Female Sexual Dysfunction

Possible causes of FSD are diverse and overlapping, and the initial etiology is sometimes an enormous challenge to discern. Etiologies include organic elements such as hormonal, neurological and vascular issues, as well as psychosocial factors such as relationship issues, social stressors, mood, history of physical or sexual abuse, and psychiatric history. In terms of physiology, neurotransmitters play an important role. Appropriate female sexual function requires a delicate balance of dopamine for desire, and epinephrine, norepinephrine, and serotonin for arousal and orgasm. Disorders and medications that disrupt these elements may lead to FSD. Hormonal deficits may be another factor in pathophysiology. The decrease in estrogen associated with menopause may induce decreased sexual desire and atrophy of genital tissue that leads to painful intercourse.[11]

Past estimates of the incidence of FSD range from approximately 10% if distress is used as a criterion, to 75% of menopausal women, if symptoms alone are used as the criterion. The peak age group for female sexual dysfunction (FSD) consists of women aged 51-59 years, around the time of menopause; however, FSD can occur in women of all ages.[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]

Prognosis is greatly dependent on the underlying etiology, the ability for the patient and partner to recognize the underlying problem, and the compliance of the couple with treatment. Although therapies exist for all types of sexual dysfunction, the prognosis is different depending on the severity of the dysfunction and the underlying etiologies. Prognosis may also vary based on whether the dysfunction is primary or secondary, and whether it is situational or generalized.[7, 12, 13, 14, 11]  

It is important for patients to understand that sexual function is a part of women’s health, that normal sexual function is different from one person to the next, and that misinformation and lack of education are common barriers to discussing the topic. Many patients lack the language or the knowledge needed to openly and comfortably engage in working through this problem. Patients may have difficulty using the correct anatomic terms and knowledge of anatomic structure and function may be limited, including lack of awareness of the clitoris and female orgasm. It is the healthcare provider’s role to educate the patient about these issues, and to provide the patient with the tools necessary to establish a healthy discourse, negotiate safe and reasonable goals, and then identify potential solutions to her problems.[11]

When orgasm and arousal difficulties are associated with insufficient or ineffective genital stimulation, education related to ensuring stimulation may be helpful.[9] Some women may be unaware of the importance of clitoral stimulation in inducing arousal, and education regarding clitoral anatomy can be useful.

Many patients are reluctant to disclose sexual problems owing to social stigma; fear of embarrassment; nontraditional gender roles or different sexual orientation; concern about the embarrassment of the healthcare provider; distrust in the provider’s ability to help; or a history of sexual, physical, or emotional abuse. Using a routine screening question during history-taking is therefore essential to open a dialogue about sexual concerns. Examples of questionnaires include the 19 question Female Sexual Function Index, a 12 item Female Sexual Distress Scale, and the 4 item Brief Sexual Symptoms Checklist for Women.[15]  A thorough nonjudgmental sexual history with open-ended questions is vital to making a diagnosis of sexual dysfunction and to identifying contributing elements. Most elements of the sexual history will apply to any evaluation for sexual dysfunction; those that are particular to a specific diagnosis are outlined separately below.

Questions should specifically address the nature of the concern, and whether the patient has difficulty with sexual desire, arousal, orgasm, sexual pain, or some combination thereof.  It is important to understand how long the problem has lasted, and whether the onset was abrupt or gradual.  A temporal relationship to a historical element such as childbirth, assault, or surgery may shed some light on the cause of the problem. While sexual, emotional, or physical abuse may not be disclosed by the patient at the first interview, building trust within the healthcare provider/patient relationship is essential, as this may be disclosed at a later time.

