Estrogen and lifelong brain health, testosterone fraud

Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.

Men dosing testosterone are called meatheads for a reason, they would logically throw off their other hormones and functionally retard themselves. Because this ONE time, you can trust the pill people. No IQ studies in testosterone supplementing men, I guess there’s a good reason. They just forgot?

The results are, unfortunately, controversial and puzzling. Dosing, timing, even the application route seem to considerably affect the outcomes. 

You’re not trying to rig it at all, huh?

Reduction to dihydrotestosterone by 5-alpha reductase increases the androgen activity; conversion to estradiol by aromatase converts the androgen to estrogen activity.

Holy shit.

That’s hilarious.

Recently, the non-genomic effects of testosterone on behavior bypassing the nuclear receptors have attracted the interest of researchers. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences.

Not known.

a very important study in rhesus monkeys showed that pharmacological castration reduced and testosterone supplementation normalized anxiety levels (Suarez-Jimenez et al., ).

on the other hand, in both men and women, testosterone supplementation leads to improvement of depressive symptoms (Pope et al., ; Miller et al., ). However, not all interventional studies confirmed the anti-depressant effect of testosterone. At least in one published randomized controlled trial, the effects of testosterone were comparable to placebo effects (Seidman et al., ). Similarly, not all observational studies show a consistent picture. At least in one small study, depressive women had higher testosterone (Weber et al., ).

Another experiment on intact rats revealed that the effect of testosterone on depression is dose-dependent (Buddenberg et al., ).

Over the counter won’t work.

During the productive ages and even in early adulthood, men generally outperform women in spatial abilities (Linn and Petersen, )

Even for a few years you’re in college? Is that it?

Spatial thing is probably due to error, thus would be discounted under a valid method.

Error rate as well as the reaction time negatively correlated with testosterone (Hooven et al., ).

In another study, actual testosterone was not associated with spatial abilities, but prenatal testosterone correlated positively with spatial abilities in women (Kempel et al., ).

Congratulations, you’re on the female level. Apply your non-toxic internet cream.

In line with these findings is the lack of an association between actual salivary testosterone levels and mental rotation in men and women (Puts et al., ).

Actual science, no replication issue.

However, in a large observational study analyzing spatial abilities in adult men from various age categories, low testosterone was associated with better spatial visualization (Yonker et al., ).

Actual science, no replication issue.

Plus multiple ages in ADULT men, important.

Good work.

In a very interesting study, it was found that in men, the pubertal concentrations of testosterone are negatively associated with mental rotation in the adulthood (Vuoksimaa et al., ). In the same paper, the comparison of twins is reported. The twin with higher testosterone scored worse in the mental rotation tests. The results are contradictory, but may depend on the test used for the assessment of spatial abilities.

Counting fluke correct answers and not errors to force a finding is scientism. Bad method.

When virtual Morris water maze was used, a positive correlation between testosterone and spatial navigation was found in women, but not in men (Burkitt et al., ). The size of the corpus callosum seems to add complexity in the relationship between spatial abilities and testosterone (Karadi et al., ). This might be one of the causes for negative findings in studies where some of the determinants are missing (Kubranska et al., ). Another cause is likely the selection of the tested population. In gifted children, a negative correlation between salivary testosterone and spatial abilities was found (Ostatnikova et al., ).


Negative findings are real science.

And that’s important.

In Chinese men, the accuracy in mental rotation tests was comparable to Americans, but the reaction times were longer indicating that cultural differences could add to the variability of published results (Yang et al., ).

No they didn’t rush the test out of boredom. Lower error rate, I’d bet.

Last but not least, genetic factors likely modulate the effect of testosterone. We have previously shown that at least in gifted boys, genetic polymorphisms influencing testosterone metabolism affect also its relationship to mental rotation (Celec et al., ). Especially, the CAG short tandem repeat in the exon 1 of the androgen receptor gene seems to be important for the action of testosterone and its metabolites (Nowak et al., ). Despite all complexity, the current picture indicates that the association between testosterone and spatial abilities is curvilinear and sex-dependent.

aka more is NOT better and it’s genetic, morons

In women higher testosterone is associated with better mental rotation, in men lower testosterone is associated with better spatial abilities. This seems to be true both for actual testosterone (Moffat and Hampson, ) and for prenatal testosterone (Grimshaw et al., ). Supplementation of testosterone in older men results in improvement of spatial abilities, but it is accompanied with changes in estradiol metabolism and it is likely that this interferes with modifications of spatial abilities (Janowsky et al., ).

They only studied spatial, not global, I checked.

Even in rats, testosterone administration affects the strategy of the animals in spatial tasks (Spritzer et al., ). However, the interaction between testosterone and mental rotation tests is bidirectional. It has been shown that mental rotation testing affects testosterone, at least in women (Durdiakova et al., ).

Doing smart things causes the brain to…. adapt? Really?

Does our pulse increase when we run? Some Sherlock Holmes do a fucking study.


Moreover, participants with complete androgen insensitivity syndrome presented with female-like neural activation pattern in the parietal lobe, indicating that gonadal hormone exposure rather than genetic sex itself plays role in brain functions (Van Hemmen et al., ).

Supplementing won’t work, you’re worse than the trannies. They don’t claim brain benefits.

The menstrual cycle and thus the involvement of sex hormones, including testosterone, in spatial abilities was further confirmed by Pletzer et al. In their study, error rates linked with deactivation of inferior parietal lobes and prefrontal lobes were higher during luteal phase for verbal tasks, while in the follicular phase, spatial abilities in females were confirmed (Pletzer et al., ).

One of the major factors that might explain the differences between the results of various studies is the variability of the examined populations. As mentioned above, the cultural differences, sex and age have all been shown to impact the physiological effects of testosterone. 


Standardization in this area would surely improve our understanding of the neuroendocrinology of testosterone. More systematic research using the whole spectrum of available tools and looking at the various physiological aspects is needed. However, to be able to publish such research, journals should accept manuscripts based on the design and not on the results. Otherwise, the publication bias that is obvious in the so far published literature will continue to be a big issue. Many researchers in this field complain about negative results that are very difficult to publish in the relevant journals. The number of such unpublished observations and experiments is unknown. But based on our humble experience, the negative results will probably be more common than the published positive ones. And if the contradictory published findings are added, the picture gets even more confusing. Large systematic research projects with more cooperation between the most productive research teams is definitely needed.

You can’t because the low IQ men will complain if you publish negative findings.


Testosterone plays a role in the organization of behavior during development. The authors examined whether testosterone could play a maintenance role in behavior as well. In a double-blind manner, verbal and visual memory, spatial cognition, motor speed, cognitive flexibility, and mood in a group of healthy older men who were supplemented for 3 months with testosterone were assessed. The increase in testosterone levels to 150% of baseline levels resulted in a significant enhancement of spatial cognition, but no change in any other cognitive domain was found.

You’ll be slightly more able to parallel park. Like when you were young.

Louder for the slow:

no change in any other

cognitive domain was found





Did I stutter?

Testosterone supplementation influenced the endogenous production of estradiol, and estradiol was found to have an inverse relationship to spatial cognitive performance. These results suggest that testosterone supplementation can modify spatial cognition in older men; however, it is likely that this occurs through testosterone’s influence on estrogen.

I’m sure the health effects will be golden.