This chapter should be cited as follows:
Savickaite K, Louis L, Glob Libr Women's Med
ISSN: 1756-2228; DOI 10.3843/GLOWM.418643

The Continuous Textbook of Women’s Medicine Series – Gynecology Module

Volume 4

Benign gynecology

Volume Editor: Professor Shilpa Nambiar, Prince Court Medical Centre, Kuala Lumpur, Malaysia

Chapter

Female Sexual Dysfunction

First published: January 2025

Study Assessment Option

By completing 4 multiple-choice questions (randomly selected) after studying this chapter readers can qualify for Continuing Professional Development awards from FIGO plus a Study Completion Certificate from GLOWM
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TERMINOLOGY

We respect diverse gender identities and encourage inclusivity, using preferred terminology when addressing individuals based on their self-identified gender. In this chapter, we use the words ‘woman/women’ and ‘female’ to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary. We adopt the terminology ‘women’ or ‘female patients’ based on what is used in the cited studies.

INTRODUCTION

Sexuality is a fundamental aspect of human life that carries a profound meaning beyond reproductive function only. Female sexual dysfunction – a distressing sexual condition – is defined as a sexual health problem that adversely affects interpersonal relationships (within families and workplaces), day-to-day functioning and health-related quality of life. Female sexual dysfunction can afflict women of any age, and its presentation changes with the endocrinology of advancing years. This condition entails a complex interaction of biological, psychological, sociocultural and interpersonal aspects of a woman’s life. Therefore, sexual health is recognized as a key public health issue. In the UK, the improvement of sexual and reproductive health remains a public health priority.¹

Population-based epidemiological studies in various countries worldwide report that three or four in every 10 women have sexual dysfunction,^2,3,4,5 but less than half of those women report associated distress.^4,6,7 Women’s sexual dysfunction includes recurrent or persistent disorders that may be primary (lifelong) or secondary (acquired), situational or total. These sexual problems may occur at any phase of the sexual response cycle (e.g. desire, arousal, orgasm).

Female sexual dysfunction became a legitimate diagnosis within the International Classification of Diseases (ICD‑10). Classification of sexual dysfunction is complicated because several dysfunctions may overlap. According to the American Foundation for Urological Diseases Consensus,⁸ women’s sexual disorders and dysfunctions may be classified into four categories, ranging from lack of sex drive to sexual pain. These include sexual desire disorders (hypoactive sexual desire disorder, sexual aversion disorder and excessive sexual desire), sexual arousal disorder, orgasmic disorder and sexual pain disorders (dyspareunia, vaginismus and other sexual pain disorders).

The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‑5) merged two female sexual dysfunction disorders into female sexual interest/arousal disorder and removed sexual aversion disorder. The formerly separate pain disorders dyspareunia and vaginismus are now classified together under genitopelvic pain/penetration disorder. This diagnostic manual (written by the American Psychiatric Association) also defines substance/medication-induced sexual dysfunction as well as other specified or unspecified sexual dysfunctions.⁹

Sexual dysfunction may present at any time and at any stage in life. However, with a globally aging population, it is likely that a greater number of older patients who are and want to remain sexually active will present concerns about their sexual function at some point.^10,11 Another population who are likely to develop sexual problems is cancer survivors. It is recognized that after cancer treatment, including surgery, chemotherapy, radiotherapy and hematopoietic cell transplantation, people of any age may present with sexual dysfunction.^5,12 This dysfunction may have both a physical and psychological basis.

PREVALENCE

Female sexual dysfunction is a frequently encountered concern, with a prevalence varying from 29.7% to 43% across the world.^2,3,4,5 Notably, its prevalence surpasses that of erectile dysfunction in men. A cross-sectional study conducted in general practices in London, UK, revealed that 39.6% of women aged 18–75 years old received at least one ICD‑10 diagnosis related to sexual dysfunction.³

Despite the high prevalence of identified sexual problems in certain phases of the sexual response cycle, significantly fewer women reported experiencing personal distress associated with sexual dysfunction, and the extent of distress declined with advancing age. When comparing the prevalence of sexual problems in different age groups, such as young women (18–44 years old), middle-aged women (45–64 years old) and older women (over 65 years old), the prevalence of sexual dysfunction was 27.2%, 44.6% and 80.1%, respectively. However, associated personal distress was the lowest in elderly women (12.6%) and was present in 25.5% and 24.4% of middle-aged and younger women, respectively.⁴

Identifying how various difficulties in a woman’s sex life affect their wellbeing is crucial. Many people do not regard lack or loss of sexual desire as a serious problem. Therefore, more evidence is needed to offer medical treatment for this relatively common complaint. Several authors have emphasized the importance of taking a very reserved approach and trying not to over-medicalize identified inhibition of sexual desire in women facing stress, tiredness, threatening behavior from their partners or an unsatisfactory relationship in general.^3,13,14 Reduced sexual desire is considered a healthy and functional response to the current distressing situation.

RISK FACTORS

It is recognized that the etiology of sexual dysfunction is multifactorial.¹⁵ Kaschak and Tiefer identified several leading causes for sexual dysfunction, including sociocultural, political, economic, relationship-related, psychological and medical.¹⁶ All of these can precipitate a ‘discontent or dissatisfaction with any emotional, physical, or relationship aspect of [the] sexual experience’.¹⁶ The DSM‑5 similarly groups factors related to the sexual partner, relationships, individual vulnerability factors, psychiatric comorbidity, physical health, stressors, and cultural or religious factors.⁹ Common precipitating and predisposing factors for sexual problems are summarized in Table 1.

