Etiology

Etiology of sexual dysfunction is usually multifactorial, involving personal, psychological, contextual, sociocultural, and sometimes medical factors.[24][25]

Underlying depression and anxiety symptoms are common. Even when a clinical diagnosis of mood or anxiety disorder is absent, women with desire disorders show more mood lability, low self-esteem, and anxious and depressive thoughts than women without sexual problems.[3][4][5][6]

Sexual and nonsexual experiences in early development and adolescence also shape psychosexual development, such that neglect, abuse (verbal/emotional/sexual), trauma, or intolerance of the child showing emotions may be etiologically important.[26][27]

Poor quality of the current interpersonal relationship, lack of sexual environment and sexual stimuli that are conducive to the woman's arousal, sexual dysfunction in her partner, and sociocultural pressures and restrictions are further contributors.[3][6][20][25] Chronic medical conditions and interventions may also contribute, including use of certain medications, particularly selective serotonin-reuptake inhibitors.[28][23][29][30] Other drugs that can negatively affect sexual function include antihypertensives (beta-blockers, thiazide diuretics), lithium, antipsychotics, benzodiazepines, anticonvulsants, gonadotropin-releasing hormone agonists, aromatase inhibitors, antiandrogens (e.g., spironolactone), opioid analgesics, cocaine, and alcohol.[31] Further research is needed on the role of oral contraceptives in sexual dysfunction, as studies have yielded contradictory results.[32][33]

Bilateral oophorectomy (BSO) in a young woman may contribute, although elective surgery in midlife women does not appear to be associated with subsequent sexual dysfunction.[15][16][34] These findings suggest that loss of ovarian androgen may not be the relevant factor linking BSO to sexual sequelae. Estrogen deficiency can cause loss of sexual sensitivity of genital and nongenital skin and dyspareunia, both contributing to reduced sexual interest. A lack of appropriate sexual learning, either via sex education or through experience, may be etiologically related to lifelong women's orgasmic disorder.[35]

The etiology of persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) is unknown, but obsessive-compulsive symptoms, hypervigilance to body sensations, catastrophizing of those symptoms, and resulting anxiety seem to be characteristic.[36][37] Restless legs syndrome (RLS) and overactive bladder may accompany PGAD/GPD.[38][39] Treatment of RLS with clonazepam or a dopaminergic medication may reduce symptoms of PGAD/GPD.[38] Given that there is only limited research on PGAD/GPD, its pathophysiology and treatment are not further discussed.

Pathophysiology

Women sexually engage for a variety of reasons, often to enhance emotional intimacy, even if desire is not present initially.[40] Desire is often triggered later during the experience, and once aroused, arousal and desire become indistinguishable.[24][40][41] Arousal involves complex brain circuitry linking cortical, limbic, and paralimbic regions that are associated with cognition, attention, motivation, and emotions, with areas modulating the autonomic nervous system.[29] Thus sexual response is affected by negative emotions, inability to attend to sexual stimuli, or absence of reasons to be sexual.[42]

The underlying biologic mechanisms are not fully understood but involve multiple neurotransmitters, peptides, and hormones. Norepinephrine, dopamine, melanocortin, oxytocin, and serotonin acting on some serotonin receptors are prosexual, whereas prolactin, serotonin acting on other receptors, and neurotransmitter gamma-aminobutyric acid (GABA) are inhibitory. There is complex interplay between the neurotransmitters and peptides and sex hormones, and between environmental and neuroendocrine factors. Thus the sexual circumstances, as well as medical conditions or medications modulating neurotransmitters and/or hormones, may interrupt sexual response.

Genital congestion, a reflex autonomic response occurring within seconds of a sexual stimulus, causes genital engorgement and increased vaginal lubrication, even when there is no subjective sexual arousal.[43] The degree of genital congestion correlates poorly with sexual excitement and subjective arousal, but is important for comfort with intercourse and genital sexual sensitivity.[43][44] This response can be interrupted by neurologic disease, estrogen deficiency (which reduces vascularity and expansion via decreased bioavailable nitric oxide, the major neurotransmitter in the clitoris, and reduced bioavailable vasoactive intestinal polypeptide, the major neurotransmitter in the vagina) or severe vascular disease. Androgen deprivation may also be associated with loss of genital sexual sensitivity, but it does not underlie the loss of subjective arousal identified in women diagnosed with desire/arousal disorders. Large epidemiologic studies refute an association between levels of sexual desire and levels of serum testosterone, and in one small study an inverse relationship between free testosterone and arousal was identified.[45] However, testosterone synthesized intracellularly from adrenal precursors (intracrine production), including dehydroepiandrosterone (DHEA), is not reflected in serum levels. Androgen metabolites can now be measured to reflect total androgen activity (from gonadal and intracrine sources). In two studies, there were no group differences in total androgen metabolites in women with and without low desire and arousal.[46][47] Although surgical menopause is associated with lower testosterone levels than natural menopause, one study suggests no difference in sexual desire and arousal, only diminished lubrication after surgical menopause.[48] Studying sexual function of 33,000 women across the menopause transition, investigators concluded that the observed modest association of serum testosterone with sexual response implies that the relationship is subtle and of questionable clinical significance.[49] One study of 6392 women examining how sex steroid levels vary with age reports that from age 70 years, testosterone and estrone increase with age (despite a steady decline in DHEA), such that testosterone levels in the women in their study did not differ from premenopausal levels.[50] The authors cite consistency with earlier work that reported a nadir for testosterone levels at 62-63 years, followed by an increase up to the age of 75 years. They assert that given the estimated 30% decline in DHEA (the primary precursor), testosterone biosynthesis which maintains testosterone levels is dependent on enzyme activity rather than precursor availability.[51]

In contrast, a number of studies report low DHEA levels in women with hypoactive sexual desire disorder (HSDD).[52] This low DHEA may reflect past childhood traumas associated with blunting of stress hormones in adult life, thus increasing vulnerability to disease and disorders. Women with HSDD show such blunting of stress responses.[52]

Classification

Diagnostic and statistical manual of mental disorders, fifth edition, text revision (DSM-5-TR)[1]

The DSM-5-TR divides sexual dysfunction in women into:

  • Female sexual interest/arousal disorder

  • Female orgasmic disorder

  • Genito-pelvic penetration pain disorder

  • Substance/medication-induced sexual dysfunction

  • Other specified sexual dysfunction

  • Unspecified sexual dysfunction.

Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD)[13]

PGAD/GPD is not recognized as a diagnosis in the DSM-5-TR or ICD-11, but is an entity of increasing clinical attention and research. The International Society for the Study of Women's Sexual Health defines PGAD/GPD as persistent or recurrent, unwanted or intrusive, distressing sensations of genital arousal that persist for ≥3 months and may include other genito-pelvic dysesthesia.[13]

Use of this content is subject to our disclaimer