Cognitive Downsides of Modern Oral Contraception and the Economic Dominance of the Services Industries
Among other things, it turns out that fertile women can, much of the time, make better decisions than most of the men around them...
Wherein a very large portion of the modern human population is suspected of having unwittingly tied one to two of its mental arms behind its back, and thus unconsiously released a very large measure of cultural and social chaos into the human portion of the biosphere
Preamble
In my experience, the intellectualization and the word play that us humans use so constantly, seriously, and ostentatiously in our own heads and then throw towards one another is, more often than not, only the empty and inconsequential equivalent of magical thinking, constituting just a large-scale, especially noisy cargo cult.
This is not at all to say that a very useful amount of pointed human thinking and word-slinging isn’t carried out (and has been carried out) by humanity. It has indeed: consider the various hard and soft goods produced by modern and historical human lives – notably, those provided by agriculture, mining, manufacturing, construction, the various trades -- and by engineering and science in general.
What I am getting at is this: humans are quite commonly so distracted and taken in by their own and others’ word play that they remain completely unaware of the effects of much more powerful, but less visible, influences on human life. As an incremental stab at watching our mutual six, this post reports on some of what recent science has found out about some of these invisible influences.
Introduction
So, male and female humans co-evolved with each other, and are therefore obligately symbiotic for all kinds of reasons and in all kinds of directions. What might happen, do you think, if large parts of the human population suddenly surrendered major mental power boosts evolutionarily bequeathed to them by Mother Nature?
Maybe this:
That Most Critical of Humanity’s Natural Hardwares
To understand how the exampled large-scale schism within humanity illustrated above may have come about, it first serves to consider key aspects of the basic decision-making process in the human brain – and then later examine recent human history for changes in everyday human life that likely have sufficient power to push this human decision-making process off its rails — and then keep it off.
Quoting from the Wikipedia summary entry on the prefrontal cortex, the ‘deciding center’ or ‘executive center’ of the brain:
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, and BA47.
The basic activity of this brain region is considered to be orchestration of thoughts and actions in accordance with internal goals. Many authors have indicated an integral link between a person's will to live, personality, and the functions of the prefrontal cortex.
This brain region has been implicated in executive functions, such as planning, decision making, working memory, personality expression, moderating social behavior and controlling certain aspects of speech and language. Executive function relates to abilities to differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outcomes, expectation based on actions, and social "control" (the ability to suppress urges that, if not suppressed, could lead to socially unacceptable outcomes)[emphasis added].
The activity of the prefrontal cortex is dependent on the chemical concentration of dopamine, a neurotransmitter. Concentration of dopamine in the brain is, in turn, determined by genetics, as well as internally- and externally-sourced agents like hormones and enzymes, acute exercise/physical fitness, and certain minor substances that humans commonly take in from their environment (for examples of these, think of coffee, tea, nicotine, and sugar).
Once released within the nerves of the prefrontal cortex, the time that dopamine is usefully active in that part of the brain is determined by the concentration of several enzymes that break down the dopamine after it is released. According to the Wikipedia entry for dopamine:
“Dopamine is broken down into inactive metabolites by a set of enzymes—monoamine oxidase (MAO), catechol-O-methyl transferase (COMT), and aldehyde dehydrogenase (ALDH), acting in sequence. Both isoforms of monoamine oxidase, MAO-A and MAO-B, effectively metabolize dopamine. Different breakdown pathways exist but the main end-product is homovanillic acid (HVA), which has no known biological activity. From the bloodstream, homovanillic acid is filtered out by the kidneys and then excreted in the urine.”
Given the importance of the prefrontal cortex in controlling the executive functions of human planning, decision-making, and problem-solving, recent scientific efforts to identify likely gene-level controls of the behavior of the brain’s executive center have focused on the already mentioned dopamine-degrading enzyme operating within the neuronal synapses of the prefrontal cortex, COMT (catechol-O-methyltransferase). Again, this enzyme largely controls the chemical concentrations of the dopamine in the prefrontal cortex by chemically breaking down this neurotransmitter after it has first been produced.
The three genotypes or polymorphisms of the gene producing the COMT enzyme acting in the brain are COMT(Met,Met), COMT(Met,Val), and COMT(Val,Val) -- where (Met,Met) represents a mutational homozygous substitution or replacement of the amino acid methionine for the amino acid valine in the COMT gene responsible for constructing the COMT enzyme; (Met,Val) represents the heterozygous form of this enzyme-building gene; and (Val,Val) generates what is believed to be the original ancestral or ‘wild type’ form of the COMT dopamine-degrading enzyme.