Situational, psychiatric and psychosocial dysfunction play a significant role in sexual function. Interest in engaging in sexual activity is strongly affected by fear of unwanted pregnancy or sexually transmitted infections, worries about their partner’s arousal, and lack of privacy or sufficient time.²⁹ A safe environment, high self-esteem and an attractive and available partner are crucial for normal female sexual desire. Hypoactive sexual desire disorders are common in women following broken relationships or the death of their partner.³⁰ On the other hand, women in committed long-term relationships learn how to live with their medical problems, adapt to changes in their partner’s physical health and sexual function, and focus on other positive factors in their relationship, and therefore a decrease in sexual activity may not cause significant distress.¹¹

Sexual and mental health issues are inter-related. Several studies have shown that women living with depression have a 50–70% increased risk of sexual dysfunction. Conversely, women suffering from sexual dysfunction have a 130–210% increased risk for any depressive disorder.^31,32 Among women, previously diagnosed depression is associated with a higher likelihood of lubrication problems, and stress caused by financial difficulties is positively associated with the inability to reach sexual climax.¹⁸

A French case–control study confirmed a higher prevalence of sexual dysfunction in women with multiple sclerosis compared with controls (69.2% and 26.9%, respectively). According to this study, this neurological condition mainly affected sexual desire, arousal and orgasm.²¹

Infertility is another risk factor for sexual dysfunction.³³ Months of unsuccessful attempts to conceive may lead to negative associations with sex, such as inadequacy, failure or frustration. Women with primary ovarian insufficiency have lower levels of estradiol, total testosterone and androstenedione. Women living with primary ovarian insufficiency report sexual problems associated with decreased sexual arousal, reduced lubrication and increased associated genital pain.³⁴ In menopause, estradiol levels are very low. This leads to vasomotor symptoms that commonly result in sexual aversion and loss of sexual desire. Likewise, atrophic vaginitis can cause severe dyspareunia and worsen sexual problems.³⁵

Sexual function and satisfaction undergo notable transformations over the course of a woman’s life, with menopause and childbearing events being closely linked to substantial alterations in her sexual experiences. Postmenopausal women exhibit a higher likelihood of experiencing sexual dysfunction (OR, 1.51) compared with their premenopausal counterparts. Menopausal women report low desire and arousal, as well as orgasm and lubrication disorders. However, childbearing was found to improve sexual function (OR for dysfunction, 0.75), mainly in the domains of lubrication (OR, 0.61), orgasm (OR, 0.77) and sexual pain (OR, 0.60).⁵

Regarding various gynecological problems, women with a history of pelvic inflammatory disease report sexual issues associated with lubrication (OR, 1.38) and sexual pain (OR, 1.55). Pelvic organ prolapse significantly affects sexual desire but has no negative impact on other domains.⁵

Medications associated with female sexual dysfunction

Examples of medications associated with desire, arousal and orgasm disorders are shown in Table 2. It is widely acknowledged that specific classes of antidepressants, notably selective serotonin re-uptake inhibitors (SSRIs), serotonin/norepinephrine re-uptake inhibitors (SNRIs), tricyclic antidepressants and monoamine oxidase inhibitors, are associated with induction of sexual dysfunction in certain individuals. This adverse effect may be mitigated through dose reduction, a change in antidepressants or addition of an antidote. Risperidone or first-generation antipsychotics may also cause sexual dysfunction, and, for this reason, it may be useful to check prolactin levels in patients treated with these antipsychotics.³⁶ Contemporary data suggest that prolactin plays a physiological role in modulating the release of dopamine and serotonin, which are key factors in the regulation of sexual function, particularly the post-orgasmic phase of sexual arousal in both males and females. Furthermore, elevated prolactin levels causing gonadal suppression may impact sexual function. Consequently, elevated prolactin levels, whether of short or extended duration, have the capacity to exert an influence on areas within the central nervous system that are responsible for the regulation of sexual function, including the genital response.³⁷ Prolactin receptors are prevalent throughout the central nervous system, with a notable presence in brain regions such as the cortex, hippocampus, amygdala and hypothalamus, all of which play critical roles in governing sexual behavior and activity.³⁸

In the context of other commonly prescribed medications, it is essential to consider the impact of the combined oral contraceptive pill. As combined oral contraceptive pill usage can elevate serum sex hormone-binding globulin levels, subsequently reducing free testosterone levels, it is advisable that women who present with sexual concerns and who are using combined oral contraceptive pills undergo assessments of their sex hormone-binding globulin levels, as well as total and free testosterone levels. It has been shown that individuals in this patient cohort have exhibited improvements in sexual desire through administration of androgen therapy.³⁶

SEXUAL DESIRE DISORDER

‘There are absent or diminished feelings of sexual interest or desire, absent sexual thoughts or fantasies and a lack of responsive desire. Motivations (here defined as reasons/incentives) for attempting to become sexually aroused are scarce or absent. The lack of interest is considered to be beyond the normative lessening with life cycle and relationship duration’.⁴⁰

Sexual desire disorder is a common sexual problem affecting 17–43% of women.^3,4,5,18,19 Approximately one in 10 women find it distressing.⁴ According to a study analyzing the effect of antidepressants in 107 patients with major depressive disorder, the frequency of impairment of sexual drive/desire in women ranged from 26% to 32%.⁴¹ Sexual aversion was reported in approximately 4% of women.

