The third stage

The third stage of this project was conducted during the period December 13, 2014 and December 15, 2015, having the following objective: to determine whether there would be a possible practical application of the results obtained in previous stages, namely whether sexual side effects of finasteride could be somewhat predictable. As specific activities, the third stage involved: establishing lots according to the selection criteria, investigation of participants (cognitive, clinical, laboratory, assessment based on questionnaires), delineation of subgroups (according to the dominant hand and sexual orientation), administration of finasteride, collection of the data related to adverse reactions recorded and their correlation with the previously delineated subgroups (through the two elements, the dominant hand and sexual orientation).

In respect to the third objective (a possible practical application of the results obtained in the previous stage), the obtained data correlate with the primary objective of this study (namely that finasteride induces sexual side effects predominantly in right-handed men). In other words, the right handed men should be advised prior to treatment with finasteride, that have a higher risk of developing adverse effects than the other (predominantly left-handed) men, a risk that appears to be higher in subjects reporting that have a homosexual orientation. These findings were presented in the form of published papers (see: Finasteride adverse effects in subjects with androgenic alopecia: A possible therapeutic approach according to the lateralization process of the brain; Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia), which are listed at the end of 2016 reporting form, and also within the dedicated section at http://www.scholar.ro/finasteride/results. We consider that new studies are necessary in our opinion to further clarify all these aspects, involving significantly larger and multicenter samples, the lifestyle and mentalities (drinking, coffee and/ or nicotine consumption) contributing also perhaps to predictability, magnitude and persistence of finasteride adverse effects. 

All these data / findings should be interpreted contextually, in order to understand the distribution of finasteride adverse effects. For this reason, there are presented below several theoretical considerations and observations/ data, which are considered to be relevant in respect to sexual neuromodulation.

The initial data indicate that sexual side effects induced by finasteride occur primarily in right men handed. These results were reconfirmed through this project, a fact that further support the idea that neuroendocrine mechanisms of sexual neuromodulation  would occur (through sexual hormones) in accordance with the lateralization process of the brain. Yet, this observation is also supported by the results of another study (published during this project), showing that tamoxifen induce sexual side effects predominantly in left-handed men. 

It is relatively difficult to argue in a single paper why sexual hormones (androgens/ estrogens) would act differentially, either on the left hemibrain or on the right hemibrain. In this regard, in the same time with presenting the results of this study (Articles related to the study), we also began to publish a series of data and explanations related to the existing interrelationship between mental and sexual processes (Articles related to the project topic, published by members of the team during this study).

In fact the process of the brain lateralisation seems to be critical, meaning that it favors cognitive capabilities (Gotts SJ, et al. Two distinct forms of functional lateralization in the human brain. Proc Natl Acad Sci USA 2013, 110: 3435- 44) while a poor lateralization would predispose to mental disorders or severe mental illnesses such as schizophrenia (Alary M, et al. Functional hemispheric lateralization for language in patients with schizophrenia. Schizophr Res 2013, 149: 42- 7). As a result, mental processes such as attention and cognition are related to the lateralization process of the brain. Due to the fact that sexual activation is dependent in humans by cognition (through voluntary focusing of attention on a certain partner/ area of the body), it results that the process of human sexual activation (libido, sexual arousal) would be also interrelated (via cognition) with the lateralization process of the brain. Moreover, sexual hormones are directly involved in the process of sexual activation (external stimuli acquiring sexual connotation through sexual hormones, a process that is extremely obvious at puberty). Consequently, sexual hormones seem to be interrelated in humans (via sexual activation and cognition) with the lateralization process of the brain.    

In addition to the anatomical dichotomy presented (a consequence of the brain lateralization, left versus right), studies show that there is also an informational dichotomy of the brain. This informational dichotomy refers to the existence of two distinct mental domains (Default Mode Network and Task Positive Network), which have separate routes for receiving external information from environment (BJUI). Thus, according to a study based on imagistics (PET and fMRI) which was published in the Journal of Sexual Medicine (Huynh HK et al, High-intensity erotic visual stimuli de-activate the primary visual cortex in women), the highly intense erotic visual stimuli deactivates the primary visual cortex. But this primary visual cortex is actually the first cortical station (the gateway) for external information/ visual stimuli. Consequently, the progression/ ascension of external visual information (from optic nerve to midbrain, to thalamus and further towards the cortex) is blocked. In this situation, it could become evident a question, namely how would be able these visual stimuli to penetrate however towards the cortex and our mind, to become aware? The answer already presented is as follows: the respective visual stimuli ascend towards the cortex through a parallel input route, represented by the ventral-hypothalamic input route (BJUI).     

So, there could be a double dichotomy of the brain (implying also sexuality), the first dichotomy being anatomically (related to the lateralization process of of brain, namely left versus right) and the second being informationally (related to the two distinct domains of the brain, namely Default Mode Network and Task Positive Network, which are two distinct mental domains that inhibit each other not only during activity but also during the resting state).

The current study related to finasteride, as our previous study related to tamoxifen, show the fact that the sexual neuromodulation occurs according to lateralization process of the brain. Interestingly, this lateralization seems to be valid not only for sexual hormones, but also for sexual pheromones. Thus, homosexual men seems to be activated sexually by male sexual pheromone (Savic I et al, Brain response to putative pheromones in homosexual men. Proc Natl Acad Sci USA), while heterosexual men are sexually activated by female hormones (Berglund H et al. Brain response to putative pheromones in lesbian women. Proc Natl Acad Sci USA). Thus, sexual orientation appears to depend on one hand by nature of sexual pheromones (male/ female) and, on the other hand, sexual orientation appears to be also linked to the lateralization process of the brain (Hu SH et al., Patterns of brain activation during visually evoked sexual arousal differ between homosexual and heterosexual men. AJNR Am J Neuroradiol). For these reasons we consider that sexual orientation and sexual hormones are elements that should be also taken into account in the forthcoming studies on sexual topic. 

For the next step our objective is to continue dissemination of the results and contextual interpretation of the data, which means that we will further follow the literature data in respect to administration of finasteride, related to post-finasteride syndrome, and also regarding implications of hormones and pheromones in sexuality.