Women's Sexual Function and Dysfunction. Irwin Goldstein MD

Nonhormonal medical treatment options for female sexual dysfunction

Salvatore Caruso

Introduction

Sexual disorders have recently attracted much attention, generating new research in the epidemiology, pathophysiology, and pharmacotherapy of female sexual dysfunction. Such interest, paradoxically, was stimulated when scientific research defined the efficacy of oral medication to inhibit the enzyme phosphodiesterase type 5. This class of drug was initially used experimentally in cardiology and, “by chance and unexpectedly”, displayed side effects that produced erection in male test subjects.1

The success of selective phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction raised the question of whether similar medication could also be efficacious in the treatment of female sexual dysfunction.2 One of the impediments to research and clinical development in the female sexual dysfunction field has been the lack of definite diagnostic procedures and limited basic science research.3 Specifically, the biologic mechanism of sexual excitement and orgasm is not yet well defined,4 although it has become increasingly evident that female sexual dysfunction can have an organic basis secondary to medical problems, even if risk factors for female sexual dysfunction are both psychologic and physiologic.5

The availability of selective phosphodiesterase type 5 inhibitors to treat erectile dysfunction in men has spurred new interest and attention in medical research for the treatment of sexual dysfunction in women. This recent attention to medical research in female sexual dysfunction will shed light on possible causes of problems, and describe potential therapeutic approaches. Furthermore, clinicians who treat women suffering from female sexual dysfunction have begun to consider a possible role of selective phosphodiesterase type 5 inhibitors in treating female sexual arousal disorder.

Selective phosphodiesterase type 5 inhibitors have revolutionized sexology, which, until the 1990s, was almost dormant. At that time, there was a clear dichotomy between biologic attempts at treatment, which were often rudimentary and fundamentally ill-founded, and psychotherapeutic methods, which were widely espoused for female sexual disorders.

The considerations that led to diametrically opposite treatments between men and women were based on clinical speculation that female sexuality was more expressive than male sexuality. The ignorance of female pathophysiology has produced major difficulties in defining medical treatment. It is easier to define female sexuality as more complex, less accessible, and thus psychologic. The heirs of the Freudian culture managed female sexology with the complicity of a medical community that was ignorant of female sexual pathophysiology.

Today three schools of thought on female sexual dysfunction treatment exist. These include purely psychologic, purely biologic, and a hybrid of psychologic-biologic. The psychologic and biologic cultures are opposed, and often clash. The former affirms that it would be an oversimplification to treat a women affected by sexual dysfunction pharmacologically; the latter, in contrast, sees a therapeutic option aimed at reducing the time under therapy. However, psychotherapists have always tried to use short-term therapy aimed at triggering behavioral change.6

Currently, medical and physiologic factors are considered to cause female sexual dysfunction, including reduction of the vaginal and clitoral blood flow, previous gynecologic operations, alterations of the pelvic floor due to childbirth, or disorders secondary to hormonal alterations7 (see Chapters 6.1-6.5). Magnetic resonance imaging showed that during female sexual arousal, changes occur in the anterior vaginal wall and the clitoris8 (see Chapter 10.2). It is accepted that the clitoris plays a functional role during sexual arousal.9-16 All these aspects constitute the biologic pathways that could be treated with pharmacologic agents.

Improved understanding of the structures involved in normal sexual function, as well as of age-related changes, help practitioners evaluate and manage women with female sexual dysfunction. The continued quest to understand female sexual function and dysfunction requires more education and research on the treatment of underlying medical conditions and the use of pharmacologic therapies.17,18

Sexual arousability largely depends on the sympathetic nervous system and nonadrenergic/noncholinergic neurotransmitters. For instance, vasoactive intestinal polypeptide and nitric oxide are involved in smooth muscle relaxation and enhancement of genital blood flow, while various hormones may influence female sexual function19-21 (see Chapters 5.1-5.5).

Today there are no drugs approved for the safe and effective treatment of female sexual dysfunction.22 There are independent studies supported by pharmaceutic companies investigating the efficacy and safety of hormonal and nonhormonal agents that act on genital tissues, the vascular system, and the peripheral and/or central sexual pathways. Phosphodiesterase type 5 inhibitors are a commonly studied nonhormonal pharmacologic agent.

Selective phosphodiesterase type 5 inhibitors

The introduction of selective phosphodiesterase type 5 inhibitors23 for the treatment of men affected by erectile dysfunction represented a major advance in understanding and managing the neurovascular mechanisms of the male sexual response.

