The average woman & her dog (& likely every other member of her household, be they furred or otherwise), can tell you that sudden changes in sex hormones can undermine, derange, psychopathise, impact her mind and mood.  Hey, for me most days reverse parking is my mild super power, the envy of all, but on day 26 of my menstrual cycle, I can struggle with a ‘nose-to-kerb’! But if we are quick to attribute this to the fluctuating sex hormones produced by our ovaries, alone, we’d be making a mistake.  A portion of these peripheral steroids do cross the BBB and act in our brain, so changes to these levels during any kind of transition: follicular to luteal, pregnant to post-partum, menstruating to menopausal, early adulthood to andropause, will be ‘felt’ but the sex (hormones) we have on our brains at any given time, are far more abundant, potent and complex than this, thanks to the brain’s ability to make its own.

So in fact, the amount of sex hormones active in the brain represent an intersection between peripheral and central steroidogenesis. 
These Neurosteroids, made ‘on site’, are as much produced in response to our mood, our neurobiology, our psychological and environmental stress, to help us navigate these, as they are the creators of mood itself.

Yes, these particular sex hormones, due to their actions in our brain, belong to that growing list of CNS celebrities: the Non-Classical Neuromodulators.  Which, for the otherwise neurotransmitter-centric & obsessed among us (that’s everyone), makes mental health and illness much more complex than ‘serotonin deficiency’ or ‘glutamate excess’ and a whole lot more real.  We now need to consider other entities like: ‘suboptimal LDLs’, 5 alpha reductase over or under-expression & ‘xs inhibitory tone via progesterone’.

The ‘sex on the brain’ of any patient therefore is impacted by both their Endocrine (ovaries, testes, adrenals) and Synaptocrine (neural) contributions – and these demonstrate some shared dependence (for cholesterol & healthy mitochondria etc) and independence.

We all know the depressing stats in support of the ‘ovarian withdrawal hypothesis’ and the risk to women’s mental health with each reproductive transition, and also in andropause in men, but the time has come to now deepen our understanding and to recognise  we can have an imbalance of ‘sex’ on the brain – regardless of the ‘balance’ we might see in the periphery and put our thinking caps on about the options we have to address steroidogenesis either side of the blood brain barrier.

When it comes to a modern take on how sex hormones impact both the structure & function of our CNS, we need to blend the ‘old’ with the ‘new’.  The ‘old’ tells us, production of sex hormones is in the gonads and action at a distant target anywhere else in the body, including our brain. And the ‘new’ is in the form of the ‘Synaptocrine’ – where production of these sex steroids is actually within neural tissue itself and their immediate actions occur close-by, in the synpase and at the post-synaptic neuronal membrane. These two contributive pathways show some shared dependence but also independence from one another and the balance of both has now been recognised to be integral to the overall health of the nervous system.
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