Chad P. Hubsher, MD
■ Adam Luchey, MD
■ Stanley Zaslau, MD, MBA, FACS
■ Sexual function in women is a highly variable, multifaceted process involving several components:
■ Given the complex nature of sexuality in females, little consensus currently exists on the definition of a “normal sexual response.”
■ Although aspects of female sexual function, such as vaginal lubrication and orgasmic contractions, seem to be widespread in normal, sexually functioning women, the subjective or emotional aspects are highly individual. These aspects are subject to learning and cultural factors, as past experiences play an important role in shaping expectations regarding sexual response in women.
■ Female Sexual Response Cycle
■ Over the past 45 years, several models have been proposed to aid in the understanding of the female sexual response cycle.
■ These models provide a conceptual framework of the sequence of physiological events and psychological processes that comprise normal sexual response for most
women. However, to date, none of the proposed female sexual response models have been shown to be universally applicable.
The Masters and Johnson (Four-Stage) Model
■ Masters and Johnson first characterized the female sexual response cycle in 1966 based on laboratory observations of approximately 700 men and women.1
■ They proposed a model of female sexual response consisting of four successive phases, each of which has associated genital and extragenital responses (Figure 7.1):
The Three-Stage Model
■ In 1974, Kaplan proposed a three-stage model that acknowledged the importance of subjective, psychological, and interpersonal aspects of sexual response.2
■ In this model, the sexual response cycle was reconceptualized to consist of three essential phases:
■ This three-stage model was used in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as the basis for the classification of female sexual dysfunction. It was also used in the American Foundation of Urologic Disease’s 1998 reclassification per their first international consensus development panel on female sexual dysfunction.3
■ Female Sexual Anatomy
■ In order to adequately understand female sexual function, it is necessary to have a formal understanding of the female pelvic anatomy.
Figure 7.1 The Masters and Johnson Model
Source: Adapted from Masters WH & Johnson VE. Human Sexual Response. Boston, MA: Little Brown & Co.; 1966.
■ The organs and structures can be grouped into external and internal genitalia.
• The external genitalia, collectively known as the vulva, consist of:
■ The labial formation
■ Interlabial space
■ Erectile tissues, including the clitoris and vestibular bulbs
• They are bound anteriorly by the pubic symphysis, laterally by the ischial tuberosities, and posteriorly by the anal sphincter.
• The internal genitalia consist of the:
■ Fallopian tubes
■ Pelvic floor muscles
■ The labial formation is designed to provide protection to the urethral and vaginal orifices, both of which open into the vestibule of the vagina.
■ It consists of two pairs of symmetrically folded skin; the outer folds, known as the labia majora, fuse with each other anteriorly at the anterior labial commissure, while the inner folds, known as the labia minora, are continuous with the vaginal mucosa and fuse together to form the prepuce of the clitoris anteriorly, and the frenulum posteriorly.
■ The labia majora are composed of subcutaneous fat and covered by hair-bearing skin, while the labia minora are covered by hairless skin and are composed of a fat- free spongy tissue punctuated by sebaceous and sweat glands along with many blood vessels and sensory nerve endings.
■ The labial formation is innervated by the perineal and posterior labial branches of the pudendal nerve. The arterial blood supply is derived from the inferior perineal and posterior labial branches of the pudendal artery, as well as superficial branches of the femoral artery.
■ The area medial to the labia minora, bound anteriorly by the clitoris and posteriorly by the frenulum, is known as the interlabial space.
■ The urethral orifice, vaginal orifice, and greater vestibular gland, also known as Bartholin glands, all open into this space.
• The greater vestibular glands are located in the superficial perineal pouch, underneath the bulbs of the vestibule, and secrete a small amount of lubricating mucus into the vestibule of the vagina during sexual arousal.
■ The clitoris is an erectile organ similar to the penis that arises from the same embryological structure, the genital tubercle.
■ It is cylindrical in shape, located posterior to the anterior labial commissure, and composed of three parts:
• The outermost glans or head
• The middle corpus or body
• The innermost crura
■ The glans clitoris is often hidden by the labial formations when nonengorged, but may be visualized as it emerges from the labia minora.
■ The body of the clitoris extends beneath the skin and gives rise to bilateral crura, called corpora cavernosa, which, similar to the penis, are composed of erectile tissue and separated by a septum.