In the female clitoral corpus cavernosum, the release of nitric oxide from the nonadrenergic, noncholinergic nerves and/or the endothelium activates guanylyl cyclase and increases intracellular cyclic guanosine monophosphate levels. Cyclic guanosine monophosphate modulates intracellular calcium and, in turn, regulates smooth muscle contractility and erectile func- tion.20 Phosphodiesterase type 5 plays an important physiologic role by regulating the intracellular levels of cyclic nucleotides.24 Selective phosphodiesterase type 5 inhibitors can inhibit cyclic guanosine monophosphate hydrolysis by high-affinity, selective action in intact cells and in soluble extracts of human clitoral corpus cavernosum smooth muscle cells.25In addition, phosphodiesterase type 5 has been found in clitoral and vaginal tissue26,27 

(see Chapters 5.1-5.6).

Clinical trials suggest that selective phosphodiesterase type 5 inhibitors could be an effective treatment for female sexual dysfunction.28,29 On the basis of these observations that human clitoral corpus cavernosum smooth muscle tone may be regulated by synthesis and release of nitric oxide,30 and that this pathway is dependent on phosphodiesterase type 5 activity, researchers in the sexual field hypothesized that selective phosphodiesterase type 5 inhibitors could have beneficial clinical effects for women affected by sexual arousal disorders.

In a clinical setting, selective phosphodiesterase type 5 inhibitors were shown to enhance genital blood flow and vaginal and clitoral engorgement in women affected by female sexual arousal disorder. There have been many studies on selective phosphodiesterase type 5 inhibitors over the last few years, conducted with either premenopausal or postmenopausal women, as well as healthy women without sexual dysfunction, to study female sexual pathways, and on subjects with psychotropic-induced sexual dysfunction, and the results of these studies follow.

Premenopausal studies

A pilot study on the effect of the selective phosphodiesterase type 5 inhibitor sildenafil on subjective and physiologic parameters of the female sexual response determined its safety and efficacy for use in women with sexual arousal disorder.31 Physiologic measurements, including genital blood flow, vaginal lubrication, intravaginal pressure-volume changes, and genital sensation, were recorded before and after sexual stimulation at baseline and after administration of 100 mg sildenafil. Poststimulation physiologic measurements improved significantly. Subjective sexual function complaints, including reduced arousal, low desire, diminished sexual satisfaction, difficulty in achieving orgasm, decreased vaginal lubrication, and dyspareu- nia, also improved significantly.

The major findings of a double-blind, crossover, placebo- controlled study on premenopausal women with normal ovulatory cycles and normal levels of steroid hormones, affected by female sexual arousal disorder without hypoactive sexual desire disorder, were that subjects may benefit from treatment with the selective phosphodiesterase type 5 inhibitor, showing improvement in arousal, and indirectly in orgasm, and frequency and enjoyment of sexual intercourse.32 These aspects could explain the differences in the results from studies treating postmenopausal women that showed little or no improvement.

Postmenopausal studies

Another study treated postmenopausal women with sexual dysfunction, based on history, with an open-label, nonrandomized study.33 Overall, only 18.1% had a significant therapeutic response, while clitoral discomfort and hypersensitivity occurred in 21%. Side effects included headache, dizziness, and dyspepsia. The data suggest that the selective phosphodiesterase type 5 inhibitor sildenafil is well tolerated in postmenopausal women with sexual dysfunction, but overall sexual function did not improve significantly, although there were changes in vaginal lubrication and clitoral sensitivity. It must be noted that vaginal engorgement insufficiency and clitoral erectile insufficiency in postmenopausal women resulted from organic vascu- logenic dysfunction due to pathophysiologic variations in endogenous hormones, as in estrogen deprivation. An important point in treating postmenopausal women with female sexual arousal disorder is that they also need an adequate testosterone level to receive benefits from selective phosphodiesterase type 5 inhibitor treatment.