The homozygous (Met,Met) gene form of the COMT-producing enzyme breaks down dopamine in the brain 3-4Xs more slowly than the COMT(Val,Val) wild type, thereby causing the average prefrontal cortex dopamine levels in people with this homozygous (Met,Met) mutation to be higher than they are in people with the ancestral homozygous (Val,Val) form of the COMT-producing gene. And, because the Val and Met alleles are co-dominant in effect within the COMT-making gene, people that possess the heterozygous (Met,Val) form of the COMT-producing gene show intermediate brain levels of dopamine; i.e, substantially more dopamine than in the (Val,Val) ancestral form -- but less concentration of that neurotransmitter maintained by the homozygous (Met,Met) version of the COMT-producing gene. This last is so because the (Met,Val) heterozygotic form of the COMT gene breaks down neuronal dopamine more slowly than the (Val,Val) homozygote, but still faster than the enzyme produced by the COMT(Met,Met) homozygote does.
Malhotra et al. (2002), among others, have demonstrated that there are significant differences in prefrontal cortex executive function operation among the three genotypes of COMT. Heterozygote COMT (Met,Val) and wild type homozygote COMT (Val,Val) both consistently make more errors on a standardized test for prefrontal cortex function than do subjects homozygous for the (Met,Met) variant of the COMT gene. Executive functioning for people with either one of the two Val-containing gene variants is, all other things being equal, therefore measurably less efficient and more prone to error-making than it is for those who possess the no-Val homozygous (Met,Met) mutation. See the graph below from Malhotra et al.
But Wait, Wait -- There’s More
Differing average prefrontal cortex dopamine levels associated with each of the three different genetic versions of the human COMT enzyme aside, the three resulting genetically characteristic levels of dopamine in individual brains can also be shifted up and down very significantly -- albeit ephemerally -- by certain substances taken in from the outside environment, by physical exercise, and by internal fluctuations in hormone levels. Indeed, these shifts can be strong enough to very markedly change – for better or for worse -- the efficiency of the prefrontal cortex’s executive functioning.
This “for better or for worse” situation comes about because COMT enzyme levels -- and their causally- associated levels of prefrontal cortex dopamine – express themselves as an inverted U-shaped curve with regard to the various human executive functions of the prefrontal cortex. The effect of this relationship on executive functioning is illustrated below using the dopamine concentration-dependent executive function characteristics of risk aversion and working memory as examples:
Tolcapone, the drug used in the Farrell et al. (2012) experiment is typically administered to help people with Parkinson’s disease. Tolcapone reduces the chemical activity of the COMT enzyme, thereby artificially increasing the level of dopamine maintained in the prefrontal cortex of the brain in the person receiving the drug.
Looking again at the qualitative graph of Farrell et al. above, note the relative positions of the (Val,Val) and (Met,Met) COMT genotypes with regard to the x-axis values of cortical dopamine. Because COMT(Val,Val) individuals not receiving tolcapone (the Val genotype placebo state) possess the fast version of the COMT-degrading enzyme that quickly breaks down dopamine, the normal level of dopamine in the cortex of their brains is sub-optimally low and they therefore usually mentally operate impulsively with relatively little risk aversion and with comparatively little working memory. On the other hand, slow COMT enzyme version (Met,Met) individuals not receiving tolcapone (the Met genotype placebo state) normally operate at higher, more optimal prefrontal cortex dopamine levels that support careful risk aversion and greater working memory.
However, because of the inverted U-shaped curve relationship between prefrontal cortex efficiency and cortical dopamine levels, these genotypical characteristics and associated prefrontal cortex executive center operating efficiencies actually become optimal for COMT(Val,Val) carriers, and become suboptimal for COMT(Met,Met) carriers when default state prefrontal cortex dopamine levels are experimentally increased for each of the genotypes by administering the tolcapone COMT enzyme inhibitor. This sort of environmentally- and/or hormonally-sourced control of prefrontal cortex operating efficiency, it turns out, is also in constant play in nature. Under the right set of conditions, those with the typically less effective (Val,Val) version of the COMT gene can actually experience better-functioning executive centers than their COMT(Met,Met) counterparts.
