The evidence-based conceptualization of women’s sexual response shown in Figure 43.1 emphasizes subjective arousal rather than genital congestion per se. In the past, women’s arousal was equated to vaginal lubrication and vulval swelling (as in the definitions of sexual disorders in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders). More accurately, lubrication is an epiphenomenon. Some lubrication is necessary when intravaginal stimulation is part of a couple’s interaction, but neither lubrication nor genital swelling nor the degree of underlying congestion correlate well with subjective arousal on empirical testing. This has been demonstrated repeatedly during the past 30 years by using a tamponlike device (vaginal photoplethysmograph [VPP]) that measures increases in genital congestion while a woman watches an erotic video and rates her subjective excitement simultaneously with the measures of congestion. Women with chronic complaints of low arousal typically show VPP measures identical to control women while watching erotic videos but report no subjective excitement. Similarly, according to preliminary studies, there is little correlation between increases in clitoral volume, as measured by magnetic resonance imaging (MRI), or ultrasound-measured increases in clitoral blood flow and women’s subjective arousal as they view erotica. Unlike penile erection in men, genital congestion in women does not robustly reinforce their subjective excitement.

Women’s genital congestion appears to be automatic and nonselective. Women (but not men), when watching visual stimuli that were considered by healthy volunteers to be sexual but not erotic or arousing (videos of primates mating), had evidence of genital congestion in response to the stimulus. Both lesbian and heterosexual women show substantial genital response to both preferred and nonpreferred genders depicted in erotic videos. However, men show patterns of responding that correspond to their preferred gender.

Feelings of sexual desire can be triggered by internal cues such as memories of sexual experiences or by external ones such as a romantic environment and are dependent on certain, and as yet not fully understood, biologic mechanisms. Multiple neurotransmitters, peptides, and hormones modulate desire and subjective arousal: noradrenalin, dopamine, melanocortin, oxytocin, and serotonin acting on some serotonin receptors are prosexual, whereas prolactin, serotonin acting on 5-hydroxytryptamine 2 and 3 (5HT2, 5HT3) receptors, glutamate, vasopressin, and gamma-aminobutyric acid (GABA)
are inhibitory. There is complex interplay between the neurotransmitters and peptides and the sex hormones. There also is complex interplay between environmental and neuroendocrine factors. For instance, even in animal models, either dopamine or progesterone can act on receptors in the hypothalamus to cause an increase in sexual behavior in the oophorectomized estrogenized female rat. Of note, however, is that the presence of a male animal in an adjacent cage can cause an identical change in sexual behavior without the administration of either progesterone or dopamine. One corollary in women is that intensity of sexual response can be increased by raising serum testosterone levels in midlife women to those of younger women, by administering a dopaminergic drug such as bupropion, or by beginning a new relationship with a new partner. Animal experiments also demonstrate how the female assesses the context of potential sexual activity, relates it to past experience and therefore to expectation of reward, and adjusts her sexual behavior accordingly. In women, it is known that factors such as attitudes to sex, feelings for the partner, past sexual experiences, duration of relationship, and especially mental and emotional health more strongly modulate desire and arousability than do the biologic factors that have been investigated so far. It should be noted, however, that the data supporting the issues mentioned stem from nationally representative samples of women, not specifically from women with chronic disease, who may make up a large percentage of a gynecologist’s practice. The disease itself and its treatment as well as its psychologic effects can all add to the interpersonal, personal, and contextual issues mentioned that impact on sexual response.

Physical changes of sexual arousal include increases in blood pressure, heart rate, muscle tone, respiratory rate, and temperature in addition to genital swelling, increased vaginal lubrication, breast engorgement, nipple erection, increased skin sensitivity to sexual stimulation, and a characteristic mottling of the skin or “sexual flush” consisting of vasodilation over the face and chest. The response of the autonomic nervous system increasing blood flow to the vagina occurs within seconds of a visual sexual stimulus. There is increase in blood flow through the arterioles supplying the submucosal vaginal plexus, which increases the transudation of interstitial fluid from the capillaries across the epithelium and into the vaginal lumen. This rapid transit alters the electrolyte composition such that there is less potassium and more sodium than in the lubrication fluid in the unaroused state. There also is relaxation of smooth muscle cells around the blood spaces or sinusoids in the clitoral tissue. The latter includes the rami, shaft, and head of the clitoris as well as the extensions of clitoral tissue known as vestibular bulbs. As the clitoris becomes more swollen, the shaft elevates to lie near the symphysis pubis. The inner two thirds of the vagina lengthen and extend, elevating the uterus. It has been hypothesized that during intercourse, penile thrusting on the cervix might cause reflex contraction of the pelvic muscles, thereby facilitating the “ballooning” of the upper vagina, while the same muscle contraction constricts the lower vagina. This is described as a “cervical motor reflex,” whereby touch to the cervix reduces pressure in the upper portion of the vagina and increases pressure in the middle and lower portions with documented increased electromyographic activity in the levator ani. It is possible that the elevation of the uterus for sexual arousal is in part due to a further recently described reflex. Reduced uterine tone has been demonstrated in response to mechanical or electrical stimulation of the clitoris. It was apparent that clitoral stimulation abolished the background tonic uterine muscle contraction, such that uterine pressure declined. External changes include swelling and darkening of the labia minora. The increased congestion of the introitus actually narrows its diameter.

