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Hormones : Urban Legends

The following article is adapted from IndigoWiki.

Introduction

There are few, if any, areas of medicine more poorly studied or understood than MTF and FTM HRT (hormone replacement therapy). What few studies have been done have generally been poorly constructed, had minute sample sizes, and have lacked controls or double-blinds. Definitive they are not, in the best of cases they hint at possible truths, areas in need of more study. In most cases they aren’t even useful as birdcage liner. One doesn’t have to spend much time studying the subject to discover that MTF and FTM HRT works not because of our level of knowledge, but in spite of it. That is a state that will hopefully one day change, but that day shan’t likely be any time soon.

Into this breach of HRT ignorance steps the urban legend. ‘Facts’ that have been repeated so often that everyone believes them, even though there’s no particular evidence for them and many of them don’t even make much sense. Many are morphed versions of old and questionable rules-of-thumb, a few have more sinister origins. All interfere with gaining a better understanding of HRT, all should be questioned and, if found wanting, discarded.

Urban Legend #1: “Excess” estrogens can be back-converted to androgens (trans women rumour)

The Particulars

As everyone hopefully remembers from Hormonal A&P-101, estrogens are converted from androgens. Androstenedione is converted to estrone and testosterone to 17β-Estradiol, both via the enzyme aromatase. Oft repeated urban legend has it that ‘excess’ estrogens in the bloodstream (what exactly might constitute ‘excess’ is open to interpretation) will be converted back to androgens (presumably androstenedione and/or testosterone).

The Truth

There is no known back-conversion pathway. The conversion from androgens to estrogens via aromatase is strictly mono-directional. Anyone claiming that estrogens can be back-converted to androgens would need to demonstrate a viable back-conversion pathway for their claim to be taken seriously.

Likely Source of Legend

Certain Doctors attempting to control their patient’s actions through ignorance, fear, and lies. That many MTFs ‘supplement’ their doctor-prescribed regimens is widely believed in the medical community, not entirely without reason. That many MTFs fear androgens more than they fear cobra venom is likewise well known. Ethically challenged physicians and medical personnel routinely try and use that fear as a control handle, this urban legend is an egregious example of that.

Urban Legend #2: The ‘Within a cup size’ rule (trans women rumour)

The Particulars

This rather elderly urban legend comes in a couple of different flavours and variations. The most common is the claim that an MTF just starting HRT will end up ‘around’ a cup size smaller than their closest female relative. Variations change this to ‘within a cup size’ and/or require one somehow ‘average’ the size of one’s closest female relatives or specify a particular female relative (generally mother or sister).

The Truth

As nothing even remotely like an in-depth study of this subject has been done, no one really knows.

The basics of this urban legend do suffer from a number of obvious problems. Cup-size is an extremely gross measure of breast size. At least here in the United States (presumably this is also the case elsewhere), many women do not wear what is probably the optimal band/cup-size bra for their figure. Roughly speaking, a band size can be traded for a cup size — id est, a 36C and a 38B are roughly equivalent. Cup and band sizes vary fairly widely between manufacturers, often by as much as a cup/band size or more.

Beyond the problems inherent in trying to use cup-size as a measure, there is the issue of range. In the United States five cup sizes — A, B, C, D, DD — cover the vast majority of the adult female population, with C-cup being the most common. Given a gross and extremely imprecise measure, small range, and non-even distribution, any prediction is lacking in much utility and most variations of this urban legend do nothing but state the statistically obvious.

Likely Source of Legend

MTFs just starting HRT often ask about their potential development and often have somewhat unrealistic expectations. The ‘Within a cup size’ rule gives an often satisfactory, if not particularly useful or accurate, answer to a common question that has no real answer (at least none beyond ‘Whatever size they get to’) and has the added side-benefit of sometimes deflating expectations back to the realm of reality.

Urban Legend #3: The younger you are, the better you’ll do (trans man and trans women rumour)

The Particulars

Another oldie but (not-so) goodie. Originally this one varied between the simple claim that the younger you were, the better your response to hormones would be, to the more specific (and ludicrous, in the absence of a time machine) claim that (if you’re MTF) your bust size would be a cup-size smaller per decade past puberty than it otherwise would have been. Today claims about age-related HRT differences range from the amazingly (and often laughably) specific, such as assigning ages to Tanner Stages (if your age is X, you will ‘only’ get to Tanner Stage Y), to the more dire claim that unless you start hormones before a particular age (eighteen and twenty seem popular) you will have a poor or no response to HRT.

The Truth

Unsurprisingly, nothing even remotely like an in-depth study of the subject has been done. Any correlation between age and hormonal efficacy is speculative at absolute best.

When discussing the matter of age versus HRT response, inevitably two explanations are given to support the notion of an age correlation. The first boils down to anecdotal evidence, the second, basically, ‘It just makes sense!’

