on cardiovascular disease aspects of their use, but this section of the article does summarize what exists. For women without specific risk factors that require these treatments, the lack of good data on their risks should certainly raise a flag that they cannot be taken as completely benign and that simply choosing them in fear of one thing, usually cancer, may raise other risks. As ever, it's all about balancing risks and to do this effectively, we need to set aside our fears of one specific boogeyman and look very specifically about our own personal risk factors in a number of areas. This section begins to lay the groundwork on this category of hrts.

Finally, in conclusion they sum up the situation:

CHD forms a significantly greater burden of disease than breast cancer or stroke, and the menopause is a pivotal time for reducing future cardiovascular risk.

They note the importance of lifestyle and diet in overall risk management, something that we would like emphasize here as well. They go on to note that

Cardiovascular risk is determined by a combination of genetic, lifestyle and environmental factors, but sex steroids can play an important role in modulating risk.

And then for the payoff:

Current evidence points to a window of opportunity, where greatest benefit in preventing atheroma progression is seen when HRT is initiated early after menopause. HRT may cause adverse cardiovascular effects through coagulation activation and abnormal vascular remodeling, although the use of age-appropriate doses and transdermal routes can help minimize these risks.

And that, right there, is where WHI was trying to go but, due to flaws in the study design, went dangerously and disastrously astray.

Important points to take away from this article

First of all, it is a good overview of the whole topic, appropriate for us to read and share with other women but also appropriate to share with our doctors should they still be stuck in the post-WHI "OMG HRT kills!" mentality.

While there is much mention made these days of a woman's "individual choice" there are still many, many women, even in surgical meno, who feel pressured to "do it the natural way" as though there are some merit points to be won in withstanding misery and poor health. We think articles like this are things all women at perimenopause or surgical menopause should read, so that they better understand that against the "all natural" glamor can be stacked the true risks of the situation. This article is good on true risks.

Hot flashes cause cardiovascular disease. As noted above, it's likely that over time and with more research, this will be seen as a profound oversimplification, in which we have a correlation rather than a causation. Never mind; for the moment we can use this to our advantage if we are being denied hrt and feel that we must campaign for its prescription.

Cardiovascular disease prevention is not a case for treating hrts like drugs: this is the antithesis of a quick, dose-related response. Instead, we need to take a longer view of hrt use when we're talking cardiovascular disease, and so while the "least dose required to meet needs" premise of risk management is not at all contradicted here, the arbitrary discontinuation of hrt at some set age or interval is strongly called into question. This is important for us to understand and very important to convey to our doctors if they are not conversant with current thinking on this.

We can, each of us, resist the mindless panic brought on by the post-WHI media frenzy, and it's these sorts of articles that can help us make a more realistic evaluation of our risks with respect to hrt use. Further, by sharing this kind of updated, serious, and medically sound information with other women, we can help them make better, less emotional decisions for themselves. And by bringing this to our doctors, we can help them stay more up to date where they might not otherwise have the time or interest to pursue all the small studies that have, over the past decade, contributed to a much more realistic and accurate picture of hrt actions and options.

Surgical menopause boosts cardiovascular risks

Update note: the study cited below, "Surgical Menopause Boosts Cardiovascular Risks" no longer seems to be available online. Nonetheless, the discussion around it remains valid and we are retaining this post for that reason.

We've known for some time now that overall cardiovascular risk rises at natural menopause to approach men's generally higher rates. This was long assumed to be the result of the shifting of balance away from the heavily estrogen-dominated profile that distinguishes (fertile lifestage) women from men. Indeed, it was cardiovascular risk that was really the underlying focus of the infamous Women's Health Initiative study: women well past menopause who had developed cardiovascular disease were put on hrt to see if it would improve their status. Sadly, no such findings resulted. Nonetheless, the generally better cardiovascular status of women on HRT as compared to women without continues to fuel research on the "critical timing" premise, that proposes that functions supported without interruption by covering hormone needs in menopause without a significant time lag are protective, but that once hormone support lags, women cannot regain that lost protection.

We also know that testosterone may worsen cardiovascular risks as it brings us closer to the male profile of risks. That's part of why the US Food and Drug Administration did not approve the female testosterone patch: it didn't improve the libido in some women (where testosterone deficiency wasn't the problem) and it did boost risks. For women with Polycystic Ovarian Syndrome, that's a special concern, since their disease is often characterized by lifelong elevation of testosterone levels. The literature is not yet clear on this hormone and cardiovascular risk

Cardiovascular risk also relates to elevated progesterone levels. A progesterone-heavy hormone balance tends to make us insulin resistant, raising both the risks of type II diabetes and cardiovascular disease in a special combined disorder called "metabolic syndrome." Metabolic syndrome is considered of the established risks of menopause.

Estrogen and cardiovascular disease

What kind of cardiovascular disease specifically? All sorts, actually. In addition the the hypertension seen as part of metabolic syndrome, hypertension alone can be a sudden-onset disorder upon oophorectomy. It saddens us to read of doctors withholding hrt from women who spike sudden high pressures when they come out of surgery out of concern for stroke risk. In fact, it can be the loss of estrogen's relaxing effect upon the walls of blood vessels that can cause this, so they're withholding the one thing that can treat the problem out of a mistaken focus on the symptom instead of the cause. Other women, less catastrophically, may find their pressure creeping up when they are advised to abstain from supplementing their hormones back up to more normative, menopausal levels or when their HRT is suboptimal.

We also know that estrogen has a beneficial effect on lipid levels and types, although oral hrts provide a different assortment of effects in this regard than transdermal do.

But today we have another small study, Surgical Menopause Boosts Cardiovascular Risks [no longer available online], that looks more closely at just what goes into that shifting CV profile with estrogen loss. Although this is a rather small study of only 90 participants, what they found was that the carotid blood vessels (major arteries in the neck that supply the brain, which are taken as representative of general vascular condition throughout the body) are narrowed in women who had oophorectomies before natural menopause age and who did not supplement their hormones back up to normative levels.

Now, they were working with living study participants, so they couldn't go slicing into these major arteries to find out precisely what had them gummed up. The assumption is that this is an atherosclerotic process, the plating out of metabolic gunk, mostly fat- and calcium-based (think about the condition of your bathtub drain: atherosclerotic placque is roughly as appealing, only with a bit less hair), on the inside of the vessels that, much like the situation in your bathtub drain, gradually reduces blood flow until it may stop it altogether or a bit breaks off and stops flow someplace else (which is what a stroke represents in mechanical terms).

