Archive for April, 2012

HPA Axis: Psychosocial Stress and Hypothalamic Amenorrhea


04 2012

HPA axis: Metabolic Distress and Hypothalamic Amenorrhea


04 2012

HPA axis: What is pregnenolone steal?

Answer: Bad.

At Paleo For Women (!).


04 2012

The female body and why I’m an advocate

At my new blog (!).


04 2012

Paleo For Women

Today I have some of the most exciting news.

First, you were all right.  Jimmy Moore was right.  I would like to devote a significant portion of my life to this work.  So I am going to.

Secondly, this means that my online activity is going to change.  It’s going to increase, but it will be changing form.  I am going to continue writing and maintaining this blog, here as Pepper.  Yet I am going to split my writing time and content between two separate websites. Here, I will keep all of my vitriol.   I will keep all of my diatribe.  I will keep my more personal posts.

My scientific, more clinical work is moving.  I spent the last week setting up a new website, Paleo For Women.  The goal of Paleo For Women is to become an advocate of women’s health issues in the Paleo sphere.  It’s to bring evolutionary ideas and natural health to women struggling with endocrine problems.   It’s to explore how natural methods can be specifically tailored to optimize female well-being and happiness.  My blog here aims to advance women’s issues with fire.  There, I will advance them with science.  Of a sorts.

While I am doing that, I will still let this blog know about and link over to the other site when new posts go up.

THANK you.

Paleo For Women


04 2012

HPA axis dysfunction

Hi friends! What up.  Today is another doozy.


There are two primary ways in which the HPA axis can malfunction.  It’s activity can increase, or it’s activity can decrease.

The HPA axis jumps into action when stressed or stimulated.   This is a good thing when the body is faced with short-term stressors.   In this event, adrenal activity increases.   Along with several other key responsibilities, the adrenal glands’s primary purpose is to help us survive in the face of a threat: they rally all of the body’s resources into “fight or flight” mode using cortisol and adrenaline.   Healthy adrenals instantaneously increase heart rate and blood pressure, release energy stores for immediate use, shut down digestion and other secondary functions, and sharpen the senses. But since they are programmed to respond to every kind of stress — physical, emotional, perceived, psychological, environmental, infectious, or any combination of these — a person under chronic stress can get into a fair bit of trouble.  It can knock the whole HPA axis off kilter.  Conditions related to increased activity are: Chronic Stress, Depression, Anorexia, OCD, Anxiety disorders, Excessive exercise, Alcoholism, Withdrawal, Diabetes, Obesity, Metabolic Syndrome, Hypothyroidism.  

The converse is perhaps just as bad.  The HPA axis suffers decreased activity either when hormones tell it to down regulate (as is the case with low leptin signalling!), or it has simply become exhausted by being in a high-stress, hyper-active mode for too long a time period.  Conditions related to decreased activity include: Chronic fatigue, Fibromyalgia, Adrenal insufficiency, PTSD, rheumatoid arthritis, hypothyroidism, asthma, and eczema.

Since cortisol plays a big role in our health and feelings of well-being, and since it also plays a crucial feedback role in up or down regulating the activity of the hypothalamus, stress will be a big piece of the rest of this post.  I’ll talk about different kinds of stress here, and then later detail the effects of cortisol on our bodies.

Clinicians generally divide stress up into four primary categories: emotional stress, sleep disorders, metabolic dysregulation and chronic inflammation.  In my book, they are virtually inseparable.  If you’re signed up for one, you’re almost always signing your life away to all of them.  BUT: they are each handled somewhat differently by the HPA axis.

Mental-emotional stress originates in the brain, and it eeks into the rest of the body via the hypothalamus, which is the hub of connectivity between your brain and the endocrine system.  This drives up the production of ACTH, which stimulates cortisol production later down the line.  Fortunately, this kind of stress is mediated by personality, perception of novelty, uncertainty, control in the situation, and how threatening the stimulus seems.  Low self esteem also makes it easier for the hypothalamus to jump into high gear.

