Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Blood flow: duplex Doppler ultrasound

Sandra Garcia Nader, Scott R Maitland, Ricardo Munarriz, Irwin Goldstein

Introduction

The biologic evaluation of women with sexual health problems involves an assessment of the integrity of multiple systems contributing to physiologic sexual function, including endocrino- logic, neurologic, and vascular factors1 (see Chapters 10.1, 10.2, and 10.4-10.7 of this book). Concerning genital hemodynamic physiology in women, sexual arousal is dependent on the structural and functional integrity of tissue, primarily of vascular and nonvascular smooth muscle as well as arterioles, and involves complex neurovascular processes modulated by various local neurotransmitters, vasoactive agents, sex steroid hormones, and growth factors2 (see Chapters 5.1-5.6). The increased pelvic blood flow through the ilio-hypogastric-pudendal arterial bed leads to increased perfusion of the sexual organs, specifically the vagina, clitoris, and labia (see Chapters 4.1—4.3). The resultant increase in blood flow leads to increased engorgement of the clitoral, labial, and vaginal erectile tissues; increased diameter of the clitoral corpora cavernosa and the labial corpora spon- giosa (vestibular bulb erectile tissue); and increased diameter and length of the vagina.2,3

Vasculogenic female sexual dysfunction

Animal model data indicate that arterial occlusive pathology in the ilio-hypogastric-pudendal arterial bed is associated with impaired sexual (pelvic nerve stimulation) arousal response.3-7 The altered sexual response includes diminished arterial inflow, diminished lubrication, decreased vaginal wall pressures, decreased vaginal length and width changes, and increased intraluminal pressures compared to control animals. Park et al. reported in the animal model that atherosclerosis of the hypogastric-vaginal-clitoral arterial bed was associated with marked impairment in pelvic nerve-mediated changes in genital blood flow.6 These findings were associated with caver nosal artery atherosclerotic changes, loss of corporal smooth muscle, and increase in corporal connective tissue in atherosclerotic compared with control animals. It was concluded that vaginal and clitoral engorgement depend on increased blood inflow and that atherosclerosis is associated with vaginal and clitoral engorgement insufficiency. This and other studies have suggested that at least some cases of female sexual arousal dysfunction might be associated with arterial vascular insufficiency3-7 (see Chapter 5.6).

Selective internal iliac arteriography of women with peripheral vascular disease and claudication reveals that there is significant arterial occlusive disease in the pudendal and caver- nosal arteries. An unpublished pilot study at our center reviewed pelvic arteriographic studies performed in women who presented with claudication and peripheral vascular disease symptoms. Twenty-seven per cent of the women had severe or completely occluded internal pudendal arteries, 23% had severe or complete occlusion of the hypogastric arteries, and 9% had severe or complete occlusion of the common iliacs. It was concluded that women with peripheral vascular disease had pelvic atherosclerotic arterial occlusive disease.

The clinical relevance of hemodynamic investigations has not yet been established in women with sexual dysfunction. It is likely that there are sexual arousal problems and tissue integrity changes in women that are associated with ilio-hypogastric- pudendal arterial occlusive disease.8 Vascular assessment by duplex Doppler ultrasound may be important in the evaluation of women with sexual dysfunction, particularly in women with arousal disorders.9-11 Women in the menopause and women associated with vascular risk factor exposure may be candidates for duplex Doppler ultrasonography.12 Nevertheless, it must be emphasized that the presence of arterial pathology is not always indicative of organic sexual dysfunction. Further research is needed to clarify the relationship between the hemodynamic integrity of the hypogastric-pudendal arterial bed and peripheral genital arousal responses.