But that's just an assumption, at this point. There is certainly also an element to do with that reduced vessel size/relaxation as well. Beyond that, we don't exactly know and won't until there's more autopsy/surgical data that analyzes what those vessels actually look like on the inside. Still, this is an important step because it does validate that there is actual pathology in place, and that pathology correlates to a woman's specific hormonal status.

Of note, the article concludes:

Dr. Ozkaya said, "We should think twice and discuss it with the patient, should we consider performing oophorectomy before menopause."

Now, would everyone whose doctor warned them about increased cardiovascular risk with this surgery, especially those advised that hormone deficiency would be therapeutically necessary, please raise their hands? Nope, we didn't expect so. This is the elephant in the room that never really gets discussed pre-operatively or that gets hand-wavy assurances of "you'll take this little pill and everything will be fine." Right? And so this is what women need to be able to find out on their own...or with whatever help they can find.

Should women refuse an oophorectomy on these grounds? Oh, goodness no: there are often much more dire consequences and quality of life issues represented by the pathology for which we choose this surgery. On the other hand, this does add more weight on the side of turning down the "oh while we're in here we'll just take out those healthy ovaries because you don't need them any more" sales pitch. It really all comes down to weighing risks, and that has to be done by each woman for herself.

Managing cardiovascular risk in menopause

Yeah, but most of us here have already been through the surgery. How do we manage those risks now?

First of all, by simply being aware of this, aware of the body of literature we've linked to above, that is all legitimate medical research that you can share with your doctor in discussing this aspect of surgical menopause. We need to be monitoring this risk: we need to keep an eye on our blood pressure, we need to get lipid levels checked as part of our annual checkup, and we need to be prompt in seeking actual treatment if either of these start to rise.

Beyond that, though, we can work to forestall these effects through other means, nonmedical things we can do for ourselves. That's right: we're going to talk about those unpopular topics of good diet and exercise along with weight reduction. 

Right now, proponents of the high-fat/low-carb diets continue to duke it out in research studies with those supporting the so-called "Mediterranean diet." Our bookmarks account has a huge section on research and recommendations about diet: go read and make up your own mind. What you should know, though, is that diet is considered to be a major factor in cardiovascular risk and it's one we can manipulate ourselves. And by that we don't mean a week of good intentions when you give up a bowl of ice cream and really do mean to get more veggies; we mean a serious restructuring of what we eat every day for the rest of our lives. Although the site's main focus is cancer, the American Institute for Cancer Research has a lot of good, applicable material on what constitutes a healthy diet as well as tips on this next topic coming up just below.

And then there's exercise. Exercise does so very many good things for our bodies. It doesn't need to be crushing, but it does need to be regular and it does need to be at least brisk. Current recommendations from the US Centers for Disease Control and the American Heart Association are a place to start, although of course this needs to be discussed with your doctor if you have any issues that might complicate the situation. And yeah, it takes time and oh dear how do I fit that in my already busy life and maybe I'll start tomorrow yeah tomorrow for sure...we understand that whole argument because we struggle with it ourselves. The bottom line, however, is that that heart attack is going to be a whole lot more disruptive of our lives when we're spending a week in intensive care, if we happen to survive it. And, unless we get serious about prevention, that heart attack, statistically speaking, is in our future. Isn't that worth a little work to push back?

Last of all, we can't neglect the role of hormone balance in all of this. Imbalanced hormones, whether an excess of testosterone or progesterone, are likely to edge us higher in cardiovascular risk. Normative estrogen levels look as though they edge us a bit away from that risk.

That means that we need to look carefully when we're offered testosterone to make sure it's truly a situation of testosterone deficiency and we've exhausted other efforts to restore libido before we reach for this option. Using testosterone as a bandaid to cover up for poor estrogen HRT delivery: just raising our risks.

This also means we need to be cautious in supplementing progesterone. The "just because" premise of taking it, without regard for actual demonstrated need, looks less appealing with insulin resistance and metabolic syndrome keeping it company. Using progesterone as an hormonal hammer to bludgeon us into sleeping more in the face of estrogen excess: also less appealing when accompanied by cardiovascular risks.

But what about people who must deliberately induce a progesterone-heavy imbalance for therapeutic purposes? Those with endometriosis or who have a uterus are facing increased risk of endo growth and cancer if they skimp on progestogens in their HRT. Does that mean they are doomed? Certainly not, although they possibly do experience a raised level of risk and should therefor also be more vigilant about protective measures and monitoring. And they can consider, especially if they have other familial cardiovascular risks, whether they might prefer to use a vaginal progestogen to enhance pelvic circulation of that hormone without such high systemic exposure.

So does that mean if we take our HRT, we're safe? That's hard to say, but it looks as though the answer is not that clearcut. Even individuals in natural menopause experience increasing risk as their hormone levels decline, even though they are notionally still producing enough to meet their post-fertile needs. And since the level of hormonal coverage individuals with their ovaries produce in natural menopause is the situation we are seeking to emulate with HRT in surgical meno, we can assume that even if we've started taking HRT from the time of surgery and have had few disruptions in it, we still share roughly that level of risk.

And in case the question occurs to you, no, we're not advocating achieving higher-than-natural-meno estrogen levels as cardiovascular disease prevention. In that direction seem to lie increased hormone-mediated cancer risks, an equally unsavory option. So as with so many things hormonal, the middle ground of normative hormone levels and no more, along with a healthy lifestyle, seems to provide an undramatic but undeniably healthier plan.

In the news: Progestogens and lung cancer

Estrogen-only therapy may not up lung cancer deaths was the headline of  Reuters press release that came across our desk some time ago. According to the article, while the Women's Health Initiative Study showed that women in natural menopause taking conventional combined estrogen + progestin hrt had an increased risk for lung cancer (free signup required), women in surgical menopause taking estrogen hrt only did not show that risk elevation.

Interestingly, the research is mixed on this topic. An article "Dietary boron and HRT reduce lung cancer risk in women" published in 2008 in the American Journal of Epidemiology, stated that, based upon an "ongoing case-control study in Houston, Texas...[with]...763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT," found that "HRT use was associated with a 31% reduction in lung cancer risk."

Okay, so how do we interpret this for our use? Does this mean we should quit using progesterone?

No, this probably doesn't mean that we can't or shouldn't ever use progestogens (progesterone and its synthetic cousins the progestins), but that answer may no longer be valid across all types of use in surgical menopause, so let's look at this a bit more closely.

