What are the most obvious behaviour changes when on the hormonal birth control?

The synthetic hormones from HBC signal to the brain not to stimulate the ovaries to mature/produce any egg follicles. It gives a daily dose of the same hormonal message, i.e. a relatively high level of synthetic progesterone, which is called a progestin, and really low levels of synthetic oestrogen (or none at all). Getting that same daily message from your birth control of choice makes the brain believe that it's in the luteal phase of the cycle, which is the phase of the cycle that occurs right after an egg has been released, and the body is waiting to see whether an implanted embryo is going to implant itself. The high levels of progestin/low levels of oestrogen shut down the the second half of the cycle. This should be when progesterone is being released and when this happens the brain tells the ovaries not to do anything because it's waiting to see what happens from that last one before it tells it to start stimulating egg follicles again. that process down.

This does a few things: prevents ovulation, good for those of us who don't want to get pregnant. Unfortunately, ovulation is the primary way that women produce their own sex hormones. If your body doesn't go through the ovulation process, it doesn't produce oestrogen. This is because the hypothalamus under normal circumstances would release the hormones gonadotropin-releasing hormone and luteinising hormone. Gonadotropin-releasing hormone makes the pituitary gland produce follicle stimulating hormone. This hormone, as the name suggests, starts the development of the egg within the follicle (the follicle is like a sac where the egg is matured). Follicle stimulating hormone then causes oestrogen to rise in your body.
Oestrogen matures the egg within the sac (or follicle) and gets the egg ready to be released.
If, instead, your hypothalamus receives a daily message of high levels of synthetic progesterone along with low (or no) levels of oestrogen, it is fooled into behaving as if your body is in the luteal phase of the cycle. This state of affairs does nothing to promote female sexual desire because oestrogen is the hormone of conception and sex. All of the changes we see in naturally cycling women when women are at high fertility/have sexual desire, the driver behind that is oestrogen. Keeping oestrogen low is not good for women's libidos and women report this issue at a high rate.

Modern stress is bad for us: it's associated with anxiety, weight gain, heart problems, low immune function insomnia and much more. While too much stress is bad for us, so is too little stress, as without it you can feel sad, bored and apathetic. Stress, then, is not something we want to avoid altogether. A moderate amount is good. Not all stress is the negative type: good news and a new opportunity or sexual encounter are examples of exciting, enjoyable types of stress. Stress can just mean that you are having an experience that is biologically meaningful or consequential and your body needs to change what it's doing as a result.

The way our body deals with this is through the stress response: the specifics of which differ depending on what's caused the stress, e.g. sex vs being chased by a lion. The stress response, however, always has a few things in common.

First: stress kicks your sympathetic nervous system SNS into gear. The SNS response carries out its objectives through the release of norepinephrine and epinephrine and is responsible for the fight or flight response. This response includes a racing heart, feeling panicked, and so on. Most of our stress feelings come from the SNS. Women on HBC still fully experience this SNS response (and as such are just as stressed as everyone else) and still have the full ability to fight or flee, which is a good thing if you really needed it.

Second: stress kicks your hypothalamic pituitary adrenal (HPA) axis into gear. This is made up of three systems working together: your hypothalamus, your pituitary gland, and your adrenal glands (which are on top of your kidneys). The activities of the HPA axis, just like those of the HPG axis, are initiated by the hypothalamus and are executed by another three-system group. First the H releases corticotropin-releasing hormone CRH, which stimulates the PG. The PG then passes this info onto the adrenal glands through the release of adreno-corticotropic hormone, ACTH. Lastly ACTH stimulates the adrenal glands, which prompts the release of the stress hormone cortisol into the bloodstream.

The primary biological signature of the HPA stress response is a surge in cortisol. This can usually be detected in blood and saliva within 3-5 minutes of encountering something that makes us feel stressed. Cortisol release is not directly associated with noticeable stress-like feelings. However, the SNS response plays a key role in managing the big picture of the stress response. e.g. it redistributes energy that was being used for things like growth and bodily repair to parts of the body that need an energy boost to deal with the stressor. It also affects the brain; e.g. cortisol promotes perceptual vigilance and revs up the neural processes involved in learning and memory so we can better embed lessons from the stressor in our brains for later use. This earmarks biologically relevant events helps us to adapt to our environment by allowing us to deal more effectively with similar situations in the future.

