Female Sexual DysfunctionWhat We Know, What We Suspect, and Enduring Enigmas

June 8, 2009

From time to time, health conditions emerge that are relative “orphans” when it comes to having the resources of a health care discipline or subspecialty to take ownership or accept responsibility for developing the body of knowledge that underlies their systematic evaluation and treatment. Female sexual dysfunction (FSD) is such a class of conditions.

From Pedophilia to Addiction, Robert T. Segraves, MD

Female Sexual Dysfunction, Leonard R. Derogatis, PhD

Psychopathology and Personality Traits of Pedophiles, Lisa J. Cohen and Igor Galynker

Sexual Addiction Update, Aviel Goodman, MD

From time to time, health conditions emerge that are relative “orphans” when it comes to having the resources of a health care discipline or subspecialty to take ownership or accept responsibility for developing the body of knowledge that underlies their systematic evaluation and treatment. Female sexual dysfunction (FSD) is such a class of conditions. In large measure, this is because until recently female sexual functioning itself was very imperfectly understood and frequently was defined simply as the absence of sexual dysfunction.1 In addition, confusion arises because FSD can possess elements that fall within the purview of multiple health care disciplines: endocrinology, gynecology, psychiatry, psychology, and urology at times all address various aspects of FSD.

Some argue that these conditions are not medical disorders but rather variations in the continuum of normal sexual behavior. With these circumstances as a backdrop, it is small wonder that most health professionals perceive female sexuality and its accompanying spectrum of dysfunctions as enduring mysteries and report little confidence in their ability to diagnose or treat these conditions.

Theories of female sexual function
Although there have been earlier significant contributors, it is important to recognize Kinsey’s early observation concerning the enormous variation that exists in women’s responses to sexual stimulation.2 Although not recognized as a pivotal finding at the time, this observation has since become a core realization in our appreciation of female sexual functioning.

A leap of several decades brings us to the work of Masters and Johnson,3 who developed a linear 4-stage conceptual model of female (and male) sexual functioning. Masters and Johnson’s paradigm involved several stages of sexual excitement followed by orgasm and ultimately resolution. Interestingly, Masters and Johnson’s model held no place for sexual desire. The formal integration of sexual desire into the official model that described female sexual functioning had to await the work of Helen Singer Kaplan4 and Harold Lief5 (both psychiatrists). The resulting 3-stage model made its way into DSM-III in 1980.6

In contrast to the linear, sequential models of Masters and Johnson and DSM, Rosemary Basson7 has more recently put forward a competing model of female sexual functioning that is cyclic and intimacy-based. There is no prescribed sequential arrangement among the elements of desire, arousal, etc, in this schema. Basson argues that in many, if not most instances, women begin a sexual encounter from a sexually neutral position rather than having spontaneous sexual desire; they experience elements such as the need for emotional intimacy, sexual arousal, and sexual desire in a cyclic accumulating fashion. Basson contends that wom­en’s principal motivation for sex is more often the need for intimacy or emotional closeness than sexual satisfaction.

Currently, there are adherents to both theories, whom I suspect tend to focus on those aspects of female sexual functioning that their theory best explains. At present, the situation is akin to the field of physics with its 2 theories of light (quantum and wave); each explains certain phenomena very well, and their disjunctive features are ignored.

In the most frequently quoted report on the prevalence of FSD in the general population, 43% of women and 31% of men reported having sexual “complaints.”8 This report arose from a large stratified survey focused primarily on HIV, which, although it was well constructed, resulted in several design limitations-among them an age ceiling of 59 years. More recent prevalence percentages range from the low 20s to mid-30s.9 These figures vary widely depending on whether the DSM-IV criterion of “manifest personal distress” was used. When distress is included as a criterion for diagnosis, reported rates of FSD are considerably lower.9,10 Also, rates drop as a function of duration of FSD.

