Sex hormones are critically important for the maintenance of a normal mind but are equally involved in the development of mental illnesses.

Never the less, most mental problems are treated forcefully & unnaturally at excessive doses with psychiatric drugs that directly, crudely & forcefully assault the neural networks, instead of harnessing the curative powers of these potent, hormonal, naturally occurring forces. 

Anxiety

Anxiety is at least twice as commonly occurring in women as in men, for hormonal reasons.  Masculine levels of testosterone protect men from the ravages of this loud, intrusive "mental" illness. Dipping estrogen levels are a major contributor to generalized anxiety disorder (GAD) so that anxiety can be observed as a prominent component of PMS/PMDD, on a recurring, regular monthly basis in predisposed women.  When these same women enter their early to mid-forties, levels of estradiol & testosterone become far more erratic than ever before, but now ovulation & the generous amount of progesterone secretion that naturally accompanies it during the second half of each menstrual cycle also begin to fail.  In this way the customary backdrop against which dipping estradiol levels (estrogen withdrawal) normally take place is lost.  This is important because natural progesterone is by its very nature a significant force against anxiety & buffers the impact of dipping estrogen levels, & for good reason.

First of all the natural derivatives or metabolites of progesterone, notably allo-pregnanolone, although by nature hormonally inactive do have barbiturate-like effects & in addition progesterone is a naturally occurring anti-caffeine like drug. Caffeine fuels anxiety by being a natural antagonist to the purinergic system in the brain, a system with naturally sedative qualities, including its familiar anti-palpitation drug, adenosine.  In contrast progesterone, once again operating in a non-hormonal manner, functions as a significant purine agonist.  It follows that anxiety, even panic may be prominent during the pre-menopausal years, when progesterone has become deficient.  Far too often women so afflicted are casually treated with benzodiazepine drugs such as Xanax, Ativan & so forth, instead of attempts being made to stabilize their estradiol levels. Drugs that re-calibrate the stress response mechanisms may also be a highly effective counter to anxiety, a profoundly stress-sensitive disorder resonating to the strategic influences of the adrenal hormone cortisol.   

Major depressive disorder

Major depression is twice as frequently seen in women as in men, not because they are weaker or less resilient but because of their greater sensitivity to the sexual & adrenal steroid hormones.  This amplified frequency in women is clearly hormone-sensitive in the sense that rather than being more frequently seen throughout the life-cycle, depression crops up at times of major hormonal flux such as during the erratic hormonal excursions typical of the teenage years, on a monthly basis pre-menstrually in those women whose brain circuitries are depression-prone, during the early months following the delivery of a baby (post-partum or post-natal), during the hormonally unstable 40's & around the menopause. 

The kind of depression that occurs pre-menopausally is of the loud, anxious, angry, agitated type that is associated with extremely erratic estradiol levels & high levels of cortisol, whereas once the body has become severely depleted of estrogen the depression tends to be of what is called the atypical form, & cortisol levels are low.  Depression is prominent in those women who happen to possess a depression-prone neural substrate, the tip-off being a positive family history for depression.  The atypical form becomes activated after menopause as estrogen levels become thoroughly depleted.  A similar situation may accompany an early, artificial menopause, for example after surgical removal of the ovaries, once the estrogen levels have bottomed-out.  A frequently effective treatment for atypical depression is the use of mono amine oxidase (MAO) inhibitors, but guess what; estradiol itself is by its very nature a very user-friendly MAO inhibitor, which does not require a special, tyramine-free diet unlike the pharmacological MAO inhibitors, & is far less prone to side-effects!

Agitated depression

The louder, more frequent, more typical agitated form of depressive disorder relates to estrogen withdrawal (EW) instead of estrogen depletion (ED).  And far too often the knee-jerk approach to this condition is to make a shoot from the hip 'psychiatric' diagnosis without thinking of or testing for hormonal disturbances & then arbitrarily throwing the afflicted patients on heavy doses of anti-depressant, even at times anti-psychotic drugs, without much time or thought given to the process.  This is becoming an increasingly more prevalent approach in peri-menopausal women.  In fact after the Women's Health Initiative (WHI) study was reported in 2002, many women misguidedly quit their hormone therapies & experienced severe hormone withdrawal complications including anxiety, depression & in some cases suicide as a result.  Those who were switched to anti-depressant drugs often gained weight, experienced cognitive dysfunction, lost their sexual desire & orgasmic potential & in some cases became depersonalized.  Lives were destroyed, as were marriages.  And to top it off while estrogen therapy was in the process of being demonized, regulatory & government bodies strongly recommended anti-depressant drugs instead, for the treatment of hot flashes & related vasomotor symptoms, in lieu of hormone therapy, even though menopausal women taking the SSRI group of anti-depressant drugs happen to have an increased risk for the development of strokes. Talk about heading in exactly the wrong direction!   

