Yoram Vardi, Uri Gedalia, Ilan Gruenwald
Neurologic disorders, such as multiple sclerosis, peripheral neuropathy, and lumbar radiculopathy, are major and frequent potential etiologies of female sexual dysfunction (see Chapters 16.5 and 16.6 of this book). Nevertheless, female sexual dysfunction due to neurologic causes has been poorly explored. Clearly, the integrity of the genital innervations plays a significant role in the sexual cycle, and any damage to the somatic or autonomic neural system may affect the normal sexual response (see Chapters 4.1—4.4 and 5.3). In the female, even more than the male counterpart, intact genital sensation is a major component in this process.
Therefore, the need for quantitative measurement of the neural function of the female genitalia, specifically sensory function, has become obvious (see Chapter 10.6). In suspected neurologic disorders, vibratory, thermal, or painful stimuli are often used for quantification of sensation because they provide information on the neuroanatomic pathways with their discrete fiber types.1 We have implemented this neurophysiologic technique, using quantitative sensory testing (QST) to study sensation in the female genital organs, and have established a set of age-corrected normal threshold values of vibratory and thermal sensations. Moreover, we were able to show that in neuropathic female patients, quantitative sensory testing could identify abnormal sensory states with high specificity, and could aid in diagnosis of neurogenic female sexual dysfunction.2
In this chapter, we will describe this diagnostic test and its role in the evaluation armamentarium for women’s sexual disorders.
Fibers innervating the genitalia
It is assumed that any neural lesion, central or peripheral, that causes female sexual dysfunction should have sensory deficit as its mainstay. The important role of the sensory neural pathways is anatomically expressed by the rich innervation of the external genitalia, mainly at the clitoral level.
These afferents include three principal fiber subtypes, the first of which is the large (and fastest conducting), peripheral A- beta myelinated fibers, responsible for conveying sensations of touch, mild pressure, and vibration. These fibers most probably have a major role in normal sexual function, since vibratory stimuli are known to evoke an intense sexual excitatory response. Their dysfunction could potentially affect some of the sensory input, and could hinder the natural progression of the sexual cycle. On the other hand, the small-fiber system mediates modalities of temperature and pain. This fiber system is composed of small, A-delta myelinated fibers that mediate cold sensation and initial pain, and of smaller, C-unmyelinated fibers (slowest) that mediate warm and major pain sensation. In sexual dysfunction, these sensations probably are of secondary importance. However, the true value of performing a test to evaluate these small fibers in the female genitalia lies in their structural and functional similarity to the autonomic nerve fibers (which are also small C-nerve fibers). Therefore, pathologic results in thermal testing may indirectly suggest dysfunction of the autonomic fibers. As a result, quantitative sensory testing may help to detect autonomic nerve fiber damage in neurologic disorders such as diabetic neu- ropathy3 or multiple sclerosis.4,5 These data are crucial, as, until now, there was no direct test that could provide such quantitative information on autonomic nerve function, rendering this test the closest one available to autonomic evaluation.
Quantitative sensory testing
Quantitative sensory testing is a common test used in neurophysiologic laboratories to assess sensory function in neurologic disorders (as in pain disorders, peripheral neuropathies, toxic neuropathies, uremic neuropathy, and legal proceedings).1 Only during the last few years was it adapted and applied to the evaluation of sensory function in the female genitalia. This test, in essence, is based on the administration of quantified stimuli (such as temperature or vibration) in a controlled manner. The subject determines the sensation threshold either verbally or by electronic means (i.e., pressing a button). The collected data are compared with a normal set of threshold values to determine whether sensory hyper- or hypo-sensitivity is present.
