Sunday, December 2, 2018

More unintended consequences

Fond memories, by Raimundo de Madrazo y Garreta (1841-1920). The hormonal state of pregnancy causes women to have a lower capacity for multitasking and remembering future activities. What happens when oral contraceptives maintain this hormonal state for years and years?

In my last post I reviewed the literature on oral contraceptives and behavior. Women invest more in sexual attractiveness near the time of ovulation, putting on more makeup and sending out other visual, behavioral, and olfactory cues. Oral contraceptives seem to suppress this desire to be attractive.

Parallel to these attitudinal and behavioral changes over the menstrual cycle, we also find cyclical changes to certain brain regions:

[...] a large sample of 55 women was scanned three times along their menstrual cycle in concisely defined time windows of hormonal changes. Accordingly this is the first study using a large enough sample size to assess menstrual cycle dependent changes in human brain structure with sufficient power. Results confirm a significant estradiol-dependent pre-ovulatory increase in gray matter volumes of the bilateral hippocampus, but also show a significant, progesterone-dependent increase in gray matter volumes of the right basal ganglia after ovulation. No other areas were affect by hormonal changes along the menstrual cycle. These hormone driven menstrual cycle changes in human brain structure are small, but may be the underlying cause of menstrual cycle dependent changes in cognition and emotion. (Pletzer et al. 2018).

The same research team earlier reported differences in brain structure between oral contraceptive (OC) users and non-users. OC users were closer to men in their brain structure:

Men had larger hippocampi, parahippocampal and fusiform gyri, amygdalae and basal ganglia than women. Women showed larger gray matter volumes in the prefrontal cortex, pre- and postcentral gyri. These sex-dependent effects were modulated by menstrual cycle phases and hormonal contraceptives. We found larger volumes in the right fusiform/parahippocampal gyrus during early follicular compared to mid-luteal cycle phase. Women using hormonal contraceptives showed significantly larger prefrontal cortices, pre- and postcentral gyri, parahippocampal and fusiform gyri and temporal regions, compared to women not using contraceptives. (Pletzer et al. 2010).

This study was criticized because it made no distinction between progestin-only OCs and combined progestin/estradiol OCs. The results were quite different when another research team repeated this study with participants who used only the second type of pill. OC users now had less, not more, brain volume, particularly in certain regions of the cerebral cortex: 

In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. (Petersen et al. 2015 - h/t to Wanda!)

These differing results may reflect the different types of OCs in use. Because progestin, like progesterone, has anti-estrogenic effects, long-term use would tend to masculinize a woman's brain; there is consequently more gray matter in the parahippocampal and fusiform gyri, which are likewise bigger in men than in women. In contrast, when women prevent conception by taking a mix of progestin and estradiol, which more closely mimics the hormonal state of pregnancy, certain regions of their cerebral cortex will tend to atrophy.


This atrophy may have an evolutionary cause. Keep in mind that a pregnant woman has to cope with a different pattern of cognitive demands: 

Pregnant women often have difficulty with multi-tasking and remembering future activities; however, they show improvement in memory for faces and recognition of emotional changes, particularly in men. They tend to have an increased sensitivity to odors, many of which are perceived as unpleasant. Perceptions of taste alter throughout pregnancy, with cravings for sweet foods in the second trimester and for salt in the third; sour tends to be preferred throughout the pregnancy. (Stadtlander 2013)

In general, the overall cognitive load is lower during pregnancy, so it makes sense that a pregnant woman’s body would allocate more resources to her developing child and fewer to her brain. The brain is, after all, the costliest organ of the human body, and it can probably cope with being a lower priority over the short term. Problems develop only if the hormonal state of pregnancy is artificially maintained for years and years.


Petersen, N., A. Touroutoglou, J.M. Andreano, and L. Cahill. (2015).Oral contraceptive pill use is associated with localized decreases in cortical thickness. Human Brain Mapping 36(7): 2644-2654. 

Pletzer, B., T. Harris, and E. Hidalgo-Lopez. (2018). Subcortical structural changes along the menstrual cycle: beyond the hippocampus. Scientific Reports 8: 16042

Pletzer, B., M. Kronbichler, M. Aichhorn, J. Bergmann, G. Ladurner, and H.H. Kerschbaum. (2010). Menstrual cycle and hormonal contraceptive use modulate human brain structure. Brain Research 1348: 55-62.