Sidebar: All world human populations are strongly dominated by COMT(Val,Val) and COMT(Val,Met) gene carriers – more than 70% of the people in the US, for example, carry one of the two Val-containing COMT genes. European-derived populations are, however, anomalously (along with the Maya Indian population) rich in people who carry the COMT(Met,Met) gene. See the Table below for more detail.
Here’s One of the Extra Mental Arms Originally Provided to a Very Substantial yet Select Portion of Humanity by Mother Nature
The data behind the Malhotra et al. (2002) graph provided above indicate a 90% probability that, in addition to genotype, the sex of the tested person plays a significant part in the effectiveness level of prefrontal cortex executive operations. While COMT(Met,Met) individuals of both sexes generally have anomalously higher levels of dopamine in their prefrontal cortex, and therefore handle environmental information better than the other Val-containing COMT genotypes much of the time, it also turns out that pre-menopausal women possessing one of the two Val-containing COMT genes quite often have better functioning executive centers than most of their male COMT genotype counterparts. This is because (Tunbridge 2010, p. 14):
The robust downregulation of COMT [by estrogen] is consistent with the evidence reviewed briefly above that COMT activity is lower in women than men. Furthermore, it is also consistent with data showing that COMT activity is further reduced in women with high estrogen states, e.g., during the third trimester of pregnancy, compared to women with normal estrogen levels (Briggs and Briggs, 1973) and with the dramatic drop in COMT activity observed in post-menopausal women (Bjornerem et al., 2004).
What these observations regarding estrogen and the activity of the dopamine-degrading COMT enzyme in pre-menopausal women mean is that the efficiency of the executive functions in the prefrontal cortex of pre-menopausal women of all COMT genotypes is not only controlled by their inherited COMT enzyme genetics, but also by the fluctuation in levels of serum estrogen that occurs throughout their monthly menstrual cycle and during pregnancy. See the graph below for a qualitative illustration of monthly female estrogen fluctuations in non-pregnant, pre-menopausal women not taking oral contraceptives
The cyclical character of female problem-solving behavior and ability as a function of inherited COMT genotype and menstrual cycle variation in their estrogen levels was closely mapped and confirmed in work reported by Diekhof et al., 2021. Knowing that cyclical increases of estrogen decrease the rate of breakdown of dopamine in women, the authors tested the problem-solving behaviors of pre-menopausal women through time to determine if there were any changes in these learning behaviors under the low-estrogen conditions of the early follicular phase of the menstrual cycle, and the high-estrogen conditions of the late follicular phase of the menstrual cycle. The fluctuations of estrogen’s systemic concentration in blood serum during a complete menstrual cycle are marked by the gray line of the Wikipedia illustration above.
The general findings of the Diekhof et al., 2021, study were that, during the low estrogen conditions of the early follicular phase of the menstrual cycle – when concentrations of dopamine in the prefrontal cortex are relatively low because of high COMT enzyme activity and low serum estrogen levels – women tend to, on average, solve problems and make decisions employing the more inefficient and less accurate strategy of random trial and error (model-free learning). Under the later high estrogen follicular phase of the menstrual cycle, however, when dopamine levels are higher because higher serum levels of estrogen and the associated slowdown of the COMT enzyme breakdown of dopamine – women instead utilize the more effective and accurate Bayesian strategy of constructing and using models based on their observations of environmental conditions (model-based learning).
All other things being equal, then, it appears that the estrogen-rich female of the human species has evolved an estrogen-dependent biochemical mechanism that much of the time permits most of the sisters – by nature -- to be much more careful and circumspect in their choices and decision-making than most males.1 Unfortunately, in the United States, combined oral contraceptives (“the pill”) for women were approved by the FDA that pharmaceutically wipe out this cognitive female evolutionary advantage. The flat-lining effect of the pill on systemic levels of estrogen is illustrated below:
The next graph indicates how widely and rapidly the pill penetrated the world of women (and men) over the first couple of decades after it was introduced in 1960.
