As regular readers of this magazine will recall, a few years ago the editor and some of his clinical research colleagues began to question the long-prevailing cultural cliché that females with migraine are somehow less “sexual” than females free of migraine. This led them to conduct a study which they assumed would show that no such difference existed, but to the surprise of those investigators the results demonstrated that females with migraine appeared to have a higher level of self-perceived sexuality and more positive sexual function than matched controls free of migraine. The migraine population reported a significantly higher frequency of heterosexual intercourse, more satisfaction with intercourse and, specifically, a higher likelihood of intercourse resulting in orgasm. The married subgroup of the migraine subjects had more offspring than married female non-migraineurs (average number of children 3.1 versus 1.7).

More or less coinciding with this was a publication from another group of investigators indicating that between 1990 and 2019 there had been a 16% increase in the global prevalence of migraine in females. 

So what? Perhaps the result recorded by the editor and his colleagues in their investigation of female migraineur sexuality was an “outlier” resulting from selection bias, simply reflecting, say, the relatively affluent, well-educated and geographically-restricted (metropolitan DC area) population studied. Well…maybe, but there was a matched control group. Perhaps the migraine subjects who were migraine patients threw the game by recording answers they felt the investigators would prefer. Well…maybe, but there was a group of migraineurs studied who were not migraine patients, and the results were the same in that group. Perhaps this result cannot be generalized to larger and more diverse populations; as only heterosexually self-identifying and sexually active females were included in the study. It could be that inclusion of female migraineurs who are not heterosexually active would have yielded a very different result. Well...maybe, but…so what? This was not intended to be a study of females who were not heterosexually self-identifying or sexually inactive. 

Or the result could have been skewed by some other and as-yet unidentified confounder or methodologic defect Maybe. It’s certainly true that confounders are common in clinical research, and the potential for confounders may be especially high in clinical research involving issues related to sex and sexuality. Maybe the results of the study mean little, and maybe the apparent increase in global prevalence of migraine in females is simply an artifact of increased public awareness of the disorder.

Maybe, but what if the findings from this these two very different investigations are very much intertwined? What if female migraineurs are in fact more “sexual” and sexually active than female non-migraineurs, and what if the global prevalence of migraine in females is in fact actually increasing? What if the two results are indeed linked? Why would this be?

We have discussed the topic of migraine and natural selection previously in this magazine. Briefly, migraine has been with us for a long time. Millennia. Writings that date back nearly 4,000 years to the ancient civilizations of Mesopotamia poetically describe what clearly is migraine (Headache is like the dread windstorm… blowing… flashing… scorching… hostile… [and] no one knows its course). How has migraine persisted for so long? Why should a disorder that inflicts so much suffering and cost remain so prevalent in the human species? While natural selection sometimes may require a long period of time to prune a useless branch off the evolutionary shrub, in some cases a species change can occur in no more than a single lifetime. Where are you, natural selection?

Could it be that genetic migraine conveys some evolutionary advantage that was, at least until relatively recent times, useful to human survival? For most of our existence on this planet we lived primarily as hunter-gatherers, dispersed in tribes believed to have numbered no more than 25 individuals. Migraineurs have sensitive brains…brains sensitive to changes in the internal environment (eg, fluctuations in sex hormone levels) but also to changes in the external environment: weather changes, stress, maybe even - who knows? – impending movements of the buffalo herd or other game. Perhaps every tribe of 25 needed 1 or 2 sensitive-brained migraineurs to serve as weather forecasters. Even shamans.

But we largely shifted from a nomadic hunter-gatherer society of small tribes to an agrarian and settled society of far larger groups at the onset of the Neolithic Revolution approximately 12,000 years ago. Without a need for wild game and a weather-savvy shaman, who needs a bunch of “sensitive brain” migraineurs hanging around to bore you with anecdotes about how barometric pressure changes trigger their headaches?  12,000 years! Surely enough time to dust off and use those pruning shears of natural selection.

Or maybe natural selection just doesn’t care. If natural selection is focused on procreation and thus preservation of the species, and if there is nothing inherent to migraine that hinders procreation, maybe natural selection has better things to do than be bothered with eliminating migraine.

Maybe. But…what if migraine actually serves to favor human procreation? Would not natural selection, in turn, actively favor migraine? And if this is occurring, should we not expect to see a gradual increase in the prevalence of migraine…especially in females, as far more than males they serve as the resource most critical to sustained procreation? If female migraineurs have an increased inclination to engage in heterosexual intercourse and this results in their producing relatively more offspring, would not natural selection favor the genetic permutations that predispose to migraine…resulting in a progressive increase in female migraineur prevalence as the decades and centuries pass. Simplistic? Definitely. Difficult to prove? Most certainly. Plausible? I think so.

So where might redheads fit in? As with female migraineurs, female redheads have come in for their fair share of cultural slings, arrows and clichés: fiery, tempestuous, quick-tempered. Temperamental temptresses. Witches, even. 