In women with this disorder, the desire for sexual activity is significantly reduced or absent, often including an absence of sexual thoughts or fantasies. Low libido affects women of all ages, with a peak in associated distress at midlife. For clinical diagnosis, low desire must be associated with clinically significant distress and last for at least 6 months.⁴² Sexual desire disorder is further classified into lifelong or acquired and generalized or situational.⁹

A cross-sectional study involving women in the USA aged between 20 and 70 years (the Women’s International Study on Health and Sexuality) revealed that those experiencing reduced sexual desire often also reported diminished sexual arousal, decreased sexual gratification and difficulties in achieving orgasm.¹⁹ These observations held true across age groups and regardless of their menopausal status. It was also observed that women encountering this specific sexual issue displayed infrequent initiation of sexual intercourse, self-stimulation or participation in other sexual activities. According to this study, women living with hypoactive sexual desire disorder report significantly worsening mental health, role limitations due to emotional problems, decline in social function and vitality and overall worse general health perceptions. However, they do not report worsening physical function.¹⁹

SEXUAL AROUSAL DISORDER

In women with sexual arousal disorder, the desire for sex may be intact, but there is an inability to build or maintain arousal during sexual activity. It is important to acknowledge that women diagnosed with sexual arousal disorder usually do respond to erotic genital stimulation, with physiologically healthy vasocongestive responses in their genitalia.⁹ Therefore, this condition is not the failure of genital congestion (an increase in blood flow to the vagina and vulva) but instead the primary cause of their distress is subjective arousal. It is also important to recognize the subtypes of sexual arousal disorder listed in Table 3. The reported prevalence of female sexual interest/arousal disorder is 21.5%.⁵ The prevalence of associated distress varies from 3.6% to 6.1%.^3,4

Multiple factors may serve as precursors to sexual arousal disorder, including stressful and adverse life events, psychosocial dysfunction, depression, medical and gynecological disorders, use of regular medication and disruptions in androgen production.^{35,44,45,46,47} Common medical conditions associated with an increased likelihood of sexual arousal problems are anxiety, hypothyroidism, arthritis, urinary incontinence and inflammatory or irritable bowel disease.⁴ Women taking antidepressants commonly report associated sexual arousal disorder.^46,47 Pain due to genitourinary syndrome after spontaneous or iatrogenic menopause also seriously affects sexual arousal.^35,48

ORGASMIC DISORDER

‘Despite the self-report of high sexual arousal/excitement, there is either lack of orgasm, markedly diminished intensity of orgasmic sensations or marked delay of orgasm from any kind of stimulation’.⁴⁰

The reported prevalence of orgasmic disorder varies from 18% to 41%.^3,5,18 Associated distress was reported by only 4.7% of women.⁴ Primary orgasmic disorder is when a woman has never had an orgasm. It is usually associated with trauma or abuse, but may remain unexplained. Secondary orgasmic disorder is generally the result of another sexual dysfunction, usually hypoactive sexual desire disorder (HSDD). Diagnosis of orgasmic disorder is made when failure to achieve orgasm causes marked distress or interpersonal difficulty.

In a global study on sexual attitudes and behaviors among individuals aged 40 to 80 years, factors such as the frequency of sexual activity, engagement in foreplay and partnership status did not show statistical significance.¹⁸ Nevertheless, reduced expectations regarding the continuation of future relationships were found to be linked with heightened dissatisfaction and difficulties in achieving orgasm in female participants.

The reasons contributing to a woman’s inability to achieve orgasm may include:

• fear or insufficient knowledge about sexual experiences
• difficulty in allowing oneself to fully engage
• inadequate and ineffective stimulation
• relationship challenges
• experiencing feelings of depression or heightened stress
• past traumatic sexual experiences

SEXUAL PAIN DISORDERS

It has been shown that 14% report sexual pain, i.e. pain associated with sexual stimulation or vaginal contact.⁵ Sexual pain disorders include genitourinary syndrome of menopause, pelvic floor hypertonus (also known as vaginismus) and dyspareunia. The prevalence of these conditions has been reported in the literature as 4.6% for non-organic vaginismus and 2.9% for non-organic dyspareunia.³

Vaginismus

‘The persistent or recurrent difficulties of the woman to allow vaginal entry of a penis, a finger, and/or any object, despite the woman’s expressed wish to do so. There is often (phobic) avoidance and anticipation/fear/experience of pain, along with variable involuntary pelvic muscle contraction. Structural or other physical abnormalities must be ruled out/addressed’.⁴⁰

In some cases, pelvic floor hypertonus (vaginismus) is not associated with pain, and may occur because of anticipated pain. For some women, vaginismus is experienced during sexual activity, but in other cases, it may be present only because of the fear of penetration or pelvic examination. Vaginismus does not mean that women cannot and do not enjoy sexual activity. Women can experience orgasms but still have vaginismus. However, penetration is not possible. There is a strong link between vaginismus and HSDD/sexual aversion. Interventions that target HSDD are usually effective in treating vaginismus. It is essential not to forget about organic causes of vaginismus, such as vestibulitis or endometriosis. Treating these conditions can significantly improve associated vaginismus.

Dyspareunia

Dyspareunia is persistent or recurrent pain with attempted or complete vaginal entry and/or penile/vaginal intercourse.⁴⁰ This genital pain is not caused exclusively by lack of lubrication or vaginismus. The pain may be felt at the entry or deep inside. Dyspareunia is frequently linked with HSDD and shares very similar situational and psychosocial causes. Therefore, dyspareunia may resolve in response to treatment of HSDD. Certain gynecological disorders (e.g. endometriosis, vestibulitis and uterine fibroids), chronic medical conditions or drugs can cause dyspareunia.^49,50

Sex after menopause

During menopause, estradiol levels markedly decrease, resulting in estrogen withdrawal. This in turn heightens tissue fragility, and contributes to a heightened risk of recurrent vaginal and urinary infections, urogenital pain, dryness and susceptibility to vaginal tissue trauma. Many women, especially those who maintain an active sex life, frequently report symptoms such as vaginal dryness, reduced lubrication and discomfort. Indirectly, these manifestations also affect sexual desire, as vulvovaginal atrophy resulting from estrogen depletion leads to trauma and pain during sexual penetration.⁵¹ Moreover, it is important to note that neuroendocrine estrogen depletion is associated with mood swings, hot flushes, irritability and insomnia, and all these changes adversely affect the sexual response.³⁵

