Advancing Women’s Health: A Scoping Review of Pharmaceutical Therapies for Female Sexual Dysfunction

Abstract

Background: Female Sexual Dysfunction (FSD) encompasses a range of conditions that can profoundly impact quality of life and intimate relationships. The primary classifications of FSD include female sexual interest and arousal disorder (FSIAD), genitopelvic pain and penetration disorder (GPPPD), female orgasmic disorder (FOD), and substance or medication-induced sexual dysfunction (SM-ISD). Despite its prevalence, FSD is often underdiagnosed and undertreated. Objectives: This scoping review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the existing literature on both U.S. Food and Drug Administration (FDA)-approved and off-label pharmacotherapies for FSD by study type, outcomes, and limitations. Eligibility Criteria: Eligible studies comprised randomized controlled trials (RCTs), systematic reviews, and cohort studies involving adult women (≥18 years) with any subtype of FSD. These studies assessed pharmacologic interventions against a comparator and reported at least one treatment efficacy outcome. Studies outside this scope were excluded. Sources of Evidence: A 25-year literature search was conducted using PubMed/MEDLINE, the Cochrane Library, reference lists of relevant articles, academic handbooks, and targeted journals. Charting Methods: Three independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Findings were organized into summary tables and categorized by pharmaceutical agent, pertinent study information, outcomes, and limitations. Results: A total of 44 human-based pharmacologic studies met inclusion criteria. FDA-approved agents were the most thoroughly studied pharmacotherapies. Hormonal, topical, and adjunctive agents demonstrated less robust evidence. Heterogeneity in outcome measures and inadequate long-term data were common limitations. Conclusions: Pharmacologic treatment for FSD shows promise but requires further research. Individualized, multifaceted care is essential for optimizing FSD outcomes.

1. Introduction

Sexual dysfunction is defined as a persistent impairment in sexual interest, arousal, ability to achieve orgasm, and sexual pain, and it can significantly impact a patient’s quality of life and potential reproductive capacity [1,2]. Historically, research and treatment advances for sexual dysfunction have been directed toward male erectile dysfunction, despite the condition affecting both male and female patients. This emphasis has inadvertently led to a critical gap in understanding and addressing female sexual dysfunction (FSD).

FSD is a highly prevalent condition affecting almost 41% of premenopausal and 50% of postmenopausal women [3,4]. Despite its widespread occurrence, many women do not seek treatment, generally due to primary barriers such as lack of knowledge, emotional and psychological factors, socio-cultural stigma, and reduced access to specialized care [5,6]. Additionally, healthcare providers report inadequate treatment options in managing patients with FSD [7]. FSD is therefore an underdiagnosed and undertreated condition, highlighting the need for recognition, expanded research, and improved treatment strategies.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides the most comprehensive diagnostic criteria for FSD. It represents a shift in clinical thinking that moves away from the traditional, linear model of the sexual response cycle and attempts to be less gendered in the criteria for sexual dysfunctions [8,9]. The disorders of FSD present with distinct yet overlapping symptoms, adding complexity to the diagnosis and treatment of FSD. Symptoms must be present for at least 6 months, cause significant personal distress, and cannot be attributed to relationship conflict, cultural or religious beliefs, known medical conditions, or other probable causes. Symptoms should be elucidated through a comprehensive gynecologic and urologic history and are defined by intensity and onset (Table 1).

Classifications of FSD in the DSM-5 include the following:

• Female sexual interest and arousal disorder (FSIAD);
• Genitopelvic pain and penetration disorder (GPPPD);
• Female orgasmic disorder (FOD);
• Substance or medication-induced sexual dysfunction (SM-ISD).

Table 1. Evaluation considerations for FSD.

History [10]	Assessment [11,12]	Diagnostics [11,12]
Intrapersonal: Medical history, contributing health conditions, medication list, psychological health Interpersonal: Sexual history, relationship dynamics, partner-related factors Sociocultural: Culture, religious beliefs, personal values, attitudes on sexuality	General appearance Abdominal exam Genital inspection Vulvoscopy	Microbiological: Vaginal pH, cotton swab, microscopy Hormonal: Estradiol, follicle-stimulating hormone (FSH), free androgen index, total and free testosterone, sex hormone-binding globulin (SHBG), prolactin Metabolic: Thyroid function, lipid profile, serum glucose Nutritional: Serum ferritin

Table 1. Evaluation considerations for FSD.

History [10]	Assessment [11,12]	Diagnostics [11,12]
Intrapersonal: Medical history, contributing health conditions, medication list, psychological health Interpersonal: Sexual history, relationship dynamics, partner-related factors Sociocultural: Culture, religious beliefs, personal values, attitudes on sexuality	General appearance Abdominal exam Genital inspection Vulvoscopy	Microbiological: Vaginal pH, cotton swab, microscopy Hormonal: Estradiol, follicle-stimulating hormone (FSH), free androgen index, total and free testosterone, sex hormone-binding globulin (SHBG), prolactin Metabolic: Thyroid function, lipid profile, serum glucose Nutritional: Serum ferritin

FSIAD is a relatively new term used to describe a reduction in sexual interest, arousal, or sensation leading to significant distress. By replacing the previous diagnoses of hypoactive sexual desire disorder and female sexual arousal disorder, FSIAD exists as a more comprehensive diagnosis, given that reduced sexual interest and decreased sexual pleasure often occur simultaneously rather than independently of each other [13]. It is frequently underdiagnosed and undertreated due to its complex nature, sociocultural barriers, and limited clinician understanding of treatment options.

GPPPD is a newly defined condition offering a diagnosis for patients experiencing pain during sexual intercourse that is distinct from dyspareunia, vaginismus, or vulvodynia [14]. The most common subset of this disorder is genitourinary syndrome of menopause (GSM), characterized by vulvovaginal atrophy (VVA) symptoms that result from a hypoestrogenic state [15].

FOD is associated with difficulty experiencing sexual pleasure or orgasm in the presence of significant stimulation. It is a clinically distinct diagnosis from FSIAD, as patients are interested in sexual arousal but are unable to achieve sexual pleasure through clitoral stimulation or vaginal penetration [13]. While factors such as anxiety surrounding pregnancy, cultural beliefs, nerve damage, and medications can contribute to a patient’s inability to achieve sexual pleasure, these are risk factors rather than driving causes.

SM-ISD is the fourth subtype of FSD, caused by substance use or a medication side effect. Symptoms typically resolve upon discontinuation. However, provider awareness of this condition is essential to prevent medication non-compliance [13].

For a summary of the diagnostic criteria for each of the disorders of FSD, see Table 2.

Table 2. Diagnostic criteria for disorders of FSD.

Disorder	Symptoms	Exclusions	Evaluation
FSIAD [13]	At least 3 required: 1. Absent or reduced sexual interest 2. Limited or no thoughts about sexual activity 3. Decreased initiation of sexual activity 4. Reduced pleasure during sexual encounters 5. Decreased sensation during intercourse	Not attributed to relationship conflict, cultural or religious beliefs, medications, or known medical conditions	Requires extensive personal, gynecological, and urologic history
GPPPD [13]	At least 1 required: 1. Persistent difficulties with vaginal penetration during intercourse 2. Vulvovaginal or pelvic pain during vaginal intercourse 3. Fear or anxiety prior to or during vaginal penetration 4. Significant tensing of the pelvic floor muscles during attempted vaginal penetration	Not attributed to partner violence, relationship stress, or a non-sexual mental health condition	Requires extensive physical and psychological history
FOD [13]	At least 1 required: 1. Delay or absence of orgasm during all or almost all instances of sexual activity 2. Reduced orgasmic sensations during all or almost all instances of sexual activity	Not attributed to relationship factors, life stressors, medical conditions, or a non-sexual mental health condition	Requires effective history-taking to explore medical, psychological, and interpersonal factors
SM-ISD [13]	Severe impairment in sexual function, manifesting in proximity to exposure to the following: 1. A substance or medication known to cause such effects 2. Pharmacotherapy withdrawal	Not attributed to a previously-mentioned sexual dysfunction	Requires adequate review of a patient’s medication and substance use to determine timing of symptoms and rule out other potential causes

Table 2. Diagnostic criteria for disorders of FSD.