A careful social history is important, which should explore the nature of the patient’s relationship with her partner, whether this problem existed with other sexual partners, and for whom the sexual problem is causing distress. It is also important to understand that not all patients have a heterosexual or a monogamous relationship, and for those healthcare providers with moral objections to a person’s sexual choices, referral to another provider who can professionally and objectively handle the sexual complaint is essential. A psychological history is important, eliciting elements such as depression symptoms, history of psychiatric disease, and any history of alcohol or substance abuse. Understanding what the patient has tried to resolve the sexual problem can also be an important window into the patient history.[16, 11]

Female Sexual Interest/Arousal Disorder

In taking a sexual history from a patient with a complaint of “low libido” or “decreased sex drive,” specific information about their libido is important.  The next step is to establish what the level of desire was at baseline before the patient detected a problem. Helpful questions might include whether the patient has any spontaneous sexual thoughts or fantasies, whether she masturbates, and whether she has ever initiated episodes of intercourse within the relationship.

Female Sexual Pain/Penetrative Disorder

Sexual pain is often classified as being insertional, which usually involves external or vaginal structures, or deep, which would suggest intraperitoneal structures as a source. The sexual history of a woman complaining of sexual pain should target the nature and severity of the pain, sexual positions associated with the pain, the location, whether the patient needs to stop intercourse due to pain, the time course, and the previous evaluation and interventions attempted.

Female Orgasmic Disorder

For those patients with a primary complaint of orgasmic difficulty, questions should be directed to their experience of orgasm. It would be important to know whether orgasm was achieved previously, and if so under what circumstances (eg, with vibratory stimulation, with the same or different partner, or in a particular environment). Asking about the patient’s expectations and her knowledge of her own anatomy may also be helpful. 

Most female sexual dysfunction (FSD) issues do not directly relate to physical findings, and the physical examination may be focused with the following in mind. Thyroid disease may be contributory to Female Sexual Interest/Arousal Disorder (FSIAD), and a thyroid examination may be included. Pelvic examination is most helpful in women who complain of sexual pain and should specifically look for findings of atrophy or areas of tenderness that may relate to their complaints. Some patients with a history of trauma or abuse may not be ready for a pelvic examination on initial evaluation, and pelvic examination may need to be delayed to accommodate patient needs.

In examining external female genitalia, look for any skin lesions or atrophy. For patients with sexual pain, performing the bimanual exam before the speculum exam is ideal, as a bimanual exam may cause less trauma to the vaginal tissues than the speculum. For some patients with severe sexual pain, the speculum examination causes substantial trauma, and a subsequent bimanual examination is inaccurate and invalid owing to residual pain from the speculum.

The bimanual examination should specifically identify areas of tenderness that contribute to pain with penetration.  Some specific areas of focus in the pelvic exam include the vulvar vestibule (as occurs with localized provoked vulvodynia), levator and perineal body muscle soreness (vaginismus), rectovaginal nodularity (endometriosis), pelvic side wall tension or tenderness (myofascial pain syndrome), and anterior wall/ bladder (interstitial cystitis or painful bladder syndrome). Cervical motion tenderness is a non-specific finding that may suggest some intraperitoneal inflammatory changes.[9]  Common gynecologic conditions including vaginitis, sexually transmitted infection, leiomyomata, endometriosis, adnexal masses, cervical cancer, vulvar dermatoses, pelvic organ prolapse, vulvodynia, vaginismus, and adenomyosis may be identified on pelvic examination.[11]

History-taking is the most important aspect of the workup for sexual dysfunction. It is crucial that the provider allow ample time for discussion of the patient’s concerns, which may sometimes require scheduling a separate visit. Establishing an honest and trusting relationship is important, and the provider should take care to explain the nature and purpose of intimate lines of questioning, and assure the patient that privacy and confidentiality are guaranteed.[16, 11]

It is essential to meet the patient where they are with their problem, their requests and expectations, and their possible etiologies in setting up further diagnostic testing and treatment. A stated, negotiated treatment goal that is both fulfilling for the patient and medically reasonable given the situation may be helpful. For patients with female sexual dysfunction related to a trauma history, performing a pelvic exam may need to be delayed until further psychological treatment for the trauma can be obtained. Other patients may need marital counseling for relationship issues like poor communication or infidelity before real work on the sexual problem can begin. Patients with a psychiatric disorder may need to seek help for this issue before making real improvement with their sexual problem. A focused physical examination may or may not be appropriate, which can be determined after the history is obtained.[18, 16, 7, 11]