Progesterone is different, isn't it?

First, let's set aside the whole "progesterone is natural so it doesn't carry this risk the way progestins do" issue.

So far as we have solid information on this, this statement represents nothing but wishful thinking. We have no serious population study data that differentiates between progesterone and a progestin, let alone between different progestins. There is one study, Progesterone--promoter or inhibitor of breast cancer, that says:

Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection.

In other words, this seems to say that if we take enough of it to do us any good, the risk is severe enough to show up. Which doesn't mean that no risk accrues to lower doses, but rather that the effect could be more subtle or take longer to show up.  There's a unknown related to degree of use, here, that we can't yet fill in.

The WHI study was done with Provera, a specific progestin, and the results have not been checked in any large study against other progestins so we don't know—and analyses of the study results have pointed this out—whether this is a Provera issue or a progestin issue or a progestogen issue. Because one is taken as standing in for the whole, the media coverage and the doctors who get their continuing education from CNN will assume that it means all progestogens and panic accordingly. But each progestin has very different chemical characteristics and there is some reason to question whether this relationship with lung cancer is due to the elements progestogens have in common or an element Provera possesses uniquely. Until that distinction is made more clear, we really don't know. And until we do, we are as liable to panic and jump in the wrong direction as the right one.

So what should we do about this new demonstration of raised risks?

A lot probably depends upon how we use it

Now let's look at different categories of women and HRT use.

Women in surgical menopaue who do not have a uterus and who are taking plain estrogen, whose progesterone needs are being met adequately (as they define them) by their own progesterone production and the progestogens they acquire through environmental contamination, are shown by the WHI Study results as not experiencing this elevated risk. No one has suggested that they require hormone blockers to reduce their own progesterone production for further protection, which suggests that hormone levels appropriate to natural menopause with ovaries (which is what we emulate with hrt in surgical meno) are not presently interpreted as carrying this risk.

Women in surgical meno who do not have a uterus and who are supplementing both their estrogen and progesterone may be at an elevated risk level. As we noted above, we can't rule out risk based on the type of supplementation (progestin vs progesterone) at this time, so we can only work from the safer, more conservative position that increased progestogen exposure equates to some unknown level of increased risk.

But let's not get caught in the binary reasoning trap of research questions. This is probably not an either/or situation. That is, taking one molecule of a progestogen most likely does not slam us straight into the lung cancer risk category seen in the WHI. These women in the study who were on combined hrt were on levels of progestin designed to protect an intact uterus from developing cancer due to the estrogen stimulation. And they were on a fixed, study-mandated dose of estrogen, with no regard to their personal level of needs, especially at their age (they were women mostly in their 60s and up, taking a "standard" hrt dose for women a decade younger). So these women were being exposed to relatively higher levels of estrogen than we typically use in surgical meno if we are following the basic "as little as meets present needs" rule that is the current recommendation by the various medical specialty groups that have looked closely at all aspects of hrt use and menopause. In other words, they were taking a progestin at a therapeutic, not minimal-needs, level of dosing.

But that's not what we typically do when we supplement progestogens in surgical meno if we don't have a uterus. We take a dose only large enough to make up the shortfall between what we can produce and what our bodies need to balance out the estrogen we're taking. So the conceptual test we can apply here is that if women in natural menopause are not advised to have their ovaries removed and take hormone blockers to prevent their postmenopausal progesterone exposure, we may not be raising our risk exposure significantly when we simply mimic natural menopause with ovaries...as is the goal of surgical menopausal hrt. Now, we cannot promise you that this is entirely safe, but what we can suggest is that this seems reasonable based upon what we presently know.

But some women supplement to higher levels, and we're not sure how comfortable they should be about their risks. Who would do this? Many doctors prescribe high levels of progesterone to counteract excessive estrogen doses or to use progesterone as a hammer to bludgeon women on high or ill-fitting estrogens into being able to sleep. How high? Women who are taking 100mg or 200mg or even more of Prometrium or the equivalent are trending out of the supplemental range and into therapeutic dosing. And their risk picture is much less clear. They are approaching the level of supplementation that the WHI participants who saw that raised lung cancer risk were using, and that raises the question of whether they would be safer using some other approach for dealing with their problems than their therapeutic levels of progesterone intake. This is not a question we can answer yet, but it's probably one women should raise when they're looking at these higher progestogen doses.

And finally, the third group of women: those required to use therapeutic progestogen doses to treat some other risk. These would include women in surgical menopause who retained their uterus, or women with endometriosis. They must take more than a balanced dose to produce this therapeutic effect, and this places them right into the WHI risk profile.

So how can this set of risks be managed? On the one hand, we can look at relative incidence of endometrial cancer and compare it to the lower risk of lung cancer. Are there modifying factors? Surely familial history and smoking exposure will also play into the lung cancer side of things, yes.

Is there anything these women can do to lower their overall progestogen exposure and still obtain the benefits of therapeutically effective doses where they need it? Yes, in fact there is: use of a vaginal progestogen provides higher levels in pelvic circulation, where therapeutic effect is needed, and less in general circulation, where it is not. There's more information on this in our discussion of hrt for women with a uterus but no ovaries, as well as in a discussion of a news article about contraceptive patches.

While we don't know what "safe" is in this context, surely whatever we can do to lower our exposure risk until it's better understood is at least doing what we can to approach safer.

The bottom line

We don't have enough information yet to be able to draw any sort of safe-or-not line. We may never have this: research isn't about what we want to know; it's about what someone will fund a study to find out, and that's often dependent upon who thinks they can make money from its results. At the moment, though, this correlation between progestogen use and several types of cancer suggests that we should use only as much of any progestogen as we demonstrably need, and it probably makes sense that we should do what we can to limit our systemic as opposed to therapeutic exposure.

Should we panic and give up progestogens entirely? Oh goodness no: we don't begin to know enough to say this, and even the risk factors as they stack up don't begin to suggest that level of panic is necessary.

Should we figure that because progesterone is a natural hormone manufactured by our own bodies that it's safe? Nope, not this either: we know that our own estrogen poses cancer risks that we can reduce by controlling our exposure, and this may well turn out to be the same sort of situation. So no, the old Dr. Lee premise that you can't have too much progesterone is looking as shaky as those 1950s articles touting estrogen as the magic agent to keep us "forever young."