Disorder	Symptoms	Exclusions	Evaluation
FSIAD [13]	At least 3 required: 1. Absent or reduced sexual interest 2. Limited or no thoughts about sexual activity 3. Decreased initiation of sexual activity 4. Reduced pleasure during sexual encounters 5. Decreased sensation during intercourse	Not attributed to relationship conflict, cultural or religious beliefs, medications, or known medical conditions	Requires extensive personal, gynecological, and urologic history
GPPPD [13]	At least 1 required: 1. Persistent difficulties with vaginal penetration during intercourse 2. Vulvovaginal or pelvic pain during vaginal intercourse 3. Fear or anxiety prior to or during vaginal penetration 4. Significant tensing of the pelvic floor muscles during attempted vaginal penetration	Not attributed to partner violence, relationship stress, or a non-sexual mental health condition	Requires extensive physical and psychological history
FOD [13]	At least 1 required: 1. Delay or absence of orgasm during all or almost all instances of sexual activity 2. Reduced orgasmic sensations during all or almost all instances of sexual activity	Not attributed to relationship factors, life stressors, medical conditions, or a non-sexual mental health condition	Requires effective history-taking to explore medical, psychological, and interpersonal factors
SM-ISD [13]	Severe impairment in sexual function, manifesting in proximity to exposure to the following: 1. A substance or medication known to cause such effects 2. Pharmacotherapy withdrawal	Not attributed to a previously-mentioned sexual dysfunction	Requires adequate review of a patient’s medication and substance use to determine timing of symptoms and rule out other potential causes

While recognition and diagnosis of FSD has increased, treatment options are still in development. Traditionally, patient education and behavioral therapies have been the mainstay of treatment, grounded in the understanding that psychological and relational factors often contribute to sexual dysfunction. However, many women do not respond adequately to these approaches, prefer medical treatment, or face barriers such as time, stigma, or lack of access to trained providers. Thus, pharmacotherapy is becoming an increasingly prominent component of care for these patients. Pharmacologic agents potentially offer practical, widely accessible, and biologically targeted approaches to addressing the hormonal, neurological, and vascular components of FSD. Although various agents have been investigated, pharmacologic strategies that target the personalized nature of FSD remain largely underdeveloped.

This scoping review builds upon previous work to evaluate the current body of literature on FSD pharmacotherapies [8]. We assess both U.S. Food and Drug Administration (FDA)-approved and off-label FSD agents by study type, outcomes, and limitations, as well as by mechanism of action, dosing, and side effects. By integrating clinical trial data, treatment guidelines, and emerging research, we support a more personalized and evidence-based approach to FSD management.

2. Materials and Methods

A comprehensive search for pharmacotherapy for FSD was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review protocol was not pre-registered. The search strategy included a combination of keywords, specifically “female sexual dysfunction”, “female sexual interest and arousal disorder”, “FSIAD”, “genitopelvic pain and penetration disorder”, “GPPPD”, “female orgasmic disorder”, “FOD”, “substance or medication-induced sexual dysfunction”, and “SM-ISD”. These terms were combined with treatment-related keywords including “pharmacotherapy”, “drug therapy”, “treatment”, and “pharmacologic treatment”. Filters and limitations applied to searches included (1) studies published in English; (2) human participants; (3) publication date range from 1 January 2000 to 1 March 2025; (4) randomized controlled trials (RCTs), systematic reviews, and meta-analyses; and (5) studies with available full-text articles. The date of the last search was March 1, 2025.

Data were gathered from the following sources: (1) PubMed/MEDLINE for peer-reviewed literature on FSD and pharmacologic interventions; (2) the Cochrane Library for systematic reviews and evidence-based guidance; (3) reference lists of included articles, systematic reviews, and meta-analyses; (4) academic handbooks and clinical guidelines, including the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Handbook of Social Sciences and Global Public Health; and (5) manual searches of journals including The Journal of Sexual Medicine, Sexual Medicine Reviews, Obstetrics & Gynecology, BMC Women’s Health, and Mayo Clinic Proceedings.

Inclusion and exclusion criteria were defined by all authors prior to screening. Studies were eligible if they met the following criteria: (1) randomized controlled trial (RCT), meta-analysis, systematic review, or cohort study published in a peer-reviewed journal; (2) comprised adult women (≥ 18 years) diagnosed with any form of FSD, including but not limited to FSIAD, FOD, GPPPD, and SM-ISD; (3) evaluated pharmacological treatments targeting FSD symptoms; (4) included a comparator such as placebo, no treatment, or another pharmacologic agent; and (5) reported at least one measurable outcome related to treatment efficacy. Exclusion criteria included non-pharmacologic interventions, studies focused solely on male sexual dysfunction, observational studies, case reports, editorials, letters, and conference abstracts without full data, as well as animal or in vitro studies, non-English publications, and articles without full-text access.

To determine study eligibility, three independent reviewers screened titles and abstracts for relevance, followed by a full-text screening against the predefined inclusion and exclusion criteria. Discrepancies during this phase were resolved through discussion. Studies that met eligibility criteria underwent independent data extraction by the same reviewers using a standardized data collecting form. The primary outcome was pharmacotherapy efficacy, measured by a change in sexual function using validated tools or indices. All results that were relevant to this domain were included. A variety of effect measures were extracted from included articles: scores from standardized questionnaires and scales, clinical or physiological measures, statistical effect measures, and subjective or self-reported outcomes. Additional variables extracted were study design, participant characteristics, intervention and comparator details, and risk of bias. No assumptions were made about missing or unclear information. A formal appraisal tool was not used. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Each study was independently evaluated by the three reviewers, with discrepancies resolved through discussion. As a final step, all sources were evaluated by a board-certified urologist to confirm study eligibility and clinical relevance. No automation tools were used in the search or screening process.

3. Results

The PRISMA flow diagram (Figure 1) below outlines the study selection process. Initially, 1054 records were identified through databases (n = 999) and registers (n = 55). Duplicate data were excluded, and the most appropriate sources were identified. A total of 44 original, human-based pharmacologic studies with sufficient data quality were included in the final review.

Findings from the included studies were organized into summary tables and categorized according to the following domains: (1) study design; (2) type of FSD; (3) pharmaceutical agent; (4) number of participants and/or articles cited; (5) presence of a control group; (6) variable(s) measured; (7) results; and (8) limitations. Additional data were extracted from the included studies and supplemented with information from new sources. These data were compiled into tables summarizing the (1) type of intervention; (2) pharmaceutical agent; (3) mechanism of action; (4) recommended dosage; and (5) reported side effects.

The following tables present the most relevant studies found on FSD pharmacotherapies, grouped by RCTs, review articles, and cohort studies (n = 44).

Table 3. Summary of RCTs.

Reference	Type of FSD	Pharmaceutical Agent	Number of Participants	Control Group	Variable(s) Measured	Results	Limitations
Katz et al., 2013 [16]	FSIAD	Flibanserin (Addyi)	1087 premenopausal women	Placebo	Female Sexual Function Index (FSFI)	+1 (SD = 0.3) FSFI desire vs. +0.7 (SD = 0.3) in control	Restricted to heterosexual women with partners
Thorp et al., 2012 [17]	FSIAD	Flibanserin (Addyi)	1581 premenopausal women	Placebo	Satisfying sexual events	Statistically significant increase with 100 mg flibanserin	Restricted to heterosexual women with partners
DeRogatis et al., 2012 [18]	FSIAD	Flibanserin (Addyi)	880 premenopausal women	Placebo	Satisfying sexual events	1.6 encounters vs. 0.8, p < 0.05	Restricted to heterosexual women with partners
Simon et al., 2019 [19]	FSIAD	Bremelanotide (Vyleesi)	272 premenopausal women	Placebo	FSFI, Female Sexual Distress Scale (FSDS)	FSFI: +0.77 (0.54–1 95% CI) in placebo, vs. +1.3 (0.98–1.62, 95% CI); +0.7 (0.42–0.98 95% CI) in placebo, vs. +1.25 (0.93–1.56 95% CI), no significant difference in FSDS between arms	High dropout rate
Kingsberg et al., 2019 [20]	FSIAD	Bremelanotide (Vyleesi)	2449 premenopausal women	Placebo	FSFI, FSDS	FSFI +0.35 (p < 0.01), FSDS −0.33 (p < 0.01)	High dropout rate
Fooladi et al., 2014 [21]	FSIAD	Topical testosterone	44 pre- and postmenopausal women	Placebo	Satisfying sexual events, Sabbatsberg Sexual Self-Rating Scale (SSS)	No significant difference in SSS, significant increase in satisfying events	Insufficient recruitment
Davis et al., 2013 [22]	FSIAD	Estradiol valerate (non-androgenic)	191 premenopausal women	Ethinyl estradiol (androgenic)	FSFI	Desire and arousal increased 5.9 vs. 5.7 points, p < 0.001	No placebo arm
Nijland et al., 2008 [23]	FSIAD	Tibolone	403 postmenopausal women	Topical estradiol	FSFI, FSDS	FSFI improved significantly vs. estradiol, p < 0.025	No placebo
Dasgupta et al., 2004 [24]	FSIAD	Sildenafil citrate (Viagra)	19 women with multiple sclerosis	Placebo	SFQ	Lubrication and sensation improved	Small cohort, select population
Johnson et al., 2024 [25]	FSIAD	Topical sildenafil	200 premenopausal women	Placebo	Sexual Function Questionnaire (SFQ), arousal	+2 SFQ arousal (SD = 0.62) vs. +0.08 (SD = 0.71) demonstrating moderate improvement	Underpowered with respect to comorbidity subsets
Safarinejad, 2010 [26]	FSIAD	Bupropion	218 premenopausal women	Placebo	FSFI	All domains showed statistically significant improvements	Select cohort of antidepressant users
Caruso et al., 2004 [27]	FSIAD	Apomorphine	50 premenopausal women	Placebo	Personal Experiences Questionnaire (PEQ)	Statistically significant improvement, 3 mg dose significantly better than 2 mg (<0.05)	Small cohort
Bechara et al., 2004 [28]	FSIAD	Apomorphine	24 pre- and postmenopausal women	Placebo	Subjective survey	Statistically significant improvement over placebo	No validated instruments, subjective responses
Rubio-Aurioles et al., 2002 [29]	FSIAD	Phentolamine vaginal or oral	41 postmenopausal women	Placebo	Vaginal plethysmography and questionnaire	Statistically significant benefit with vaginal and oral phentolamine	No validated measurements, small cohort
Muin et al., 2015 [30]	FSIAD	Oxytocin	30 pre- and postmenopausal women	Washout and crossover	FSFI, Sexual Quality of Life-Female (SQOL-F), FSDS, Sexual Interest and Desire Inventory-Female (SIDI-F)	No statistically significant improvement over placebo	Small cohort, heterogeneous population
Labrie et al., 2015 [31]	GPPPD	Dehydroepiandrosterone (DHEA) (Intrarosa)	482 postmenopausal women	Placebo	FSFI	Total score, desire, arousal, lubrication, orgasm, satisfaction, pain improved over placebo by 41.3% (p = 0.0006), 49% (p = 0.011), 56.8% (p = 0.002), 36.1% (p = 0.0005), 33% (p = 0.05), 48.3% (p = 0.001), and 39.2% (p = 0.001), respectively	Cohort selected for dyspareunia as opposed to sexual dysfunction
Labrie et al., 2019 [32]	GPPPD	DHEA (Intrarosa)	482 postmenopausal women	Placebo	FSFI	Vaginal pH decreased over placebo, sexual pain −1.42 over placebo (p < 0.01)	Cohort selected for dyspareunia as opposed to sexual dysfunction
Constantine et al., 2015 [33]	GPPPD	Ospemifene	919 postmenopausal women	Placebo	FSFI	Improved pain domain scores, p < 0.05	FSFI improvement not primary outcome
Goetsch et al., 2015 [34]	GPPPD	Lidocaine	46 menopausal cancer survivors	Placebo	SFQ, FSDS	SFQ pain score decreased 15.5 points, p < 0.01	Select population, may not be broadly applicable