In a randomized trial of selective phosphodiesterase type 5 inhibitor in postmenopausal women with female sexual arousal disorder that were receiving estrogen but not androgen therapy, no significant improvement in sexual arousal was found.34 To assess efficacy, patients completed the Global Efficacy Questions, the Life Satisfaction Checklist, an event log of sexual activity, and a 31-item sexual function questionnaire. To assess safety, adverse event data were recorded. Estrogenized and estrogen-deficient women were diagnosed with female sexual arousal disorder, but it was the primary presenting symptom in only 46% and 50% of the women, respectively. It was concluded that any genital physiologic effect of selective phosphodiesterase type 5 inhibitor was not perceived as improving the sexual response in estrogenized or estrogen-deficient women with a broad spectrum of sexual dysfunction that included female sexual arousal disorder. Estrogenized postmenopausal women with female genital sexual arousal disorder and orgasmic impairment based only on clinical assessment do not benefit from selective phosphodiesterase type 5 inhibitor. However, photoplethysmography could have a predictive value: those women showing low vaginal pulse amplitude response benefited from selective phosphodiesterase type 5 inhibitor compared with women with a higher response. Thus, estrogenized women diagnosed with acquired female genital sexual arousal disorder may be a heterogeneous group, and photoplethysmography might be useful in their further characterization.35 It is well known that hormone therapies usually improve vaginal epithelial thickness and engorgement in postmenopausal women, but also decrease serum androgen levels due to decreased luteinizing hormone- driven, ovarian, stromal steroidogenesis.36 Thus, sexual arousal in postmenopausal woman and other aspects of female androgen-dependent sexuality are unlikely to be improved by exclusive treatment with selective phosphodiesterase type 5 inhibitor.

Selective phosphodiesterase type 5 inhibitor efficacy in postmenopausal women with female sexual arousal disorder who had adequate estradiol and free testosterone concentrations, or were receiving estrogen and/or androgen therapy, was assessed by a double-blind, placebo-controlled study.37 Women with female sexual arousal disorder without hypoactive sexual desire disorder had a significantly greater improvement in sexual arousal, orgasm, intercourse, and overall satisfaction with sexual life during sildenafil intake compared with placebo, while no efficacy was shown for women with concomitant hypoactive sexual desire disorder.

Efficacy studies in healthy women

To determine the changes in female sexual pathways with selective phosphodiesterase type 5 inhibitor, and to verify the safety, a randomized, double-blind crossover, placebo-controlled study was conducted with premenopausal women asymptomatic for sexual disorders, with normal ovulatory cycles and with normal levels of steroid hormones.38 The selective phosphodiesterase type 5 inhibitor sildenafil improved arousal, orgasm, and enjoyment with respect to placebo. The major finding of the study was that a selective phosphodiesterase type 5 inhibitor could improve general sexual behavior. The benefits that the group felt were above the physiologic peripheral dimensions of sexuality, confirming what has been found by using selective phosphodiesterase type 5 inhibitors on males affected by erectile dysfunction. As a consequence, this study showed that the qualitative aspects of sexuality and the quantitative aspects, such as multiple orgasms, are significantly improved with respect to the pretest baseline values. The majority of the adverse events associated with the use of selective phosphodiesterase type 5 inhibitors were related to vasodilation, such as headache; or to gastrointestinal events, such as nausea; or to visual effects. Each of these adverse events reflects the well- known pharmacologic properties of selective phosphodiesterase type 5 inhibitors, which usually increase in incidence with increasing drug dose. The study suggested that selective phosphodiesterase type 5 inhibitors act on different sexual pathways in healthy women, improving their sexual experience.

Selective phosphodiesterase type 5 inhibitors were also found to be effective in enhancing vaginal engorgement during erotic stimulus conditions in healthy women without sexual dysfunction, but were not associated with an effect on subjective sexual arousal.39 Women without sexual dysfunction were randomly assigned to receive either sildenafil or placebo. Subjective measurements of sexual arousal were assessed after participants had been exposed to erotic stimulus. Vaginal vaso- congestion was recorded continuously during baseline, neutral, and erotic stimulus. At the end of each session, subjects were asked to specify which treatment they suspected they had received. Significant increases in vaginal vasocongestion were found with the selective phosphodiesterase type 5 inhibitor treatment compared with placebo. There were no differences between treatments on subjective sexual arousal experience. Analyses by “suspected treatment received” found that significantly stronger sexual arousal and vaginal wetness were reported for the treatment that was believed to be selective phosphodiesterase type 5 inhibitor than the treatment that was believed to be placebo.