Hormones are active agents that are active throughout our bodies. Something this active is never likely to fall into entirely-safe territory. What we need to learn and can hope that research will begin elucidating is just what the parameters are of the risks that progestogens pose. Only then can we make sound decisions between our various risks to make sure that we're only engaging in the ones we deem acceptable for the benefits gained.

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.

HRT and cancer risk

Many individuals come to our discussion forums and post that although they are in surgical menopause, they cannot take hrt because they have relatives with cancer. Or they come to us because either the media or their doctors have assured them that if they take hrt, it will give them cancer.

It's not actually that simple. And a lot of the discussions we have on that topic are to explore that situation in a lot more detail. Although it's easy to paint a picture where the risks are all on one side of the issue, that is absolutely not the case. So let's take a more in-depth look at this whole concern.

What kind of cancer risk?

The first part of the exploration anyone owes themself when making a decision of this magnitude is just what kind of cancer risk they actually have. One uncle with prostate cancer, to use a fairly easy example, is not the same thing as having one's mother, two aunts and three sisters all die of estrogen-receptor breast cancer. Even within the realm of breast cancer, there are cancers sensitive to estrogen, cancers sensitive to progesterone, and cancers indifferent to both hormones, as well as a number of distinct and different types of breast cancer.

Given that, then, an informed decision about personal risk really must begin with working with an oncologist, a cancer specialist, to explore our own personal risk level. This will include taking a detailed history, not only about our own health, but about those relatives who had cancer. It may include genetic testing. It may involve a medical records search for exact pathology of previous family cancers. It should be very thorough.

And when it's done, the question to ask is not "should I take hrt?" Any responsible oncologist will answer that question with a resounding "no!" Their specialty focus is preventing and combating cancer, so they generally view no cost at all (and we'll get into those costs a bit more further along in this discussion) as outweighing any degree of cancer risk.

Instead, it may be more useful to ask the question: "what are my relative risks?" Another way of asking this question is "if I had kept my ovaries, would I have had to have them removed in menopause in order to prevent a high probability of developing cancer?"

Because our goal with hrt supplementation in surgical menopause is really just bringing us up to a level of support that those in natural menopause receive from their ovaries, that's really the equivalent situation. In other words, if our menopausal ovaries would not have presented an unacceptably high level of risk, there's some question as to whether supplementing our hormones with hrt to that same level would present any greater risk. (That's qualified, however, because those who take certain progestins as part of their hrt may in fact experience a higher level of risk from that particular type of hrt.)

Yeah, but if there's any risk at all, shouldn't I abstain from hormones?

The problem is that risks aren't one-sided. There are many beneficial things that estrogen enables.

For example, those who take hrt have a well-documented lower incidence of colon cancer, which is a major killer in the US. If you have no family history or special genetic risk of breast cancer but do have a colon cancer family history, then you might want to weigh this decision differently from someone whose risks stack up on the breast cancer side. There are no guarantees and there are many lifestyle factors that also play into risks or can be used to help mitigate them, but it's important to keep in mind that we can't let the word "cancer" make our brains short out entirely.

While the exact role of estrogen's preventative actions is still being thrashed out by researchers, the overall maintenance of functional hormone levels does have some pretty compelling evidence for its importance. Doctors used to feel that ovarian production of hormones was essentially insignificant for health if an individual was no longer fertile, and that guided many to recommend removal of healthy ovaries as part of any hysterectomy on the grounds that this would reduce any chance of subsequently developing ovarian cancer. And since those hormones weren't needed and hrt was linked with breast cancer, many found themselves up to their ears in symptoms of surgical menopause with no support beyond what non-ovarian estrogen their own bodies could make and whatever xenoestrogens they picked up from food and their environment. Still, that was healthier, according to their doctors.

That position was reconsidered a few years ago when studies on young women who had oophorectomies without subsequent hrt support revealed that by the time they reached the "normal" age of menopause, they had experienced a 70% increased incidence of mortality compared to women of the same age who had kept ovaries (supporting articles). In fact, in no group studied for risk (all causes, fatal and nonfatal coronary heart disease, or lung cancer) was oophorectomy associated with increased survival (source). Other studies have suggested that the same issue of increased risk exists with Parkinson's disease and dementia (source).

While these studies typically follow younger women, there's no reason to suggest that this risk is tied to any specific age. More broadly speaking, then, we have to question whether life in hormone deficiency at any age also carries significant risk of death by these other disorders, or at least an enhanced risk of developing them. There is no research to date that suggest that there is any sort of shelf date on our hormone needs.

And that really complicates our decision process. If, for example, an individual has a high incidence of cardiovascular disease in their family, such that most family members die by age 50 of heart attack or stroke but no one ever lived long enough to develop cancer, they might well want to think long and hard about their personal relative risks. It's not just a quality of life issue—although that's plenty significant for many of us. It's instead a health issue of just as much potentially fatal magnitude as that cancer risk on the other side.

If we make this anti-hormone decision based on cancer risk, we're making a cancer treatment decision

Many of those who choose not to supplement their hormones due to a documented or perceived cancer risk find themselves miserable and desperate to improve their quality of life. "How can I feel good?" they demand on our discussion forums.

To some extent, we can alleviate some of the symptoms of hormone deficiency with non-hormonal measures. Some of those options are discussed elsewhere on this site.

But these hopeful sufferers may be disappointed to find that not all of their areas of concern or symptoms have a non-hormonal "fix." Even where help is available, those approaches themselves often have pretty significant risks or side effects, or they may only reduce but not alleviate the problem. The bottom line is that not only are they embracing specific health risks with this strategy, but they are also going to have to put up with compromises in terms of quality of life.

Now this is where the medical sites all cheerily assert that life can be just fine with the proper attitude. All we need is a positive outlook or our religious faith and these minor bumps in our otherwise delightful life can be overcome. If that works for you, great. You probably don't need to read any further and can go on with your life. We're really happy for you.

Now, we're not saying that attitude isn't important. But if you're still grappling with the idea, here's a concept that may help you keep a balanced perspective: the things you are choosing to undergo in terms of hormone-deficiency-related effects are the specific choices you are making as part of treating your cancer. It doesn't matter whether you actually had cancer in the past or you just feel that you have such a high certainty of developing cancer in the future that this is your health priority. What you are engaged in is a medical treatment. And in common with all medical treatments, there are costs. These hormone-related symptoms are your costs.