Abbreviations: FSFI, Female Sexual Function Index; FSDS, Female Sexual Distress Scale; SFQ, Sexual Function Questionnaire; PEQ, Personal Experiences Questionnaire; SQOL-F, Sexual Quality of Life-Female; SIDI-F, Sexual Interest and Desire Index-Female; SSS, Sabbatsberg Sexual Self-Rating Scale.

Table 3. Summary of RCTs.

Reference	Type of FSD	Pharmaceutical Agent	Number of Participants	Control Group	Variable(s) Measured	Results	Limitations
Katz et al., 2013 [16]	FSIAD	Flibanserin (Addyi)	1087 premenopausal women	Placebo	Female Sexual Function Index (FSFI)	+1 (SD = 0.3) FSFI desire vs. +0.7 (SD = 0.3) in control	Restricted to heterosexual women with partners
Thorp et al., 2012 [17]	FSIAD	Flibanserin (Addyi)	1581 premenopausal women	Placebo	Satisfying sexual events	Statistically significant increase with 100 mg flibanserin	Restricted to heterosexual women with partners
DeRogatis et al., 2012 [18]	FSIAD	Flibanserin (Addyi)	880 premenopausal women	Placebo	Satisfying sexual events	1.6 encounters vs. 0.8, p < 0.05	Restricted to heterosexual women with partners
Simon et al., 2019 [19]	FSIAD	Bremelanotide (Vyleesi)	272 premenopausal women	Placebo	FSFI, Female Sexual Distress Scale (FSDS)	FSFI: +0.77 (0.54–1 95% CI) in placebo, vs. +1.3 (0.98–1.62, 95% CI); +0.7 (0.42–0.98 95% CI) in placebo, vs. +1.25 (0.93–1.56 95% CI), no significant difference in FSDS between arms	High dropout rate
Kingsberg et al., 2019 [20]	FSIAD	Bremelanotide (Vyleesi)	2449 premenopausal women	Placebo	FSFI, FSDS	FSFI +0.35 (p < 0.01), FSDS −0.33 (p < 0.01)	High dropout rate
Fooladi et al., 2014 [21]	FSIAD	Topical testosterone	44 pre- and postmenopausal women	Placebo	Satisfying sexual events, Sabbatsberg Sexual Self-Rating Scale (SSS)	No significant difference in SSS, significant increase in satisfying events	Insufficient recruitment
Davis et al., 2013 [22]	FSIAD	Estradiol valerate (non-androgenic)	191 premenopausal women	Ethinyl estradiol (androgenic)	FSFI	Desire and arousal increased 5.9 vs. 5.7 points, p < 0.001	No placebo arm
Nijland et al., 2008 [23]	FSIAD	Tibolone	403 postmenopausal women	Topical estradiol	FSFI, FSDS	FSFI improved significantly vs. estradiol, p < 0.025	No placebo
Dasgupta et al., 2004 [24]	FSIAD	Sildenafil citrate (Viagra)	19 women with multiple sclerosis	Placebo	SFQ	Lubrication and sensation improved	Small cohort, select population
Johnson et al., 2024 [25]	FSIAD	Topical sildenafil	200 premenopausal women	Placebo	Sexual Function Questionnaire (SFQ), arousal	+2 SFQ arousal (SD = 0.62) vs. +0.08 (SD = 0.71) demonstrating moderate improvement	Underpowered with respect to comorbidity subsets
Safarinejad, 2010 [26]	FSIAD	Bupropion	218 premenopausal women	Placebo	FSFI	All domains showed statistically significant improvements	Select cohort of antidepressant users
Caruso et al., 2004 [27]	FSIAD	Apomorphine	50 premenopausal women	Placebo	Personal Experiences Questionnaire (PEQ)	Statistically significant improvement, 3 mg dose significantly better than 2 mg (<0.05)	Small cohort
Bechara et al., 2004 [28]	FSIAD	Apomorphine	24 pre- and postmenopausal women	Placebo	Subjective survey	Statistically significant improvement over placebo	No validated instruments, subjective responses
Rubio-Aurioles et al., 2002 [29]	FSIAD	Phentolamine vaginal or oral	41 postmenopausal women	Placebo	Vaginal plethysmography and questionnaire	Statistically significant benefit with vaginal and oral phentolamine	No validated measurements, small cohort
Muin et al., 2015 [30]	FSIAD	Oxytocin	30 pre- and postmenopausal women	Washout and crossover	FSFI, Sexual Quality of Life-Female (SQOL-F), FSDS, Sexual Interest and Desire Inventory-Female (SIDI-F)	No statistically significant improvement over placebo	Small cohort, heterogeneous population
Labrie et al., 2015 [31]	GPPPD	Dehydroepiandrosterone (DHEA) (Intrarosa)	482 postmenopausal women	Placebo	FSFI	Total score, desire, arousal, lubrication, orgasm, satisfaction, pain improved over placebo by 41.3% (p = 0.0006), 49% (p = 0.011), 56.8% (p = 0.002), 36.1% (p = 0.0005), 33% (p = 0.05), 48.3% (p = 0.001), and 39.2% (p = 0.001), respectively	Cohort selected for dyspareunia as opposed to sexual dysfunction
Labrie et al., 2019 [32]	GPPPD	DHEA (Intrarosa)	482 postmenopausal women	Placebo	FSFI	Vaginal pH decreased over placebo, sexual pain −1.42 over placebo (p < 0.01)	Cohort selected for dyspareunia as opposed to sexual dysfunction
Constantine et al., 2015 [33]	GPPPD	Ospemifene	919 postmenopausal women	Placebo	FSFI	Improved pain domain scores, p < 0.05	FSFI improvement not primary outcome
Goetsch et al., 2015 [34]	GPPPD	Lidocaine	46 menopausal cancer survivors	Placebo	SFQ, FSDS	SFQ pain score decreased 15.5 points, p < 0.01	Select population, may not be broadly applicable

Abbreviations: FSFI, Female Sexual Function Index; FSDS, Female Sexual Distress Scale; SFQ, Sexual Function Questionnaire; PEQ, Personal Experiences Questionnaire; SQOL-F, Sexual Quality of Life-Female; SIDI-F, Sexual Interest and Desire Index-Female; SSS, Sabbatsberg Sexual Self-Rating Scale.

Table 4. Summary of review articles.