Female genital mutilation

Female genital mutilation refers to the deliberate alteration, injury or cutting of female genital organs in the absence of medical justification. Detailed explanations of female genital mutilation types may be found in the GLOWM chapter on female genital mutilation.⁵² Female genital mutilation is typically performed on young girls (before the age of 10 years). Acute hemorrhage and infections are common because of the unhygienic conditions under which these procedures are often undertaken. Due to the nature of genital mutilation, many girls live with chronic morbidity, including recurrent urinary and reproductive tract infections, dyspareunia, and in rare cases (especially with type II and III mutilation) vesicovaginal fistula.⁵³ Recognized internationally as a harmful traditional practice, female genital mutilation remains prevalent in specific regions, particularly in sub-Saharan Africa and certain Southeast Asian countries. Women who have experienced female genital mutilation commonly complain of difficulties and pain having sex.⁵⁴

ASSESSMENT OF WOMEN’S SEXUAL DYSFUNCTION

Routine primary care visits, especially for gynecological health, already address specific aspects of sexual health through simple questions regarding sexual activity, safe sex practices and contraception. Incorporating questions focusing on any sexual concerns or sexual function will allow the opportunity to identify previously neglected and potentially treatable sexual health problems. Simple screening questions such as ‘How is your sex life?’ or ‘How is your intimate wellbeing?’ and others listed in Table 4,^29,55 are an excellent conversation starter and help to identify underlying problems. Any doctor who identifies a sexual health problem during regular health checks should consider referral to a counselor or therapist specializing in sexual and relationship issues. According to the American Psychiatric Association guidelines,⁹ to establish diagnosis of sexual dysfunction, the sexual problem must be persistent or recurrent for at least 6 months and cause personal distress or interpersonal difficulty.

Factors contributing to inadequate communication include the reluctance of patients and physicians to instigate such conversations,^56,57 together with disparities in sex and age between patients and their healthcare providers.⁵⁷ Additionally, negative societal attitudes concerning women’s sexuality and sexual health in older age may act as a barrier to open dialog.^56,58

Medical and psychosocial history

Obtaining a comprehensive sexual history, medical history (including medications) and psychosocial history is paramount for all types of sexual dysfunction. A complete reproductive health history is essential. Information about periods, previous pregnancies or infertility, type of contraception, previous sexually transmitted infections and gynecological surgeries can highlight issues affecting sexual response. More thorough questioning is needed if a patient discloses a history of past sexual abuse. The physician involved needs to assess the woman’s recovery from this incident and whether she underwent therapy. The current and past medical history (e.g. endocrine disorder, neurological or cardiovascular disease), including current medications, psychiatric illness, substance abuse, level of fatigue and the presence of non-sexual pain is crucial.⁵⁹ For example, if a patient reports the onset of low libido starting at the menopause, beginning with genitourinary syndrome of menopause, hot flushes and sleep disruption, treatment of menopausal symptoms can successfully improve their libido. Likewise, if changes in arousal and orgasmic response are noted at the onset of depression and initiation of antidepressants, the change of medication is likely to improve their sexual function.

To make a diagnosis of HSDD, use of the decreased sexual desire screener⁶⁰ in addition to obtaining a sexual health history is recommended. Alternatively, the female sexual function index is a more extensive questionnaire that helps to assess female sexual function. This diagnostic tool collects self-reported information across six domains, focusing on sexual desire, arousal, lubrication, orgasm, satisfaction and pain.⁶¹ These groups are very similar to the previously mentioned sexual dysfunction categories. The female sexual function index has been shown to be a gold standard, assisting in standardization of diagnosis and treatment guidance, as well as determining responses to gynecological and non-gynecological surgeries and pharmacological, psychological or physical therapies.⁶²

Physical examination

A genital examination can be highly informative; however, it is very intimate in nature and must be justified. A focused genital examination is recommended in female patients presenting with dyspareunia, vaginismus, known neurological disease affecting pelvic nerves, pelvic trauma, any disease potentially affecting genital health, or when the history indicates that screening for sexually transmitted infections or a Pap smear may be useful. Other investigations may include inspection for the classic signs of the genitourinary syndrome of menopause or vulval disorders (e.g. lichen sclerosus), gentle bimanual examination to elicit tender points and scarring, or cotton-bud evaluation of the vestibule for localized tenderness if indicated by the history. A normal examination has a reassurance value in patients who present with acquired or lifelong orgasmic disorders or combined arousal disorders.⁵⁹

Laboratory investigations

Most of the time, no laboratory investigations are needed for complete assessment of sexual dysfunction. However, certain blood tests to determine fasting blood glucose, hemoglobin or thyroid-stimulating hormone levels, for example, may identify an underlying medical condition. In cases in which an infective cause may have precipitated dyspareunia symptoms, vaginal, cervical and vulval discharge microscopy, cultures and a nucleic acid amplification test will help to identify the causative micro-organism and guide treatment. It is important to mention that certain female sexual dysfunction treatments adversely alter liver function and lipid values, which should be assessed prior to initiation of medication.^63,64 When exogenous androgen therapy is considered, accurate assays of free testosterone or total testosterone and sex hormone-binding globulin are required.⁵⁹

MANAGEMENT

Overview

Options for treatment of female sexual dysfunction may be broadly categorized into two main forms: non-medical or medical interventions. Within the realm of non-medical treatments, various factors can often be addressed through open and candid communication with one’s partner. This approach holds the potential to bolster emotional and sexual intimacy, as studies indicate that many couples rarely engage in discussions concerning their sexual lives.⁶⁵ Therefore, it is difficult to resolve differences in sexual desire with a partner over a lifetime, and communicating personal views, beliefs and feelings may be helpful. On the other hand, medical interventions, including pharmacotherapy or surgical intervention, can address somatic and physiological causes of sexual dysfunction. It is important to note that quantifying the female sexual response has proven to be a more intricate task in comparison with that of men. Consequently, researchers often encounter challenges when assessing the effectiveness of pharmacological therapies.¹⁴

Before starting any treatment, assessing the woman’s goals is crucial, so that her identified targets may be used to evaluate progress. This is an opportunity for a clinician to set realistic expectations while assessing a patient’s attitudes and beliefs related to her sex life. The female sexual distress scale,⁶⁶ a validated sexual function questionnaire, is a valuable adjunct for improvement tracking. It is also essential to assess whether the level of distress is significant enough to consider treatment options that carry the risk of adverse effects.