So when you are hot flashing or lying awake at night or even wondering where your sex life went, while you're working on finding a set of good non-hormonal maintenance practices, you can remind yourself that you are not a helpless victim here: you have cancer and you are treating it. You are choosing these things specifically to battle your cancer. You're fighting back with every hot flash. Sure, they're miserable and you are wishing for the happily ever after you thought we were all promised, but you have cancer and you're fighting back in this way. The glass may only be half full, but cancer treatment is what it contains. That may not make it all better, but it does give it worthy purpose.

Another critical question to ask

If my risk is so high that I need to treat it with hormone deprivation, should I also be taking drugs to suppress my own hormone production and use? Should I be observing special dietary precautions to limit exposure to xenoestrogens (estrogens from outside sources)?

Again, this isn't a question you can entirely answer on your own. But when you consult an oncologist, it's a good one to kick around. It's easy to for doctors to tell us not to do something and once they put our file folder away in the office records room, our hot flashes won't be keeping them awake at night. But if our risk is so severe that we have to endure hormone deficiency and we have to embrace an up to 70% risk that we'll die early anyway, shouldn't we do even more to reduce that risk?

Yeah, that casts things in a different light. When we ask a doctor to do something, like prescribe hormone-blocking drugs for us, then they have to much more explicitly consider the risks of that treatment. Then they may admit that the symptoms caused by these drugs make a lot of their patients give them up, or that these drugs have some significant risks. But hrts are only a small incremental exposure to hormones (even in surgical menopause, we make most of our post-ovarian estrogen in our adrenal glands), so if we have only that slight a risk and don't need to take that further step, do we really need to limit our hormones below normal menopausal levels at all?

This isn't a pep talk to make you see your way towards taking hrts. There truly may be a compelling reason why just this much deprivation and no more is exactly and totally what you need to be safe from cancer. All we're trying to do is suggest some ways to explore the options from different angles, to make sure that the treatment you select really is one that makes sense for you and will really do what it is you are wanting. "Don't take hrt and you won't get cancer" is a very simplistic thing to recommend, and because of that, we need to hold it up to close examination to make sure it's totally valid for our own personal situations. Because if we can do this, if we can embrace the sense of whatever measures we decide to take to treat our cancer, then we can live with the consequences of that decision with greater grace.

Are there other things I should do to reduce my risk?

This is a great question for all of us to ask, not just those who are actively treating a cancer or cancer risk. To some extent, we're all at risk and so we all should do what we can to minimize that risk. Even if we don't want to skip hrt, even if we don't want to practice hormone deprivation therapy, we can all work on risk reduction.

The first way we can reduce our risk is to supplement our hormones with only the minimum amount of hrt that otherwise meets our goals. We can do that by approaching our needs by working up from a low dose, by stopping increasing as soon as we feel okay. We can do that by challenging ourselves every few years with a trial of a small dose decrease, to see if our needs have changed over time, as is typical. These are easy things, but because our overall risk of estrogen-related breast cancer is related to our cumulative lifetime estrogen exposure, this is a real risk reduction measure.

There are all sorts of dietary risk reduction strategies that we can find out there, some of which have good foundations in actual medical research and some of which are dramatic, profit-making wishful thinking. Just how far each of us wants to go with this is up to us, of course. But here is some of what we know.

Dietary fiber seems to hold a real relationship with reduced breast cancer incidence. Fruits and veggies do as well, although the actual components that have this effect have not been isolated so recommendations are for whole foods rather than refined elements taken as nutraceuticals. We know that there are xenoestrogens found in fruits and vegetables grown using pesticides and that much commercial meat raising involves dosing the animals with estrogens and other hormones that persist after slaughter. Alcohol and grapefruit raise our circulating estrogen levels and our risks, but coffee and tea don't test out as doing so. Red meat and a high fatty intake also raise risks.

There are also more subtle things we can look at to manipulate risk. The glycemic load of our diet and our fasting blood sugar level have been found to be tied to breast cancer risk. Anything that increases our proportion of body fat increases risk and losing weight lowers risk. All by itself, increasing exercise lowers risk. All of these things have actual research backing them up, and you can read articles on diet and breast cancer for yourself in our bookmarks account.

So that's a lot of lifestyle stuff we can work with to pitch in to the effort. And yes, they're maybe hard to want to change and to stick with. But remember: this is part of treating cancer risk. How much fat/red meat/inactivity/whatever is to (literally) die for? It's up to us but we owe it to ourselves to be honest about our efforts. No one's checking up on us or keeping a scorecard. If it's important enough to be worth not taking hrt for, isn't also important enough to modify our habits for?

The bottom line

Cancer isn't for wimps and neither is cancer treatment. That's why we need to be sure that we're not just responding in knee-jerk panic at the very thought of cancer. Realistically and with expert advice looking at our exact, personal level of risks and what we can do to reduce them is actually going to be much more effective. We have choices that range from blocking our body's ability to use any hormones to just reducing our hormone supply slightly to using other factors to help reduce our risk while we meet our minimal level of post-fertile hormone needs. Each choice has its own costs and level of benefits, and we have to remember that no choice is safe. Shall we say that again? There are no safe or easy choices. We only get to choose which of the risks we will experience.

What if I choose quality of life and the cancer risk that goes along with it?

That's a legitimate choice and many individuals, especially those who've successfully battled cancer, are asking just that. While their oncologists are advising them that the best way to reduce risk is to abstain from hrt forever, these individuals understand that there is more than one kind of risk and they're willing to undergo some risk to feel better now. Here's how one forum member put her choice:

This past Saturday I discovered a mass in my left breast, above and to the left of the original tumor site. Recurrence is most likely in the first two years following diagnosis; it also has the poorest prognosis, especially given the aggressive treatment I had already gone through for the original cancer. I couldn't call for an appointment until Monday; once I called, they couldn't schedule me until Tuesday. My breast hurt, a dull achy pain with occasional sharper twinges - pretty much identical to what I had felt with the original tumor.

I had three days in which to worry and despair and think about what came next if it was a Terrible Bad Thing - yes, there's an 80% cure rate, but someone has to be in the 20%, and I'm well aware it could me. I kept very busy, trying not to think, and there were times when I sank to the floor weeping regardless.

The mass is fat necrosis, a result of radiation treatment - the fat cells in the breast die off when their blood supply is compromised, and they can then form a thickened layer of scar tissue and dying cells. The pain and discomfort will probably abate in time. I'm fine.

It was profoundly interesting to me though, that throughout that time - as I was contemplating a single or bilateral mastectomy, and whether I would opt for reconstructive surgery, and what course of adjuvant therapy I would be willing to consider, and how to tell everyone - there was truly no moment in which I regretted my decision to pursue ERT, even though I knew that had it been a recurrence, ERT would doubtless have been seen as a contributing factor.