Nonultrasound genital blood flow measures in women

Physiologic measures to assess genital blood flow during arousal in women have been used for psychophysiologic research since the 1970s. The first physiologic method involved vaginal photoplethysmography13-15 (see Chapter 10.1). Vaginal photoplethysmography consists of a tampon-sized device containing a light source (infrared) to illuminate the capillary plexus in the lamina propria under the vaginal epithelium, and a phototransistor as a light detector that senses the backscattered light from the vaginal epithelium. With alternating current coupling, the phasic changes in vaginal engorgement with each heartbeat are measured by “vaginal pulse amplitude”. The higher the vaginal pulse amplitude, the greater the vaginal tissue blood content. Although the vaginal photoplethysmograph can be inserted by the subject and is well tolerated, it is not reliable during movement such as masturbation, clitoral vibration, and orgasm.16,17

The other physiologic method involves an oxygen- temperature measuring system and was developed in 1977 by Levin and Wagner18 (see Chapter 10.4). The oxygen- temperature measuring system consists of an oxygen electrode heated by an electric current to a set temperature, and joined to the vagina via a suction cup. During an increase in vaginal blood perfusion, the electrode records increased heat loss. A greater power output is needed to maintain the electrode at the set temperature. The electrode also measures the amount of oxygen, reflecting transient changes in blood flow, diffusing across the vaginal epithelium. Although the oxygenation- temperature measure does not seem to be impaired by movement such as masturbation, clitoral vibration, and orgasm, the electrode needs to be attached by the experimenter (not the subject) and cannot be applied for long periods.

Ultrasound genital blood flow measures in women

Despite the recognition that medical factors are associated with sexual dysfunction, there have been limited medically focused diagnostic evaluations in women with sexual dysfunction. Duplex ultrasonography can be adapted for measuring vaginal, clitoral, and labial blood flow during arousal. Lavoisier et al. first reported on the use of Doppler ultrasonography to measure blood velocity in the clitoral cavernosal artery and to record changes in flow associated with intravaginal pressure changes.19 Sarrel utilized laser Doppler velocimetry to measure vaginal blood flow in postmenopausal women receiving estrogen alone versus estrogen and androgen.20 While such studies suggest that genital blood flow can be objectively measured by ultrasound technology, there have been few publications concerning duplex ultrasonographic findings in women with sexual dysfunction.9-11

Duplex Doppler ultrasonography with a high-frequency (12.5 MHz) external probe can be used to provide continuous, real-time imaging of arterial and erectile tissue components recorded at baseline and after sexual stimulation with an erotic video on a surround sound headset and a vibrator. Only visual stimulation is maintained during the actual ultrasound examination.

Duplex Doppler ultrasonography can assess the changes in peak systolic velocity in centimeters per second that occur in the right and left clitoral cavernosal and labial artery during sexual arousal9-11 or after intracavernosal clitoral injection.21 Genital tumescence is visually demonstrated on ultrasound, anatomically by increased venous pooling, and physiologically by increased end-diastolic velocities in the genital arteries. Duplex Doppler ultrasonography can also be used to assess the changes in clitoral and labial diameter associated with sexual stimulation. A transvaginal probe may be used to measure right and left vaginal, iliac, and uterine arterial peak systolic velocity changes.

Duplex Doppler ultrasonography is useful as a measure of genital blood flow before and during arousal in women who present for sexual dysfunction evaluation. Of great concern is the paucity of “control” duplex Doppler ultrasound data in women without sexual dysfunction. Prior to consideration of the use of duplex Doppler ultrasonography in the evaluation paradigm, women seeking treatment should undergo psychologic interview and history and physical examination.1 If indicated, consideration should be given for blood testing for steroid hormones and laboratory tests such as duplex Doppler ultrasonography.1

Clinical experience with duplex Doppler ultrasound in a women’s sexual health clinic

The following issues need to be addressed before duplex Doppler ultrasound becomes a robust component of the diagnostic evaluation of women with sexual dysfunction. Data are needed regarding normal values of volumetric/morphologic and hemodynamic data in women without sexual dysfunction. Technical issues such as probe size and ultrasound frequency need further development. The equipment utilized in duplex Doppler ultrasonography is summarized in Table 10.3.1.

A critical consideration is that the audiovisual-mechanical sexual stimulation in the office setting may result in incomplete genital smooth muscle relaxation yielding suboptimal vascular responses. Vasoactive pharmacologic strategies with or without sexual stimulation should be employed to maximize smooth muscle relaxation and vascular responses.