While this is useful, chronic activation of the HPA axis wreaks havoc in the body. It keeps all the body's resources tied up with stress management. This prevents investment in life-sustaining activities such as digestive, immune and cardiovascular function and increases the risk of (among other things) infection, disease, weight gain and decreases the rate of making new brain cells, [increases?] brain cell damage and cell death and reduces brain [hypothalamic] volume. This is because cortisol increases levels of triglycerides and glucose in the blood which put you at greater risk for heart attack, type-2 diabetes, infection and cancer. One of the ways your body protects itself from potentially nasty bacteria and neoplastic growth (cancer) is by keeping blood sugar relatively low most of the time. Since cortisol causes blood sugar to rise, and both bacteria and cancer cells thrive in sugar-rich environments, chronic activation of the HPA axis is highly deleterious. Given this, the body will do all it can to try to shut this down.

The hippocampus, which has more receptors for cortisol than any other part of the brain, will start signalling to the H to stop releasing CRH. The PG and AG will start ignoring the signals telling them to release more ATCH. If this isn't enough to lower cortisol levels, the liver starts releasing corticosteroid-binding globulins CBGs to inactivate part of the cortisol, which dampens the signal to the rest of the cells in the body. This happens because the body can't function in a chronic state of stress or trauma: it goes into shut-down mode. This is why it's so alarming that the bodies of women on HBC appear to be doing the very same thing.

Research has been done on women on HBC where they are subjected to stressful experiences such as having to do a presentation and being tested on mental arithmetic (the TSST). Naturally cycling women have a normal cortisol-releasing response to stress, whereas women on HBC release low levels of cortisol, no cortisol at all or even a negative response where cortisol levels drop. Women on HBC also do not exhibit much of an HPA axis response to the stress-inducing drug, Naltrexone, or to strenuous exercise (both of which should elicit a strong HPA axis response) so it's not that they simply deal with the TSST better.

One study tested naturally cycling women vs women on HBC after a strenuous exercise routine. Both groups of women felt less anxious, sad and angry after exercising than they did beforehand, which is to be expected as exercise is known to improve mood and mental health. Both groups also experienced similar SNS responses where their heart and respiration rates increased as they're supposed to. Women on HBC, however, had a much lower cortisol response than the naturally cycling women. This shows that women on HBC lack an HPA axis response to stress.

Their HPA axis responses are dysfunctional in other ways too; e.g. women on HBC have an entirely different cortisol rhythm from other people. Cortisol follows a circadian rhythm that reaches its daily peak 30 or so mins after we wake up and gradually declines throughout the day. Women on HBC, however, have a lower morning cortisol peak and they release cortisol more consistently across the day that what's observed in most healthy adults. These women are also less able to regulate cortisol that's administered in a lab than NCW. They continued to do this even in a week when they were given a hormone-free sugar pill. This suggests that whatever is going on with HBC and the HPA axis may continue after a woman stops being on it. Rather than simply blunting the stress response, HBC might totally redefine the functioning of women's HPA axes. FUCK THIS IS SCARY

Researchers don't really know why the HPA axes of women on HBC go into such disarray. They have known about this for more than 2 decades [hello?? why does nobody warn you of this??] but very few non-academics know about it.

HBCW don't only exhibit higher levels of CBG than NCW, their HPA axes show dysregulation at every turn. This suggests that something much bigger is going on with HBC and the HPA axis. Researchers as of 2018 (when the book was written) don't know why this is. For ex. here are some of the big differences we see between the HPA axes of HBCW and NCW: we already know the blunted free cortisol response to stress + their daily cortisol rhythms are also blunted but their overall amount of cortisol across the day is higher -- a graph of their cortisol levels (including free cortisol and cortisol bound with CBG, which makes cortisol inactive) would look more like a plateau than a mountain.

If you give HBCW a dose of CRH (a peptide released by the brain that triggers the PG to initiate release of ACTH) they release less ACTH than men or NCW do in response to the same dose of CRH. i.e. their ACTH response is blunted. If you give HBCW a dose of ACTH which stimulates cortisol release by the adrenal glands, the subsequently measured levels of free cortisol are lower than those of NCW who are given the same dose. If you give HBCW a dose of cortisol, which you can do with a hydrocortisone pill, and then measure their unbound levels of the hormone, the levels are higher than those of NCW that are given the same dose, suggesting their ability to manage excess cortisol is already maxxed out.

There's no part of the signalling pathway that looks like it does in NCW. Each link in the HPA axis communication pathway seems to be trying to quiet the stress signal. The adrenal glands are releasing less cortisol than they should be in response to a fixed dose of ACTH. The PG is releasing less ACTH than it should in response to a fixed dose of CRH and the liver is releasing tonnes of CBG to render inactive the cortisol that's already been released.

Putting all this together suggests that the blunted stress response might not be a result of HBC itself dialling down the activities of the HPA axis. Instead the pattern of HBCW's HPA axis function looks similar to that of someone who has experience chronic stress, suggesting that HBC might actually cause the HPA axis to go into overdrive, requiring it to take coordinated action to blunt itself.