Interventions that address multiple issues

Attentive counseling focusing on the multifactorial origin of sexual problems is helpful in engaging patients. It provides an opportunity for shared decision-making, by actively involving them in management planning. It is imperative to convey to the patient that, in many cases, there is no straightforward or immediate remedy, and various management strategies may yield only modest or no improvement for a given patient. Involving the patient’s partner should be considered. Emphasis on the principal factors associated with a satisfying sex life, including physical and psychological wellbeing as well as the quality of a couple’s relationship, is key. Lifestyle changes and other measures taken by women to optimize their physical and emotional health and strengthen their partnership often simultaneously improve their sexual function.

Counseling

There is still confusion and uncertainty as to whether referrals ought to be directed to couple counselors or sex therapists. This uncertainty comes from a lack of knowledge of the difference between these services, and how they can benefit the person presenting with sexual problems. The general advice would be to consider referral to a couple counselor if the concern comes from communication problems or conflicts, and to a sex therapist if the identified concerns are specifically sex-related.

Psychotherapy and psychopharmacology

Psychological interventions offer support and appear to be immediately helpful; however, there is insufficient evidence of long-term efficacy. In some cases, cognitive behavioral therapy with a focus on relationship context and improvement of sexual satisfaction and arousal has been shown to be effective.⁶⁷ Cognitive behavioral therapy can also challenge a detrimental assumption about a woman’s lack of attractiveness, and encourage her to respond to signs of interest and desire from her partner or others.⁶⁸ Mindfulness is an effective intervention to decrease cognitive distractions (e.g. body-related thoughts) and enhance connection and sexual experience.⁶⁹

Sex therapy consists of various psychological interventions, including behavioral therapy, cognitive behavioral therapy and mindfulness. Mindfulness-based therapy, in particular, may be helpful in the management of HSDD as it can help with cognitive distractions during sexual activity. Several studies of cisgender women have demonstrated the efficacy of mindfulness and cognitive behavioral therapy interventions in improving sexual desire.^{70,71,72,73,74}

As discussed previously, psychiatric disorders, especially depression and anxiety, increase the likelihood of sexual dysfunction. Appropriate treatment of the underlying psychiatric problem can subsequently improve the patient’s sex life. For patients requiring pharmacological treatment, antidepressants and antipsychotics with fewer side-effects on sexual function should be considered. Examples are listed in Table 5. Previously experienced physical, emotional or sexual abuse or substance abuse should be addressed through effective counseling.

Lifestyle changes

Excessive stress and fatigue are substantial contributors to female sexual dysfunction, potentially exacerbating a range of sexual issues, including reduced libido. Focusing on good sleep hygiene, adjusting sleep and work hours, sharing household responsibilities, and finding assistance with a childcare or care for a dependent adult often improves sexual function. It is also advisable to avoid excessive drinking, to stop smoking, to incorporate regular exercise into a daily routine and to follow a healthy diet. Allocation of time for leisure and relaxation plays a pivotal role in enhancing overall wellbeing and health, with noteworthy implications for healthy sexual responses.

A small study analyzing yoga’s effects on sexual function showed that, after completing a yoga session, all participants engaging in this complementary alternative therapy reported significant improvement in all six domains (desire, arousal, lubrication, orgasm, satisfaction and pain). The improvement was more noticeable in women over 45 years of age.⁸⁴

Women in committed long-term relationships should be encouraged to schedule regular dates, try new things (e.g. different positions and sexual stimulation, sex toys, other items to increase sexual pleasure), read books about sexuality, and in other ways bring novelty to their current relationship. Childcare arrangements to ensure privacy may be helpful in improving sexual interest and response.

Improving body image

Girls often start reporting dissatisfaction with their bodies from a young age (4–11 years).⁸⁵ Women are more likely than men to have distracting thoughts associated with their body image that often elicit anxiety and adversely affect their sexual function.⁸⁶ A study by Quinn-Nilas et al. showed that women who evaluate their bodies more harshly strongly believe that they are unattractive, report significantly reduced sexual desire and arousal, and also struggle to experience orgasm.⁸⁷ These women agreed that their sexual behavior is greatly influenced by negative body image.⁸⁷ Overweight women (BMI >30 kg/m²) are more likely to report sexual problems than those of normal weight.⁸⁸ Moreover, improved sexual function has been observed following bariatric surgery.⁸⁹ Likewise, positive changes in sex life can be achieved through conservative interventions such as increased physical activity. Many women acknowledge improvement in their sex life after engagement in a regular exercise program.