Reference	Type of FSD	Pharmaceutical Agent	Articles Cited	Variable(s) Measured	Results	Limitations
Goldstein et al., 2017 [35]	FSIAD	Flibanserin (Addyi)	3 (1548 participants)	Sexual desire, sexually-related distress, number of satisfying sexual events in premenopausal women	Statistically significant improvements in sexual desire and satisfaction, decreased sexually-related stress. Sexual desire improvement reported by 54–58% vs. placebo (40–48%). Similar efficacy and safety results for postmenopausal women	Short duration of use 8-week discontinuation threshold
Simon et al., 2019 [36]	FSIAD	Flibanserin (Addyi)	3 (2465 participants)	Satisfying sexual events	Mean 2.1 +/− 0.14 vs. 1.2 +/− 0.11 satisfying events	Restricted to heterosexual women with partners
Achilli et al., 2017 [37]	FSIAD	Testosterone	7 (3035 participants)	Profile of Female Sexual Function (PFSF)-desire domain, Personal Distress Scale (PDS). Satisfying sexual episodes, sexual activity, orgasm, and adverse events	Statistically significant increase in PFSF desire domain scores (MD = 6.09, p < 0.00001) and decrease in PDS scores (MD = −8.15, p < 0.00001). Statistically significant increase in frequency of satisfying sexual events (MD = 0.9, p < 0.00001), sexual activity (MD = 0.96, p < 0.0001), orgasms (MD = 1.16, p < 0.00001), and sexual desire (MD = 6.09, p < 0.00001). Increase in acne (RR = 1.14) and hair growth (RR = 1.56) androgenic side effects; no significant increases in other side effects or adverse events	Lack of long-term safety data, heterogeneity in estrogen use and progestin co-intervention
Reis & Abdo 2014 [38]	FSIAD	Testosterone	20 (5561 participants)	No standard scales	300 mcg testosterone increased desire, satisfaction and orgasm in a majority of studies	No consistent measurement instruments
Lara et al., 2023 [39]	FSIAD, GPPPD	Estrogen	36 (23,299 participants)	Sexual function composite score	Slight improvement in sexual function among symptomatic or early postmenopausal women (MD = 0.50, CI: 0.04–0.96, 3 studies). Little to no effect (SMD = 0.64, CI: −0.12–1.4, 6 studies) in long-term postmenopausal women or those not selected based on symptoms. Pooled data: modest overall benefit in sexual function (MD = 0.60, CI: 0.16–1.04, 9 studies)	Heterogeneity across studies, multiple outcomes rated as very low- or low-quality evidence, 19 studies received commercial funding
Cappelletti & Warren, 2015 [40]	FSIAD	Estrogen and testosterone	20 (3196 participants)	PFSF, SSS, self-reported scales	Androgens alone did not increase desire. Estrogens alone with increased estradiol levels showed increased desire	Heterogeneity of studies
Formoso et al., 2016 [41]	FSIAD, GPPPD	Tibolone (Livial)	46 (19,976 participants)	Vasomotor symptoms, bleeding, and long-term safety	Statistically significant reduction in vasomotor symptoms (35–45% tibolone vs. 67% placebo). Less effective compared to combined menopausal hormonal therapy (MHT) (35–45% tibolone vs. 7% MHT)	Risk of bias due to pharmaceutical company funding or limited funding disclosures
Martins et al., 2024 [42]	FSIAD	Sildenafil citrate (Viagra)	6 (1188 participants)	FSFI, SFQ, Female Intervention Efficacy Index (FIEI), Golombok–Rust Inventory of Sexual Satisfaction (GRISS). Orgasm latency, clitoral sensitivity	Statistically significant improvements in sexual satisfaction, arousal, orgasm, lubrication, and desire (4 studies). No significant efficacious findings (2 studies)	Variable hormonal therapy status use and dosing regimen, 3 studies received industry funding
Brown et al., 2009 [43]	FSIAD	Sildenafil citrate (Viagra)	12 (780 participants)	FSFI	Possible positive effect of sildenafil on symptoms	Small sample sizes, articles not comprehensive
Razali et al., 2022 [44]	FSIAD	Bupropion	11 (961 participants)	Overall sexual function, sexual desire, arousal, lubrication, orgasm, satisfaction, pain, pleasure, frequency, fantasy, partner response, distress, tolerability	Statistically significant improvement in overall sexual function (7 studies). More effective by 2.8x than placebo for sexual desire (pooled OR = 2.845, CI: 0.215–5.475, p = 0.034). Additional improvements in arousal, orgasm, satisfaction, pleasure, and frequency	Variability in study design (6 RCTs, 5 uncontrolled time-series), short durations (4–16 weeks)
Wexler et al., 2023 [45]	FSIAD	3,4-methylenedioxymethamphetamine (MDMA)	6	Sexual desire, arousal, lubrication, orgasm, and pleasure	Increased sexual desire (4 studies). Improved arousal and lubrication (3 studies). Orgasm was often delayed but reported as more intense and pleasurable. Mixed evidence for arousal and lubrication	Largely qualitative findings, small number of studies, overall heterogeneity
Caira-Chuqinevra et al., 2024 [46]	FSIAD	Visnadine	2 (96 participants)	FSFI total and domain, FSDS. Satisfaction, clitoral blood flow, and tolerability	Statistically significant increase in total FSFI scores. FSFI arousal domain improved in 1 RCT	Small number of RCTs and sample sizes; methodological variability (daily vs. on-demand applications)
Cieri-Hutcherson et al., 2021 [47]	FSIAD	L-arginine	7 (717 participants)	FSFI total and domain. Vaginal pulse amplitude (VPA), oxidative stress, vaginal dryness, menopause symptoms	Statistically significant improvement in FSFI total score or in multiple domains (6 studies). Significant increase in VPA (1 study)	Small sample sizes, some studies lacked individual L-arginine monotherapy arm
La Rosa et al., 2019 [48]	GPPPD	DHEA (Intrarosa)	2	Vaginal pH, dryness, FSFI	DHEA doses of 6.5 mg intravaginally improves sexual function domain scores and vaginal parameters (pH, dryness, cell proliferation)	Small number of studies
Buzzaccarin et al., 2021 [49]	GPPPD	Hyaluronic acid (HA)	17 (1441 participants)	FSFI, FSDS, Patient-Reported Outcomes Measurement Information System (PROMIS)- sexual function. Vaginal dryness, itching, burning, dyspareunia, pH levels	Significant improvement in FSFI scores across most studies. Some studies showed improvements in FSDS and PROMIS sexual function scores. Majority of studies demonstrated significant symptom relief (vaginal dryness, itching, burning, dyspareunia, and pH levels)	Heterogeneity in study design, interventions, and outcomes measured
Parenti et al., 2023 [50]	GPPPD	Botulinum toxin A (BoNT-A)	22 (1127 participants)	Mixed	Significant improvements in symptoms of vaginismus, dyspareunia, and chronic pelvic pain	Studies had different definitions, variables, and administration techniques; heterogeneous study types and lack of meta-analysis
Mardiyan Kurniawati et al., 2024 [51]	GPPPD	Platelet-rich plasma (PRP) injections	15 (600 participants)	FSFI, Female Sexual Distress Scale-Revised (FSDS-R), Genital Self-Image Scale (GSIS), Vaginal Health Index (VHI)	Statistically significant improvements in FSFI, FSDS-R, FGSIS, and VHI scores	Heterogeneous study types and lack of meta-analysis
Dankova et al., 2023 [52]	GPPPD	PRP injections	12 (327 participants)	FSFI, FSDS, VHI	Statistically significant improvement in FSFI, FSDS, and VHI scores	Heterogeneity in PRP administration protocols; high risk of bias in RCT
Ragucci & Culhane, 2003 [53]	FSIAD, GPPPD	Bupropion, L-arginine, estrogen sildenafil, phentolamine	10 (428 participants)	No standard scales	Best success rates when pharmaceuticals used on physiological symptoms and psychological therapy used on emotional causes	No consistent measurement instruments

Abbreviations: PFSF, Profile of Female Sexual Function; PDS, Personal Distress Scale; FIEI, Female Intervention Efficacy Index; GRISS, Golombok–Rust Inventory of Sexual Satisfaction; PROMIS, Patient-Reported Outcomes Measurement Information System; FSDS-R, Female Sexual Distress Scale- Revised; GSIS, Genital Self-Image Scale; VHI, Vaginal Health Index; VPA, vaginal pulse amplitude.

Table 4. Summary of review articles.

