As we've written in our article Androgens and Depression : Are they Nature's Intended Prozac - we know from science and Experience, that androgens have an anti-depressant effect - but its also possible, that in some cases Androgens may protect against Psychosis/psychotic behavior [1].

A study in 2013 noted that following androgen-deprivation "therapy" - many subjects developed Psychosis, including refractory Psychosis.

Of course, the picture is fairly complicated, we KNOW that Schizophrenia occurs more in Men, than Woman. From that and well-written articles like this one - it would seem Testosterone would be an anti-target.

Unfortunately - nothing is that simple; the same article also reviewed that while Testosterone in some cases facilitated development of Schizophrenia, it also protected against severe Cognitive deficits and ...when added to antipsychotic treatment, proved to reduce negative symptoms in a major way.

Additionally, there have been other studies showing Testosterone treatment improved Positive symptoms of Schizophrenia, as well. These of course, have been very few in comparison to the studies on its relevance to negative symptoms.

ESTROGEN AND PSYCHOSIS/SCHIZOPHRENIA

Estrogen is a whole 'nuther ball game when it comes to Schizophrenia. Not only have drugs like Raloxifene, which affects Estrogen receptors been proven to improve Cognitive and Mood symptoms in both Men & Women with Schizophrenia [2] but a large Review also indicated that Aromatase/Estrogen themselves have the largest role among all sex hormones in both the development of Schizophrenia and the course of it [3].

However - that role is exceptionally sophisticated given the multitude of differing study results...generally it seems that Estrogen plays a "protective" role - however, the excitotoxicity that can be achieved by Estrogen-dominance, may also precipitate Psychosis and / or worsen Schizophrenia symptoms [4]. Apparently, this is in part related to Estrogen's ability to weaken the immune system from viruses that may lead to degeneration of the Brain Regions involved in Schizophrenia [5].

Other studies have also noted that elevated Estrogen levels in Women associated with menstruation/ovulation are associated with Schizophrenic/Psychotic symptoms (positive association) - and thus, in some cases, SERMs can be used to block excessive estrogen-activity rather than utilizing other treatments.

Even if Low levels of Estrogen are generally a risk-factor for both the development of or the exacerbation of Schizophrenia [6] it is still prudent to note that excessive levels may cause a more severe form of it as well.

Since Estrogens can increase the general EXCITATION level of the nervous system...this can promote particularly dramatic presentations of Schizophrenia; where lability, Aggression, delirium are predominant symptoms.

SPECIFICS AND PHARMACOLOGY OF SEX HORMONES

Testosterone does not and is not capable of affecting the Brain neurotransmitters itself. It is only when it "converts" into its 5-Alpha-reduced metabolites; DHT and 3-alpha-diol that it can cross into the nervous system and exhibit effects on various aspects of neurochemistry [7].

The predominant effects of strong Androgens include.
Enhancement of GABA-release [8].
Increasing NMDA-glutamate receptors [9].
Decreasing serotonin levels/receptors [10].
Improving acetylcholine release [11].
Regulating norepinephrine/adrenaline [12].
None of these effects are exactly consistent with the prerequisites for development or exacerbation of Psychotic disorders in any form...but its possible that a functional imbalance between Androgens and Estrogens may lead to a "fluctuating" rather than excessive dopamine, state.

Those fluctuations may be particularly dramatic - especially in individuals with other risk factors.

Dihydrotestosterone and other Androgens also seem to promote neurogenesis (growth of new brain cells/synapses) - particularly in coordination with Exercise [13].

ESTROGEN'S ROLE

Estrogen has been found to have acute and chronic anti-dopaminergic effects [14] under certain conditions - however, it also can stimulate the Dopamine system in Humans [15] and inhibit the Dopamine transporter and its expression [16]. These effects along with the well-regarded research on Estrogens critical role in the male and female libido would seem to indicate that Estrogen can promote Dopamine activity [17].

Another review uncovered a critical role for Estrogen and Motivation in Humans and animals [18]. Suggesting again, a pro-dopaminergic role for Estrogen.

In light of these findings/reviews, it would seem that both sex hormones are well-capable of contributing to Psychotic symptoms - but the picture can get more complicated...since Schizophrenia also involves other neurotransmitters like Serotonin...to which is frequently ELEVATED in Schizophrenics [19].

ANDROGEN & ESTROGEN
ROLES IN SHORT-TERM PARANOID PSYCHOSIS

Up until this point we have evaluated primarily the role for Male and Female sex hormones in Schizophrenia and generally, Psychosis. What we haven't evaluated in detail, is their role in short-term bouts of Paranoia or stress-related Psychosis.

First - let's dive into a specific aspect of Paranoid Psychosis.
Paranoid Schizophrenics tend to have elevated Norepinephrine levels, also called Noradrenaline [20].
This is specific to them, since catatonic and typical Schizophrenics don't show this remarkable elevation...at least as often [21].
Anabolic-Steroid abusers tend to exhibit, out of all Psychotic symptoms, a disproportionate amount of Paranoia [22] - versus other symptoms such as Delusions or Hallucinations.
Paranoid personality traits often arise in long-term anabolic steroid abusers [23], probably related to the increase in Adrenaline and CNS activity caused by steroids...hence why powerful anabolic agents such as Tren and Deca raise blood pressure remarkably. Its the Adrenaline.
Estrogens on the other hand, at least in moderate amounts, tend to relieve/alleviate Paranoia [24].

****** CONCLUSIONS******

Although both Androgens and Estrogens can play positive, helpful roles in the treatment of Psychosis/Schizophrenia, it seems that on the whole, Estrogen seems more beneficial.

However - these studies showing such results should be interpreted with great caution - as high/elevated Estrogen is just as much a risk factor for ALL mental disorders.

In fact, because of the complicated relationship between Estrogen and immune activity - it may be overall worse for long-term Mental Health and specifically, BRAIN AGING, to have elevated Estrogen levels, regardless of possible ameliorative effects of Estrogen on Psychotic symptoms.

It is the conclusion AND responsibility of this article, and the Authors of this blog - to inform the Public that the correct interpretation of this information is that HORMONE BALANCE is the ideal state. That is, that neither a deficient level of Testosterone, other Androgens OR Estrogens is acceptable nor ideal - and can possibly promote multiple Psychiatric disorders; including Schizophrenia.

Therefore, to Bodybuilders, fitness enthusiasts - or just people interested in hormone health. It is recommended you frequently see a Doctor if you have some concerns about levels of sex hormones.
As always, follow the steps to get and stay healthy - such as eating right, optimizing macronutrient/micronutrient intake, cutting body fat and improving motivation levels.

If you do have a Low-Testosterone level, you can follow the suggestions in this article to boost it.
If you HIGH Estrogen - consider a natural supplement like 7-methoxyflavone - if that doesn't do the trick, Arimidex can be purchased at store name redacted for a good price. :-)
If you have LOW Estrogen/E2 levels, the best bet is to use something like Clomid along with a mild-gonadal agent like E-Pharm Test Force II - whose ingredients raise BOTH Testosterone AND Estrogen.

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