Neurotransmission of genital congestion is incompletely understood. Far more studies have been done to clarify male genital sexual physiology than female. The major neurotransmitter involved in clitoral engorgement is nitric oxide (NO), which is released from parasympathetic nerves along with vasointestinal polypeptide (VIP). Simultaneously, acetylcholine (Ach), which blocks noradrenergic vasoconstriction and promotes NO release from the endothelium, is released. Somatic, sympathetic, and parasympathetic nerve pathways are far less separate from each other than was formerly believed. There is documented communication between the NO containing cavernous nerve to the clitoris and the distal portion of the somatic dorsal nerve of the clitoris from the pudendal nerve. Recent work shows that input from the ganglia of the caudal sympathetic chain containing noradrenalin and perhaps neuropeptide Y produces, as one would expect, vasoconstriction by the way of α-adrenergic and peptidergic receptors. On the other hand, input from the hypogastric nerve (sympathetic) passing through ganglionic relay stations in the pelvic plexus can produce vasodilation and vulval congestion as well as the opposite. Of note is that an increase in sympathetic tone brought on by exercise, hyperventilation, or experimental ephedrine administration increases the physiologic arousal response of genital congestion. Similarly, in sexually functional women, the prior viewing of visual triggers that provoke anxiety increases the physiologic genital arousal response to subsequent erotic visual cues.

The clitoris is the most sexually sensitive structure, but there is little research into the transmission of sexual sensation. Recent immunohistologic studies have confirmed neurotransmitters thought to be associated with sexual sensations (substance P and calcitonin gene-related peptide [CGRP]), concentrated directly under the epithelium of the glans. It is important to note that clitoral stimulation is usually enjoyable only if nonphysical and nongenital physical stimulation have previously occurred. Without
existing arousal, direct stimulation can be unpleasant, too intense, and even painful.

The physiology of orgasm remains unclear. Definitions are not established but include “a psychic phenomenon, a sensation (cerebral, neuronal discharge) elicited by the accumulative effect on certain brain structures of appropriate stimuli originating in the peripheral erogenous zones” or “the acme of sexual pleasure of rhythmic contraction of perineal/reproductive organs, cardiovascular, and respiratory changes, release of sexual tension.” Given that men and women with complete spinal cord injury can experience orgasm, it currently is considered that orgasm primarily is a cerebral event. Recent positron emission tomography (PET) has shown women’s orgasm to be mainly associated with profound decreases of cerebral blood flow in the neurocortex compared with control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus, and anterior temporal lobe. Measuring extracerebral markers of orgasm, such as rectal pressure variability, showed significant positive correlations between the rectal pressure variability and cerebral blood flow in the left deep cerebellar nuclei. Thus, it currently is proposed that decreased blood flow in the left lateral orbitofrontal cortex signifies removal of behavioral inhibition during orgasm and that deactivation of the temporal lobe is directly related to high sexual arousal. The deep cerebellar nuclei may be involved in motor activity—the orgasm-specific muscle contractions, but as well the cerebellum is now known to be involved in emotions and integrating sensory information. It also is possible that involvement of the ventral midbrain and right caudate nucleus is indicative of a role for dopamine in female sexual arousal and orgasm. The cerebral changes lead to reduction of inhibitory serotonergic tone from the nucleus paragigantocellularis to the so-called orgasm center in the lumbosacral cord.

The sexual stimulus eliciting orgasm may be to the genitalia but also may be to the breasts and nipples or from sexual fantasy or sexual dreams. Women with complete spinal cord injury above spinal cord level T10 can have orgasms from vibrostimulation of the cervix, possibly mediated by branches of the vagus nerve. Damage to the pelvic autonomic plexuses from radical hysterectomy, for instance, does not preclude orgasm. The necessary autonomic nerves probably travel with somatic fibers S2, S3, and S4. Branches from the sympathetic ganglia to the union of S2, S3, and S4 parasympathetic and somatic fibers proximal to the superior hypogastric plexus have been identified. Despite clinical impressions to the contrary, weakening of the pelvic floor from vaginal deliveries has not been scientifically proven to correlate with sexual dysfunction. In keeping with the known physiology of orgasm, the most common drugs that impede orgasm are the selective serotonin reuptake inhibitors (SSRIs).

Uterine contractions accompany orgasm, and a subset of women report altered orgasms after hysterectomy. The contractions of the pelvic floor muscles around the vagina during orgasm are variably perceived by women, and studies show the rhythmic contractions extend over many more seconds than the period of time during which women can feel their occurrence.

There is little study of the neuropharmacology of the later stages in sexual response. The body gradually returns to its baseline state, and genital vasocongestion reverses. Any functional role of oxytocin or prolactin has yet to be established in humans. Increases in oxytocin with arousal have been inconsistently reported, and the more consistently reported increases in prolactin after orgasm have not been shown to have functional implications.

An unknown proportion of women report that massaging the anterior vaginal wall approximately one third of the way up from the introitus causes increasingly intense sexual pleasure, arousal and may lead to orgasm. It currently is thought that it is the massaging of the periurethral erectile tissue (the equivalent of the corpus spongiosum around the male urethra in the penis) that underlies this phenomenon. There is no anatomical evidence of any structure to correspond to a specific “spot.”

A number of factors have been shown to correlate with women’s sexual function and satisfaction, the most robust correlations being with mental health, the sexual relationship, and partner sexual function.