Recently, the effect of a single oral dose of 50 mg sildenafil on the uterine and clitoral arterial blood flow in healthy, naturally postmenopausal women was studied. Color Doppler sonography, performed before and 1 h after sildenafil administration, showed clitoral and uterine blood flow improvement without erotic stimulus.40

Sildenafil for psychotropic-induced sexual dysfunction

Women reported significant improvements in all domains of sexual function, with improvement in overall sexual satisfaction, after selective phosphodiesterase type 5 inhibitor treatment. Significant improvements were reported regardless of psychotropic medication type. Patients taking selective serotonin reuptake inhibitors reported less improvement in arousal, libido, and overall sexual satisfaction than did other patients, whereas patients taking benzodiazepines reported significantly more improvement in libido and overall sexual satisfaction.41

Patients who had normal premorbid sexual function and who had developed sexual dysfunction, particularly anorgasmia with or without other sexual disturbances, i.e., loss of libido, lubrication difficulties, and uncomfortable or painful intercourse, were treated with a selective phosphodiesterase type 5 inhibitor. The subjects showed improvement of the presenting condition, usually depression, anxiety, or both, and experienced sexual side effects continuously for more than 4 weeks. Patients took selective phosphodiesterase type 5 inhibitors and reported a complete or very significant reversal of their sexual dysfunction. This included return of effective duration and intensity of adequate arousal, lubrication, and orgasmic function.28

In conclusion, selective phosphodiesterase type 5 inhibitors seem to be more effective in premenopausal women with sexual arousal disorder than in postmenopausal women. This could be explained by the important role played by sexual steroids in genital trophism. In fact, the best efficacy of sildenafil was in women affected by genital arousal dysfunction. These studies show that subjects with other sexual dysfunctions, such as hypoactive sexual desire disorder, do not benefit from sildenafil. Consequently, defining specific subgroups of women is the first step in treating their dysfunction.

Table 14.1.1 summarizes selective phosphodiesterase type 5 inhibitor use with sildenafil as a treatment for women with female sexual dysfunction.

D1/D2 dopamine receptor agonist

The use of a D1/D2 dopamine receptor agonist, such as sublingual apomorphine, for the treatment of erectile dysfunction provides strong evidence of the participation of the dopaminergic system in the control of sexual function.42 The use of apomorphine to treat erectile dysfunction has not always been effective, as the exact involvement of dopamine in sexual motivation and in the control of genital arousal in humans is unknown. However, the daily intake of apomorphine seems to be effective,43 even if multicenter and multiethnic studies need to confirm evidence obtained by studying small numbers of subjects. In contrast, experimental data suggest an implication of dopamine at all these stages of the copulatory behavior in rodents.44 Apomorphine induces a patterned behavioral sexual arousal response and obvious genital vasocongestive engorgement in female rats. The frequency of the apomorphine- induced responses varied during the estrous cycle and decreased after oophorectomy, revealing the hormonal dependency.45

Table 14.1.1. Summary of sildenafil treatment in women with female sexual dysfunction and in healthy women

Authors

Sexuality

Number of patients

Type of study

Measurement

Sildenafil

mg

Female sexual response (FSR)

Berman et al.31

FSAD

48 postmenopausal

Prospective

Physiologic

100

Improvement

Caruso et al.32

FSAD

51 postmenopausal

Double-blind, crossover, placebo

PEQ

25-50

Improvement

Kaplan et al.33

Sexual

disorders

30 postmenopausal

No randomly, Open-label

IFSF

50

Insufficient

Basson et al.34

FSAD

577 estrogenized and 204 control postmenopausal

Randomized,

placebo-controlled

GEQ and PSQ

10-100

Not effective

Berman et al.37

FSAD

202 postmenopausal E-A treated

Double-blind,

placebo-controlled

FIEI

25-50-100

Improvement

Caruso et al.38

Healthy

women

50 postmenopausal

Double-blind, crossover, placebo

PEQ

50

Improvement

Laan et al.39

Healthy

women

12 postmenopausal

Randomized,

placebo-controlled

Physiologic

50

Enhancing

vaginal

engorgement

Alatas et al.40

Healthy

women

25 postmenopausal

Open-label

Color Doppler sonography

Single dose 50

Improved clitoral blood flow

FIEI = Female intervention efficacy index; FSAD = Female sexual arousal disorder; GEQ = Global efficacy question; IFSF = Index of female sexual function; PEQ = Personal experiences questionnaire; PSQ = Perceived stress questionnaire.