Risk factors for FSD have been repeatedly demonstrated to be age, health (including mental health), and various health behaviors (eg, smoking).9,10 It is probably safe to conclude that FSD is highly prevalent in our society, and that its prevalence increases significantly with age, the presence of chronic health conditions, and at-risk health behaviors. Hypoactive sexual desire disorder (HSDD) has been consistently shown to be the most prevalent of the FSDs.11

Depression, SSRIs, and FSD
The close association between clinical depression and FSD has been noted for many years; estimated rates among individuals with clinical depression often top 50%.12,13 Depressive disorders are more prevalent in women and clinical depression is one of the principal risk factors for FSD.9 In general, the large majority of cases involve low sexual desire. Orgasmic and arousal disorders are less evident or present as secondary aspects of a primary low-desire problem.

Before the introduction of flu­oxetine, sexual dysfunction in a depressed patient was usually treated as a fundamental aspect of the depression. Most clinicians believed that the sexual dysfunction would respond consistently as symptoms of the mood disorder improved. With the advent of fluoxetine and other SSRIs, this relatively straightforward relationship became much more complex. To be sure, there had been occasional reports of treatment-induced sexual adverse effects with the monoamine oxidase inhibitors and the tricyclic antidepressants, which usually involved delayed orgasm. However, with the advent of SSRIs, after an initial “don’t ask, don’t tell” period when everyone reported very low rates of sexual adverse effects, the dramatic sexual liability of this class of drugs became well established.13

The good, the bad, and the not-so-bad
First and foremost, it is important to recognize that all SSRIs and serotonin norepinephrine reuptake inhib­itors carry some degree of liability for FSD-regardless of the attempts of pharmaceutical companies to downplay these adverse effects. Although these drugs can cause problems throughout the range of the sexual response cycle, drug-related dysfunctions tend to primarily disrupt orgasm and to result in delayed orgasm and-in some cases-anorgasmia. In contrast, depression-related dysfunctions predominantly involve sexual desire.

SSRI-induced dysfunctions usually emerge during the first or second week following treatment initiation, considerably before the antidepressant effect is manifest. This is one of the reasons it is important to establish a clear sexual functioning baseline for each patient-ideally before the current depressive episode, so that differential effects can be recognized.

Although there is no reliable metric concerning the relative liabilities of different antidepressants to generate sexual adverse effects, a substantial amount of work on the subject has resulted in a rough rank ordering of the differential risk for FSD of the drugs currently on the market (Table 1). The drug consistently judged to have the least potential for FSD is bupropion, followed by nefazodone, mirtazapine, and duloxetine.13-15

There is also some evidence that the recently introduced melatonin agonist agomelatine may have a favorable profile regarding FSD, but ex­perience with the drug is currently limited.16

The cumulative evidence suggests that the remaining SSRI antidepressants are approximately equivalent in their risk for FSD. The exception is paroxetine, which may have a slightly higher liability.13

Treatment of antidepressant-induced FSD
The clinician’s primary responsibility is, of course, to first ensure that the patient’s depression is being effectively treated before turning attention to what some might consider inevitable adverse effects. The difficulty is that for many patients, sexual adverse effects are perceived as an unacceptable burden. These adverse effects are among the leading causes of discontinuation of antidepressant therapy, which can exacerbate the mood disorder.

Fortunately, a number of options are available to treat drug-induced FSD (Table 2). Decreasing the dos­age is one option, either through direct reduction or drug holidays. The risk is that the dosage may be too low to be effective, and depression may recur. It is also possible to switch antidepressants with the hope that a new agent may treat the mood disorder without inducing FSD. Another alternative is to try adding a new drug to the treatment regimen as an antidote. The major issue with this approach is simply: will the antidote work?

Balon and Segraves17 recently surveyed approximately 30 psychiatrists in the field of antidepressant-induced sexual dysfunction regarding their treatment practices. These experts most frequently preferred a change in either the drug or the dosage of the antidepressant, adding other drugs (eg, bupropion, a phosphodiesterase type 5 inhibitor), or adding testosterone to treat patients with desire disorders.