Many women with sexual concerns ask about or demand hormonal evaluation due to a perceived influence on sexual functioning.  In truth, such testing is rarely helpful, as literature does not support a direct relationship between levels of either androgens or estrogens and the capacity for sexual desire or arousal.[19] When use of supplemental hormone treatment is considered, the treatment is titrated to symptoms and not based on serum levels.  Obtaining serum androgen levels may be useful as follow-up in women after treatment to prevent the exposure to supraphysiologic levels of androgens. The diagnosis of estrogen deficiency is usually made clinically based on symptoms of menopause, but estrogen or follicle-stimulating hormone (FSH) levels may be helpful when the diagnosis is in doubt, as in women post-hysterectomy. A thyroid-stimulating hormone (TSH) screen may be helpful for patients with Female Sexual Interest/Arousal Disorder to rule out thyroid etiology, particularly when other symptoms such as irregular menses are present.[11]  

Transvaginal ultrasound may be helpful for patients with sexual pain who have cervical, bladder, uterine, or adnexal tenderness or masses on pelvic examination. In the absence of a palpable lesion, imaging is rarely useful.[11]

Reassurance and education, when appropriate, go far in allaying patient concerns and improving treatment success. Setting reasonable goals and expectations is important, and the provider may explain that improvement may take time and require multiple visits.  Sexual dysfunction, particularly when it is of long duration, is unlikely to resolve quickly. Usually starting with the problem bothering the patient the most is most helpful, although this order may need to be changed at the provider’s discretion.[2, 3, 12, 20, 16]  [11]

The PLISSIT model has also been found to be helpful.[21] In this model, the health care provider first gives the patient Permission to discuss the sexual problem, then provides Limited Information to the patient about the sexual problem. Specific Suggestions are next, where the healthcare provider provides concrete next steps to the patient, followed by a referral for Intensive Therapy if needed, so the patient can pursue a long-term appropriate solution that meets the stated treatment goals. For example, if a patient presents to a healthcare provider with a complaint of perimenopausal low sexual desire, the provider can provide the patient with Permission and Limited Information by saying, “Many people have trouble discussing this common problem near menopause, but I am glad that you were able bring this up with me today.” A Specific Suggestion could be that, “Successful long-term sexual relationships need a sufficient amount of variety and novelty, where partners are encouraged to spend ample time together and independently.”[11]  Additional information on treatment options may be provided, including resources and reading information.[12, 4] The provider could also refer the patient to a sex therapist in the area or have the patient return for a visit solely devoted to the sexual problem, for continued counseling and monitoring of progress.[11]

Treatment of sexual dysfunction depends on the underlying disorder. As mentioned above, treatment may include counseling, education, and reassurance. Once correctable causes have been addressed or ruled out, medical intervention may be considered. Recommendations are given separately below for each category of female sexual disorder.

Female Sexual Interest/Arousal Disorder

Because Female Sexual Interest/Arousal Disorder (FSIAD) may be a side effect of medications, a frequent solution is adjustment of other prescriptions. Although a host of pharmaceuticals have been implicated in impacting sexual desire and arousal (including antihistamines, beta blockers, diuretics, and hormonal contraceptives), the most common culprits are selective serotonin reuptake inhibitor (SSRI) antidepressants.  Sexual dysfunction is noted in as many as 56% of women who are prescribed SSRIs, and 70% of women who discontinue their prescription cite this effect as the primary reason. Improvements in sexual function may result from lowering the prescribed SSRI dose, or from changing to a different class of antidepressant such as bupropion or mirtazapine. However, it is important to do so in conjunction with a mental health care provider in order to avoid the detrimental effects of suddenly discontinuing antidepressant medication.[22, 14]

One medication that is FDA-approved to treat Female Sexual Interest/Arousal Disorder is flibanserin, a 5HT1A/2B agonist/antagonist. It is indicated for premenopausal women with low sexual desire. It is taken nightly and requires daily use. Due to the risk of syncope and hypotension, use of alcohol is proscribed for women on this medication.[23]