Reference	Type of FSD	Pharmaceutical Agent	Articles Cited	Variable(s) Measured	Results	Limitations
Goldstein et al., 2017 [35]	FSIAD	Flibanserin (Addyi)	3 (1548 participants)	Sexual desire, sexually-related distress, number of satisfying sexual events in premenopausal women	Statistically significant improvements in sexual desire and satisfaction, decreased sexually-related stress. Sexual desire improvement reported by 54–58% vs. placebo (40–48%). Similar efficacy and safety results for postmenopausal women	Short duration of use 8-week discontinuation threshold
Simon et al., 2019 [36]	FSIAD	Flibanserin (Addyi)	3 (2465 participants)	Satisfying sexual events	Mean 2.1 +/− 0.14 vs. 1.2 +/− 0.11 satisfying events	Restricted to heterosexual women with partners
Achilli et al., 2017 [37]	FSIAD	Testosterone	7 (3035 participants)	Profile of Female Sexual Function (PFSF)-desire domain, Personal Distress Scale (PDS). Satisfying sexual episodes, sexual activity, orgasm, and adverse events	Statistically significant increase in PFSF desire domain scores (MD = 6.09, p < 0.00001) and decrease in PDS scores (MD = −8.15, p < 0.00001). Statistically significant increase in frequency of satisfying sexual events (MD = 0.9, p < 0.00001), sexual activity (MD = 0.96, p < 0.0001), orgasms (MD = 1.16, p < 0.00001), and sexual desire (MD = 6.09, p < 0.00001). Increase in acne (RR = 1.14) and hair growth (RR = 1.56) androgenic side effects; no significant increases in other side effects or adverse events	Lack of long-term safety data, heterogeneity in estrogen use and progestin co-intervention
Reis & Abdo 2014 [38]	FSIAD	Testosterone	20 (5561 participants)	No standard scales	300 mcg testosterone increased desire, satisfaction and orgasm in a majority of studies	No consistent measurement instruments
Lara et al., 2023 [39]	FSIAD, GPPPD	Estrogen	36 (23,299 participants)	Sexual function composite score	Slight improvement in sexual function among symptomatic or early postmenopausal women (MD = 0.50, CI: 0.04–0.96, 3 studies). Little to no effect (SMD = 0.64, CI: −0.12–1.4, 6 studies) in long-term postmenopausal women or those not selected based on symptoms. Pooled data: modest overall benefit in sexual function (MD = 0.60, CI: 0.16–1.04, 9 studies)	Heterogeneity across studies, multiple outcomes rated as very low- or low-quality evidence, 19 studies received commercial funding
Cappelletti & Warren, 2015 [40]	FSIAD	Estrogen and testosterone	20 (3196 participants)	PFSF, SSS, self-reported scales	Androgens alone did not increase desire. Estrogens alone with increased estradiol levels showed increased desire	Heterogeneity of studies
Formoso et al., 2016 [41]	FSIAD, GPPPD	Tibolone (Livial)	46 (19,976 participants)	Vasomotor symptoms, bleeding, and long-term safety	Statistically significant reduction in vasomotor symptoms (35–45% tibolone vs. 67% placebo). Less effective compared to combined menopausal hormonal therapy (MHT) (35–45% tibolone vs. 7% MHT)	Risk of bias due to pharmaceutical company funding or limited funding disclosures
Martins et al., 2024 [42]	FSIAD	Sildenafil citrate (Viagra)	6 (1188 participants)	FSFI, SFQ, Female Intervention Efficacy Index (FIEI), Golombok–Rust Inventory of Sexual Satisfaction (GRISS). Orgasm latency, clitoral sensitivity	Statistically significant improvements in sexual satisfaction, arousal, orgasm, lubrication, and desire (4 studies). No significant efficacious findings (2 studies)	Variable hormonal therapy status use and dosing regimen, 3 studies received industry funding
Brown et al., 2009 [43]	FSIAD	Sildenafil citrate (Viagra)	12 (780 participants)	FSFI	Possible positive effect of sildenafil on symptoms	Small sample sizes, articles not comprehensive
Razali et al., 2022 [44]	FSIAD	Bupropion	11 (961 participants)	Overall sexual function, sexual desire, arousal, lubrication, orgasm, satisfaction, pain, pleasure, frequency, fantasy, partner response, distress, tolerability	Statistically significant improvement in overall sexual function (7 studies). More effective by 2.8x than placebo for sexual desire (pooled OR = 2.845, CI: 0.215–5.475, p = 0.034). Additional improvements in arousal, orgasm, satisfaction, pleasure, and frequency	Variability in study design (6 RCTs, 5 uncontrolled time-series), short durations (4–16 weeks)
Wexler et al., 2023 [45]	FSIAD	3,4-methylenedioxymethamphetamine (MDMA)	6	Sexual desire, arousal, lubrication, orgasm, and pleasure	Increased sexual desire (4 studies). Improved arousal and lubrication (3 studies). Orgasm was often delayed but reported as more intense and pleasurable. Mixed evidence for arousal and lubrication	Largely qualitative findings, small number of studies, overall heterogeneity
Caira-Chuqinevra et al., 2024 [46]	FSIAD	Visnadine	2 (96 participants)	FSFI total and domain, FSDS. Satisfaction, clitoral blood flow, and tolerability	Statistically significant increase in total FSFI scores. FSFI arousal domain improved in 1 RCT	Small number of RCTs and sample sizes; methodological variability (daily vs. on-demand applications)
Cieri-Hutcherson et al., 2021 [47]	FSIAD	L-arginine	7 (717 participants)	FSFI total and domain. Vaginal pulse amplitude (VPA), oxidative stress, vaginal dryness, menopause symptoms	Statistically significant improvement in FSFI total score or in multiple domains (6 studies). Significant increase in VPA (1 study)	Small sample sizes, some studies lacked individual L-arginine monotherapy arm
La Rosa et al., 2019 [48]	GPPPD	DHEA (Intrarosa)	2	Vaginal pH, dryness, FSFI	DHEA doses of 6.5 mg intravaginally improves sexual function domain scores and vaginal parameters (pH, dryness, cell proliferation)	Small number of studies
Buzzaccarin et al., 2021 [49]	GPPPD	Hyaluronic acid (HA)	17 (1441 participants)	FSFI, FSDS, Patient-Reported Outcomes Measurement Information System (PROMIS)- sexual function. Vaginal dryness, itching, burning, dyspareunia, pH levels	Significant improvement in FSFI scores across most studies. Some studies showed improvements in FSDS and PROMIS sexual function scores. Majority of studies demonstrated significant symptom relief (vaginal dryness, itching, burning, dyspareunia, and pH levels)	Heterogeneity in study design, interventions, and outcomes measured
Parenti et al., 2023 [50]	GPPPD	Botulinum toxin A (BoNT-A)	22 (1127 participants)	Mixed	Significant improvements in symptoms of vaginismus, dyspareunia, and chronic pelvic pain	Studies had different definitions, variables, and administration techniques; heterogeneous study types and lack of meta-analysis
Mardiyan Kurniawati et al., 2024 [51]	GPPPD	Platelet-rich plasma (PRP) injections	15 (600 participants)	FSFI, Female Sexual Distress Scale-Revised (FSDS-R), Genital Self-Image Scale (GSIS), Vaginal Health Index (VHI)	Statistically significant improvements in FSFI, FSDS-R, FGSIS, and VHI scores	Heterogeneous study types and lack of meta-analysis
Dankova et al., 2023 [52]	GPPPD	PRP injections	12 (327 participants)	FSFI, FSDS, VHI	Statistically significant improvement in FSFI, FSDS, and VHI scores	Heterogeneity in PRP administration protocols; high risk of bias in RCT
Ragucci & Culhane, 2003 [53]	FSIAD, GPPPD	Bupropion, L-arginine, estrogen sildenafil, phentolamine	10 (428 participants)	No standard scales	Best success rates when pharmaceuticals used on physiological symptoms and psychological therapy used on emotional causes	No consistent measurement instruments

Abbreviations: PFSF, Profile of Female Sexual Function; PDS, Personal Distress Scale; FIEI, Female Intervention Efficacy Index; GRISS, Golombok–Rust Inventory of Sexual Satisfaction; PROMIS, Patient-Reported Outcomes Measurement Information System; FSDS-R, Female Sexual Distress Scale- Revised; GSIS, Genital Self-Image Scale; VHI, Vaginal Health Index; VPA, vaginal pulse amplitude.

Table 5. Summary of cohort studies.

Reference	Type of FSD	Pharmaceutical Agent	Number of Participants	Control Group	Variable(s) Measured	Results	Limitations
Steinberg et al., 2005 [54]	GPPPD	Capsaicin	52	None (retrospective chart review)	Kaufman touch test (vulvar pain), Marinoff dyspareunia scale (intercourse pain)	Significant improvement in Kaufman Touch Test scores (pre: 13.2 +/− 4.9 to post: 4.8 +/− 3.8, p < 0.001) and Marinoff dyspareunia scores (p < 0.001)	Retrospective design, no control group
Levesque et al., 2017 [55]	GPPPD	Capsaicin patch	60	None (prospective cohort)	Patient Global Impression of Change (PGIC)	24% reported significant improvement	No control group
Bertolasi et al., 2009 [56]	GPPPD	BoNT-A	39	None (prospective cohort)	FSFI, pain scale	63% reported pain free intercourse, dyspareunia improved	No control group
Serati et al., 2015 [57]	GPPPD	Estrogen and HA	31	Estrogen vs. HA	FSFI, pain scale	Both treatments effective, vaginal estrogen may be significantly more effective	No control group

Abbreviations: PGIC, Patient Global Impression of Change.

Table 5. Summary of cohort studies.

Reference	Type of FSD	Pharmaceutical Agent	Number of Participants	Control Group	Variable(s) Measured	Results	Limitations
Steinberg et al., 2005 [54]	GPPPD	Capsaicin	52	None (retrospective chart review)	Kaufman touch test (vulvar pain), Marinoff dyspareunia scale (intercourse pain)	Significant improvement in Kaufman Touch Test scores (pre: 13.2 +/− 4.9 to post: 4.8 +/− 3.8, p < 0.001) and Marinoff dyspareunia scores (p < 0.001)	Retrospective design, no control group
Levesque et al., 2017 [55]	GPPPD	Capsaicin patch	60	None (prospective cohort)	Patient Global Impression of Change (PGIC)	24% reported significant improvement	No control group
Bertolasi et al., 2009 [56]	GPPPD	BoNT-A	39	None (prospective cohort)	FSFI, pain scale	63% reported pain free intercourse, dyspareunia improved	No control group
Serati et al., 2015 [57]	GPPPD	Estrogen and HA	31	Estrogen vs. HA	FSFI, pain scale	Both treatments effective, vaginal estrogen may be significantly more effective	No control group

Abbreviations: PGIC, Patient Global Impression of Change.

