Female sexual dysfunction: a focus on flibanserin

Figures & data

Table 1 Summary of DSM-5 criteria for female sexual dysfunction

Female sexual dysfunction types	DSM-5 criteria
Female sexual interest/arousal disorder	A. Lack of, or significantly reduced, sexual interest/arousal, as manifested by at least three of the following:
	1. Absent/reduced interest in sexual activity
	2. Absent/reduced sexual/erotic thoughts or fantasies
	3. No/reduced initiation of sexual activity and typically unreceptive to a partner’s attempts to initiate
	4. Absent/reduced sexual excitement/pleasure during sexual activity in almost all or all (75%–100%) sexual encounters (in identified situational contexts or, if generalized, in all contexts)
	5. Absent/reduced sexual interest/arousal in response to any internal or external sexual/erotic cues (eg, written, verbal, visual)
	6. Absent/reduced genital or non-genital sensations during sexual activity in almost all or all (75%–100%) sexual encounters (in identified situational contexts or, if generalized, in all contexts)
	B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months
	C. The symptoms in Criterion A cause clinically significant distress in the individual
	D. The sexual dysfunction is not better explained by a non-sexual mental disorder or as a consequence of severe relationship distress (eg, partner violence) or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
	Specify whether:
	Lifelong: The disturbance has been present since the individual became sexually active.
	Acquired: The disturbance began after a period of relatively normal sexual function.
	Specify whether:
	Generalized: Not limited to certain types of stimulation, situations or partners.
	Situational: Only occurs with certain types of stimulation, situations or partners.
	Specify current severity:
	Mild: Evidence of mild stress over the symptoms in Criterion A.
	Moderate: Evidence of moderate distress over the symptoms in Criterion A.
	Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
Female orgasmic disorder	A. Presence of either of the following symptoms and experienced on almost all or all (approximately 75%–100%) occasions of sexual activity (in identified situational contexts or, if generalized, in all contexts):
	1. Marked delay in, marked infrequency of, or absence of orgasm
	2. Markedly reduced intensity of orgasmic sensations
	B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months
	C. The symptoms in Criterion A cause clinically significant distress in the individual
	D. The sexual dysfunction is not better explained by a non-sexual mental disorder or as a consequence of severe relationship distress (eg, partner violence) or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
	Specify whether:
	Lifelong: The disturbance has been present since the individual became sexually active.
	Acquired: The disturbance began after a period of relatively normal sexual function.
	Specify whether:
	Generalized: Not limited to certain types of stimulation, situations or partners.
	Situational: Only occurs with certain types of stimulation, situations or partners.
	Specify if:
	Never experienced an orgasm under any situation.
	Specify current severity:
	Mild: Evidence of mild stress over the symptoms in Criterion A.
	Moderate: Evidence of moderate distress over the symptoms in Criterion A.
	Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.
Genito-pelvic pain/penetration disorder	A. Persistent or recurrent difficulties with one (or more) of the following:
	1. Vaginal penetration during intercourse
	2. Marked vulvovaginal or pelvic pain during vaginal intercourse or penetration attempts
	3. Marked fear or anxiety about vulvovaginal or pelvic pain in anticipation of, during, or as a result of vaginal penetration
	4. Marked tensing or tightening of the pelvic floor muscles during attempted vaginal penetration
	B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months
	C. The symptoms in Criterion A cause clinically significant distress in the individual
	D. The sexual dysfunction is not better explained by a non-sexual mental disorder or as a consequence of severe relationship distress (eg, partner violence) or other significant stressors and is not attributable to the effects of a substance/medication or another medical condition.
	Specify whether:
	Lifelong: The disturbance has been present since the individual became sexually active.
	Acquired: The disturbance began after a period of relatively normal sexual function.
	Specify current severity:
	Mild: Evidence of mild stress over the symptoms in Criterion A.
	Moderate: Evidence of moderate distress over the symptoms in Criterion A.
	Severe: Evidence of severe or extreme distress over the symptoms in Criterion A.

Note: Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright ©2013). American Psychiatric Association. All Rights Reserved.¹

Abbreviation: DSM-5, Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.

Table 2 Comparison of select endpoints evaluating the use of flibanserin treatment