Slow-wave sleep suppresses cortisol release, which is I believe the primary reason sleep is so important for health.   Exposure to chronic stressors results in a disruption of normal hormone fluctuations that occur throughout the day.   This means that cortisol will often jump up at night, creating a vicious cycle of decreased sleep, and therefore increased cortisol, and further decreased sleep, and even great cortisol levels.  No wonder I’ve been such a wreck for the last twenty years.

The most accepted model of how HPA axes dysfunction  asserts generally that stimulation drives the axis into an overactive state for some time, but that after a while the system becomes unresponsive.   Cells become cortisol-resistant.  This is where the popular term adrenal fatigue comes from, though much of the literature verges on pseudo-science.  While “adrenal fatigue” is certainly problematic, many scientists believe that this is an adaptive, and maybe even productive, response.  Hypercortisolism is bad.   Decreased HPA axis gives the body a bit of a break.  Or at least is intended to.

Why hypercortisolism bites

1)  Cortisol is immunosupressive.  It impairs cytokine production and function, induces the loss of tissues important to immune cell production, and may in fact play a causative role in the development of autoimmune disease.  Being immunosupressive means that cortisol inhibits inflammation.  Generally this is a good thing, but when it goes on for too long, important inflammatory reactions, including the immune reactions I just mentioned, fail to function when they are needed.

2)  Cortisol decreases hormonal output.  It signals to the hypothalamus to down-regulate, such that growth hormone, thyroid releasing hormone, and gonadotropin releasing hormone are released at much lower rates by the hypothalamus.  Yikes!  Without GH you don’t grow; without TSH your thyroid doesn’t work properly; and without GnRH your pituitary fails to signal reproductive activity.   GnRH is a factor in just about every single endocrine disorder.   YEAH.  To top it off, these hormones act as cortisol antagonists.   They typically mitigate the effect of cortisol in the blood.  This makes their absence is even more insidious.  Without them, cortisol can increase without ever being checked.

3) Cortisol increases insulin levels.  This fact, coupled with the decrease in androgens from decreasing hormonal output in general, leads to fat deposition. Visceral fat has buckets full of glucocorticoid receptors, which makes it very easy for cortisol and insulin to shuttle more and more triglycerides into fat cells.  I can’t emphasize how important this is.   The cardiovascular and all adipose-related issues from cortisol hyperactivity increase the aull-cuase mortality risk of patients two to three times and decrease life expectancy by several years.

4) Increases in cortisol-induced abdominal fat are associated with an increase in both total oxidative stress and in the number of inflammatory cytokines.

5)  Cortisol can destroy healthy muscle and bone tissue.

Why hypocortisolism bites

1)  Immune system up-regulation.   This can really improve health in some cases.  But up-regulating cellular immunity can induce tissue damage and excessive inflammation via the over-production of pro-inflammatory cytokines.    Low cortisol also makes catecholamine (epinephrine and norepinephrine) levels go unchecked.  These further increase inflammatory cytokines.  They also disrupt T-cell signalling.   The result is susceptibility to inflammatory diseases, including autoimmne diseases, mood disorders, malignancy, obesity  and chronic pain syndromes.  This can also increase susceptiblity to assaults by infectious and environmental pathogens.

2)  Bowel disturbances, PTSD, fibromyalgia, low back pain, burn out, and atypical depression.

3)  High-stress sensitivity, chronic fatigue and chronic pain.    These three occur so frequently and in such concert with low cortisol states that they are referred to as the “low cortisol triad” by some authors.  I know.  Catchy.


DHEA-S is produced in the adrenal cortex.  It is an androgen, and it is considered one of the dominant precursor hormones.  This makes it critical for endocrine and reproductive function.   DHEA-S is produced in other organs, but it’s primary source is the adrenal glands.

High levels of DHEA-S are often associated with hyper-activity of the adrenal glands- so in this case both cortisol and DHEA-S are elevated in the blood.   The HPA axis has started pumping, and it doesn’t know how to stop. Women with PCOS often have high levels of DHEA-S precisely for this reason.   This is bad for them because it makes it much easier to create androgens such as testosterone.  And without parallel increases in estrogen from the ovaries, the excess testosterone will wreak havoc.