■ The paired crura of the clitoris are homologous to the male corpora and are comprised of:
• Lacunar sinusoids
• A trabecula of vascular smooth muscle
• A collagen connective tissue surrounded by a thick fibrous sheath known as the tunica albuginea
■ Unlike the bilaminar structure found in the penis, the tunica albuginea in the clitoris is unilaminar. There is thus no mechanism for venous trapping in the clitoris and as a result, sexual stimulation produces clitoral engorgement, not erection, as is seen in the penis.
■ During sexual stimulation, blood flow to the clitoris almost doubles, resulting in an increase in length and diameter, as was demonstrated by Park and colleagues using duplex ultrasounds.4
■ The iliohypogastric arterial bed is the main arterial supply to the clitoris. The internal iliac artery traverses the pudendal canal (Alcock’s canal), after it gives off its last anterior branch, the internal pudendal artery.
• The internal iliac then terminates as the common clitoral artery, which gives off the dorsal clitoral artery and clitoral cavernosal arteries.
• It is these arteries that are responsible for engorgement of the corporeal bodies upon sexual stimulation and arousal.
■ The nerve endings located in the clitoris are comprised of autonomic and somatic innervation.
• The autonomic innervation of the clitoris is formed by the pelvic and hypogastric plexuses. These plexuses carry sympathetic (T1-L3) and parasympathetic (S2- S4) fibers that join together at the base of the broad ligament, on each side of the supravaginal part of the cervix, to form the uterovaginal plexus and send direct fibers to both the clitoris and vagina.
• Somatic sensory innervation of the clitoris arises in the skin and travels to the sacral spinal cord via the dorsal nerve of the clitoris and pudendal nerve.
■ Within the clitoris there is a dense collection of Pacinian corpuscles, Meissner’s corpuscles, and Merkel tactile disks, which are responsible for transmitting information to the brain concerning pain and pressure, light touch, and texture, respectively.
■ The other erectile tissues of the female genitalia are the vestibular bulbs.
■ These are 3-cm-long paired structures that lie beneath the skin of the labia minora, directly along the sides of the vaginal orifices.
■ They are homologous to the corpus spongiosum of the penis. However, unlike the penis, the vestibular bulbs are separated from the clitoris, urethra, and vestibule of the vagina.
■ The recent cadaver dissections of O’Connell and associates revealed that the bulbs lie on the superficial aspect of the vaginal wall, not forming the core of the labia minora. They also discovered that there are considerable age-related variations in the dimensions of the vestibular bulbs in young, premenopausal women versus older, postmenopausal women.5
■ The vagina is a midline cylindrical organ that is approximately 7—9 cm in length.
■ It extends from the cervix of the uterus to the vestibule of the vagina, and its walls are composed of four layers:
• An inner mucosal layer
■ The inner vaginal mucosa is a stratified squamous nonkeratinized mucus type epithelium that undergoes hormone-related cyclical changes during the menstrual cycle in which a slight keratinization of the superficial cells occurs.
• A lamina propia
■ The lamina propia separates the mucosal layer and the muscularis.
• A muscularis layer
■ The vaginal muscularis is composed of outer longitudinal and inner smooth muscle cell fibers, as well as an extensive tree of blood vessels.
• An outer adventitial supportive mesh layer
■ The surrounding outermost fibrous layer is rich in collagen, and provides structural support to the vagina. It is this outermost layer that is responsible for expansion of the vagina during childbirth and intercourse.
■ During sexual arousal, there is increased blood flow to the subepithelial blood vessels, resulting in genital vasocon- gestion and subsequent engorgement of the vaginal wall.
■ According to Levin, the increase in pressure inside the subepithelial vascular bed results in passive transudation of plasma through the vaginal epithelium.6 Along with secretions from the uterine glands, this helps lubricate the vaginal canal.
• Initially, as the vaginal lubricative plasma flows onto the surface of the vagina, sweatlike droplets form. These eventually coalesce to create a lubricative film covering the vaginal wall.
• Further moistening during sexual arousal originates from secretions of the greater vestibular glands located in the interlabial space.
■ The nerve endings located in the vagina are comprised of autonomic and somatic innervation.
• The uterovaginal nerves, which originate from the hypogastric and sacral plexuses, contain both parasympathetic and sympathetic fibers, and supply autonomic innervation to the proximal two-thirds of the vagina, as well as the corporeal bodies of the clitoris.
