On this board we distinguish between finasteride’s “mental” and “physical” effects. Since we know that finasteride has two major mechanisms of action - in the brain, mediated by 5AR-1, and in the urogenital tract mediated by 5AR-2 - it often seems reasonable to suppose that perceived “mental” effects are the result of 5AR-1 inhibition, and “physical” effects the results of type 2 inhibition.
But it has made more sense to me lately that testosterone is the major culprit here. For one, we know that human 5AR-1 contains a four amino acid sequence that makes it largely resistant to finasteride’s effects. Though this system was certainly affected to some degree, we can probably say with some certaintly that it was not significantly affected. In fact it has been shown that decreases in allopregnenalone should, if anything, act to enhance the HPTA. This clearly stands in conflict of what we have seen. Nevertheless, it often seems tempting to attribute perceived “mental” effects to finasteride’s limited neuroactivity.
We also know from recent discussion that there is a clear relationship between testosterone and dopamine. Increases in testosterone (putatively ) lead to increases in dopamine.
As far as we can tell from the lab results posted here, as far as we know in terms of real quantitative data, finasteride’s lasting effects manifest themselves as prolonged imbalances of sex hormones. Low/average gonadotropins in a setting of low testosterone is widely apparent. Additional dysfunction in estrodiol and SHBG are also common. On this internet forum where speculation and conjecture are so common (namely, due to myself), this is as objective as we can get.
In the “other studies” section I have posted a study on testosterone’s effects on cognition propeciahelp.com/forum/viewt … highlight=
Of particular interest it states:
Only in cells where it encounters a receptor does [testosterone] form a complex that will influence protein synthesis in the nucleus of a neuron and modify cell function. This modification can be in the form of specific changes in neurotransmitter production and release, synapse conformation that modifies efficacy, as well as many other possibilities (see Figure 1). For instance, gonadectomy selectively reduces acetylcholine in hippocampus and anterior cingulate cortex but not other regions [5] and transiently decreases then increases dopamine innervation in cingulate cortex of rats [6]. Testosterone induces increased firing of serotonin neurons in male rats, although gonadectomy has no effect [7].
Studies using animal models show that testosterone modifies the physiology and function of the hippocampus. For instance, androgen deprivation causes a 40% decrease in synaptic density in the hippocampus of both rats [15] and monkeys [16] and testosterone replacement in male animals normalizes synaptic density [15]. This is likely to be particularly important in aging when the loss of synapses in hippocampus and prefrontal cortex [17] is accompanied by functional loss of memory
The accumulation of beta amyloid, a risk factor for Alzheimer’s disease, increases with testosterone deprivation [20]. Blockade of androgen receptors in transgenic mice expressing the apolipoprotein E4 allele, which is a risk gene for Alzheimer’s disease in humans, impairs memory on a maze learning task.
Testosterone replacement in hypogonadal men increases cerebral perfusion, as measured by single-photon emission-computed tomography (SPECT) [55]. Similarly, in hypogonadal men who improve on mental rotation ability with testosterone replacement, positron emission tomography (PET) shows greater metabolism during task performance [56]. Testosterone treatment normalizes PET activity induced by visually presented sexual stimuli in the right orbital and inferior frontal cortex, claustrum and insula in hypogonadal men [57]. Testosterone levels correlate with overall brain activity during a synonym- (semantic) and letter-string (perceptual) identification task in healthy, normally cycling women, suggesting nonspecific or vascular effects of testosterone in women [58].
There’s much more to this article, but the message, at least in my mind, is clear: mental problems, like perhaps many if not most of the sexual problems, are probably just another result of androgen deprivation.