The only apparatus available today that has specially designed probes for the quantitative measurement of sensation of the female genitalia is the Thermal/Vibratory Sensory Analyzer system (TSA-3000 and VSA-3000; Medoc, Israel) for the vaginal and clitoral region. The apparatus includes an adjustable arm with appropriate probe holders, in order to ensure steady and constant contact with the stimulated region. The adjustable probe-holder provides user-defined control of the pressure applied (Fig. 10.5.1). There are two special probes; each is anatomically designed for use at the vagina and clitoris, one for vibratory and the other for thermal stimulation. Both share the same basic cylindric design; the large part of the probe is for the vaginal region, whereas the distal end is used for the clitoris and is shaped like a thick button. This design reduces the need for multiple repositioning of the probes and is thus beneficial for the patient, avoiding unnecessary discomfort.
The thermal probe (Fig. 10.5.2)
The vaginal part of the probe has its metal contact element on the outside, cylindric surface, and is 28 mm in diameter and 125 mm in length. The thermal element has an active cooling/ heating area of 16 x 32 mm. The distal clitoral part (“button”) is smaller, measuring 25-mm diameter with a thermal contact element on the outer end.
This probe has a working temperature range of 0-50°C at both thermal surfaces.
The vibration probe (Fig. 10.5.3)
The vaginal part of the probe is 24 mm in diameter and 100 mm in length. The distal clitoral part is 10 mm in diameter and 5 mm in length. The vibratory probe is smaller in order to compensate for the vibration amplitude. Both parts vibrate throughout and do not have a particular point for surface contact. For both vaginal and clitoral components, the vibration frequency is fixed at 100 Hz, with an amplitude range of 0-130 gm.
Because this test is of subjective nature, the patient needs to be acquainted with the procedure. For this purpose, it is important to instruct the patient properly, and to familiarize her with the type of stimuli administered. This is achieved by first applying the stimuli to the patient’s hand.
Figure 10.5.1. Thermal/Vibratory Sensory Analyzer system (courtesy of Medoc Ltd, Israel).
The test starts with the subject lying down comfortably in the supine position. Either thermal or vibratory stimuli may be administered first; the order is of no particular importance. The thermal probe is inserted to the point where the thermode makes contact with one of the distal vaginal walls. The test can be performed on either anterior or posterior, or both vaginal walls.6 Thermal stimulus is increased/decreased gradually (for warm and cold, respectively). This is repeated four times; each time the subject indicates the onset of the perceived sensation by pressing a button. By doing so, the individual’s threshold limit to the specific sensory stimulus is defined and automatically recorded (method of limits). An average of the four recorded measurements is calculated in order to establish the mean threshold.
Figure 10.5.2. The thermal probe.
Figure 10.5.3. The vibration probe.
When the vaginal vibration probe is used, it is inserted to its full length into the vagina, without pressure on the vaginal walls. The patient is requested to report when she is comfortable with the probe in place. The adjustable holder is then locked and the probe remains set in place. Stimulation and measurements take place at this stage. The same stimuli are then given to the clitoral region by the designed probes. In general, positioning of the clitoral probe is trickier and requires a certain amount of experience.
Like any other sensory measuring test, the quantitative sensory testing is not fully objective, as it is dependent on the patients’ subjective feeling and individual reaction time until pressing the button.8 Although this method is often criticized, results are consistently repeatable and therefore can be used as a valid tool to evaluate the sensory state of the genital area in the female.9'10
Interpreting the test results
After the average threshold of each stimulus is obtained, it is plotted on the available normogram. Figure 10.5.4 depicts the age-corrected normograms for vibratory and thermal sensory thresholds at the clitoral and vaginal levels, for the upper, lower, and normal thresholds.6 As evident in this figure, the validity of the quantitative sensory testing is further strengthened by the fact that the age dependency of the genital vibratory threshold is very similar to its age dependency for the skin in the limbs.7 The smaller age effect found in the clitoris may be due to the relatively rich innervation of this organ. The normograms were constructed taking into account (log) coefficients of repeatability (r) as part of the analysis in order to minimize the unavoidable inaccuracies.