Calorie restriction and exercise both also increase DHEA-S levels.   DHEA-S is the primary hormone, and DHEA is the active form.   When calories are consumed, more DHEA is recruited form DHEA-S.   This depletes DHEA-S stories.  So calorie consumption reduces DHEA-S, but calorie restriction will keep levels higher longer.

This is important to note for those of us who restrict calories and exercise frequently.  If we have hormone problems, particularly issue with excess, we might want to think about how to optimize our DHEA-S production.  Too much DHEA-S?  Eat more.    Too little?  Try eating a bit less, or intermittent fasting.

Low levels of DHEA-S are associated with adrenal fatigue and hypocortisolism.  In this case, the HPA axis just can’t do much of anything anymore.   This is bad.  DHEA-S is considered the best “feel good” hormone by many endocrinologists.    And it is a precursor to many hormones.  Moreover, there is a growing body of evidence that healthy levels of DHEA and DHEA-S may help stave off Alzheimer’s disease, cancer, osteoporosis, depression, heart disease and obesity.   You can supplement with DHEA-S if you feel as though you desperately need it.  However, perhaps the best course is to supplement in the meantime while you address the underlying issue of decreased HPA axis activity and adrenal exhaustion.


The pituitary

Because stress is a big deal and everyone wants to know about it, most of the HPA research has focused on cortisol and the adrenals.   But the rest of the axis is important, too.

Decreasing hypothalamic activity down-regulates pituitary activity, which means that the production of sex hormones decreases.   And what causes decreased HPA activity?

One factor is a decrease in leptin levels.  If leptin signalling is weak–ie, if our body fat levels are too low, or if we exercise too often–then the lack of leptin crossing the blood-brain barrier into the hypothalamus signals to the hypothalamus that the body is starving, and certain extraneous bodily functions such as reproduction cease.

A second factor in decreased HPA axis activity is high cortisol levels.  I know that I told you earlier that high cortisol levels are associated with hyper-activity of the HPA axis, so this might be confusing, and you might think they lead to increased sex hormone production, but this isn’t necessarily the case.  Cortisol still always exhibits a dampening effect on the hypothalamus.   The amount of cortisol produced by the body relative to the general activity of the HPA axis is complicated, and has to do with the amount of stress the body is under, how long it has been under that stress, and whether or not the body has lost any of its sensitivity to cortisol.

And finally, HPA axis activity can decrease if it has become exhausted.  This is adrenal fatigue, plain and simple.

In all of these cases, the hypothalamus stops telling the pituitary gland to produce sex hormones.  The pituitary, in turn, stops telling the gonadal tissue to produce hormones themselves.  The end result is overall decreased sex hormone levels.  Sex hormones are necessary for reproductive function, as well as for a variety of other important roles such as waking the body up, putting it to sleep, being in a good mood, and having a good memory.   When sex hormones decrease,  many things can go wrong.  PCOS is one them.  Acne is another.  Loss of libido, too, and also, fertility.   Depression.  Weight gain.  Miscarriage.  Yikes.

The final big system affected by HPA axis dysfunction is the thyroid.  When the hypothalamus is suppressed, thyroid releasing hormone doesn’t get released.  And when the pituitary is suppressed, thyroid stimulating hormone doesn’t get released.  The result is wholesale decrease in thyroid activity, all the way from TSH through T4 and to T3.


So the solution?  Sleep as much as possible.  Eat the appropriate amount of food.   Rest often.  Refuse to be stressed.  I am a firm, firm believer in the power of positivity to make us healthy human beings, and the HPA axis probably plays a big role in that.  Don’t let your co-workers, your boss, whatever, all that nasty crap in your life get you down.  I mean– it’s a million times more complicated than that.  I understand.  But I really do think mitigating those stressors (especially the ones you impose on yourself!) transforms physical health.  No self-hating, no anxiety about your looks, no worries about being perfect.  Your cells will thank you.


*Thank you WomenToWomen for the awesome graphics!



04 2012