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Table 10.3.1. Equipment utilized for duplex

Doppler ultrasound

Videos

Visual stimulation with 3-D surround sound headset

Vibrator

Ultrasound duplex Doppler with high-frequency (11-12.5 MHz) small-parts probe

Ultrasound suite with quiet, relaxing, secure room for patient privacy containing an electronic communicating system enabling the patient to inform staff when she feels arousal has maximized.

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The induction of an arousal response in an office setting is not always well accepted by patients, and there is concern for lack of privacy; both factors may lead to suboptimal vascular responses. Both to improve patient acceptance and achieve more reliable hemodynamic data, Becher et al. reported on duplex Doppler assessment of clitoral vascular changes with topical prostaglandin E1 administration.22 Becher et al. documented that prostaglandin E1 gel application modified the vascular response of the clitoral artery, suggesting that vasoactive drugs might improve sexual response in patients with sexual dysfunction. In addition, Becher reported that the use of topical prostaglandin E1 administration during duplex Doppler assessment of clitoral vascular changes resulted in better patient acceptance and more reliable hemodynamic data.22

In women with sexual health concerns, duplex Doppler ultrasonography has been used to assess genital morphologic, volumetric, and hemodynamic changes during sexual arousal.9-11,19-22 Diagnostic ultrasonography is routinely performed in gray scale and duplex modes. The gray-scale ultrasound technique provides relevant clinical information on: (1) the integrity of clitoral and corpora spongiosa erectile tissue and tunica albuginea and (2) the clitoral and corpora spongiosa diameter. Classic duplex Doppler ultrasonography provides quantitative clitoral and spongiosal hemodynamic-focused data.

There have been few publications concerning duplex ultrasonographic findings in women with sexual dysfunction.9-11,19-22 One aim of this chapter is to report gray-scale, volumetric, and duplex hemodynamic ultrasound data before and after sexual stimulation in a large population of women with sexual dysfunction.

This retrospective study of 142 (mean age 38.2 ± 9.7 years) women who underwent duplex Doppler ultrasound (GE Logic 400) arousal testing for sexual dysfunction in an outpatient clinic over 12 months was Institutional Review Board approved. For consistency, the same ultrasound technologist performed all studies. The angle of the clitoral shaft formed by the suspensory ligament was the sonographic landmark used for volumetric measurement.

Technique

To simplify volumetric/morphologic data collection and to minimize the duration of the vascular evaluation, only clitoral shaft diameter data were measured. The high-frequency (MHz) small-parts probe was placed on one side of the clitoris, and clitoral diameter was measured from the medial tunica albuginea of the ipsilateral corporal body across the septum to the tunical albuginea of the contralateral corporal body at the level of the midshaft (Fig. 10.3.1). Gray-scale scanning of the tunica and corporal erectile tissue was performed. Hemodynamic clitoral data were recorded (Fig. 10.3.1C and D). While this sonographic landmark was maintained, the small parts probe was then swept laterally to evaluate the hypoechoic, ill-defined, carrot-shaped ipsilateral corpus spongiosum, which possesses a thin, occasionally visualized tunica. The width of the corpus spongiosum was obtained from the lateral to the medial aspect of the hypoechoic region at the predetermined sonographic landmark (Fig. 10.3.1B and E). Hemodynamic data from the ipsilateral corpus spongiosum artery was measured (Fig. 10.3.1E).

In summary, after audiovisual-sexual stimulation with or without vasoactive agents, diagnostic duplex Doppler ultrasonography was performed in gray-scale and duplex modes. Gray-scale ultrasound technique provides relevant clinical information on the integrity of clitoral and corpora spongiosa erectile tissue and tunica albuginea, and the clitoral and corpora spongiosa diameter before and after sexual stimulation. Classic duplex Doppler ultrasonography provides both quantitative clitoral and spongiosal hemodynamic-focused data.