As it turns out, female redheads are biologically and behaviorally distinct from non-redheads, and that distinction is paralleled by differences in how we perceive female redheads. How are they different? Well, for one they are relatively rare. Unlike the gene for, say, black hair or brown eyes, the gene for red hair, MC1R, is recessive. This gene controls the production of melanin, the pigment that gives hair, eyes and skin their color. The gene regulates melanocyte activity, and melanocyte cells produce two types of melanin: eumelanin and pheomelanin. Redheads produce mostly pheomelanin. 

Global redhead prevalence is only 1-2%, with prevalence rates highest in Ireland (at least 10%), Scotland (at least 6%), England (4%) and the United States (2-6%). There are approximately 18 million redheads in the US, and that relatively high prevalence has been attributed primarily to the Great Irish Immigration that took place between 1850 and 1920.

But enough about genetics and prevalence rates: how are redheads biologically and behaviorally different?  For one, they have a somewhat paradoxical response to pain. Although their threshold of tolerance to heat and cold is lower than non-redheads, their pain threshold overall appears to be higher. While redheads respond more effectively to opiate and opioid medications and may not require as high a dose of those medications for pain relief than do non-redheads, they are more resistant to anesthesia; it is estimated that they require anesthetic doses 20% higher than those administered to non-redheads so as to have the same clinical effect. 

Likely reflecting their geographic ancestry and their fair skin, redheads produce more vitamin D than non-redheads. On the downside, they appear to be more susceptible to skin cancers, including melanomas, and to developing both Parkinson’s disease and certain types of gynecologic cancer. Redheads smell different than non-redheads, perhaps a consequence of their having a slightly more acidic skin mantle. In 1886 one early physician investigator declared that redheaded women emitted a distinctive and singularly “intoxicating” aroma.

There may be a bit of truth to the previously described cultural characterizations of redheads. Although such variables are not simple to assess objectively, there are data to suggest the redheads are more emotionally reactive than non-redheads. Interestingly, in terms of other societal perceptions, studies have demonstrated that redheads are judged by others to be approximately two years older than their chronologic age when compared with non-redheads. While female redheads often have been characterized as “promiscuous” and “sexually liberated”, in one controlled study young males were most likely to solicit attention from blond females and least likely to solicit redheads. In what would seem somewhat incongruent with that result, a 2014 study found adult female redheads to be disproportionately overrepresented in primetime television commercials. Finally, redheads commonly have been said to possess a higher tolerance for alcohol, but the evidence to support that particular trope is thin to none.

More relevant to the issues considered here, investigators have reported that female redheads have a higher libido and engage in more heterosexual intercourse than non-redheads. Whether or not they tend to have more offspring than non-redheads is still not well-established, but in in one epidemiologic survey of redheaded female Czechs and Slovaks the redheads had more offspring than non-redheads, and at least one other study confirmed that finding in a different ethnic population and also found that redheads began having children at an earlier age.

If female redheads are more “sexual” than non-redheads and possibly more likely to procreate, this naturally leads to a number of questions:

• Is the prevalence of female redheads increasing, as it appears to be for female migraineurs? Although some authors have suggested that it is, no clear and convincing data have emerged to confirm their claim.

• Is there a correlation between redheadedness and migraine prevalence? Put another way, are female redheads more likely to have migraine than female non-redheads? Again, not clear. What we do know is that the prevalence of redheadedness increases significantly as one moves into and through northern Europe, the ultimate ancestral home of most redheads. We also know that investigators have reported the prevalence of migraine to be 3.5 times higher in women with fair skin and a lower “melanin index”…both highly characteristic of redheads. This increase in migraine prevalence appears to be linked to a relative deficiency of eumelanin, and as already noted redheads are relatively deficient in eumelanin.
  
  In our study referred to at the outset of this article we unfortunately did not record hair color, and so from our relatively small population of research subjects with migraine we cannot offer any insight as to whether redheads do or do not have a predilection for migraine.

• If the global prevalence of migraine in females is increasing, are redheads making a making a significant and disproportionate contribution to that increase? Probably not. In the study referred to earlier, an increase in migraine prevalence was observed in females even in African countries where native redheads are scarce.
  
  There are those who believe things happen for a reason and those who believe things…just happen. The former can be divided into those who take a faith-based approach that implies intervention via a power that lies beyond our ability to know and those who believe in science (with the caveat that believing in the scientific method does not by any means ensure ultimate discovery of “the reason”).

As for me, while I believe, as Loren Eiseley wrote, that “if there be magic on this planet, it is contained in water”, and although I fully acknowledge there may exist much in this life that we are not given to know, I am more inclined to preoccupy myself with science than magic. It is intensely curious to me that the global prevalence of female migraineurs seems to be increasing. I find it intriguing to hypothesize that natural selection may be favoring migraine and, in particular, redheaded female migraineurs. Now all I have to do is prove it.

Disclaimer:                                                                                                                      Given that he has been long and happily married to a female redheaded migraineur, the author cannot exclude the possibility that his observations and hypotheses may possess some small measure of bias.

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