Quality over quantity - and when it came down to the wire, I felt the same. That's good information to have, though the process of getting there was brutal.

If I do at some time face a recurrence, ERT *may* have contributed to that. I still will not regret it, and I will seek to continue therapy as palliative care.

We don't mean to suggest that everyone can or should feel this way, but we do feel that this choice belongs to you, not your doctors.  And if you'd like to see what others have written on this topic or to discuss your own concerns in this area with them, please join us on our discussion forums.

Vaginal dryness

Many of us are led to believe that, at menopause, we "just dry up." Our partners may believe this as well. Our doctors certainly do: although the condition that leads to this (we'll talk about that below) is very well known and easily diagnosed, they are apparently so reluctant to do so that incidence has been termed an "epidemic" (free signup required to read link; see also Part 2) by the medical community. With an estimated 50-60% of polled women complaining about this problem, it's not as though we don't have company.

So, what is the problem?

Its proper name is "vaginal atrophy*" or, even more broadly, "urogenital atrophy*" (see bottom of this entry for a new terminology update). Sound scary? Yeah, us too. But what it means is simply deterioration of the tissues of the bladder, vagina, and various supporting structures due to the loss of adequate levels of estrogen in those tissues.

Yes, that area of our bodies is very sensitive to estrogen levels, and after menopause, we simply may not have enough estrogen there to keep those tissues healthy. This happens with natural menopause and it happens with surgical menopause. It even happens when we are taking hrts.

If you did a double-take at that last sentence, you've got lots of company. But in fact current prescribing guidelines for estrogen hrts call for using the lowest dose that meets one's objectives in taking hrt. That's for a good reason: our breast cancer risk seems to correlate fairly well to our lifetime exposure to estrogen, so the least estrogen that works for our needs, the lower our overall risk.

But while that may work out fine for systemic (whole body) needs, it may not cover the very specific needs of these particular tissues. Wouldn't the answer then be to simply take a larger hrt dose so that it would? No, because then that risk goes back up.

Today's typical hrt strategy is to meet our greater vaginal estrogen needs in a different way, one that doesn't do as much to raise overall risks but does serve to keep those critical tissues healthy. That strategy is to use as low a systemic hrt dose as otherwise meets our needs and to supplement that with a second form of estrogen hrt that specifically meets vaginal needs. That means a little more work to manage our hrt and, yes, a little more expense, but the benefit of those costs is meeting all our needs at a lower level of health risk.

Vaginal atrophy: what it does

Let's look a little more closely at what vaginal atrophy really means for us.

Estrogen supports a number of functions in vaginal and urinary tissues. It helps maintain elasticity, moisture, lubrication, immune function, and sensation. Without estrogen, blood vessels shrivel up and become less functional, and our nerves in that area begin to deteriorate. We can't bring blood to initiate the healing processes that protect us from infection. At the same time, these more delicate tissues are even more susceptible to injury or irritation.

That means that without estrogen, vaginal (and to some extent, vulval) tissues become dry all of the time, and hence more irritated by things like soaps or even contact with underwear. It means that we may be more susceptible to infections and it means that we may be more allergic or at least more prone to irritations, rashes, or itching due to contact with products like soaps, fragrances, or laundry products, even ones that we weren't bothered by in the past.

The loss of sensation, caused by the nerves being starved, means that while we may feel irritation just fine, we tend not to feel the pleasurable sensations of arousal or orgasm. "Dead down there" is a common way of expressing this. Because we don't have the capability to respond to arousal with tissue swelling and lubrication, we literally don't feel aroused. And the lack of elasticity and lubrication means that even if we go ahead with penetration, it will be at best uncomfortable and unpleasing, and at worst cause tearing and further irritation. No matter whether or not we provide a systemic "itch" for sexual contact with testosterone, if we can't respond physically because of the effects of low estrogen in these tissues, we will not seek or enjoy sexual relations. We'll talk more about the issue of libido support in another post here, but this is the important relationship: if the equipment isn't working, it doesn't matter how hard you push it. And estrogen is the foundation of "working" here.

So what do we do?

Luckily, treatment of vaginal atrophy is easy, has relatively inexpensive options, and is generally successful within a short time.

HRTs intended specifically to meet vaginal estrogen needs are different from those for systemic needs. It's especially important not to confuse them with products for systemic use that are also delivered through vaginal tissues. Our estrogens HRTs page distinguishes these, so check out your brands there to make sure you've got the correct one for your intentions: even health practitioners have been known to mix this up.

Vaginal estrogen HRTs are all designed to be delivered in vehicles that are non-irritating to atrophied vaginal tissues and well-absorbed by them. Even more importantly, they deliver only a very low dose of estrogen, only enough to meet the local tissue needs. The objective of this is to have all of the dose absorbed and used in those local tissues rather than being passed along to systemic circulation. And that means that adding a vaginal estrogen supplement doesn't mean making an adjustment to our systemic HRT to take that addition into account.

It also means—and this is important—that we can use it intermittently. Our systemic HRT, you'll remember from discussions elsewhere on this site, needs to be kept at a fairly consistent level to avoid causing symptoms from fluctuating hormone levels. But because vaginal HRTs don't affect systemic levels, they can be used only as often as needed to provide the level of maintenance coverage we turn out to need.

Most vaginal HRTs are given at a relatively frequent dose interval, usually daily, for a six- to eight-week period. This provides a steady supply of estrogen to promote recovery of health.
Often, we use a cream for this treatment phase: it spreads out well and provides maximal contact with tissues. Further, these are older products and doctors are more familiar and comfortable with them, hence more likely to prescribe them.

Other options are available, however: typically these are rings and vaginal tablets, either retail prescription or compounded. While they may be less messy than creams, because they are low doses meant for maintenance, this first, treatment phase can take longer with these forms. Whether or not this is a good idea for any particular individual really depends upon just how uncomfortable they are and how rapidly they want to turn things around.

It's perfectly legitimate to use a combined approach: a cream for the treatment phase and then a switch to another form for long term maintenance. Alternatively, one can continue using a cream and simply use a smaller amount of it at a less frequent interval, making it less messy and inconvenient. All of the commercial vaginal estrogen HRTs work, so it's really a matter of preference.