The nursing staff carefully instructed patients and were available for assistance. Patient privacy was maximized. An electronic communication system was used to inform staff when the patient felt that arousal was maximized. Sexual stimulation was achieved and maintained with a 15-min standardized erotic video (Sinclair Institute; Femme Productions) on a 3-D surround sound headset (I.O. Display Systems LLC) and a vibrator (Ferticare, ILTS, Inc.) (frequency: 100 Hz; amplitude: 2.5 mm). After arousal, gray-scale, hemodynamic, and volumetric measurements were repeated by similar sonographic techniques (Fig. 10.3.1).

Gray-scale scanning of the clitoris revealed that 138 women had homogeneous erectile tissue throughout, with a smooth, continuous tunica albuginea (thickness - 2 mm). The labial corpora spongiosa erectile tissue was uniformly hypoe- choic with a thin or absent tunica albuginea in 139 women. Volumetric and hemodynamic data in the subject population are summarized in Table 10.3.2. We found that the increase in pre- and postarousal clitoral and corpus spongiosum diameter directly correlated (p < 0.05) with an increase in both the pre- and postarousal clitoral and corpus spongiosum end-diastolic velocity values. All data were analyzed by paired t-test. Differences between paired comparisons were considered statistically significant when p values were less than 0.05. Duplex Doppler ultrasound data (peak systolic velocity, end-diastolic velocity, resistive index) were expressed as the mean ± standard error of the mean.

Duplex Doppler ultrasound studies in women with sexual dysfunction were useful in a diagnostic and therapeutic context. A woman with persistent sexual arousal syndrome was found to have elevated peak systolic velocity values in the clitoral cavernosal artery (Fig. 10.3.2A) and the corpus spongiosum artery (Fig. 10.3.2B), and a pelvic arteriovenous malformation was noted during vaginal ultrasound (Fig. 10.3.2C). Another patient with persistent sexual arousal syndrome had elevated peak systolic velocity values in the clitoral cavernosal artery (Fig. 10.3.3A) and the corpus spongiosum artery (Fig. 10.3.3B), but no abnormal arteriovenous malformation was noted during vaginal ultrasound. Another patient with persistent sexual arousal syndrome had significant prolapse of urethral mucosa and elevated peak systolic velocity values in the urethral artery. No abnormal arteriovenous vessels were noted during vaginal ultrasound (Fig. 10.3.4A and B). Another patient had pudendal nerve entrapment after childbirth with prolonged forceps use. We perform interval vaginal ultrasound-directed pudendal nerve blocks, administering the steroid-lidocaine mixture just lateral to the pudendal artery, as visualized easily on ultrasound (Fig. 10.3.5). Another patient fell onto a bicycle bar as a child. Ultrasound revealed a hyperechoic lesion just above the tunica consistent with thickening of the tunica (Peyronie’s disease) (Fig. 10.3.6).

Figure 10.3.1. (A) Schematic illustration of the sonographic landmark for transducer probe placement. (B) Gray-scale ultrasound provides clinical information on the diameter of the clitoral corpora cavernosa and corpus spongiosum. (C) Gray-scale ultrasound provides diameter of the clitoral corpora cavernosa before and after sexual stimulation. Classic duplex Doppler ultrasonography provides quantitative, hemodynamically focused data, including clitoral peak systolic velocity values and clitoral end-diastolic velocity values.

(D) A patient undergoing gray-scale ultrasound diameter determination of the clitoral corpora cavernosa. Duplex Doppler ultrasound revealed quantitative, hemodynamically focused data, including clitoral peak systolic velocity values and clitoral end- diastolic velocity values. (E) A patient undergoing gray-scale ultrasound diameter determination of the corpus spongiosum. Duplex Doppler ultrasound revealed quantitative, hemodynamically focused data, including corpus spongiosum peak systolic velocity values and end-diastolic velocity values.