The FDA approved bremelanotide in June 2019 for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It is administered as a subcutaneous injection about 45 minutes before an anticipated sexual activity. Approval was based on clinical trials that demonstrated both improvement in sexual desire score and decrease in distress score relative to placebo.[24, 25, 26]

Supplemental androgens have not been approved in the US for sexual dysfunction. However, multiple randomized controlled trials have demonstrated a positive effect of testosterone in improving sexual desire in postmenopausal patients complaining of decreased libido, particularly in surgically menopausal women. Most evidence supports the use of transdermal preparations of testosterone which are not available in the US, but which may be compounded from commercially available preparations that are approved for men. Virilizing side effects are a concern for women exposed to high and prolonged levels of androgens, so use of such medication should include routine monitoring for androgen excess during brief courses of treatment at the lowest effective level.[27, 28, 11]

Genitopelvic Pain/Penetration Disorder

When sexual pain is insertional and associated with vaginal dryness, treatment may be helpful to reverse vaginal atrophy. Women with peri- or post-menopausal atrophy may benefit from topical estrogen, which improves vaginal epithelial integrity, reduces sensitivity and improves elasticity of the vaginal tissues. Topical estrogen is available as a cream, tablet, or continuous-release ring. Topical prasterone (DHEA) has recently been FDA-approved for the same indication, and can be applied nightly as a vaginal suppository. Ospemifene, an oral selective estrogen receptor modulator, is also approved to treat dyspareunia by reversing genital atrophy.[29, 13, 23, 14, 27]

Nonestrogen lubricants and moisturizers may also be helpful for patients with Genitopelvic Pain/ Penetration Disorder. These products are available over the counter, and are generally risk-free. These include silicone- or water-based solutions that are required with each sexual act (lubricants), or hydrophilic agents applied intermittently (moisturizers), which may relieve dryness independent of coitus.[2]

Fractional CO2 laser treatment has also been proposed as a therapy for sexual pain related to vaginal atrophy, but adequate studies have not been completed and this modality is not FDA-approved.[11]

When sexual pain is associated with restrictive disease from vaginismus or narrowing of the introitus, additional therapy may be needed. Pelvic floor physical therapy may be necessary in conjunction with specific counseling to help with painful muscular contraction of the vaginal muscles.  For patients with restrictive disease due to atrophy or radiation injury, dilator therapy is another useful tool.[2]

Surgical care may be appropriate occasionally for patients with deep dyspareunia associated with a distinct pelvic diagnosis, for example adenomyosis, endometriosis, or adhesive disease. When such an issue is suspected, laparoscopy may be useful as a diagnostic test.

Vestibulectomy is an effective surgical treatment for women with provoked vulvodynia localized to the vaginal vestibule in sufferers who have failed other forms of medical management. Patients should be counseled about the risks and benefits of surgery, and the limitations in offering relief from sexual pain.[2, 11]

Female Orgasmic Disorder

Inhibition of orgasm is another common side effect of SSRIs. As with FSIAD, women with orgasmic dysfunction may benefit from an adjustment in antidepressant therapy. Again, consideration must be given to the balance between the medication side effects and benefits of continuing effective antidepressants.

Although phosphodiesterase 5 inhibitors such as sildenafil have been effective for treating arousal and orgasmic difficulties in men, there is little evidence for an effect in women. Nevertheless, such medication may be useful in certain circumstances, such as in women with inhibited arousal on SSRIs.[11]

When orgasm and arousal difficulties are associated with insufficient or ineffective genital stimulation, education related to ensuring stimulation may be helpful.[9]  Some women may be unaware of the importance of clitoral stimulation in inducing arousal, and education regarding clitoral anatomy can be useful. An FDA-approved battery-powered suction device intended to increase arousal and improve orgasm by increasing blood flow and engorgement may be helpful for some patients; however, it is unclear whether this device has advantages over other over-the-counter vibrators. Drawing attention to the importance of adequate stimulation may include education on foreplay, lubricants, vibrators, and similar implements that may be useful for stimulation.