What we can expect from vaginal estrogen supplementation

Beginning vaginal estrogen HRT can sometimes be annoying and uncomfortable. Some individuals have such damaged tissues that even the creams, meant to be non-irritating, are too much to tolerate immediately. If you have a reaction of burning or rash upon beginning any vaginal HRT, by all means call your doctor right away and ask for something else: it's not an effect that will go away quickly and there's no point to suffering. If nothing else, a compounding pharmacy can make you a preparation containing the same amount of estrogen as the retail products, but in a hypoallergenic base. In extreme situations, we may need to use the cream externally only for a period, and then gradually increase penetration to progressively treat vaginal tissues.

It's not at all uncommon to see reports of vaginal infections in the early weeks of treatment. These are due to the impaired immune function recovering at a different pace from other aspects of tissue healing, such that the vagina becomes a fertile place for bacterial growth before we're really able to fight those bacteria off. Additionally, using the cream runs the risk of introducing infections through the applicator and tube if we are not careful with their cleanliness.

Infection is not a contraindication for continued HRT use, however, and infections can (and should) be treated at the same time. It may take more than one round of treatment before health is restored and we require less intervention, so some persistence can be needed to see this process through. What's important to keep in mind, though, is that it's not the new vaginal HRT causing the infections (this is a common misunderstanding), but rather, it's the stage of healing that actually makes us susceptible to the infections.

Now, we've said above that the idea of the low dose level of these products is so that they will be consumed entirely locally, without systemic impact. And that's true. Except, maybe not so much at first. When we first begin treating established vaginal atrophy, those tissues may have lost enough of their circulatory capacity that they can't pick up and distribute all of the estrogen quickly enough and some of it does "leak" into systemic use. We may experience a few hot flashes from the fluctuation in our systemic levels, or see a slight shift in our usual state of balance.

But because even atrophied tissues can benefit from the estrogen they absorb, healing is happening. And as those tissues recover, they'll use more and more of the dose until that state of total local use is achieved. For this reason, it's generally not considered to be a situation in which we should modify our systemic HRT intake. It's temporary and so long as we're not miserably uncomfortable, we don't need to change anything; we can wait it out, knowing it's time-limited and will gradually be resolving.

So we use the HRT daily for those six to eight weeks and find that things are feeling considerably better. Normal lubrication should be restored and sensation should also be more normal, assuming we experienced no actual nerve damage from our surgeries. Now it's time for maintenance mode.

Our doctors will tell us to use our maintenance vaginal HRT on a less frequent schedule and may suggest once or twice a week. But that's only a rough guess, and we each have to consider tuning that to create our own best schedule.

If we're still using cream, we can also work on determining a reduced dose. What we hear most often is something like "a pea-sized dab a couple times a week," which is pretty vague but is an okay general guess to work from.

For those using a ring, of course, the dose is taken care of (although it's important not to neglect change dates).

For tablet users, the frequency is the only factor to be adjusted, but once to twice a week still seems to be where most users start. If symptoms of dryness or other hallmarks of atrophy return, it should be obvious that the dose or frequency or both should be stepped up a bit. If twice a week is seeming good, it might be reasonable to step down a bit to twice every week and a half, just to make sure that we're not using more than we need. In other words: we feel our way along, looking for our personal bottom limit and then aiming just above that.

The fine print

Great, so what are the drawbacks? Yeah, it's never a free lunch with menopause, so you knew there would likely be a catch or two.

In this case, vaginal atrophy treatment has to lead into vaginal health maintenance, which means that we will need it more or less the rest of our lives—or, at least, until our hormone needs drop so low as to no longer require supplementation. Maintenance requires a lower dose, generally accomplished by a longer dose interval and/or a change of product after initial healing takes place. If we stop using our vaginal estrogen supplement, our atrophy will return: this is an ongoing need, not a "disease" that we will "cure" with a one-time treatment. Just as we have to eat every day to keep nourishing our bodies, so we have to keep providing the estrogen needed to nourish vaginal health.

Vaginal estrogen supplementation isn't for everyone. Those of us who have hormone-sensitive risks in the pelvic area, such as endometriosis, are generally discouraged from using vaginal hrts because they concentrate potentially higher levels of hormones in pelvic circulation.

Those at high risk for estrogen-stimulated cancers anywhere in their bodies who are being treated by estrogen exposure restriction, either by withholding estrogen supplementation or by drugs that specifically combat estrogen exposure, used to be routinely advised not to use vaginal estrogens. Although these products nominally are fully consumed by local tissues and don't spill over into systemic circulation and hence risk, enough has been shown to escape to raise the fear that this might be just enough to help a tumor cell survive. In fact, the North American Menopause Society, in their 2017 position statement on hrt (that was cosigned worldwide) said:

Because of the potential risk of small increases in circulating estrogens, the decision to use low-dose vaginal ET [estrogen therapy] in women with breast cancer should be made in conjunction with their oncologists. This is particularly important for women on aromatase inhibitors (AIs) with suppressed plasma levels of estradiol, although no increased risk was seen in an observational trial of survivors of breast cancer on tamoxifen or AI therapy with low-dose vaginal ET during 3.5 years’ mean follow-up.

One other concern we've heard voiced is about transferring hormones to our partners. Yes, this can happen if a cream dose is still present at adequate hormone levels. Timing of use can help manage this. The ring for this use releases such a low level of output that it's certified as safe enough to leave in during intercourse (although you may, of course, remove it if either partner prefers). Otherwise yes, some care is needed but so long as the HRT isn't freshly applied and still present in volume, it's believed that the risk is minimal. For 100% protection, however, a condom can be used as a barrier.

But isn't there some natural solution?

That kind of depends on what you mean by "natural." Since it's loss of our natural estrogen that causes vaginal atrophy, we can't really think of anything more natural than simply replacing that supply.

But perhaps what you mean is you prefer something you can purchase over the counter, something made from a blend of herbs, something that doesn't carry the risk of hormones. In that case, we're sorry to have to tell you that this doesn't exist. There is no substance, whether grown in a plant or refined in a lab that can fulfill vaginal estrogen needs other than real human-type estrogen. Yes, there are many sales websites that will try to tell you differently, but in fact these products do not address the specific need for estrogen and so will not treat vaginal atrophy.

Lubricants or vaginal moisturizers may feel soothing, but will not actually promote healing or improve the other physical damages of vaginal atrophy. Some things of this type that users have found useful include commercial moisturizers, commercial lubricants, vitamin E capsules, or small balls of (chilled to harden) coconut oil. These can be good things to try if your other options are limited or you believe that dryness is the only symptom you're experiencing, but they aren't really treatments for vaginal atrophy.