As the old saying goes, the plural of anecdotal evidence is not ‘Data’, but that is only the start of the problems with trying to use our perceptions of other MTFs to distinguish any strong age-related HRT developmental correlations. First one must define what qualifies as good versus poor development. Here things inevitably turn to breast development, generally cup-size (as previously discussed, a gross measure at best) and/or Tanner Stage (a subjective measure). Given the degree of normal variation amongst the adult female population, and that breast size and shape are one of the least important aspects of getting by in the world as a woman, this would seem a somewhat poor measure. Other aspects of body feminisation and, especially, facial feminisation are far more important, but are also difficult to impossible to objectively measure. Combine wholly subjective perceptions with a knowing audience problem, the tendency for our individual samples to be small and generally skewed in both age (generally towards our own) and length of time on HRT (generally less than five years), and anecdotal evidence looks less and less useful and more and more like, as is often the case, a matter of seeing what one expects to see regardless of what’s really there.

As for the ‘It just makes sense!’ argument, well … perhaps so. Or, at least, perhaps so if one views masculinisation as some sort of progressive degenerative disease. While this view may have appeal to many MTFs, physiologically speaking there isn’t much basis for it. Put simply, the difference in masculinsation between a thirteen year old and an eighteen year old is huge. The difference between an eighteen year old and a twenty-three year old, comparatively tiny. The difference between a twenty three year old and a twenty-eight year old, minute to nonexistent. To put it mildly, the amount of ‘damage’ (from an MTF’s point-of-view, anyway) androgens cause is non-linear with age. By the very early twenties, at the absolute latest, the vast, vast bulk of that damage is said and done. From a masculinisation point-of-view, the difference between someone who is twenty-five versus someone who is forty-five is generally nil, with the forty-five year old perhaps having the edge due to generally lower endogenous Androgen levels.

Moving from masculinsation to feminisation, it is the case that many physiologic processes become slower and/or less efficient or effective as one ages. Might it be the case that the processes involved in feminisation become less effective as one ages? The problem is that we don’t understand those processes to begin with, let alone how age might or might not change them. Not all physiologic processes change much, or at all, with age. Few, if any, change in anything like a linear manner or on anything like a consistent schedule. In the absence of any real understanding of the processes involved or any objective empirical data, we once again find ourselves standing firmly in the land of pure speculation.

‘It just makes sense!’, much like ‘Everyone knows …!’, can be made to argue either way and is worth about as much as the air used to utter those phrases. Anyone who’s worked in industry, science, or, especially, medicine is aware that the fact that something making sense does not come even remotely close to making it so. What is readily demonstrable counts for a lot more, and when it comes to HRT and age two things are readily demonstrable — being younger does not guarantee a good feminisation response, being older does not guarantee a poor feminisation response. In short, it is demonstrable that in the specific age is not an overly useful predictor. In the general is age a statistical predictor? Unknown. It certainly may be, but there is no strong evidence one way or the other.

Note that this discussion excludes HRT in the pre-pubescent and those in puberty. Both involve medical and ethical issues not otherwise present, the general efficacy and specific wisdom of either remains an open question. Also the above excludes those with Intersex conditions that substantially alter hormonal physiology and/or those who are otherwise naturally Androgyne.

Likely Source of Legend

Too many obvious ones to mention, really. Currently given the most life via peer pressure amongst younger MTFs, which is what makes this urban legend so dangerous. There are many good reasons one might give for starting HRT, fear and peer pressure are not amongst them.

Urban Legend #4: Pre-op vs. post-op HRT (trans men and trans women rumour)

The Particulars

A favourite of the medical community since (seemingly) the dawn of time, this urban legend holds that post-op (for these purposes, generally either SRS or an Orch for MTFs, or a Hysterectomy (including oopho) or just oopho for FTMs) HRT levels can be dropped dramatically from pre-op levels without compromising development. Generally post-op regimens drop any anti-androgens (for MTFs), lower or eliminate any Progestins (if used – for MTFs), and drop estrogen (for MTFs) or testosterone (for FTMs) levels by as much as half or more.

The Truth

Put simply, as HRT is practiced today, this makes no sense.

In terms of MTFs, removal of the testes certainly can have a strong effect on hormonal physiology; doing so removes the primary source of bio-active androgens (the prostate generally remains and can produce bio-active androgens, and the Adrenals still produce non-bioactive androgens), but any competent pre-op HRT regimen would already be keeping endogenous androgen levels low either through various anti-androgens, GnRH agonists, or a sufficient level of estrogens to shut down the LH/FSH axis. Removing the Testes almost certainly removes the need of any anti-androgen aspect to one’s regimen, but how does it otherwise alter the levels of estrogens and Progestogens needed for proper development?