• The uterovaginal nerve fibers, which travel within the uterosacral and cardinal ligaments before reaching the vagina, play a major role in sexual function, and thus serve as a potential site of injury and resultant sexual dysfunction from female pelvic surgery.
• The somatic sensory innervation of the vagina is primarily provided by the pudendal nerve.
■ The arterial supply to the vagina varies by location. Vaginal branches of the uterine artery supply the superior aspect of the vagina, the hypogastric artery supplies the middle vagina, and branches of the middle hemorrhoidal and clitoral arteries supply the distal aspect of the vagina.
■ The uterus is a midline, mobile organ located between the rectum and urinary bladder that connects with the proximal aspect of the vaginal canal via the cervical os.
■ During sexual arousal, uterine and cervical glands secrete mucus to help lubricate the vaginal canal.
■ Surgical menopause, brought on by hysterectomy with oophorectomy, significantly impacts sexual function.
• Furthermore, as described by Carlson, hysterectomy alone, without removal of the ovaries, can also result
in sexual dysfunction postoperatively.7 Removal of the uterus disrupts the pelvic autonomic and cervical plexus, as well as the uterosacral and cardinal ligaments and the associated autonomic fibers. As previously discussed, this disturbs innervation to the vagina and clitoris, resulting in alteration in sexual function.
Pelvic Floor Muscles
■ The pelvic floor is a collection of tissues that span the opening within the bony pelvis and function to:
• Support the abdominal and pelvic organs
• Maintain continence of urine and stool
• Allow for parturition and intercourse
■ Pelvic support is primarily provided by the levator ani muscles, urogenital diaphragm, and the perineal membrane, which consists of the ischiocavernosus, bulbocav- ernosus, and superficial transverse perineal muscles.
• Voluntary contraction of the perineal membrane plays a role in sexual response by intensifying orgasm of both the female and male partner.
■ The pelvic floor muscles can also cause sexual dysfunction.
• At times, nonvoluntary pelvic floor spasms are associated with vaginal penetration.
• Laxity and hypotonia of the pelvic floor result in symptoms of vaginal anesthesia, coital anorgasmia, and incontinence during intercourse or orgasm.
• Women with pelvic floor disorders often present with coexisting urological and sexual complaints.
■ Female Sexual Response
■ The female sexual response cycle, described earlier, is initiated by neurotransmitter-mediated vascular and nonvascular smooth muscle relaxation. The result is:
• Increased pelvic blood flow
• Vaginal lubrication
• Clitoral and labial engorgement
■ These mechanisms are mediated by a combination of neuromuscular and vasocongestive events that are under neurogenic and hormonal regulation.
■ Physiology of Sexual Arousal
■ Sexual arousal in the female is associated with a variety of changes in the female sexual anatomy.
■ The increase in pelvic blood flow via the iliohypogastric arterial bed, and simultaneous relaxation of the vaginal wall and clitoral cavernosal smooth muscle, is responsible for the observed engorgement of the labia minora, vagina, and clitoris during sexual arousal.
• In the labia minora, the increase in blood flow, especially to the vestibular bulbs that lie directly beneath the skin of the labia, result in a two- to threefold increase in diameter of the labia, along with eversion and exposure of its inner surface.
• In the vagina, the infiltration of blood in the extensive vasculature of the muscularis layer leads to vaginal wall engorgement and a concomitant expansion of the outermost fibrous layer to allow continued structural support of the vaginal canal.
• Via the clitoral cavernosal arteries, the clitoris also experiences an enhancement blood flow during sexual arousal. The resultant increase in intracavernous pressure leads to extrusion and tumescence of the glans clitoris, unlike the rigidity as seen in the male penis.
■ Goldstein and Berman reported that unlike the penis, the clitoris lacks a subalbugineal layer between the tunica albuginea and erectile tissue.8
■ The subalbugineal layer in the male contains a rich venous plexus, and with sexual arousal, will expand against the tunica albuginea, causing a reduction in venous outflow and inducing rigidity in the penis.
■ Consequently, the absence of this venous plexus and subalbugineal layer in the clitoris allows only tumescence to be obtained.
■ Increased lubrication of the vaginal canal during sexual arousal is achieved primarily via two mechanisms: transudate originating from the subepithelial vascular bed and secretions from uterine glands.
• As previously described, vaginal engorgement enables a process of plasma transudation to occur, in which increased pressure within the blood vessel helps transudate to form and plasma to flow through the epithelium and eventually create a lubricative film that covers the vaginal wall.