Douching, especially with perfumed products, is not recommended in vaginal atrophy because douche solutions can actually damage tissues further and increase infection risk. Similarly, while douching with live-culture yogurt or other probiotic agents may help restore a good flora balance after health is restored, they will not alone restore that health and will not do so durably.

Must it be treated? Of course not. It's up to us to choose what we consider important. Some have said they feel the loss of sexual responsiveness grants them a return to a purer, more childlike condition. Others don't find the symptoms troubling or find that simple over the counter lubricants and a switch to unscented washing products are adequate to deal with the degree of atrophy that develops.

Each of us gets to decide these things for themself. What we want you to know, however, is that this is a treatable condition, not a life sentence. Menopause does not mean "dead down there" or intractable pain. If you aren't happy with the state of your vaginal health, it needs to start by speaking up. Yes, we know it's hard if you're not used to discussing this part of your body or your sexual needs. You may be embarrassed, or you may worry that your doctor may make you feel wanton or unclean. But this is perfectly normal physiology and your doctor really should be a mature enough individual to handle such a request politely and smoothly. In fact, shame on them for not asking directly whether you need treatment of this kind in the first place. At some point, though, one or the other of you needs to suck it up and just raise the question, and since you're the one who's hurting, yes, we're looking at you.

Not sure what to say? How about something along the lines of "Doctor, I'm concerned about developing vaginal atrophy. Lately I've been experiencing dryness and loss of sensation, and I'd like to consider using some supplemental vaginal estrogen to help keep things healthy. Would you write me a prescription for this?"

More questions?

We have a number of bookmarked articles on this topic in our general bookmarks account, and you may find it helpful to do more reading on this.

Beyond this, we're always happy to discuss specifics on our forums, so feel free to join us there.

*Update: A new name for this has been proposed for this condition, GSM or "Genitourinary Syndrome of Menopause." This doesn't represent a change in thinking about treatment, but it is hoped that it will make it easier to discuss. You can read more about this proposed change in terminology in a separate entry.

Making sense of transdermal HRT doses

While the gel hrts are proving very successful for some users, others are having puzzlingly disappointing results with them. There's a lot of individual difference in how well we each may take up any given transdermal medium, but in the case of gels, this doesn't seem quite in sync with what these same users may find with other transdermal media.

The one way that gels stand out from, say, creams or lotions, is that they dry on the skin rather than having the hrt, medium and all, absorbed into it. Product labels warn of enhanced risk for transferring gel-delivered hormones to others and for diminishing the delivered dose by washing too soon after application (where "too soon" is a much longer period than with other media).

The gels

It's also puzzling to users trying to calculate doses when they switch from one form to another of hrt just how the relatively large amounts of estrogen in the typically-recommended gel hrt doses should be compared to the amounts delivered by other hrt forms.

One of the members of our discussion list shared with us this excellent article that may shed some light on all of this: "Comparison of the transdermal delivery of estradiol from two gel formulations." According to this test, which compares two widely-sold gel hrts, the delivered dose of the hormone was only 13-20% of the amount applied.

All hrt deliveries involve some losses: that's one reason why we can't just convert from one hrt to another of a different route and go on using the same dose numbers. But in the case of gels, we need to recognize that there will be a big difference because such a small amount of the hormone actually gets into our bodies this way. And with such a low proportional delivery when used according to directions, it doesn't take much imagination to suspect that this could be further reduced by incorrect application.

Yes, that's a lot of loss. Where does it go? Well, onto our partners and kids, if we're not careful. Onto our clothing and towels and bed linens, I'm sure. Ultimately, down the drains of our showers and washing machines, into our sewers and septic systems, thus contributing to the contamination of water supplies that today test in community after community as having elevated estrogen contents and perhaps contributing to the cancer and other hormone risks of an entire population. It's not our place to advocate for ethical issues here, but this might be a point that users would want to consider when they make their own choices.

Other transdermals

As we said above, each hrt, even within the family of transdermals, has its own delivery profile. That includes things like how the uptake "feels" to us and how efficiently it moves the hormones it contains into our systems. We've seen way too many users just slam themselves with excessive doses when they thought that because they needed X mg of dose in one transdermal hrt, they needed to multiply normal doses of another hrt to get that same number.

That's not how it works.

We can get a better sense of dose equivalency from the "usual starting dose" figure that's part of the basic prescribing information with any hrt. That's the dose that incorporates enough to make up for losses in delivery and still provides enough to make up "usual" coverage in a user's system.

Yes, this is confusing. One of our discussion list members assembled this very handy chart comparing dose to delivered amounts in transdermal products available in the US and the UK. It doesn't cover every hrt or all the generics, but it does give us a great overview of how much variation there is in all of this.

So how do I use this information?

Basically, it reinforces the premise that we really can't do an absolute conversion from any one hrt to any other hrt. But it does help us feel more comfortable letting go of dose numbers as even a rough conversion factor and switching our attention to more useful figures.

What we can ask, in moving from one hrt to another, is how we felt on what dose of our original hrt. If we felt sort of okay on, say, the usual starting dose of our old hrt, then we might want to start the new hrt at whatever is pegged as the usual starting dose for that one. Similarly if we were one standardly sold dose up or down from the usual starter of our old hrt (or we would have preferred to have been), we might look to that many iterations off of usual starting for the new one. It's a really rough and imprecise system and no, the manufacturers aren't going to provide us with anything better because their profit lies in holding us captive to their brand, not in facilitating our moving to someone else's.

We can also use our understanding of this to help explain why we may feel really different when we switch brands. We typically see this when we're having problems with one brand and our doctor switches us to another and whammo, we're feeling as though our hrt has just evaporated. Many doctors may not be up to date with the trend that some hrts now come out in ultra low doses meant for those in natural menopause who just want a tiny hormone boost for its value in combating osteoporosis. Those doses aren't typically enough for most users in surgical meno, so even swapping to the "usual starting dose" of the ultra-low hrts is a huge dose cut. Again, when we look at the figures for what is being delivered, we can get a sense that we've actually had a big cut in what our bodies have to work with. So in this case, we're not crazy: we actually aren't taking anywhere near the same thing and we need to take this fact back to our doctors to use in troubleshooting our correct dose.

Obviously, dose amount and delivery amount aren't the only factors in working with the behavior of different transdermal hrts, but they are an important factor to understand when we are troubleshooting.