The release of dopamine at the level of the nucleus accum- bens, which is innervated by the mesolimbic dopaminergic pathway originating in the ventral segmental area, is positively implicated in the precopulatory or appetitive phase in male rats. There is also a permissive role in the copulatory or consumatory phase for dopamine released at the level of the median preoptic area, which receives projection from the dopaminergic hypothalamic pathway within the hypothalamus. It is noteworthy that the participation of the dopaminergic system is not specific to sexual behavior but rather reflects the more general involvement of dopamine in the regulation of cognitive, integrative, and reward processes. Due to its role in the control of locomotor activity, the integrity of the nigrostriatal dopaminergic pathway is also essential for the display of copulatory behavior. More specifically to sexual function, it is likely that dopamine can trigger genital arousal by acting on oxytocinergic neurons located in the paraventricular nucleus of the hypothalamus, and perhaps on the proerectile sacral parasympathetic nucleus within the spinal cord.

The regulation of genital arousal by dopamine has not yet been well established in females. However, a placebo-controlled study was performed to verify whether a D1/D2 dopamine receptor agonist was effective in premenopausal women affected by arousal disorder with hypoactive sexual desire disorder.46 Women were randomly allocated to treatment in one of six possible sequences of three 2-week double-blind, crossover study periods with the D1/D2 dopamine receptor agonist apomorphine 2 mg or 3 mg, washout, and placebo. The daily intake of the drug was effective with both the 2-mg and 3-mg dosages compared with placebo for arousal and desire. The effects of 3 mg apomorphine were better than those obtained with 2 mg. The orgasm, enjoyment, and satisfaction with frequency scores improved during treatment with daily D1/D2 dopamine receptor agonist compared with baseline and placebo. Adverse events were mild or moderate, occurring both during the “as required” part and during daily usage, and were mainly nausea, vomiting, dizziness, or headache. However, during the placebo period, two women had adverse events, mainly headache.

Recently, a randomized, double-blind, placebo-controlled study was performed to evaluate changes in female sexual response in premenopausal women with orgasmic sexual dysfunction treated with 3 mg sublingual apomorphine. Sexual response was evaluated objectively by Doppler sonography, and subjectively by self-reported questionnaire, after vibrator stimuli with the addition of apomorphine or placebo. Clitoral hemodynamic changes were higher with the D1/D2 dopamine receptor agonist than placebo, even when there were no differences between D1/D2 dopamine receptor agonist and placebo in regard to orgasm, probably due to confounding factors such as study situation, lack of intimacy, and a single apomorphine dose.47

In conclusion, a D1/D2 dopamine receptor agonist could be efficacious in treating women affected by sexual arousal disorder and hypoactive sexual desire disorder because of its action on the dopaminergic system. At present, an intranasal formulation of D1/D2 dopamine receptor agonist for treating female sexual dysfunction is being studied. Dopamine agonists in sexual dysfunction could be a promising research area in the development of treatment for female sexual dysfunction.

Other medications

There have been few studies of drugs targeting the central nervous system to date. Bupropion may have a beneficial effect on premenopausal women with hypoactive sexual desire dis- order.48 Bupropion can also be an effective antidote to selective serotonin reuptake inhibitor-induced sexual dysfunction. In a placebo-controlled trial, bupropion produced an increase in desire and frequency of sexual activity compared with placebo. However, frequency was correlated to total testosterone level at baseline and during treatment.49

The efficacy of various medications, such as L-arginine, yohimbine, phentolamine, and prostaglandin E1, in the treatment of female sexual dysfunction is still under investigation.50 In a randomized, double-blind, three-way crossover study, the combined oral administration of the nitric oxide-precursor L-arginine and the alpha 2-blocker yohimbine for subjective and physiologic sexual arousal in postmenopausal women with female sexual arousal disorder increased vaginal pulse amplitude responses to erotic stimuli compared with placebo.51

Phentolamine is a combined alpha 1- and alpha 2- adrenoceptor antagonist that has been used to treat erectile dysfunction by intracavernosal injection. Results of a pilot study with a single-blind, dose-escalation design indicated a mild, positive effect of oral phentolamine across all measurements of arousal, with significant changes in self-reported lubrication and pleasurable sensations in the vagina.52 All subjects had received a single dose of 40 mg oral phentolamine and placebo. Dependent variables for the study included vaginal pulse amplitude, as measured by vaginal photoplethysmography, selfreported measures of sexual response, and patient- and physician-based assessments of adverse events. In another study, physiologic readings by vaginal photoplethysmography were significantly different from placebo in the women using hormone therapy with 40 mg phentolamine.53 No significant differences were found among women not receiving hormone therapy, so that phentolamine may show promise as a treatment for female sexual arousal disorder in estrogenized postmenopausal women.