Hormone-based treatments

Optimizing hormone therapy in a very precise manner that employs the steady-state delivery of non-oral, natural estradiol, while paying strict attention to not only the fine-tuning of dosages but also to steadiness of estradiol delivery patterns will often lead to the prompt relief of depressive symptoms while avoiding the complications so frequent with anti-depressant drugs,  At the same time we need to be cognizant of the capability of progesterone & synthetic progestins to frequently drive a depressive disorder, or to prevent estradiol or testosterone from healing one when it occurs. Some studies have been published claiming the ineffectiveness of estrogen treatments for depression, but they involved the use of orally administered, erratic forms of estrogen or were based on the older forms of estradiol patch which fail to delivery a steady stream of hormone.  In other words precision is key, & scientific principles should alays trump poorly designed clinical trials. 

So what about progesterone & the progestins? In The vast majority of side-effects associated with menopausal hormone therapy have to do with the progestins, but we can adjust for this while minimizing exposure of the brain to this group of hormones.   In the case of MPA, the specific progestin involved in the WHI study, this drug tends to promote depression in about 50% of its users, & I never use it in this context.  The powers that be tend to down-play the use of low dose testosterone at the menopause but this hormone, when applied at an appropriate dosage in those women whose testosterone levels are deficient, is a remarkable drug with breast cancer reducing, anti-depressant, pro-sexual influences while donating a general feeling of well being.  Testosterone therapy in female-appropriate dosages can be a remarkable treatment.  And finally, since cortisol & the stress response machinery are at the very core of the mood disorders, cortisol-modifying drugs have the capacity to reboot the system leading to further improvements in the treatment-resistant mood disorders. 

In another section of this site as well as in my linked website known as mindhormones.com, I will discuss the use of sexual hormone modification in the treatment of bipolar mania & psychotic depression.  That psychosis is hormone sensitive is demonstrated by the high prevalence of psychosis in men compared with women & the occurrence of post-partum psychosis in psychosis-prone females.  Estradiol serves to protect women, in contrast to men, from the development of psychosis, even in psychosis-prevalent females with strong family histories of the problem & psychosis, like OCD is more prevalent in women suffering from PCOS with high androgen levels, than in hormonally normal women.  The cortisol-modulating drugs have been effectively used to treat patients with psychotic depression.  

Why should the sex hormones be so mentally potent?

The hormones of the thyroid, the adrenals & the gonads, the testes in men, the ovaries in women, working in concert & operating both through the classical hormone receptor-mediated mechanisms, the same ones that mediate the sexual effects of sex hormones, and a newly appreciated set of novel mechanisms that target immunity, inflammation, the body's small blood vessels & the so called 'limbic brain', have a massive influence on the mind.  This influence is felt not only over the long term while defining our personalities & temperaments,  but changingly, from moment to tiny moment while tracing out our vibes, our mental fluctuations, our harmonic paroxysms. 

They have a regulating effect on the inflammatory cytokines, those ubiquitous local hormone-like chemicals which regulate inflammation, & inflammation is now being seen as a major mover in the development of mental illnesses by in turn controlling the balance between new cell activation & old cell discontinuation in the plastic brain, in a sense its cellular cash-flow.  Mental illness is not really 'psychiatric' it is neurologic, or at least nano-neurologic, a mini-variant of the conditions known as the neuro-degenerative diseases ( such as Alzheimer's dementia & Parkinsonism).  So one large way for the sexual hormones such as estradiol can alter the mental music of our lives is via its potent influences on inflammation. 

Another important upstream effect of the sex hormones is on the machinery of the stress response located in the hypothalamus, based on the adrenal hormone cortisol.  But in addition to having a monumental effect on the hippocampus, our most critical emotional limbic pivot, these hormones also regulate cellular 'cash-flow' in the hippocampus itself, & cortisol is our own natural anti-inflammatory.  And finally these steroidal hormones have major regulatory influences on a variety of 'neuro-peptides including our internal opiates, & on the major groups of regulatory neurotransmitters in the brain, including GABA, serotonin, nor-epinephrine, dopamine & acetyl-choline.

Hormones & the synapse

One of the major defining qualities resident in neural networks in the functioning of the synapse, which can be defined on the basis of pre-synaptic, trans-synaptic & post-synaptic mechanisms for the transferal of data from upstream to downstream nerve cell.  And now revelations coming out of the scientific as opposed to the clinical end of medicine validate the hitherto unsuspected ability of the sexual hormones to control synaptic function widely & strategically. And these influences aren't just just curiosities limited in their influences to lab rats, these are real, definable & exploitable effects.  Thus hormones such as estradiol have the capacity to influence neurotransmitter metabolism at the pre-synaptic level, neurotransmitter dynamics or cash-flow across the structures of the synapse, and receptor as well as post-receptor mechanisms in the post-synaptic compartments. 

It follows that the sexual hormones, by virtue of their potent, strategic limbic influences, have a major impact on emotive function & mental illness. When disrupted they can fuel emotional, intellectual &behavioral dysfunctions including the personality disorders, anxiety, OCD, major depression, mania, bipolarity & even psychosis, the whole mental gamut.  The other side of the coin however, is that since hormonal disruptions frequently kindle these mental problems, surely they must also, when corrected & stabilized, have the power to ameliorate or even to fully relieve them, even over the long haul, while allowing us to dispense with or at least reduce the doses, side-effects & complications of psychiatric drug therapy.