Patients and doctors: a conspiracy of silence
Many patients are reluctant to discuss details of their sexual functioning, and a similar number of health care professionals are also uncomfortable with the topic. Most patients take their cues from the clinician. Thus, if the physician does not ask about sexual dysfunction, the patient will rarely raise the issue. These tendencies lead to a complex series of misperceptions, rationalizations, and denials that result in FSD going completely undetected and untreated in many cases.

Data show that simple direct questions about the quality of a woman’s sexual functioning do not usually make a patient uncomfortable.

Montejo-Gonzlez and colleagues18 reported a 4-fold increase of positive reports (14% vs 58%) concerning SSRI-induced sexual dysfunction when direct questions replaced spontaneous reports. Landn and coworkers19 reported an even greater distinction (6% vs 41%). Most patients reported being embarrassed to raise the issue and feared embarrassing their physician by doing so. They also rationalized that nothing could be done, that the problem would pass, or that the problem would persist as just another sign of aging.

Often, the clinician can ease the discussion by asking 2 simple questions: “How are things going for you sexually-is everything okay?” and “Is your partner having any sexual problems?” These questions do not have to be asked literally, as long as they elicit answers. The conspiracy of silence about sexual problems must end if we are going to make progress with treatment of these conditions, and as professionals, we must take the lead.

Treatments for FSD
The predominant psychological interventions are psychotherapy (in myriad formats), sex therapy, and couples or relationship therapy. An important consideration for the psychological approaches is the nature of the condition and its suspected etiology(ies). If the problem appears to arise from intrapsychic conflict, a problematic relationship, or poor sexual learning, then one or some combination of these treatment methods may prove effective. If the cause appears to be biologically based, then psychological approaches may be helpful, but they are not likely to provide lasting benefit. There are no FDA-approved drug treatments for FSDs, despite substantial research activity during the past decade.20-23 Of the many drugs evaluated in phase 2 and, in several instances, phase 3 trials, only 3 agents have emerged that appear to have a realistic opportunity to become marketed drugs in the near future.

The first of these, a testosterone patch (Intrinsa) that has been developed to treat HSDD in postmeno-pausal women, is currently marketed in Europe. The patch has shown efficacy in surgically and naturally meno-pausal women as well as in postmenopausal women not taking estrogen.24 However, the testosterone patch has failed to gain FDA approval in this country because of concerns about its long-term safety. It is unclear when and if the patch will become available in the United States. A second transdermal testosterone preparation (Libigel) is currently in phase 3 clinical trials.25 It must also pass long-term safety hurdles.

There is also a centrally acting agent, flibanserin (a 5HT1A agonist/5HT2A antagonist), that has shown considerable promise in the treatment of HSDD in premenopausal women.26 Flibanserin is fairly far along in phase 3 trials, and if it continues to perform well, could conceivably be available sometime in 2010. Currently, there are several off-label agents available to treat FSD. Bupropion has been demonstrated to have some efficacy in treating HSDD in premenopausal women.27 Although it is clear that bupropion has the lowest incidence of sexual adverse effects when used as an antidepressant, its overall record as a prosexual therapeutic agent is less consistent.

Another popular off-label pharmacological approach is the use of transdermal testosterone gel prepared by local compounding pharmacists. Typically, a 2% percutaneous gel is applied to the clitoris, labia, and vulva, beginning daily for approximately 2 weeks and then according to a protocol that best accommodates patient needs. Response is often positive, but several months of treatment may be required to restore the patient’s sexual desire.


Drugs Mentioned in This Article
Agomelatine (Valdoxan, Melitor)
Bupropion (Wellbutrin, Zyban)
Citalopram (Celexa)
Duloxetine (Cymbalta)
Flibanserin (Ectris)
Fluoxetine (Prozac, Sarafem, Symbyax)
Fluvoxamine (Luvox)
Methyltestosterone and estrogen (Estratest)
Mirtazapine (Remeron)
Nefazodone (Serzone)
Paroxetine (Paxil)
Sertraline (Zoloft)
Sildenafil (Viagra, Revatio)
Testosterone patch (Intrinsa)
Venlafaxine (Effexor)


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