Patients with relationship stagnation, infidelity, or other relationship problems, and/or survivors of abuse may benefit from psychological counseling referral. Some may need couple’s therapy, while other patients may request individual therapy. Psychiatric referral is helpful for patients with poorly controlled psychiatric conditions or those with psychiatric medications that may have sexual side effects.

Referral to a gastroenterologist, urogynecologist, urologist, or pelvic floor physical therapist is helpful for patients with gastrointestinal or urologic conditions that are suspected causes of their sexual pain. Pelvic organ prolapse and fecal, flatus, or urinary incontinence may be discovered upon thorough history-taking, and these problems may cause embarrassment or distress with negative effects on sexual health.

Patients for whom sexual pain is thought to arise from a musculoskeletal etiology often benefit from pelvic floor physical therapy. Because not all physical therapists have been trained in this specialized form of care, it is important to identify therapists who are appropriately certified.

Patients may benefit from routine exercise with moderate physical exertion 150 minutes per week, or 75 minutes per week of high intensity exertion, as appropriate for the patient.

There is evidence that continued sexual activity is protective against later development of sexual dysfunction in menopausal women.[30]  Although this association may partly reflect a lower risk of FSD-related problems in those who are able to remain sexually active, it is physiologically plausible that sexual stimulation leads to increased blood flow and preserved elasticity that may protect against vulvovaginal atrophy and its sexual sequelae.[11]

Although there are no formal guidelines to recommend an interval at which sexual dysfunction patients should be followed after successful treatment, patients may benefit from an appointment to evaluate treatment progress every 3-6 months while improving, and then yearly thereafter.[11]

Most of the medications that have been approved by the FDA to treat female sexual dysfunction correct vulvovaginal atrophy that may lead to sexual pain.[2, 20, 29, 13, 23, 14, 28, 9, 11]

Treatment for sexual pain due to urogenital atrophy is aimed at correcting local or systemic estrogen deficiency, as these tissues are sensitive to estrogenic stimulation and targeting estrogen receptors in these tissues results in improvement in the integrity and elasticity of vaginal epithelium.

More recently, two drugs have also been approved by the FDA to treat low sexual desire (ie, flibanserin, bremelanotide). These medications are addressed more specifically below.[24, 25, 26]

 

Class Summary

Hormones are indicated for management of atrophic vaginitis resulting from diminished levels of circulating estrogens.

Conjugated estrogens, vaginal (Premarin)

Indicated for use in women experiencing vaginal changes secondary to a deficiency of estrogen.and moderate to severe painful intercourse caused by these changes.

Estradiol vaginal (Vagifem, Estrace, Estring, Yuvafem)

Vulvar and vaginal atrophy caused by estrogen loss, which results in vaginal dryness, burning, and itching, is a major source of painful intercourse for postmenopausal women. Topical estrogen reduce pH levels and mature the vaginal, which improves vaginal epithelial integrity, reduces sensitivity and improves elasticity of the vaginal tissues.

Class Summary

Agents in this class may aid in reversing genital atrophy.

Ospemifene (Osphena)

Selective estrogen receptor modulators activate estrogen pathways on the endometrium. Activation of these pathways improve vaginal changes associated with the decrease in natural estrogen production, which in turn improves vaginal maturation and decreases vaginal pH.

Class Summary

Agents in this class immprove elasticity and pH levels in vaginal tissue, which can in turn make sexual intercourse less painful.

Prasterone, intravaginal (Intrarosa)

Reduces moderate to severe painful intercourse due to menopause.  Its mechanism of action is poorly understood.

Class Summary

Agents in this class may improve sexual desire.

Flibanserin (Addyi)

Although the drug has known mixed agonist/antagonist effects on postsynaptic serotonergic receptors, its mechanism of action on the hypoactive sexual desire disorder is unknown,

Class Summary

Melanocortin receptor agonists with high affinity for the type-4 receptor have potential to modulate brain pathways involved in sexual response.

Bremelanotide (Vyleesi)

Melanocortin receptor (MCR) agonist that nonselectively activates several receptor subtypes with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R. It is indicated for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.