3.1. FDA-Approved

Flibanserin (Addyi) and bremelanotide are the only FDA-approved medications to treat the sexual interest component of FSIAD in premenopausal women. There is a substantial body of literature that supports flibanserin’s effectiveness for FSIAD symptoms, leading to its approval in 2015. Three clinical trials (the VIOLET, DAISY, and BEGONIA trials) demonstrated increased self-reported sexual desire rates for premenopausal women on flibanserin (54–58%) compared to placebo (40–48%) [16,17,18] (Table 3). A 2019 analysis pooled results from these studies, consisting of 2465 premenopausal women with hypoactive sexual desire disorder taking flibanserin or placebo over 28 days. Participants reported a significant increase in the number of satisfying sexual experiences (p < 0.001), as well as improvement in FSFI and FSDS scores (Table 4). Flibanserin was initially rejected for FDA approval twice before being accepted, largely due to safety concerns, specifically risks of hypotension, syncope, and sedation, which worsened with alcohol consumption [58]. These risks, however, do not appear to be significantly worse than comparable central nervous system agents, such as bupropion and paroxetine, which are much more widely prescribed. Furthermore, the alcohol challenge that established these risks may not represent a typical pattern of consumption [35].

Bremelanotide (Vyleesi) is the second FDA-approved medication for hypoactive sexual desire disorder, and is administered as an injectable. It significantly improved FSFI (+1.25 to +1.30) and FSDS scores (−1.4 to −1.7) for premenopausal women with FSIAD compared to placebo (+0.70 to +0.77; −0.9, respectively) in two phase III trials [20] (Table 3). An open-label extension assessing long-term safety and efficacy of bremelanotide reported that after 52 weeks, participants initially on bremelanotide showed greater increases in FSFI scores (+1.25 to +1.30 points) and decrease in FSDS scores (−1.4 to −1.7 points) compared to those previously on placebo (+0.70 to +0.77 points and −0.9 points, respectively) [19] (Table 3).

DHEA (Intrarosa) is an FDA-approved treatment for GSM, which is the most common cause of GPPPD disorder in postmenopausal women. Studies have found that DHEA helps lower vaginal pH and enhances vaginal appearance by 86% to 121% more than placebo [31,32] (Table 3). A Phase III trial showed improvements in objective GSM measures and a reduction in pain during sexual activity with this therapy [48] (Table 4).

Ospemifene is FDA-approved for dyspareunia related to GSM. Phase III trials on ospemifene indicated improved self-reported VVA symptoms in postmenopausal women, along with positive physical changes (an increase in vaginal superficial cells, decrease in vaginal basal cells, and reduction in vaginal pH) [33] (Table 3). There are relatively few studies on its use, however, and both ospemifene and DHEA treat symptomatic vaginal dryness and dyspareunia without addressing sexual desire or psychological causes.

3.2. Hormonal

Testosterone is a conventional and longstanding approach to treating FSIAD in postmenopausal women. It is well studied, and the body of literature on testosterone includes best practice guidelines and a global position statement on its use [59]. Multiple RCTs have demonstrated that testosterone moderately increases sexual desire and activity in postmenopausal women, both with and without concurrent estrogen supplementation [38,40] (Table 4). A 2017 meta-analysis yielded similar results to the trials for postmenopausal women taking 300 μg of testosterone over the course of six months, while also noting a significant increase in the number of orgasms and decrease in personal distress [37] (Table 4).

Estrogen is a well-studied therapy for both FSIAD and GPPPD. A 2023 review evaluated the effects of hormonal therapy on sexual function composite scores in 36 studies. Treatments included estrogen alone, estrogen with progestogens, synthetic steroids, selective estrogen reuptake modulators (SERMs), and SERMs with estrogen. Estrogen monotherapy was associated with a slight improvement in sexual function among symptomatic or early postmenopausal women (MD = 0.50, CI: 0.04–0.96, three studies). Estrogen had little to no effect (MD = 0.64, CI: −0.12–1.41, six studies) in women who have been postmenopausal for a longer duration or were not selected based on symptoms (unselected postmenopausal). Pooled data suggested a modest overall benefit in sexual function (MD = 0.60, CI: 0.16–1.04, nine studies). The effects of other hormonal therapies (estrogen with progestogens, synthetic steroids, SERMs, and SERMs with estrogen) on symptomatic or early postmenopausal women and unselected postmenopausal women remain uncertain due to low-quality evidence [39] (Table 4). Estrogens have also been directly compared to androgens. At supraphysiological levels, testosterone appears to enhance sexual desire when combined with low-dose estrogen. However, this synergistic effect is not observed at physiologic testosterone levels [40] (Table 4).

Tibolone (Livial) is used worldwide to treat postmenopausal women with FSIAD and GSM. In a systematic review of 46 trials with nearly 20,000 women, tibolone was found to be more effective than placebo in reducing the prevalence of vasomotor symptoms (35–45% tibolone vs. 67% placebo) but less effective than combined menopausal hormonal therapy (MHT) (35–45% tibolone vs. 7% MHT) [41] (Table 4). Despite its benefits, tibolone has been discontinued in the US due to a concern for elevated stroke risk.

3.3. Non-Hormonal

Sildenafil citrate (Viagra) is an off-label treatment for FSIAD, and there are mixed findings on its sexual function effects. In a 2024 review of six RCTs on premenopausal and postmenopausal women with FSD, four trials noted a significant improvement in female sexual response, while two did not find any association. The review specifically notes that the multifactorial nature of FSD limits the nature and applicability of these results. In addition, there is limited generalizability with these results given that the studies mostly included generally healthy women [42] (Table 4). Recent studies suggest that topical sildenafil may be a viable treatment option for FSIAD. A phase IIb RCT in 2024 reported that premenopausal women with FSIAD using sildenafil cream for 12 weeks had significant score increases in the Arousal Sensation section of the SFQ (mean = 2.03) compared with placebo (mean = 0.08) and a greater average improvement in the SFQ28 Desire and Orgasm section. Participants also experienced a significant decrease in FSDS scores [25] (Table 3).

Bupropion was originally developed as an alternative to traditional antidepressants with significant side effect profiles, but it was later found to have beneficial sexual side effects. A 2022 review with 11 studies observed a significant improvement in sexual arousal, vaginal lubrication, orgasm quality, and sexual satisfaction with bupropion. A meta-regression following this review reported that the variation in symptomatic improvement with bupropion was attributable to dosing [44] (Table 4). Trials of bupropion to treat SM-ISD, specifically sexual dysfunction brought on by antidepressants, have also shown positive effects [26] (Table 3). Because of the potential for severe side effects, providers should obtain an extensive medical, psychiatric, and medication history prior to considering this agent for FSIAD [60].

Apomorphine is a common medication used in Parkinson’s disease management. In a placebo-controlled study investigating the efficacy of sublingual apomorphine in FSD, apomorphine showed statistically significant improvement in sexual desire with 3 mg dosing. In addition, results indicated that female patients may benefit more from daily apomorphine, given its short half-life and rapid clearance [27] (Table 3). A second small trial showed subjective but significant benefit in sexual desire [28] (Table 3).

Phentolamine mesylate primarily treats hypertension, hypertensive emergency, and pheochromocytomas. It has limited data supporting it as a treatment for FSD. A 2002 clinical trial investigated the effects of phentolamine in 41 postmenopausal women with FSIAD, who were enrolled in one of the four treatment arms: 5 mg vaginal solution, 40 mg vaginal solution, oral 40 mg, or placebo. Quantitative results were based on vaginal photoplethysmography, and qualitative measures were assessed using a subjective questionnaire. The results showed statistically significant results amongst postmenopausal women using hormone replacement therapy. Physiological readings were improved in the 40 mg vaginal solution group and subjective measures noted improvement in arousal in both the 40 mg oral and 40 mg vaginal solution arms [29] (Table 3).

Oxytocin is an endogenous hormone known for its role in childbirth, breastfeeding, and pain relief, but which also has effects on sexual desire and arousal. A 2015 randomized trial investigated the effects of long-term intranasal oxytocin on sexual dysfunction in pre- and post-menopausal women over 22 weeks. While both oxytocin and placebo groups showed improvements in FSFI, FSDS, F-SQOL, sexual activity record (SAR), Hamilton depression scale (HDS), and sexual interest and desire index (SIDI) scores, oxytocin did not demonstrate a statistically significant advantage over placebo in any category. Improvements observed were likely due to factors other than oxytocin use [30] (Table 3).

3.4. Topical/Local Agents

Capsaicin has been investigated as a treatment for vulvar vestibulitis syndrome (VVS) and chronic pelvic pain. A retrospective chart review evaluated the use of 0.025% capsaicin cream applied daily for 20 min over 12 weeks in patients with VVS. The study found a significant reduction in discomfort, allowing for increased frequency of vaginal intercourse, with 95% of patients engaging in intercourse post-treatment compared to 62% before treatment [54] (Table 5). Another study examined the use of a high-concentration (8%) capsaicin patch (Qutenza) in patients with chronic pelvic, perineal, and gluteal neuralgia. The patch was applied for 60 min every three months, with pre- and post-application cooling measures to minimize burning sensations. The study reported a significant improvement in pain for 24% of patients, with a mean pain reduction of 58% [55] (Table 5). Despite promising results, both studies had small sample sizes and non-randomized designs.