Stadtlander, L. (2013).  Memory and perceptual changes during pregnancy. International Journal of Childbirth Education 28(2): 49-53.


Sean said...

One wonders what happens to the brain of woman who takes contraceptive pills for decades.

Anonymous said...

Peter, do you believe widespread pornography and masturbation in the contemporary environment may also be having attitudinal, behavioral, and physiological effects in men?

Sean said...

For a male abstaining from masturbating (or sex) probably has massive psychological effects. Nietzsche wrote of the feeling of inviolable power it creates, and a certain Austrian whose name is better left unmentioned seems to have practiced it until his early 30s. Toxins build up, partly a sort of exhaust from the little motors that power the swimming action of sperm, and not ejaculating for more than a few days begins to poison them. Ejaculating every other day is supposed to produce the fittest sperm, but I wonder.

Micheal Ristow did an influential experiment that showed oxidative stress would eventually produce a response and promote better function. I suspect if you abstained for weeks your sperm would benefit via hormesis See here.

Anonymous said...

Is extended abstention physiologically possible, though? Don't nocturnal emissions start happening after a while?

Sean said...

It could be just a feeling of being in control, which certainly has profound physiological effects. I don't know if abstaining gives you any healthier sperm, but it could be like the mitohormesis from fasting, which is beneficial in limited duration. If I had to guess I'd say a couple of weeks. In Ristow's experiment a 100% carb free diet created a flood of free radical that was compensated for and led to enhanced function. To answer your question, the excess sperm are voided into the urine if you totally abstain.

Peter Frost said...

Sean and Anon,

There are pros and cons. The risk of prostate cancer is higher among men who masturbated as rarely as possible in their youth. On the other hand, porn seems to desensitize the male mind to sex. To get the same "kick," a man has to consume more and more porn and the porn has to be edgier. There are reports of erectile dysfunction in heavy consumers of porn, as well as inability to relate to real women. I've discussed these points in previous posts:

If a man is in a situation where women are unavailable, the healthiest option would be to buy a love doll.

Anonymous said...


There are studies that suggest that mental functioning and other physiological functions are heightened and increased during periods of fasting. An explanation offered for this is that in our evolutionary past, periods of extended fasting and hunger were common, and high mental and physical functioning were necessary for survival during these periods. Obviously a hungry hunter has to be at the top of his game precisely when he doesn't have food in order to hunt successfully and be able to eat again. The alternative view of course is that you need food beforehand to perform well mentally and physically, especially with the brain being a very expensive organ that requires lots of energy and runs on glucose. Most people these days eat excess calories, especially carbs, at regular intervals, and thus if they miss a meal they miss a big glucose hit to the brain and have "brain fog" and diminished mental functioning and greater irritability. They have to be weaned off of excess calories and carbs gradually so they don't have reactions like this.

An interesting question is why the excess carbs in our environment today are converted into fat stores instead of burned and used by the brain, when the brain is such an energy hog that runs on glucose. Is there a bottleneck that throttles the glucose into the brain? Is something else diverting it away from the brain? Are people not intelligent in enough in general to engage in mental activity to use the energy?

Anonymous said...

Back to the analogy with fasting, there have long been folk beliefs that still persist today that claim abstaining from masturbation and sex will result in greater drive and functioning. The theory offered is similar to the one for fasting: just as a hunter starving for food will need the energy and drive and peak abilities to successfully hunt and eat again, a man starving for sexual release will have greater drive and functioning to pursue mating opportunities than a man sated with frequent sexual release via masturbation or sex. This seems plausible. On the other hand, there are studies that show primates, including humans, at the top of dominance hierarchies and thus with regular mating opportunities have positive feedback with increased levels of testosterone and positive emotions, while those on the bottom with fewer or no mating opportunities have negative feedback with decreasing levels of testosterone and increase in stress hormones.

Anonymous said...

The thing is that menstruating basically the entire fertile years is almost as unnatural than being in a constant state of simulated pregnancy. Historically woman probably spend a very significant part of their fertile years pregnant. So maybe contraceptives just get women closer to the historical normal.


Sean said...

Mild oxidative stress is beneficial for sperm telomere length maintenance