It is postulated that, among patients with polycystic ovary syndrome, its negative effect on their sexuality is influenced by poor self-image secondary to hirsutism, obesity and acne.^90,91 According to a prospective, observational study conducted in Germany, there was a significant reduction in body weight and acne in patients treated with metformin for 6 months.⁹⁰ The study participants also reported more frequent sexual intercourse and overall increased satisfaction in their sex life.⁹⁰ Another group of people who are severely affected by poor body image and low self-esteem are cancer survivors. Aggressive cancer treatments lead to drastic changes to an individual’s body, firstly through changes in appearance (surgical scars, removal of affected organs and body parts, anorexia, hair loss and limb swelling) and secondly through sensory changes, including pain, tingling, burning and numbness. There are important functional changes as well, whereby people may suffer from a change in their speech, hearing, eyesight or swallowing or become incontinent. Negative effects also include loss of fertility, loss of mobility and the need to use a prosthesis.⁹² These changes to an individual’s body resulting from cancer treatment can have a substantial impact on their everyday life, particularly in relation to their body image.⁹³ Sacerdoti et al. highlight the strong feeling of loss among gynecological cancer survivors, including loss of sexual desire and pleasure and loss of femininity.¹² In the routine clinical setting, it is imperative to maintain an awareness of these challenges and provide appropriate support as necessary.

Treating pelvic floor dysfunction

Sexual problems may be exacerbated by pelvic floor dysfunction (e.g. coital urinary or fecal incontinence or pelvic organ prolapse).⁴ Women suffering from these problems, as well as dyspareunia or pelvic floor hypertonus, may benefit from pelvic floor exercises guided by physiotherapists who specialize in pelvic floor anatomy and function. Pelvic floor physiotherapy is the first-line management for first-stage pelvic organ prolapse and stress urinary incontinence.⁹⁴ According to a study by Brækken et al., 39% of women reported an improvement in their sexual function after a 6-month course of pelvic floor physiotherapy,⁹⁵ and a randomized controlled trial has shown that there was no difference between standard physiotherapy and electrical stimulation.⁹⁶ When conservative measures are ineffective, surgical treatment options should be discussed and offered to appropriately selected patients. This is important because improvement of sexual function may not be achieved by surgery, and some patients may actually develop dyspareunia.^97,98

SEXUAL INTEREST/AROUSAL DISORDER

HSDD is thought to be caused to some degree by an imbalance between excitatory and inhibitory pathways involved in the sexual response and behavior in the brain. Physiologically, dopamine, oxytocin, norepinephrine, melanocortin, testosterone, estrogen and progesterone are excitatory, whereas serotonin, prolactin, opioids and endocannabinoids are inhibitory of sexual desire and response. Pharmacological treatments for HSDD target some neurotransmitters and hormones involved in these pathways.³⁶

It is essential not to forget that multiple relationship factors can and do contribute to low sexual desire. Providing patients with information and methods to improve their sexual relationships can simultaneously increase their sexual desire. Sexual interest typically decreases with relationship duration, so encouraging interventions that increase novelty is beneficial.

Hormone therapy

Results of the American population-based study, the Women’s International Study of Health and Sexuality, showed that 20–49-year-old women with irreversible iatrogenic menopause (post-surgery) are three times more likely to experience distress associated with low sexual desire compared with premenopausal women of the same age. Regarding use of any type of hormone therapy, surgically postmenopausal women were more likely to use hormone therapy compared with naturally postmenopausal women of the same age (80% and 32%, respectively). The prevalence of hormone therapy usage in the cohort of surgically postmenopausal women was 73% among 20–49-year-olds and 80% among 50–70-year-olds.¹⁹

Androgens

In female bodies, androgen synthesis occurs in adrenal glands and ovaries. The major circulating androgens are dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, testosterone and dihydrotestosterone (in descending order of serum concentration in women). Testosterone is the most potent androgen, and is secreted by the adrenal zona fasciculata (25%) and the ovarian stroma (25%), each approximately 50 μg per day. The remaining 50% are produced from circulating androstenedione. Testosterone can be produced intracellularly from dehydroepiandrosterone sulfate.

Testosterone may be found in free form or bound to protein (albumin or sex steroid hormone-binding globulin).⁹⁹ Only a small fraction (approximately 2%) of circulating testosterone is unbound and biologically active. In women, androgen levels peak at 18 and 24 years, with a significant decline by the age of 35 years. Measured androgen levels do not vary significantly through physiological menopause. However, bilateral oophorectomy results in a sudden decrease of circulating androstenedione and testosterone that persists into menopause.¹⁰⁰ Following oophorectomy in pre- or postmenopausal women, testosterone levels decrease approximately 50% in both cases.¹⁰¹ Postmenopausally, there is an increase in free testosterone levels due to decreased sex hormone-binding globulin levels. On the other hand, free testosterone levels have been shown to be reduced in patients with hypopituitarism and those receiving estrogen replacement therapy.^34,102 Even though serum levels of endogenous testosterone cannot predict sexual function in women, androgen therapy (supraphysiological doses) in selected postmenopausal women has been shown to improve their sexual desire and frequency of sexual activity.¹⁰³

Androgen therapy should only be offered to patients who have already tried non-pharmacological interventions and optimized their lifestyles and medications for other medical conditions. Women should also understand the potential risks and side-effects (listed below). It is crucial to explain that this therapy cannot be used without estrogen replacement therapy, and data on safety (especially for long-term use) and efficacy are scarce. The recommended dose is up to 10% of the standard male dose. Women undergoing androgen therapy should be closely monitored for signs of testosterone excess.

Currently, there is no consensus regarding the recommended formulation (testosterone or methyltestosterone) and delivery methods (oral, transdermal patch, spray or topical ointment, cream, gel). The results of randomized, double-blind, placebo-controlled trials showed that use of twice-weekly transdermal testosterone patches (300 μg/day) improved baseline and the frequency of satisfying sexual activity and decreased personal distress in women diagnosed with hypoactive sexual desire disorder compared with placebo.^104,105 The improvement was noted in both naturally postmenopausal women and surgically postmenopausal women. It was concluded that this formulation, dose and mode of administration is safe and effective for 6 months in women receiving concomitant estrogen therapy.^104,105 However, despite the fact that the majority of safety or efficacy data are for transdermal patches, no such product is available on the USA or European market.

