Research Project

During the second stage (the 2014 year) there were targeted the first two objectives of the project. The first objective was intended to determine whether there are two distinct bio-psycho-sexual profiles for men, as originally expected (the existence of possible interrelations between finasteride side effects on one hand, and the dominant hand/ sexual orientation of participants, on the other hand). The second objective was aimed to determine whether the variation of dihydrotestosterone plasmatic level is correlated with magnitude of sexual side effects induced by 5α-reductase inhibitors. In the third stage it is foreseen to investigate whether there is a possible practical application of the two distinct bio-psycho-sexual profiles, which should be delineated/ confirmed during the second stage.

Regarding the first objective– highlighting the existence of two/ possible distinct bio-psycho-sexual profiles (expressed as adverse reactions that seem to occur only in a subset of men, depending on the dominant hand and/ or sexual orientation), the initial data from the time of project designing (the spring of 2013) suggested the fact that sexual hormones and pheromones are involved in the cerebral neuromodulation according to lateralization process of the brain. In other words, the left hemibrain could be under the influence of androgens and female sexual pheromones while the right hemibrain would be sexually activated rather by estrogens and male sexual pheromones. Thus, although four distinct types of sexual neuromodulators are certainly documented (androgens, estrogens, male and female pheromones), initially it was assumed that there would be only two distinct bio-psycho-sexual profiles, because androgens would act synergistically with female sexual pheromones (activating the left brain), while estrogens could act synergistically with male sexual pheromones (activating the right brain).

The literature data (updated to autumn of 2014) and the results of this study show actually that sexual hormones and pheromones could not present a synergistic mechanism of action, but rather independent (and interrelated) activating mechanisms. Sexual neuromodulation could thus be even more complex than it was originally assumed, existing therefore even four distinct bio-psycho-sexual profiles. Specifically, sexual hormones would activate the hypothalamic route (androgens for the left hemibrain and estrogens for the right hemibrain) while sexual pheromones would activate rather the thalamic route (female pheromones for the right hemibrain and male pheromones for the left hemibrain). Each of the two informational routes (thalamic and hypothalamic domains) are further divided by the lateralization process of the brain (left versus right)in two distinct subdomains, resulting thus four distinct and interrelated bio-psycho-sexual profiles.

Several literature data/ information are presented below, in order to explain the two -thalamic and hypothalamic- routes (which determine the informational dichotomy of the brain) and the corresponding lateralization process (which cause the structural dichotomy of the brain). Even though the structural and informational dichotomies of the brain are distinct processes, they belong however to interrelated mechanisms within the brain.

According to literature data, external/ environmental information is received through external receptors of the body (sensors of sight, hearing, touch, smell, etc.). From these receptors information is transmitted through afferent pathways towards central nervous system, namely to the thalamus, and then to the cerebral cortex. This is in fact the classical neurobiological pathway (the thalamic route) through which information from the external environment reaches the cortex or, more specifically, the nervous route by which the concrete environmental information reaches the cortex. The concrete information correspond to those data which describe (encoding and quantifying) the qualitative and quantitative properties of objects/ stimuli from the external/ environmental medium.

In 2014 we presented in literature a new possible informational input route for environmental data/ stimuli, which would be parallel to the thalamic route and that is involved in collecting of abstract external information. This route (and the abstract associated information) was described in the British Journal of Urology International (http://www.ncbi.nlm.nih.gov/pubmed/24053436), and will be followed perhaps by other articles that will explain and argue from physiological and psychological perspectives the existence of the two distinct nervous systems of reception (thalamus and hypothalamus) and of processing (Default Mode Network and Task Positive Network) of external environmental information (see: http://scholar.valpo.edu/cgi/viewcontent.cgi?article=1037&context=jmms; http://scholar.valpo.edu/cgi/view
content.cgi?article=1016&context=jmms).

Consequently, there are two parallel routes for collecting external information from environment, namely a thalamic (dorsal) route for concrete information and a hypothalamic (ventral) route for abstract information. These two routes correspond from a neurophysiological perspective to the two (thalamic and hypothalamic) routes described for ARAS (ascending reticular activating system). In other words, the two routes of ARAS are not functioning only as a cerebral ascending activating system (hence a local/ intrinsic function of the brain, as it is currently assumed), but they are also functioning as informational input routes for environmental data/ stimuli, the one for the concrete information (the thalamic route) and the other for abstract information (the hypothalamic route). In fact, from a neurophysiological approach, the two processes may be connected in reverse. Thus, the two routes of ARAS could function primarily as routes for collecting environmental information and, through this, they would intervene (implicitely) in the ascending activating process of the brain (because this is actually the role of external stimuli, to inform- alerting/ activating- the brain about their existence and action.

The literature data (see the next stage, 2015), the preliminary data obtained in this study with Finasteride (as antiandrogen, see: http://www.ncbi.nlm.nih.gov/pubmed/23157321), or data from other studies of ours related to the administration of tamoxifen (as antiestrogen, see: http://www.ncbi.nlm.nih.gov/pubmed/26108899), suggests that sexual hormones would modulate the receiving information through hypothalamic route (which acquire in this way a sexual connotation), while sexual pheromones modulate rather information received through thalamic route (also for acquisition of sexual connotation). Both routes are divided by neurophysiological process of the brain lateralization in two distinct subdomains, resulting thus four distinct bio-psycho-sexual profiles.     

Returning to the first objective of this study, namely to highlight the existence of two distinct bio-psycho-sexual profiles (by monitoring finasteride adverse effects, and investigating in respect to possible correlations between these adverse effects and the dominant hand and/ or sexual orientation), the data of this study confirm the preliminary results related to finasteride, according to which finasteride induces adverse reactions predominantly right-handed men. Regarding sexual orientation, the data registered are partially overlapping on data obtained in other previous study (see: http://www.ncbi.nlm.nih.gov/pubmed/20955264), namely that Finasteride induces adverse effects predominantly on homosexual men who are right-handed, and in a lesser extent to left-handed homosexual men.

According to our data that are similar with literature, finasteride decreases plasmatic level of dihydrotestosterone in all men receiving this drug. However, finasteride adverse effects are encountered only at a certain subset of participants receiving the drug, i.e. predominantly at right-handed men. Taking into account these data, we found that the variation of plasmatic level of dihydrotestosterone is partially correlated with the extent of sexual side effects induced by 5α-reductase inhibitors, and this correlation was found only in right  handed men. When this delineating criterion (hand preference) is excluded, the plasmatic variation of dihydrotestosterone no longer correlates (according to current data) with the extent of sexual side effects induced by 5 alpha reductase inhibitors, because the left-handed men are also taken into consideration and, for these persons, the dihydrotestosterone level decreases but the sexual side effects are very rare or absent.

All these data and information were presented / disseminated through several papers, which are listed at the end of 2016 reporting form, and also within a dedicated section at http://www.scholar.ro/finasteride/results.