Study and population	Dose(s)	Comparator	Select end point(s) (FSFI – desire domain score and total score)	Commonly reported flibanserin adverse effects
DAISY study Premenopausal women^Citation43 4-week baseline followed by 24-week randomized, double-blind, placebo-controlled	Flibanserin 25 mg twice daily Flibanserin 50 mg twice daily Flibanserin 100 mg once daily at bedtime (total flibanserin N=1,183)	Placebo (N=398)	Mean change (SE) from baseline to week 24 in the FSFI – desire domain score: Placebo – 0.6 (0.1) Flibanserin 25 mg twice daily – 0.8 (0.1) (P<0.01 vs placebo) Flibanserin 50 mg twice daily – 0.8 (0.1) (P<0.01 vs placebo) Flibanserin 100 mg once daily – 0.9 (0.1) (P<0.0001 vs placebo) Mean change (SE) from baseline to week 24 in the FSFI – total score: Placebo – 2.6 (0.3) Flibanserin 25 mg twice daily – 3.9 (0.3) (P<0.01 vs placebo) Flibanserin 50 mg twice daily – 3.8 (0.3) (P<0.01 vs placebo) Flibanserin 100 mg once daily – 4.1 (0.3) (P<0.01 vs placebo)	Somnolence (11.8%) Dizziness (10.5%) Fatigue (10.3%)
VIOLET study Premenopausal women^Citation44 4-week baseline followed by 24-week randomized, double-blind, placebo-controlled	Flibanserin 50 mg once daily at bedtime Flibanserin 100 mg once daily at bedtime (total flibanserin N=585)	Placebo (N=295)	Mean change (SE) from baseline to week 24 in the FSFI – desire domain score: Placebo – 0.5 (0.1) Flibanserin 50 mg once daily – 0.8 (0.1) (P<0.05 vs placebo) Flibanserin 100 mg once daily – 0.9 (0.1) (P<0.0001 vs placebo) Mean change (SE) from baseline to week 24 in the FSFI – total score: Placebo – 2.4 (0.4) Flibanserin 50 mg once daily – 3.9 (0.4) (P<0.01 vs placebo) Flibanserin 100 mg once daily – 5.0 (0.4) (P<0.0001 vs placebo)	Somnolence (9.9%) Nausea (9.6%) Dizziness (7%) Fatigue (4.8%)
ROSE study Premenopausal women^Citation47 Continued efficacy study evaluating an additional 24 weeks of double-blind treatment vs placebo in patients with a predefined response after an initial 24 weeks of open-label treatment with flibanserin	Flibanserin (50 mg or 100 mg/d) (N=738, open label) After open label, additional 24 weeks of double-blind treatment: Flibanserin therapy at optimized dosage (N=163)	Placebo (N=170)	Mean (SE) decrease from weeks 21–24 (randomization baseline) to weeks 45–48 in the FSFI – desire domain score: Placebo – 0.8 (0.1) vs Flibanserin – 0.5 (0.1) (P<0.01) Mean (SE) decrease from weeks 21–24 (randomization baseline) to weeks 45–48 in the FSFI – total score: Placebo – 4.0 (0.5) vs Flibanserin – 1.9 (0.5) (P<0.01)	Open label: (8%–14%) Somnolence, nausea, dizziness, headache, fatigue Double-blind: (5%–13%) Nasopharyngitis, upper respiratory infection, urinary tract infection, sinusitis and headache (similar adverse effects and incidence rates as placebo)
SUNFLOWER study Premenopausal women^Citation45 52-week open-label extension study to assess safety with flibanserin flexible dose in women with HSDD who had completed a trial of flibanserin or placebo prior (patients were classified as flibanserin remitters [FSFI total score at baseline indicating no clinical sexual dysfunction] and flibanserin nonremitters [FSFI total score at baseline indicating dysfunction])	Flexible-dose flibanserin (50 or 100 mg once daily at bedtime or 25 or 50 mg twice daily) (N=1,723)	–	Mean change (±SD) from baseline to week 52 in the FSFI – desire domain score: Flibanserin remitters at baseline: Increased from 2.7±1.0 to 3.6±1.4 Flibanserin nonremitters at baseline: Increased from 1.8±0.7 to 2.9±1.3 Mean change (±SD) from baseline to week 52 in the FSFI – total score: Flibanserin remitters and nonremitters: Increased from 20.1±7.6 at baseline to 25.0±8.1 at week 52	Somnolence (15.8%) Fatigue (7.6%) Dizziness (6.9%) Nausea (6.3%) Sedation (1.6%) Vomiting (1.4%)
BEGONIA study Premenopausal women^Citation46 24-week randomized, double-blind, placebo-controlled trial	Flibanserin 100 mg once daily at bedtime (N=542)	Placebo (N=545)	Mean change (SE) from baseline to week 24 in the FSFI – desire domain score: Placebo 0.7 Flibanserin 100 mg once daily – 1.0 (0.1) (P<0.001 vs placebo) Mean change (SE) from baseline to week 24 in the FSFI – total score: Placebo 3.5 (0.3) Flibanserin 100 mg once daily – 5.3 (0.3) (P<0.001 vs placebo)	Somnolence (14.4%) Dizziness (10.3%) Nausea (7.6%) Fatigue (5.7%)
SNOWDROP study Naturally menopausal women^Citation50 24-week randomized, double-blind, placebo-controlled trial	Flibanserin 100 mg once daily at bedtime (N=468)	Placebo (N=481)	Mean change (SE) from baseline to week 24 in the FSFI – desire domain score: Placebo – 0.4 (0.1) Flibanserin 100 mg once daily – 0.7 (0.1) (P<0.001 vs placebo) Mean change (SE) from baseline to week 24 in the FSFI – total score: Placebo – 2.7 (0.4) Flibanserin 100 mg once daily – 4.2 (0.4) (P=0.003 vs placebo)	Dizziness (9.9%) Somnolence (8.8%) Nausea (7.5%) Headache (6.0%)

Note: Data from.^43–47,50

Abbreviations: FSFI, female sexual function index; SD, standard deviation; SE, standard error; HSDD, hypoactive sexual desire disorder.

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