Lidocaine as a local anesthetic has naturally also been tested for use in GPPPD. In a 12-week RCT involving 133 women with vulvodynia, oral desipramine and topical 5% lidocaine buffered in Moisturel lotion, whether used as monotherapy or in combination, failed to significantly reduce pain compared to placebo. Participants were instructed to apply the cream lightly over the painful region four times daily. Results indicated that lidocaine provided only a 20% improvement in pain scores, which was not significantly different from placebo, highlighting its minimal efficacy in managing vulvodynia [25] (Table 3). Results from a smaller trial of cancer survivors did show more benefit, but the population is small and highly selected [34] (Table 3).

Hyaluronic acid (HA) is a promising non-hormonal treatment option for VVA and dyspareunia. The current literature highlights its effectiveness in reducing symptoms such as vaginal estrogen dryness, irritation, burning, and pain during intercourse. Treatment guidelines suggest that HA can be used as an alternative to estrogen therapy, particularly for patients with contraindications to hormonal treatments. A small 2015 cohort study compared HA to vaginal estrogen and noted that both were effective, although vaginal estrogen seemed more effective than HA [57] (Table 5). Research remains inconclusive due to significant study heterogeneity, variations in administration methods, and a lack of standardized protocols [49] (Table 4).

3.5. Other

Botulinum toxin (BoNT-A) has been explored as a treatment for FSD. A systematic review of 22 studies found BoNT-A to be effective in improving dyspareunia, chronic pelvic pain, and vaginismus. Doses, dilutions, administration techniques, and sedation methods varied. Most studies administered a single injection, though some repeated doses if symptoms persisted. The lack of standardized dosing, administration, and follow-up limits comparability between studies [50] (Table 4).

Platelet-rich plasma (PRP) injections are a possible treatment modality for FSD, although the mechanism of action is unclear. One systematic review of 15 studies examined the use of PRP for pelvic floor disorders, and the results indicated effectiveness in management, but more research is needed to determine optimal dosing [51] (Table 4). Another review with 12 studies investigated PRP for FSD and stress urinary incontinence, suggesting beneficial effects on FSFI and VHI scores [52] (Table 4). The current body of research remains limited by methodological inconsistencies, small sample sizes, and a lack of RCTs.

MDMA, commonly known as “ecstasy,” is a synthetic psychoactive compound with stimulant and entactogenic properties. While MDMA is widely used recreationally, a systematic review suggests that MDMA may improve aspects of female sexual function. Findings indicate that MDMA increases sexual desire in women, with studies reporting enhanced libido, lubrication, and increased pleasure intensity. However, due to the mixed nature of the limited available studies, more information is needed to determine if the therapeutic advantages are greater than the potential adverse effects [45] (Table 4).

Visnadine, a compound derived from the Ammi visnaga plant, is a vasodilator and has possible therapeutic uses in a similar fashion to sildenafil in the treatment of FSD. In a systematic review of randomized clinical trials, visnadine demonstrated potential efficacy in improving arousal, lubrication, orgasm, and overall sexual satisfaction. While only two randomized controls were analyzed, the results indicated that on-demand use of visnadine before sexual activity resulted in greater improvements in sexual function compared to daily application. Treatment guidelines remain inconclusive due to the limited number of studies, small sample sizes, and methodological variability, though findings suggest both daily and on-demand applications may be beneficial [46] (Table 4).

L-arginine, a naturally occurring amino acid, has been suggested as a treatment for FSIAD. L-arginine is available under the trade names ArginMax, Lady Prelox, Ristela, and Stronvivo. In addition to L-arginine, these products have varying compositions of other natural products, vitamins, and minerals such as L-citrulline, ginkgo biloba, Korean ginseng, damiana leaf, French maritime pine bark extract, rose hip extract, zinc, and magnesium. However, only ArginMax and Lady Prelox have published research supporting their efficacy. Although there has never been a study that has studied the effect of L-arginine alone as a monotherapy, these combination products have been shown to significantly improve sexual function in both pre- and post-menopausal women with FSD. Despite these promising findings, further high-quality research is needed, particularly well-powered RCTs that evaluate L-arginine as a standalone treatment, to better understand its specific role in female sexual function [47] (Table 4).

Additional data were extracted from the included studies (n = 44) and new sources to group treatments for FSIAD and GPPPD by mechanism of action, recommended dosage, and side effects (

Table 6. Overview of FSIAD pharmacotherapies by mechanism, dosage, and side effects.

Type of FSIAD Intervention	Pharmaceutical Agent	Mechanism of Action	Recommended Dosage	Side Effects
FDA-approved	Flibanserin (Addyi) [9,35,61]	Serotonin 1A (5-HT1A) and 2A (5-HT2A) agonist	100 mg orally once a day at bedtime	Dizziness and somnolence. The FDA recommends waiting at least 2 h before consuming alcohol
	Bremelanotide (Vyleesi) [9,61]	Melanocortin 4 receptor (MC4R) agonist, increasing dopamine levels	1.75 mg subcutaneously once per 24 h period. Monthly maximum of 8 doses	Nausea. Use cautiously in cases of cardiovascular disease
Hormonal	Testosterone [9,26,61]	Direct androgenic activity, conversion to estrogen via aromatase, enhancing estradiol in the brain	5 mg transdermally once a day. Dose may be gradually increased to 10 mg daily	Hirsutism
	Estrogen [40,62]	Enhances sexual desire in the CNS and increases vaginal lubrication locally	Varying doses transdermally or orally	Risk of thromboembolic events with oral treatment
	Tibolone (Livial) [39,41,63]	Regulates tissue-specific estrogenic, progestogenic, and androgenic effects through its metabolites. Increases VPA at baseline and following erotic stimulation	1.25–2.5 mg orally once a day	Risk of stroke in postmenopausal women with vertebral fractures. Not recommended until age of natural menopause
Non-hormonal	Sildenafil citrate (Viagra) [42,64]	Phosphodiesterase 5 (PDE5) inhibitor, increasing blood flow to erectile tissue	Varying doses orally	Headaches, flushing, visual changes
	Bupropion [44,60]	Norepinephrine–dopamine reuptake inhibitor (NDRI)	150 mg orally once a day	Hypertension, tachycardia, insomnia, tremor, drug–drug interactions, lower seizure threshold, worsened suicidal ideation
	Apomorphine [27]	Nonselective dopamine 1 (D1) and dopamine 2 (D2) receptor agonist. Triggers nitric oxide-mediated vasodilation of clitoral tissue	3 mg orally once a day	Nausea, vomiting, dizziness
	Phentolamine mesylate [27]	Alpha-adrenergic receptor antagonist, improving clitoral tissue blood flow	40 mg orally or in a vaginal solution	Shortness of breath, rhinitis, chest pain, headache
	Oxytocin [30]	Endogenous hypothalamic hormone	32 IU of synthetic oxytocin intranasally. Recommendation of 4 puffs/nostril at least 50 min before intercourse, twice weekly	Epistaxis, rhinorrhea, headache
Topical/local	Sildenafil citrate (Viagra) [25,42]	PDE5 inhibitor increasing blood flow to erectile tissue	Topical cream, 3.6%	No significant adverse events noted
Other	MDMA [45,65,66]	Increases release of serotonin, dopamine, and norepinephrine in the brain	Varying doses	Anxiety, nausea, jaw tightness, non-cardiac chest discomfort, fatigue, neurotransmitter imbalance
	Visnadine [46]	Inhibits L-type calcium channels to increase genital blood flow	Two puffs to the vulvar area	Warmth, itching, bleeding
	L-arginine-containing products [47]	Precursor to nitric oxide, increasing blood flow to erectile tissue	Varying doses	Minor gastric disturbances, heavier menstrual bleeding, headaches

and

Table 7. Overview of GPPPD pharmacotherapies by mechanism, dosage, and side effects.

Type of GPPPD Intervention	Pharmaceutical Agent	Mechanism of Action	Recommended Dosage	Side Effects
FDA-approved	DHEA (Intrarosa) [9,48]	Precursor to estradiol and testosterone	6.5 mg intravaginally	Vaginal discharge
	Ospemifene [9,63]	Selective estrogen receptor modulator (SERM) on vaginal epithelium	60 mg orally once daily. FDA recommends that patients with a uterus take ospemifene alongside a progestin	Hot flashes
Hormonal	Estrogen [40,62]	Enhances sexual desire in the CNS and increases vaginal lubrication	Varying doses transdermally or orally	Risk of thromboembolic events with oral treatment
	Tibolone (Livial) [39,41,63]	Regulates tissue-specific estrogenic, progestogenic, and androgenic effects through its metabolites. Increases VPA at baseline and following erotic stimulation	1.25–2.5 mg orally once a day	Risk of stroke in postmenopausal women with vertebral fractures
Topical/local	Capsaicin [54,55]	Selective TRPV1 receptor agonist, desensitizing nociceptive neurons	0.025% capsaicin cream or 8% transdermal patch	Burning sensation
	Lidocaine [67]	Inhibits sodium channels in nociceptors, blocking peripheral nerve transmission	Topical cream, 5%	No significant adverse events noted
	HA [49]	Hydrophilic glycosaminoglycan, maintaining tissue hydration and elasticity	Variable doses and administration techniques	Mild irritation, localized infection
Other	BoNT-A [50]	Inhibits acetylcholine release for temporary muscle relaxation. Blocks substance P to reduce pain	Varying doses, dilutions, and administration techniques	Urinary incontinence, constipation, and fecal incontinence
	PRP injections [51,52]	Growth factors that stimulate angiogenesis, collagen production, and neural regeneration	2 mL of PRP injected into the distal anterior vaginal wall monthly for three months	Minimal side effects; rare cases of transient pain or urinary symptoms

).