Table 10.3.2. Clitoral and corpus spongiosal hemodynamic and volumetric data before and after audiovisual-mechanical sexual stimulation

 

Baseline

Postarousal

p values

Clitoral diameter

0.9 ± 0.33

1.2 ± 0.48

< 0.001

Clitoral peak systolic velocity

12.2 ± 3.8

21.6 ± 7.4

< 0.001

Clitoral end-diastolic velocity

2.9 ± 1.9

6.7 ± 3.7

< 0.01

Clitoral resistance index

0.57 ± 0.11

0.69 ± 0.09

0.10

Corpus spongiosum diameter

1.2 ± 0.7

1.8 ± 0.9

0.05

Corpus spongiosum peak systolic velocity

10.8 ± 4.6

19.4 ± 9.4

< 0.05

Corpus spongiosum end-diastolic velocity

4.0 ± 3.2

7.8 ± 3.0

0.05

Corpus spongiosum resistance index

0.45 ± 0.59

0.64 ± 0.08

0.40

Conclusion

Female sexual dysfunction is a highly prevalent disorder that has underlying psychologic, physiologic, and interpersonal relationship factors. Recognized biologic pathophysiologies include: (1) hormonal insufficiency states associated with menopause and androgen insufficiency; (2) neurologic disorders, such as spinal cord injury and multiple sclerosis; and (3) arterial occlusive disease in the ilio-hypogastric-pudendal arterial bed in association with cardiovascular risk factor exposure, as in aging, hypertension, diabetes, high cholesterol, and heart disease.1,2,12 In general, there has been limited investigation of the mechanisms whereby biologic factors adversely affect sexual function in women, partly because of the lack of validated and standardized clinical diagnostic instruments and methodologies. In particular, there has been a paucity of research on vascular factors in female sexual function and dysfunction.

Figure 10.3.3. A patient with persistent sexual arousal syndrome had elevated peak systolic velocity values in the clitoral cavernosal artery (A) and the corpus spongiosum artery (B), but no abnormal arteriovenous malformation was noted during vaginal ultrasound.

The study reported in this chapter revealed that duplex Doppler ultrasonography can record significant volumetric (clitoral and corpora spongiosa diameters) and hemodynamic (peak systolic and end diastolic) changes in women with sexual dysfunction before and after sexual stimulation. These changes were greater in the clitoris than in the corpus spongiosum, probably due to differences in the size of the vascular lumina and the characteristics of the erectile tissues.

Resistive index measurements, which are indicative of veno-occlusive function, did not significantly change before and after arousal in either the clitoris or corpora spongiosa. This implies that genital arousal in women is associated with a volumetric increase not accompanied by significant veno-occlusion. In fact, it was found that the increases in pre- and post-arousal clitoral and corpus spongiosum diameters correlated with an increase in both the pre- and post-arousal clitoral and corpus spongiosum end-diastolic velocity values. This implies that genital engorgement in women is better assessed by the determination of end-diastolic velocity values.

Gray-scale imaging revealed tunical thickening and/or plaque of the clitoris in several patients. In addition, we found microcalcifications within the erectile tissue of the clitoris and/or corpora spongiosa (Fig. 10.3.6). All of these patients with abnormal gray-scale findings recalled a specific episode of blunt perineal trauma such as falling onto a bicycle crossbar.

While this duplex Doppler ultrasound study in 142 women with sexual dysfunction showed that ultrasound may by utilized in women with sexual dysfunction, there remain many issues that need to be addressed before this diagnostic modality becomes a standard part of the evaluation. First, there are insufficient data regarding normal values of volumetric and hemodynamic data in women without sexual dysfunction. Second, audiovisual-mechanical sexual stimulation in the office setting may result in incomplete genital smooth muscle relaxation, yielding suboptimal vascular responses. Third, vasoactive pharmacologic strategies with or without sexual stimulation need to be employed to maximize smooth muscle relaxation and vascular responses. Fourth, there are technical issues, such as probe size and ultrasound frequency, which need further delineation.

Figure 10.3.5. A patient had pudendal nerve entrapment after childbirth with prolonged forceps use. We perform interval vaginal ultrasound-directed pudendal nerve blocks (A), administering the steroid-lidocaine mixture just lateral to the pudendal artery, as visualized easily by ultrasound (B).

Figure 10.3.6. Ultrasound revealed a hyperechoic lesion just above the tunica consistent with thickening of the tunica (Peyronie's disease).

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