Introduction
Essentials of female sexual function
According to the World Health Organization, sexual health as a state of physical, emotional, mental, and social well-being in the context of sexuality, excludes the mere absence of disease, dysfunction, or infirmity (1).
Thus a woman's sexual function encompasses many areas; the construct of a normal function as a quality of life indicator often but not always conforms to the sexual response cycle, which is an endogenous process contributed by hormonal, vascular, neuronal, and psycho-emotional factors (2). Clinical and scientific evidence abounds about the physiological role of sex steroids viz. oestrogen, testosterone, and also progesterone in facilitating and maintaining the woman's sexual parameters (3). The neurophysiology extends from the central and peripheral nervous systems to the targeted genital structures resulting in coordinated vascular and non-vascular smooth muscle relaxation, to be accompanied by pelvic vasocongestion, vaginal lubrication, and labial and clitoral engorgement. Any detrimental impact on this normal cycle of concerted responses can result in a functional impairment or ‘female sexual dysfunction' (FSD) (4). Sexual changes, psychogenic or organic, are common in women at any age; such complaints are frequently accompanied by quality-of-life concerns, varying levels of personal distress, anxiety, depression, and also fertility concerns in younger women. To be diagnosed as a dysfunction, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) necessitates experiencing the disorder about 75-100% of the time (with exception for substance or medication-induced dysfunction), for a duration of approximately 6 months and having significant distress (5). With FSD as a medically diagnosable entity, fewer drugs have met the safety and efficacy criteria for global approval and clinical utility; this is in spite of relentless research efforts by pharmaceutical companies (4, 6, 7). That being so, in an obstetrics and gynaecology (OBGYN) setting, sexual health concerns may commonly surface during a personalized service delivery. In order to appreciate the diverse range of FSD and the extent of its physical, physiological, and psychological implications, it is important to understand the fundamentals as well as the changing paradigms in a woman's sexual functioning.The role of hormone status as the major determinant of women's sexual behaviour has been recognized. While the priming and conditioning of the brain to sexual cues is constituted and maintained by sex steroids, oestrogen and testosterone also facilitate an inherent neurochemical milieu conducive for a facilitated sexual response (8). In studies using animal models, oestrogen and progestin coordinated the proceptive and receptive behaviour; however, the mechanism by which testosterone reinforced the women's sexual function, which is otherwise essentially supported by the female hormones, is somewhat complex. Some scientific inferences are that testosterone may favourably help to modulate the peripheral levels of free oestradiol (E2) through its preferential binding to sex hormone-binding globulin (SHBG) and/or increase the central/peripheral E2 levels, which is enabled from its aromatization under the steroid pathway (8, 9).
For the depiction of the progress of sexual events in the female, several models were developed over the years to closely mimic the male sexual response cycle. Nevertheless, the necessary consensus for the transformation of a woman's sexual response is that there is an overriding influence of mind over the body. In the classical representation by Masters and Johnson, which was modified years later by Kaplan, the phases of sexual response progressed from initial excitement and desire, through the plateau and orgasm, to culminate in resolution (10, 11). The recognition of psychological and cognitive factors in the sexual trajectory and the multidimensional nature of the relational factors in women necessitated the inclusion of emotional intimacy into the creation of a circular model (12).
Also, multiple physiological accompaniments are imperative for the individual phases of the sexual response, for instance, excitement and arousal generate vascular engorgement, transudation, and vaginal lubrication, albeit the continued excitement may sometimes follow through the remaining phases without a clear distinction. The emotion-centred intimacy in a partnered relationship also dictates the excitement and arousal required for sexual satisfaction and achievement of orgasmic pleasure (4). Similar to men, the suggested mechanism for sexual receptivity in women also includes inherent inclination determined by the feelings of desire, progressing to arousal and orgasm, even in the absence of adequate physical stimulation (13). For a synchronous and combined response, the areas of brain activation have been documented through investigations using functional magnetic resonance imaging (fMRI) at the time of desire and orgasmic responses. Similarly, genital MRI studies have made it possible to visualize the end-organ changes during the progression of an arousal response (9).In view of the composite nature of a woman's sexual physiology, the desire and/ or arousal leading to sexual satiety is not only specific but also variable at different time points. To understand the diversity of the central, peripheral, and genital modulations in the sexual response, it is important to appreciate the interrelated roles of a complex mechanism incorporating the endocrine and neurovascular inputs with the psycho-emotional controls in the limbic system. It is of note that the neocortex is specifically targeted through the sensory inputs (14). The neurochemicals that are differentially modulated in the process include monoamines (dopamine, norepinephrine (noradrenaline), or serotonin/5-hydroxytryptamine (5-HT)), hormone (oxytocin, vasopressin), and neurotropic factors. In the selective conditioning of the brain towards sexual cues, the neurochemical priming appears to facilitate an excitatory rather than an inhibitory response (15).
Based on the available information, dopamine, norepinephrine, oxytocin, and melanocortin are involved in the central excitatory system while sexual inhibition is under the modulatory control of serotonin, prolactin, and endogenous opioids or endorphins. The consensus on the trophic effect of sex hormones in the genitals is also indirectly established via the impact of changed endocrine milieu during menopause. Likewise, in younger and premenopausal women, variability in the functional states will be in concert with the cyclical changes in sex steroids. Evidence points to the regulatory involvement of neurochemicals and mediators such as nitric oxide, vasoactive intestinal polypeptide, calcitonin gene-r elated peptide, substance P, cytokines, and factors at the cellular and molecular levels. The neural dynamics for these second messenger systems are inherent in the autonomic (adrenergic, cholinergic, and non-adrenergic, non-c holinergic) and somatic innervation; the specific sexual stimuli are relayed through the afferent pathways in the pudendal, pelvic, and hypogastric nerves (16). Broadly, to trace the sequence of events, sexual cues initiate sensory, autonomic, and central nervous system activation leading to a cascade of neuromuscular and vasocongestive responses at the end-organ level, both accentuated blood perfusion and transudation contributing to the vaginal lubrication. In the ensuing mechanism, the parasympathetic innervation (sacral anterior and pelvic nerves) sustains and maintains the blood flow, thereby increasing the volume of ultrafiltrate that percolates through the vaginal epithelial cells to coat the mucosal surface. Also, in the adjacent areas, favourable physio-anatomical changes (labial engorgement, trabecular and clitoral smooth muscle relaxation, and vasoperfusion) serve to reinforce the onset of a proactive genital arousal response. The sympathetic nervous system is activated in the final stages of arousal and orgasm to account for the elevated levels of systemic blood pressure and heart rate in women (15, 16). Studies using fMRI and positron emission tomography are also able to document the role of vagal innervation and activation during the orgasmic response in small clinical samples (17).