Vibration thresholds detected with quantitative sensory testing represent the function of the large, myelinated A-beta sensory fibers and their central connections. These thresholds have a better repeatability profile than the other modalities, indicating higher sensitivity and specificity in diagnosing dysfunction. In fact, preliminary data showed that vibratory threshold is the most sensitive parameter in identifying neurologic deficit in patients with female sexual dysfunction caused by peripheral neuropathies or radiculopathies.6
Figure 10.5.4. Age-corrected nomograms for vibratory and thermal sensory thresholds at the clitoral and vaginal levels, showing upper, lower and normal thresholds.
The role of sensory testing in the evaluation of a suspected neurologic etiology in women with sexual dysfunction
We suggest that genital sensory testing should be included in the evaluation of the female patient whenever a neurologic etiology is suspected (see diagnostic algorithm in Fig. 10.5.5). This should be based mainly on the patient’s history and physical examination. Quantitative sensory testing may also be of value in cases where the basic neurologic assessment is inconclusive, insufficient, or contradictory; whenever vascular or endocrine evaluations are unconvincing, there is need for more objective, quantitative data on the sensory status of the external genital region. The neurogenic origin should always be sought, as it may point to disorders that could be treated and cured (surgery for lumbosacral disk herniation, surgical release of pudendal nerve entrapment, etc.) (see Chapters 10.6, 16.5, and 16.6).
Apart from its use in the etiologic evaluation, quantitative sensory testing may have other applications for female sexual disorder. In medicolegal cases, this method can be used as part of the total assessment of patients suffering from sexual dysfunction after an accident/trauma, or from iatrogenic causes. This tool can be used to assess the initial damage caused, and can also be used to monitor recovery or deterioration. Munarriz et al. published a study on 13 women with a history of blunt perineal trauma and associated sexual dysfunction (mainly orgasmic disorders and clitoral pain). This study had also shown abnormal genital sensory testing in all subjects,11 suggesting a neurogenic etiology of sexual dysfunction.
Another potential and important clinical role for quantitative sensory testing is objective patient follow-up. Specifically, it could be used in the quantitative evaluation of pain in females with vestibulitis. Baseline pain could be quantified and progress of treatment could be monitored.12
Figure 10.5.5. Diagnostic algorithm for suspected neurologic eliology in women with sexual dysfunction. QST = quantitative sensory testing; FSD = female sexual dysfunction.
In research, quantitative sensory testing can be used to assess pre- and post-surgical genital sensory status in patients undergoing surgery, mainly pelvic procedures (i.e. hysterectomy) and vaginal deliveries. Our group has also found significant abnormal genital quantitative sensory testing findings in 41 females 3 months after undergoing hysterectomy.13
We finally have a reliable research tool that can be used to assess possible side effects of new future medications suspected of influencing the sensation of the external genitalia. For pharmaceutics, there is no doubt that this test will be of importance in assessing the efficacy of new drugs and other therapeutic options for female sexual dysfunction as they emerge. The feasibility, efficiency, and cost-effectiveness of the potential applications are yet to be demonstrated, and more studies are needed to provide sufficient data on the maximal role of quantitative sensory testing in the clinical set-up and in research of female sexual dysfunction.
The plethora of scientific studies and research in the field of female sexual dysfunction in recent years has already provided substantial theoretic and clinical knowledge. Nevertheless, our knowledge remains very limited, as this field is only in its infancy. We have yet to reach the point where the treatment solution for sexual dysfunction in women is as effective as it is for men. To achieve this goal, we need effective, validated diagnostic tools for evaluating female patients, such as quantitative sensory testing. Clinically, genital sensation deficits are probably responsible for a considerable number of the female sexual dysfunction cases. Since female sexual dysfunction with neurogenic etiology is probably more common in women than in men, and probably more significant, quantitative sensory testing can be an effective way of assessing neural deficit and the extent of the disease process. Only in the years to come will we be able to appreciate fully the contribution of this and other solid and reliable diagnostic tools to the scientific advancement of this field.
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