Currently, intravaginal application of prostaglandin E1 is under investigation to determine its efficacy in the treatment of female sexual dysfunction. In a study conducted to evaluate the efficacy of topical alprostadil cream in women with sexual arousal disorder, each subject was administered a single intravaginal dose of placebo followed by three escalating intravaginal doses of active drug at 2-week intervals. However, photoplethysmography measurement of vaginal pulse amplitude was not able to demonstrate treatment sensitivity.54 Similarly, in a randomized, double-blind, placebo-controlled study, women with sexual arousal disorder were enrolled to use 500-, 1000-, or 1500-g doses of alprostadil or placebo cream to be applied to the vulvar area prior to vaginal intercourse for a period of 6 weeks. The arousal success rate was highest in the alprostadil 1000-g group and lowest in the 500-g group, but the responses were not different from that of the placebo cream for any of the three doses of the drug.55 In contrast, a study conducted with color Doppler ultrasonography to measure clitoral hemodynamic changes showed improvement in peak systolic velocity and end diastolic velocity after topical application of 1 g of 0.2% alprostadil gel, and labial and clitoral engorgement.56 Furthermore, women with sexual arousal and orgasmic disorders seem to have better clitoral cavernosal arterial hemodynamics after topical administration of alprostadil.57

A summary of drug treatments in women with female sexual dysfunction can be found in Table 14.1.2.

Conclusions

Female sexual dysfunction is a combination of problems with both biologic and psychologic components, and is multifactorial in etiology.

The studies that have been carried out with selective phosphodiesterase type 5 inhibitors and a D1/D2 dopamine receptor agonist show that these drugs are potentially useful in treating women with a specific sexual dysfunction. We are only at the beginning of a new era in treating female sexual dysfunction, and the development of new drugs in this field can only improve the situation.

There are currently potential therapeutic options for the treatment of female sexual dysfunction that include both hormonal and nonhormonal pharmacologic therapies. However, sex therapists are discovering that integrating adjunctive use of drugs with sex therapy can accelerate the therapeutic process and improve outcome. As new pharmaceuticals are developed and approved, opportunities for medical and nonmedical sex therapies will increase.58 To date, the results of the studies on women affected by sexual dysfunction who received drug treatments have not reached uniformity of efficacy. This could be a result of the multifactorial aspect of female sexual dysfunction.59 Specific subgroups obviously need to be diagnosed exactly, as treating all sexual dysfunctions with drugs is not always effective. Finally, we are beginning to consider sexual dysfunction treatment rather than symptomatic therapy, preferably in an integrative setting.

Table 14.1.2. Summary of drug treatments in women with female sexual dysfunction

Authors

Sexuality

Type of study

Measurement

Drug

Female sexual response (FSR)

Caruso et al.47

HSDD

FSAD

Double-blind, crossover, placebo

PEQ

Apomorphine

Improvement

Bechara et al.48

FSOD

Double-blind, randomized, placebo-controlled

FSFI and color Doppler sonography

Apomorphine

Improvement

Segraves et al.49

HSDD

Open label

Questionnaires

Bupropion

Improvement

Clayton et al.50

FSD due to SSRI

Placebo-controlled

Questionnaires

Bupropion

Improvement

Meston and Worcel 52

FSAD

Double-blind, randomized, crossover, placebo-controlled

Photoplethysmography

Yohimbine plus L-arginine

Improvement

Rosen et al. 53

FSAD

Single-blind,

placebo-controlled

Photoplethysmography

Phentolamine

Improvement

Rubio-Aurioles et al.54

FSAD

Placebo-controlled

Photoplethysmography

Phentolamine

HTR dependent

Islam et al.55

FSAD

Double-blind, crossover, placebo

Photoplethysmography

Alprostadil

Not effective

Padma-Nathan et al.56

FSAD

Double-blind, randomized, placebo-controlled

FSEP and FSFI

Alprostadil

Dose-response

effect

Becher et al.57

Healthy

women

Open label

Color Doppler sonography

Alprostadil

Improved labial and clitoral blood flow

Bechara et al.58

FSAD and FSOD

Open label

Color Doppler sonography

Alprostadil

Improved clitoral blood flow

FSAD = Female sexual arousal disorder; FSD = Female sexual disorder; FSEP = Female sexual encounter profile; FSFI = Female sexual function index; FSOD = Female sexual orgasm disorder; HSDD = Hypoactive sexual desire disorder; PEQ = Personal experiences questionnaire; SSRI = Selective serotonin reuptake inhibitor.

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