Interesting in that elevated estradiol is implicated in seizure susceptibility in men, whereas DHT (and Adiol-G) exert powerful anticonvulsant activity.
For those experiencing muscle twitches/fasciculations while on/after Fin, perhaps this is part of an explanation for why.
Mass spectrometric assay and physiological–pharmacological activity of androgenic neurosteroids
sciencedirect.com/science?_o … 08093295ba
Steroid hormones play a key role in the pathophysiology of several brain disorders. Testosterone modulates neuronal excitability, but the underlying mechanisms are obscure.
There is emerging evidence that testosterone-derived “androgenic neurosteroids”, 3α-androstanediol and 17β-estradiol, mediate the testosterone effects on neural excitability and seizure susceptibility.
Testosterone undergoes metabolism to neurosteroids via two distinct pathways. Aromatization of the A-ring converts testosterone into 17β-estradiol. Reduction of testosterone by 5α-reductase generates 5α-dihydrotestosterone, which is then converted to 3α-androstanediol, a powerful GABAA receptor-modulating neurosteroid with anticonvulsant properties.
Although the 3α-androstanediol is an emerging neurosteroid in the brain, there is no specific and sensitive assay for determination of 3α-androstanediol in biological samples.
This article describes the development and validation of mass spectrometric assay of 3α-androstanediol, and the molecular mechanisms underlying the testosterone modulation of seizure susceptibility. A liquid chromatography–tandem mass spectrometry assay to measure 3α-androstanediol is validated with excellent linearity, specificity, sensitivity, and reproducibility.
Testosterone modulation of seizure susceptibility is demonstrated to occur through its conversion to neurosteroids with “anticonvulsant” and “proconvulsant” actions and hence the net effect of testosterone on neural excitability and seizure activity depends on the levels of distinct testosterone metabolites.
The proconvulsant effect of testosterone is associated with increases in plasma 17β-estradiol concentrations. The 5α-reduced metabolites of testosterone, 5α-dihydrotestosterone and 3α-androstanediol, had powerful anticonvulsant activity.
Overall, the testosterone-derived neurosteroids 3α-androstanediol and 17β-estradiol could contribute to the net cellular actions of testosterone in the brain.
Because 3α-androstanediol is a potent positive allosteric modulator of GABAA receptors, it could serve as an endogenous neuromodulator of neuronal excitability in men.
The 3α-androstanediol assay is an important tool in this area because of the growing interest in the potential to use adjuvant aromatase inhibitor therapy to improve treatment of epilepsy.