The latest pharmaceutical studies focus on the advancement of topical androgen administration. For example, Zeng et al. published a study about a testosterone film-forming gel that has the potential to reduce irritation caused by transdermal patches.¹⁰⁶

Adverse effects and contraindications

Evaluation of adverse effects is limited because of the very small number of studies of women taking testosterone therapy without estrogen. Moreover, the duration of such trials is approximately 3–12 months, and therefore there is no compelling evidence regarding long-term effects. Androgenic, metabolic or other health effects are potentially serious health concerns in women taking androgen therapy.¹⁰³ These medications should not be used in patients with known liver and cardiovascular disease, as well as those with female cancers, including breast and endometrial cancer, or endometrial hyperplasia. Use with caution is strongly advised in women who are at substantial risk for these disorders. The occurrence of venous thromboembolism, including deep vein thrombosis, pulmonary embolism or cerebral venous sinus thrombosis, is mainly associated with co-administration of estrogen.¹⁰⁷ A limited body of evidence, including a study on male participants and trans men (assigned female sex at birth),¹⁰⁸ shows an increased risk of secondary erythrocytosis without a strong link to thromboembolic events.

Monitoring for potential adverse effects is paramount. Normal lipid levels and liver function values should be confirmed prior to the commencement of androgen therapy. Repeated tests should be performed after 6 months and then annually. Annual mammograms should be performed.

Side-effects

The side-effects of androgen therapy include:

• mild androgenic effects such as hirsutism¹⁰⁹ and acne^109,110
• irreversible virilizing changes, such as voice deepening or clitoromegaly; these are rare and occur only with excessive medication intake^110,111
• a slight decrease in serum levels of high-density lipoprotein cholesterol was observed in postmenopausal women on oral testosterone therapy, but it is unknown whether this decline affects cardiovascular risk (no changes in serum lipid levels were noted for non-oral administration)¹¹²

Physiologically, androgens are aromatized to estrogens; therefore, the potential risks of estrogen therapy (discussed below) are also possible in women taking androgen therapy. Some studies have shown that women had abnormal uterine bleeding after androgen therapy; however, there is no evidence of an increased risk of endometrial hyperplasia or cancer.^105,113,114 There are minimal data on long-term use and use in naturally menopausal women without concurrent progestogen therapy. A clinical trial analyzing the safety of testosterone therapy also reported a possibly increased breast cancer risk.^109,112

Estrogens

Estrogen therapy should be considered for patients whose history and physical examination findings are consistent with estrogen depletion. The currently available forms of estrogen administration are oral, transdermal (patch, topical gels and once-a-day spray) and vaginal (intravaginal creams and tablets, and vaginal rings). Use of transdermal estradiol (an administration method that does not have a ‘first-pass effect’ through the liver) is not associated with thromboembolic events.¹¹⁵ In older women, it may be used safely to manage the symptoms of hypoestrogenism over prolonged periods of time. Although the evidence does not support the role of systemic hormonal therapy for treatment of sexual dysfunction in all postmenopausal women, appropriately selected patients with vasovagal symptoms that are affecting their previously satisfying sex life may experience improvement in their sexual problems. Finally, intravaginal estrogens or dehydroepiandrosterone are highly effective for the treatment of genitourinary syndrome of menopause and show minimal systemic absorption.¹¹⁶

Tibolone

Tibolone is a drug whose metabolites have estrogenic, androgenic and progestogenic properties. This synthetic steroid has been widely used in Europe and other countries, but is not currently available in the USA because of serious safety concerns. Tibolone is less effective than combined hormonal replacement therapy, but may be used to reduce vasomotor symptoms in menopausal women, when estrogen-containing therapy is contraindicated.¹¹⁷ Use of tibolone has also shown a significant improvement in bone mineral density.^118,119 Based on the results of randomized trials, tibolone appears to be more effective than estrogen/progestin therapy for the treatment of sexual dysfunction.^120,121,122 However, serious associated adverse effects, including recurrence of breast cancer, an increased risk of endometrial hyperplasia or cancer, and an increased risk of stroke in women over 60 years old, should be taken into consideration.^117,118,123 Therefore, tibolone should be avoided in individuals with strong risk factors for stroke, such as smoking, hypertension, diabetes and atrial fibrillation.¹²⁴ Compared with estrogen-containing hormonal therapies, tibolone does not increase the risk of venous thromboembolism.¹¹⁷

Non-hormonal medical therapy

Flibanserin

Flibanserin is a non-hormonal serotonin 1A (5‑HT1A) receptor agonist and serotonin 2A (5‑HT2A) receptor antagonist used for treatment of HSDD in premenopausal women. Due to its mechanism of action (increases in dopamine and norepinephrine levels and decreases in serotonin levels), flibanserin is region-specific. As a consequence of these effects on neurotransmitters, the restored ‘balance’ between inhibitory and excitatory factors should improve the sexual response. According to the investigators in two 6-month clinical trials, use of flibanserin was associated with a significant improvement in sexual desire, increased sexual experiences and decreased sexual distress.^125,126 Bedtime administration helps to counteract common side-effects such as dizziness and sleepiness. Risk evaluation is required for serious hypotension and syncopal events provoked by interactions with alcohol.¹²⁷

Bupropion

Bupropion is an antidepressant that is a norepinephrine and dopamine reuptake inhibitor. This pharmacological agent may be offered for female patients reporting distressing sexual dysfunction if non-pharmacological interventions are ineffective. Bupropion has clearly characterized risks and side-effects, and long-term safety data are available.¹²⁸ Women taking bupropion should be closely monitored for increased insomnia, anxiety and hypertension.¹²⁹ According to available studies, patients’ reported sexual-function improvement varied. A randomized controlled trial of premenopausal women with HSDD without depression reported improved sexual function (increased pleasure, arousal and orgasm).¹³⁰ However, a small-scale prospective, single-blind study evaluating bupropion in pre- and postmenopausal women in a long-term relationship¹²⁹ demonstrated a non-significant improvement in their sex life but significant deterioration in the partner relationship domain as measured by a relationship questionnaire.¹³¹

Buspirone

The centrally acting anxiolytic buspirone is a partial serotonin 1A (5‑HT1A) receptor agonist and presynaptic dopamine receptor antagonist. Its mechanism of action is similar to that of flibanserin. Therefore, off-label use of this drug can also improve sexual desire.