The first graph shown this particular post (replicated and annotated for reader convenience below) suggests that the initial limited introduction of oral contraceptives in 1960 to the married woman market may have at the beginning helped lessen the American divorce rate. However, after the late 1960s legalization of the pill’s use for unmarried women, it seems to have all gone downhill from there as far as the successful initial formation and long run maintenance of stable marriages were concerned. It’s probable that once many of the unmarried women carrying a Val-containing COMT genotype started taking the pill, they not only flat-lined their estrogen levels, but also became biochemically much less capable of arriving at good decisions regarding such important processes like adult pair bonding. Remember, after all, that an optimally performing prefrontal cortex allows people to:
…differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outcomes, expectation based on actions, and social "control" (the ability to suppress urges that, if not suppressed, could lead to socially unacceptable outcomes).
Humanity Starts Tying Yet Another Cognitive Arm Behind Its Back during the Same Period of Time as the Introduction of Oral Contraceptives Occurs – and This Tying Negatively Affects Men More than Women
Recall also that a very solid majority of humanity possesses a dopamine-degrading COMT gene that contains at least one valine; i.e., either a COMT(Val,Val) or COMT(Val,Met). This is important inasmuch as it has been shown that the level of efficiency of the prefrontal cortex of people possessing Val-containing COMT genes is strongly dependent on their everyday level of physical activity and resulting physical fitness (Voelcker-Rehage et al., 2015). When such people are not consistently and sufficiently physically active, and are therefore not sufficiently physically fit, their cognitive functioning defaults to the suboptimal effectiveness characteristic of those bearing the COMT(Val,Val) and COMT(Val,Met) genotypes (ibid.):
Results: Hierarchical regression analyses revealed a positive influence of overall fitness and an interactive effect of fitness and COMT polymorphisms on Flanker accuracy performance. Val/Val carriers revealed the highest positive correlation between fitness and cognition.
Conclusions: Our data suggest that particularly Val/Val allele carriers benefit from exercise by improved cognitive functioning whereas Met/Met carriers already perform closer at their optimum level.
Graphically (ibid.):
In the US case, a marked general decline in daily physical activity began soon after World War II, and was well in hand by 1960. This physical activity decline has mostly been caused by a continual reduction in the number of people employed in agriculture and the goods-producing industries in the US, and by the continual growth in employment within the service industries. See the Table below taken from Church et al. 2011, that compares and contrasts the intensity of activity characteristic of each industry.
The main conclusion of the Church et al., 2011, study is that most ( ~85%) of the increase in adult American obesity that has taken place since the 1960s has occurred because of the declining average amount of physical activity involved in the workaday occupations of the US populace. See the time-series American obesity and work-energy-expended graphs provided below documenting the nature of these developments in more detail.
As already remarked, Voelcker-Rehage et al., 2015, found that frequent physical activity and causally-associated physical fitness are critical in sustaining the soundness of the cognition of the majority of the US population; i.e., those with valine-containing COMT genes. This means that the post-1960s movement of the American economy away from the much more physically-demanding work of agriculture and other goods-producing industries, and towards the much more physically inactive service industries, has not only made a very large (sic) minority of US citizens fat, but has also materially reduced the quality of cognition being carried out in their prefrontal cortexes.
Conclusion
Generally speaking, between the effect of the decrement in the cognitive ability of premenstrual women using oral contraceptives, and the added decrement in cognitive ability of the COMT genotypic majority of both sexes relatively languidly working in the service-related industries, it should not be so puzzling why Western human culture has progressively become more and more friable, divisive, and chaotic since the 1960s.
More specifically speaking, it should also no longer be quite so puzzling why the basic urban/rural (physically inactive/physically active) divide exists, and why so many ideas and plans emanating from the urban consumer/urban services parts of the Western world seem so bizarre, weird, and random to those still working in the various, more physically-demanding production industries. On average, there appears to be a very significant, biochemically-based cognitive difference between the two human categories that is not at all curable by the application of even copious amounts of word play.
This increase in average female decision-making ability during the period of maximum fertility doubtless has much evolutionary advantage, as it could function as a volitional contraceptive. However, note that COMT(Met,Met) pre-menopausal women would probably not benefit from this evolutionary advantage during their menstrual cycles as heightened estrogen levels in their cases would increase their prefrontal cortex dopamine levels excessively and degrade their model-based decision-making capacity. Diekhof et al., 2021, https://europepmc.org/article/MED/34305543, explain how this mechanism negatively affects the cognition of COMT(Met,Met) women during the pre-ovulatory phase of their menstrual cycle.
Now that's interesting work. Much appreciated.
Interesting parallels with the theory that the decline of the Roman Empire was caused by lead plumbing