• Additional vaginal canal moistening during sexual arousal comes from secretions of the greater vestibular glands (Bartholin’s glands).
• Furthermore, as reported by Toesca and colleagues, these secretions may also serve as a mechanism to attract the male sex by emitting fluid that is odiferous.9
■ Which and how neurotransmitters modulate vaginal and clitoral smooth muscle tone are currently being investigated.
■ Recently, Burnett and colleagues and Hilliges and colleagues identified nitrous oxide (NO) and phosphodiesterase type 5 (PDE-5) in both clitoral and cavernosal smooth muscle.10,11
• PDE-5 is the enzyme responsible for the degradation of cGMP, as well as formation of NO.
• These neurotransmitters may serve as a potential therapeutic site for sexual dysfunction.
■ Vemulapalli and Kurowski determined that sildenafil, a specific PDE-5 inhibitor, causes dose- dependent relaxation of female rabbit clitoral and vaginal smooth muscle in organ bath studies.12
■ Park and associates suggest that NO, in combination with vasoactive intestinal peptide (VIP), are involved in regulation of vaginal secretory processes and relaxation.13
• VIP is a nonadrenergic, noncholinergic neurotransmitter that has been described by Levin to enhance vaginal blood flow, lubrication, and secretions.14
• Similar to the aforementioned studies performed with PDE-5, Ziessen and colleagues determined that VIP causes dose-dependent relaxation of rabbit clitoral cavernosum and vaginal smooth muscle in organ bath studies.15
■ Thus, in addition to NO and PDE-5, there may be a role of endogenous VIP as a neurotransmitter in clitoral and vaginal tissue and a mediator of female sexual response.
■ Female sexual function is greatly affected by the levels of hormones in the body, specifically estrogen and testosterone.
■ As was demonstrated by Natoin and associates, estrogens have vasoprotective and vasodilatory effects that increase arterial blood flow to the vagina, clitoris, and urethra.16
• This prevents atherosclerotic compromise to the iliohypogastric arterial bed and thus helps maintain the female sexual response.
■ Sarrel found that a decline in circulating estrogen levels, either due to aging or surgical castration, results in increased vaginal wall fibrosis caused by decreased vaginal NO levels.17 This is because estrogen regulates nitric oxide synthase (NOS), the enzyme responsible for production of NO.
■ Furthermore, it has been demonstrated that estrogen replacement therapy:
• Increases vaginal NOS expression and NO levels
• Restores vaginal mucosa
• Decreases vaginal mucosal cell death
■ In addition to having a significant role in preserving vaginal mucosa, estrogen is important in the maintenance and function of the vaginal epithelium and smooth muscle cells of the muscularis, and in lubrication of the vaginal canal.
■ In fact, in animal studies performed by Berman and colleagues, a decline in the level of estrogen results in a less acidic vaginal environment and thinner and drier vaginal walls that damage more easily.18
• These results likely correlate with complaints of female sexual dysfunction, including vaginal dryness and dyspa- reunia, often seen in women with a decline in circulating estrogen levels observed during aging and menopause.
■ Similar to estrogen, testosterone also has a significant effect on female sexual function; however, the role of androgens remains controversial, as little is understood about their exact mechanism.
■ Nonetheless, low levels of testosterone are associated with a decrease in:
• Sexual arousal
• Sexual responsiveness
• Genital sensation
■ In a study by Sherwin and Gelfand, menopausal women responded better to estrogen-androgen combinations compared to estrogen alone on measures of enhanced sexual desire, sexual arousal, enjoyment of sex, and number of orgasms.19
■ In a study by Shifren and associates of women with hypothalamic amenorrhea, testosterone increased vaginal vasocongestion, as measured by plethysmography during exposure to a potent visual stimulus.20
■ While pharmacological doses of testosterone have been shown to improve overall female sexual function, it is not known whether physiological testosterone replacement will produce clinically meaningful changes.
■ Additionally, all androgens carry the risk of inducing virilization in women. Early reversible manifestations include acne, hirsutism, and menstrual irregularities, while longterm side effects are often irreversible, including male- pattern baldness, hypertrophy of the clitoris, and voice changes.
■ Although there are significant anatomical, embryological, and physiological parallels between men and women, it is important to have a clear understanding of the differences.
■ The multifaceted nature of female sexuality further contributes to the complexity in differentiating a normal sexual response from female sexual dysfunction.
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