»Carol Davila» University of Medicine and Farmacy, Bucharest

Facultaty of General Medicine

Research Project

Contract No.: 28/ 30.08.2013

This project is supported by the Ministry of National Education, CNCS - UEFISCDI

Project Code: PN-II-ID-PCE- 2012- 4- 0409

Title: Existing cerebral correlations between sexual and psychosomatic processes could stay at origin of two distinct bio-psycho-sexual profiles in humans


Abstract

Psychosexual dualism is a relatively new theory developed in literature during the past decade. Starting from basic neurophysiological mechanisms, this new approach changed the paradigm related to neurological control of sexual responses, explain the role of cognitive and sexual neuromodulators and offer perspectives for the understanding of cerebral interferences between cognition and sexuality. Taking into account this psychosexual context, it is not surprising that studies have revealed numerous bilateral correlations among sexual and psychosomatic elements (between sexual orientation and sexual neuromodulators, between sexual orientation and hand preference, between sexual orientation and cognitive pattern, etc.). The project is aimed to verify if the existing numerous bilateral correlations (among sexual and psychosomatic elements) are interconnected as a whole, due to the fact that sexuality and cognition would correspond to interdependent neurophysiologic cerebral mechanisms. To address this, the project will study if the mentioned psychosomatic and sexual elements aggregate in two distinct bio-psycho-sexual profiles. If so, this project further investigates a direct applicability for this new (bio-psycho-sexual) entity, consisting in determination of a certain (unknown or undeterminable) variable through the other determinable elements which are associated.

Objectives/ expected results

Research team

Motofei Ion

Project Manager

Rowland David

Senior Researcher

Manea Mirela

Senior Researcher

Georgescu Simona

Senior Researcher

Popa Florian

Senior Researcher

Tampa Mircea

Postdoctoral Researcher

Baston Catalin

Senior Researcher

Haineala Bogdan

Postdoctoral Researcher

Paunica Stana

Senior Researcher

Constantin Vlad

Senior Researcher

Dumitriu Anca

Senior Researcher

Balalau Cristian

Postdoctoral Researcher

Gîngu Constantin

Senior Researcher

The first stage

The first stage of this study was nearly four months, it took place between September 02, 2013- December 20, 2013, and had the following objectives: establishing team, tasks, and technical setting of the study. As activities, this stage implied: assignment of responsibilities, administrative activities, documentation and organization.

Regarding the research activities scheduled to take place during this stage, we conducted a review of the literature data that were considered of interest to the research topic, a process that will continue during the next stages of the study. The process of team establishment was finished for this stage, and duties of each person were clearly established.

The procurement process/ logistics related to this stage has been completed in full, buying into all elements that were included in the project for this stage. Storage and use of substances that will be used for hormonal dosages in subsequent stages were established, and technical conditions for conducting the study were established. A clinical study configuration was developed (that starts in the second stage), to allow centralization, interpretation and dissemination of data once the partial results are obtained.

The objectives that were established for this project are:

To verify whether there is/ can be identified for men two distinct bio-psycho-sexual profiles. In this respect it will be followed the interrelation between dominant hand, psychological profile, sexual orientation and sexual dependence by androgen activation (sexual behavior of participants to administration of 5α-reductase inhibitors as Finasteride).

To verify if the variation of plasmatic level of dihydrotestosterone (induced by administration of 5α reductase inhibitors) is correlated with the magnitude of sexual side effects. In this respect, it was established that subjects taking finasteride will be informed about possible sexual side effects that could be inhibitory or, conversely, stimulatory. It will be examined if the variation of plasmatic level of dihydrotestosterone (pharmacologically induced) correlates with the extent of sexual side effects.

To verify if there is a possible practical application of these two expected bio-psycho-sexual profiles.

Scientific results obtained during this project are foreseen to be disseminated through national and international communications (conferences, congresses, etc.) and in the form of articles, both as partial results (starting from the second stage) as well as final results (from the third stage of the project).

The second stage

The second stage of this project was developed in the period of: December 21, 2013- December 12, 2014, and had the following objectives: establishment and validation of patients samples, preliminary assessment of participants and conducting of therapeutic stage. As specific activities, the second stage involved: establishing lots according to selection criteria, investigation of participants (cognitive, clinical, assessment based on questionnaires), dosage of sex hormones through laboratory tests, Finasteride administration and collection/ evaluation of sexual side effects to this treatment.

The selection criteria used for recruiting the study participants were: patients who presented to the dermatologist or urologist for androgenetic alopecia or benign prostatic hyperplasia, engaged in a stable couple relationship, with jobs that do not require frequent trips (so that their sexual activity not depended by a certain lifestyle) and without significant visceral or mental disorders involving medical drug treatment and/ or counseling.

In this stage- 2014 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 second objective aimed to determine whether the serum dihydrotestosterone variation is correlated to the extent of sexual side effects induced by 5α-reductase inhibitors. In the third stage it is expected to determine whether there is a possible practical application of the two distinct bio-psycho-sexual profiles, which should be investigated/ confirmed during the second stage.

Regarding the first objective (the existence of two possible and distinct bio-psycho-sexual profiles), the initial data from the time of project designing (spring of 2013) suggested that sexual hormones and pheromones are involved in the cerebral neuromodulation according to lateralization process of the brain. In other words, the left brain could be under the influence of androgens and female sexual pheromones while the right brain would be sexually activated rather by estrogens and male sexual pheromones. Thus, although four distinct types of sexual neuromodulators are documented (androgens, estrogens, male and female pheromones), initially it was assumed that there are 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 that sexual hormones and pheromones do not present actually a synergistic mechanism of action, but rather an independent one. Sexual neuromodulation could thus be even more complex than it was originally assumed, existing therefore even four distinct bio-psycho-sexual profiles. Sexual hormones would activate the thalamic route (androgens for the left brain and estrogens for the right brain) while sexual pheromones would activate the hypothalamic route (female pheromones for the right brain and male pheromones for the left brain). The two (thalamic and hypothalamic) routes are therefore divided by the lateralization process of the brain in two distinct subdomains, resulting four possible and distinct bio-psycho-sexual profiles.