4. Discussion

FSD is a highly prevalent yet underdiagnosed medical condition, and therapeutic options have been slow to evolve. Beyond the existing historical bias favoring research on male sexual dysfunction, FSD presents additional challenges in classification and diagnosis. Many women do not seek treatment for issues with sexual function, and for those who do, the diagnosis of FSD is often reliant on self-reports rather than objective measures. Moreover, the four subtypes of FSD exhibit distinct yet often overlapping symptoms. This complicates any therapy, especially pharmacotherapy, as there is rarely an underlying physiologic cause that can be targeted by a pharmaceutical agent, and symptomatic relief is often the goal of treatment.

Table 3, Table 4 and Table 5 provide a succinct overview of current pharmacotherapies for FSD grouped by RCTs, review articles, and cohort studies (n = 44). However, aside from the FDA-approved medications, no single medication has demonstrated consistent efficacy across FSD subtypes. Many of the available options have yet to explore long-term safety and efficacy data, thus it is difficult to assess the sustained impact of FSD treatments. The paucity of direct comparative studies of treatment approaches further complicates the identification of the most effective interventions. Additionally, most of the available research has focused on postmenopausal women, leaving the study of pharmacotherapy options for premenopausal populations underexplored.

Limited pharmacotherapy options are available for FOD and SM-ISD. Treatment of FOD primarily consists of psychological interventions such as cognitive, behavioral, and psychoanalytic therapy [9]. Similarly, SM-ISD is typically managed with discontinuation of the offending agent, patient education, and laboratory investigations for other potential etiologies [68]. Substances and prescription medications that could precipitate SM-ISD include alcohol, cannabis, opioids, antipsychotics, antidepressants, anticonvulsants, and antihypertensives [68,69]. A meta-analysis evaluating pharmacological treatments for antidepressant-induced sexual dysfunction specifically identified bupropion as the most effective option. However, the overall quality of evidence was low, underscoring the need for further well-designed studies to validate these findings [70].

The use of natural remedies for FSD treatment is an expanding area of research. Aphrodisiacs, including ginkgo, ginseng, maca (Lepidium meyenii), puncturevine (Tribulus terrestris), black cohosh (Cimicifuga racemosa), red clover (Trifolium pratense), chasteberry fruit (Vitex agnus-castus), zallouh (Ferula hermonis), hops (Humulus lupulus), and dong quai (Angelica sinensis), have been investigated as standalone or adjunct therapies for FSD. However, double-blind, placebo-controlled studies on the potential synergistic effects of combining natural products with pharmacotherapy for FSD remain limited [71].

Another underexplored area of FSD management involves the use of pharmacological treatments for urinary incontinence. Urinary incontinence has been linked with FSD, likely due to its psychological effects on body image, self-esteem, and sexual confidence [72]. Though few studies have directly assessed the role of anticholinergics and beta-3 adrenergic agonists on improving sexual function, these agents improve bladder control and may potentially benefit women experiencing FSD [73,74]. It is also worth noting that some women may self-manage FSD symptoms with substances perceived to enhance sexual function. Cannabis, in particular, has shown promising outcomes in observational studies but has yet to be elevated in RCTs [75].

Combination pharmacotherapy has considerable potential for FSD management. A preliminary review on hormonal therapy for FSD found that the effects of SERMs combined with estrogen on sexual function composite scores were uncertain in both symptomatic or early postmenopausal women (MD = 0.22, CI: 0.00–0.43, one study) and unselected postmenopausal women (MD = 2.79, CI 2.41–3.18, one study). Additionally, the impact of SERMs combined with estrogen remained unclear for symptomatic or early postmenopausal women (MD = 0.22, CI: 0.00–0.43, one study) and unselected postmenopausal women (MD 2.79, CI: 2.41–3.18, one study). Ultimately, these results were inconclusive due to low-quality existing evidence [39]. Combination hormonal therapies demonstrated that androgens alone did not improve desire, unlike estrogens, but androgens added to estrogen therapies did potentiate the effect of estrogen [53]. Aside from hormonal pharmacotherapies, Lorexys is a combination drug of bupropion and trazodone, which has undergone phase I and II trials to determine safety and dosage. It has been used in combination with testosterone to treat hypoactive sexual desire disorder in women; however, these trials are still preliminary in nature [76].

Non-pharmacological interventions such as cognitive-behavioral therapy (CBT), mindfulness-based cognitive therapy (MBCT), and pelvic floor physical therapy (PFPT) have also shown promise in addressing underlying contributors to FSD. Although a comprehensive review of behavioral therapies is beyond the scope of this review, potential combinatory effects with pharmacotherapies should be discussed. A 2022 state-of-the-art review recognized CBT as the most empirically-supported therapy for FSD, improving FSIAD, GPPPD, and FOD symptoms through techniques including cognitive reconstruction, sensate focus, muscle relaxation, and sex education. Moreover, a RCT comparing the efficacy of CBT and sildenafil for FSD treatment found that both interventions significantly improved sexual function, sexual satisfaction, and marital satisfaction (p < 0.001), though CBT demonstrated greater overall effectiveness [10,77]. MBCT is often used as a conjunctive or standalone therapy for FSD, with interventions aimed at enhancing awareness and acceptance of one’s thoughts and emotions. MBCT has made meaningful improvements in women experiencing FSD symptoms, including those with complex comorbid conditions such as cancer-related dysfunction, childhood sexual abuse, and spinal cord injuries [10]. PFPT has demonstrated notable therapeutic benefits in treating symptoms of GPPPD. A 2023 systematic review and meta-analysis evaluating the effects of mindfulness and PFPT on women with chronic pelvic pain noted that both treatment arms significantly reduced pain immediately after treatment (p < 0.01) and at follow-up (p < 0.00), though PFPT showed a greater positive impact on sexual function over time (p < 0.03) [78]. Despite the known benefits of non-pharmacologic interventions, very few studies have rigorously evaluated treatment with combined pharmacological and nonpharmacological therapies. This gap in research represents a missed opportunity to develop multifaceted treatment strategies that more effectively align with patients’ lived experiences and individual preferences.

Unfortunately, only a small proportion of women with sexual dysfunction end up with treatment, pharmaceutical or otherwise. Providers are often reluctant to diagnose or prescribe medications for such conditions, and patients are also often unwilling to acknowledge or treat their condition. The FDA-approved medications are relatively new, but they have not had the same rapid adoption, and concomitant financial success, that PDE5 inhibitors had with regards to erectile dysfunction [79]. These issues, as well as the gaps in the literature described, limit the utilization of these medications, despite demonstrated effectiveness.

There are several limitations to this review. The search process was limited to the most comprehensive databases, potentially missing relevant unpublished or non-peer-reviewed studies. The inclusion criteria limited reports to those published in English and excluded non-pharmacologic interventions, potentially missing important crossover studies and reports on diverse populations. The wide variety of journals publishing on this broad topic meant that not all articles were available as full-text, possibly excluding some key data. Furthermore, the potential for publication bias should be acknowledged, which may lead to an overestimation of treatment efficacy and underrepresentation of adverse effects in the literature.

Future studies should prioritize longitudinal clinical trials to strengthen the evidence base for FSD pharmacotherapies. Moreover, an integrative approach is necessary to adjust for the complexity of female sexual health. Factors including age, hormonal fluctuations, and reproductive status influence FSD, prompting further exploration into how these qualities impact care management. It is also important to evaluate the synergistic effects that pharmacologic agents may have with combination therapies in order to accurately assess interdisciplinary treatment strategies. Other directions of FSD management may entail the use of biomarkers, genetic testing, growth factor therapies, stem cell interventions, and regenerative medicine [80]. These strategies could provide a more targeted and personalized approach to FSD treatment, ultimately improving patient outcomes and expanding the scope of therapeutic possibilities.

FSD is a multifaceted condition that encompasses a broad range of conditions, and accordingly, its pharmacologic treatments are more diverse than commonly recognized. Its varied treatment mechanisms reflect the complex interplay of psychological, physiological, social, and hormonal factors in FSD, underscoring the need for individualized treatment strategies. Continued research into this field is essential for enhancing current treatment strategies and improving the health of individuals with FSD.

5. Conclusions

FSD is a broad diagnosis with varying etiologies and treatment options. FDA-approved agents are the best-studied pharmacotherapies currently available, while hormonal, topical, and adjunctive agents exhibit significant potential. This article aims to provide an up-to-date review of the current pharmaceutical interventions for FSD while emphasizing the need for further research in this realm of women’s healthcare. By adopting a comprehensive and patient-centered approach, providers can utilize this review to provide tailored treatment approaches that consider the psychological, hormonal, and social factors contributing to FSD.