The answer is, it doesn’t. If anything, it may increase the amount of exogenous estrogens required to do the same job as was being done pre-op. Why? At any given moment only a tiny percentage of the estrogens in your body are free and completely bioavailable, the rest are tied up in transport proteins. One such, Albumin, leaves any bound hormones in a ‘semi-bioavailable’ state, in that they can be disassociated at the target tissues. The other, SHBG holds any bound hormones in a non-bioavailable state. What ultimately happens to SHBG-bound hormones is a matter of debate, but the practical upshot is that an increase in SHBG levels equates to a reduction in the percentage of hormones in your body that are bioavailable and semi-bioavailable. SHBG levels are, among other things, proportional to estrogen levels, inversely proportional to androgen levels. Pre-op regimens do not generally seek to reduce androgen levels to zero (this is probably a good thing, by the way), post-op there is generally some drop in serum androgen levels and a resulting increase in SHBG levels (at least temporarily) with a resulting decrease in free estrogen levels. That this generally occurs when one has temporarily stopped estrogens prior to surgery, and then when restarted it is at a reduced level, probably contributes to the tendency many observe of there sometimes being some post-op de-feminisation.

SRS or an Orch certainly has a rather large (to put it mildly) overall effect on androgen physiology and a smaller, indirect and mostly temporary effect on hormonal physiology in general, but none of this substantially changes what level of estrogens/progestins are required for continued proper development. If you needed ‘X’ level of exogenous estrogens prior to surgery, nothing about that surgery would change that to one half of ‘X’.

Natal-female pubescent development is believed to take between five and nine years, depending on which source you listen to. It is not unreasonable (though, granted, far from proven) to assume that MTF development (again, leaving out certain IS conditions and Androgynes) would take roughly the same time scale. The amount of time between the start of HRT and SRS or an Orch can vary from between months to a decade or more, making one’s surgical status an excruciatingly poor proxy for how far along hormonal-developmentally one might be.

In terms of FTMs, while some are able to lower their T dose (sometimes only slightly) after having an oopherectomy (or hysto including oopho), others find that they actually have to raise their dose. Others find that no change in their dose is required at all after oopho to maintain their optimal hormone levels.

An alternative, and increasingly more common, way of viewing HRT regimens is not primarily as pre- vs. post-op, but instead Development Phase vs. Maintenance Phase. Development Phase, where many feel higher levels are needed, is generally taken to be the first two to nine years on HRT, depending on who you ask, with Maintenance Phase, where levels can be lower without compromising development, being thereafter. One’s ‘op’ status is still important for determining the anti-androgen aspect of one’s regimen, but is otherwise irrelevant.

Likely Source of Legend

One theory holds that prior to the widespread availability and use of effective anti-androgens (around the early 1990s in most areas), high exogenous estrogen levels (often as much as orders of magnitude over what’s commonly used today) were used to shut down the LH/FSH axis and thus endogenous androgen production. Post-op, the need for those high levels was gone, so estrogen levels were greatly reduced. Another theory holds that it was nothing more than the lazy assumption on the part of the medical community that anyone having surgery had been on HRT at least two years and that was all that was required, and, again, that the habit continued. Still another theory holds that the medical community, worrying more about legal risk to themselves than efficacy of development in any MTF, is happy to use any excuse to lower levels, the transition from pre- to post-op just makes a good such excuse. Which, if any, of these theories is true is, and will probably forever remain, unknown.

Urban Legend #5: You don’t need progesterone (trans women rumour)

The Particulars

Many endocrinologists feel that an exogenous Progestogen is not a necessary for optimal MTF HRT.

The Truth

It is hardly groundbreaking to observe that progesterone plays an important role in natal-female breast development. Why would this not also apply to MTFs?

A study published in The American Journal Of Surgical Pathology (Am J Surg Pathol. 2000 Jan;24(1):74-80.) strongly suggest it does. The study involved comparing breast tissue from 14 MTFs undergoing HRT to that of two natal-males who had been chemically castrated as part of cancer treatment. Distinct histologic differences were found —

[…]Only in male-to-female transsexuals in whom progestative chemical castration is combined with feminising estrogen therapy will full acini and lobular formation occur. Hence, combined progestative anti-androgens and estrogens is necessary for the genetically male breast to mimic the natural histology of the female breast.[…]

Note that by ‘progestative anti-androgens’ they mean Cyprotone Acetate specifically, which is generally considered a relatively weak Progestogen (though a strong anti-androgen). Also note that the sample sizes were not what you’d call impressive. However, the study’s results are hardly shocking, given that Progesterone is generally considered to be responsible for, among other things, lobular formation in the breast. They basically found what one would expect to find, that certain breast structures do not develop, or develop only poorly, in the absence of a Progestogen.

How important all of this is to optimal feminisation remains unclear and likely varies from individual to individual. What is clear is that Progestogens do play an important part in, among other things, proper breast development. Given that, and the lack of any compelling reason not to use them, it seems clear that a Progestogen should be a part of any optimal MTF HRT regimen.

Likely Source of Legend

Ignorance and general medical over-conservatism, especially where anything doctors consider elective is concerned.