Some data are presented below, in order to explain the two routes (thalamic and hypothalamic) and the corresponding lateralization process within the brain.

According to literature data, the external environmental information is received by the body through external receptors/ 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 (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 environment.

In 2014 we presented/ published in literature a new possible informational input route for environmental data/ stimuli, which is 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 (1, see bibliography), 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) external environmental information.

Consequently, there are two parallel routes for collecting information from the external 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 routes (thalamic and hypothalamic) described for ARAS (ascending reticular activating system). In other words, the two routes of ARAS does not intervene only in the ascending cortical activation (as a local/ intrinsic function of the brain, as it is currently assumed), but they also function 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 activation process of the brain, because this is actually the role of information/ external stimuli (to alert/ aware the brain about their existence).

Recent data from literature, cumulated with previous results of our studies and with the project data suggest that sexual hormones modulate the information received via thalamic route (which acquire in this way a sexual connotation), while sexual pheromones modulate information received through hypothalamic route (also acquiring sexual connotations), both routes functioning according to neurophysiological process of brain lateralization. As a preliminary conclusion related to the first objective of the project, we currently consider that there are actually four distinct bio-psycho-sexual profiles, and will try to configure the further investigations taking into account this new perspective.

The second objective had to determine whether the plasmatic dihydrotestosterone variation is correlated to the extent of sexual side effects induced by 5α-reductase inhibitors. According to an earlier study that we published in 2013 (2, see bibliography), Finasteride inhibits sexual function predominantly in right-handed men (activating the left brain). As a consequence, the plasmatic variation of dihydrotestosterone is correlated with the magnitude of sexual side effects induced by 5α-reductase inhibitors, but only in right handed men. When this criterion of delineation (hand preference) is excluded, the plasmatic variation of dihydrotestosterone is no longer correlated (according to current data) with the extent of sexual side effects induced by 5α-reductase inhibitors, because the left-handed men are also taken into consideration and, in these persons, the dihydrotestosterone level decreases but the sexual side effects are very rare.

The results of this study related to the administration of Finasteride were partially centralized, interpreted and presented so far to five scientific congresses/ journals (3, 4, 5, 6, 7, see bibliography), thereby confirming the above presented theoretical considerations that were at the basis/ motivation of the two objectives of the project. Without considering that these two first objectives of the study are finished (we continue collecting data that will underpin perhaps for other two articles/ papers to be submitted for publication), we prepare in parallel for the third stage of the project that start on December 12, 2014. Given the current complexity of the situation (possible existence of four distinct bio-psycho-sexual profiles) compared to what we anticipated initially (two distinct profiles), we do not exclude additional activities/ investigations that could help us to further support/ strengthen the results and point of views presented above.

 

References (dissemination of project results: see points 3, 4, 5, 6, 7)

  1. Motofei IG, Rowland DL. The ventral-hypothalamic input route: a common neural network for abstract cognition and sexuality, BJU Int. 2014; 113(2): 296-303. doi: 10.1111/bju.12399

  2. Motofei IG, Rowland DL, Georgescu SR, Baconi DL, Dimcevici NP, Paunica S, Constantin VD, Balalau C. A pilot study on the sexual side effects of finasteride as related to hand preference for men undergoing treatment of male pattern baldness. BJU Int. 2013; 111(4): E221-6. doi: 10.1111/j.1464-410X.2012.11580.x.

  3. Lateralized sexual side effects of Finasteride in subjects with androgenic alopecia, I.G. Motofei, D. Rowland, S. Paunica, M. Tampa, S.R. Georgescu; Journal of Investigative Dermatology (2013 Impact Factor = 6,372); 134(2), 2014.

  4. Finasteride in male pattern hair loss; lateralization of sexual side effects; Motofei I., Tampa M., Benea V., Rusu A., Sarbu I., Georgescu S.R.; 23rd European Academy of Dermatology and Venereology Congress, Amsterdam RAI Convention Centre, 8- 12 October 2014.

  5. Similarities and differences between sexual side effects of Finasteride and Dutasteride in male androgenetic alopecia; Motofei I., Georgescu S.R., Tampa M., Baston C., Haineala B., Sinescu I.; 23rd European Academy of Dermatology and Venereology Congress, Amsterdam RAI Convention Centre, 8- 12 October 2014.

  6. Lateralizarea reactiilor adverse sexuale ale Finasteridei in alopecia androgenetica, I. G. Motofei, S. Paunica, M. Tampa, I. Sarbu, O. Ghenunche, V. Danaila, S. R. Georgescu; The 13th National Congress of Dermatology with International Participation, Dermatovenerologie (Revista Societ─âtii Romane de Dermatologie); 59(P21): 101, 2014 .

  7. Finasteride in male pattern hair loss; sexual side effects and variation of DHT plasmatic level; Ion G. Motofei, David L. Rowland, Mircea Tampa, Isabela M. Sarbu, Paunica Stana, Constantin Vlad, Balalau Cristian, Simona R. Georgescu. 12th European Academy of Dermatology and Venereology Spring Symposium, Valencia, Spain, 5- 8 March 2015.