Bremelanotide

Bremelanotide is a synthetic melanocortin analog. This medication is approved to treat HSDD in premenopausal women. The available forms are intranasal¹³² and subcutaneous injections at least 45 min before sexual activity. Randomized controlled studies have shown that bremelanotide injections effectively increase sexual desire (51.0% vs 20.7%) and improve sexual satisfaction (56.9% vs 25.7%).¹³³ Common side-effects are nausea, vomiting, flushing, headache and hyperpigmentation. Despite these side-effects, this medication may be preferable for women with distressing sexual dysfunction because it does not have to be taken daily but only before anticipated sexual activity.

Phosphodiesterase inhibitors

Phosphodiesterase‑5 inhibitors (e.g. sildenafil, tadalafil and vardenafil) are well-known drugs that are effective in treating male erectile dysfunction. Despite some positive changes in sexual arousal and orgasm for women suffering from SSRI-induced sexual dysfunction,¹³⁴ these inhibitors have no generally proven effect in women. According to the best available randomized controlled trial of 800 participants, use of sildenafil was not more effective than placebo.¹³⁵ However, if the woman’s experienced sexual dissatisfaction is secondary to her partner’s erectile dysfunction, use of phosphodiesterase‑5 inhibitors by her partner (if not contraindicated) can improve the couple’s sex life.

SEXUAL PAIN

Genitourinary syndrome of menopause

Dyspareunia related to genitourinary syndrome of menopause may be initially managed using non-hormonal vaginal lubricants or moisturizers. Other routine management options include low-dose vaginal estrogen preparations, including creams, tablets, softgel vaginal inserts and rings.¹³⁶ Alternatively, according to the results of a randomized controlled trial, postmenopausal women with moderate to severe vaginal atrophy may benefit from a daily vaginally administered dehydroepiandrosterone (1%) that has been shown to reduce pain during intercourse and improve other domains of sexual dysfunction (sexual desire, arousal, lubrication and orgasm).^137,138 Ospemifene, an oral form of selective estrogen receptor modulator, may also be beneficial for people with moderate to severe symptomatic vulval and vaginal atrophy, when estrogen products are contraindicated.¹³⁹ However, risks relating to endometrial cancer, venous thromboembolism and stroke should not be forgotten.¹⁴⁰

In terms of the development and application of novel technologies for treatment of genitourinary syndrome of menopause, it is worth noting the emergence of vaginal laser and radiofrequency devices. However, it is imperative to highlight that their safety and efficacy have not been firmly established. A systematic review reported improved dyspareunia, vaginal dryness and overall sexual function among breast cancer survivors when vaginal laser treatment was used as an alternative to contraindicated estrogen therapies, although no long-term safety and efficacy data are available.¹⁴¹ While certain smaller-scale investigations have reported favorable outcomes with vaginal laser therapy for genitourinary syndrome of menopause, a substantial randomized trial, incorporating a sham control, failed to demonstrate any discernible therapeutic advantage stemming from use of three fractional microablative carbon dioxide laser treatments in terms of alleviation of vaginal symptom severity.¹⁴² Given the considerable cost, potential risks and experimental nature of their use, laser treatment is not currently recommended outside research settings.¹⁴²

Pelvic floor hypertonus, dyspareunia and other pain disorders

Regarding other pain disorders, non-hormonal options such as lidocaine ointment, topical hormonal creams or antidepressants may be used. For provoked pelvic floor hypertonus, it is crucial to identify the leading cause of this problem before starting any intervention. Available treatment options are counseling, focused on sexual education, cognitive and behavioral psychotherapy, or the use of vaginal dilators. Various studies have assessed the use of administration of botulinum toxin A injections to the puborectalis and pubococcygeus muscles as a potential solution for vaginismus that has not responded to other treatments.^143,144,145 However, this approach should only be considered in carefully selected cases and with thorough patient counseling.^143,144,145 Similarly in dyspareunia, if the pain is caused by pelvic floor spasms, the first intervention should be psychological support. Systemic desensitization achieved by cognitive behavioral therapy is the most effective method. On the other hand, if the dyspareunia is caused by vestibulitis or endometriosis, specific treatment for these conditions should improve pain and sexual function. Local tissue desensitization, electromyographic biofeedback and manual therapies are other treatment options for sexual pain. Lastly, a small body of evidence supports use of vestibulectomy in selected women suffering from vulvodynia, if no improvement is achieved using non-invasive therapeutic options.¹⁴⁶

TREATMENTS THAT ARE NOT RECOMMENDED

Herbal supplements and other over-the-counter products are not recommended. It is essential to educate patients about the unverified safety and effectiveness of these products, together with the limited regulatory supervision and the potential for significant costs. Regarding other hormonal therapies, oxytocin and progesterone have no role in treatment of female sexual dysfunction.²⁹

FOLLOW-UP

There is still not a single totally reliable, validated and comprehensive tool to assess and follow up on the multifactorial nature of sexual desire and sexual arousal disorders (physical functioning, mental wellbeing and life satisfaction), even though these disorders significantly affect health-related quality of life for women and their partners.¹⁴⁷ Developing and adopting such tools would markedly enhance consultations, help to establish realistic treatment goals, and support resolution of the disease burden experienced by women suffering from sexual dysfunction.

PRACTICE RECOMMENDATIONS

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