Female Sexual Dysfunction (FSD)

Number: 0574

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses female sexual dysfunction (FSD).

1. Medical Necessity

   Aetna considers the following medically necessary for female sexual dysfunction (FSD):

   1. Cognitive behavioral therapy/psychotherapy;
   2. Pelvic floor physical therapy for genito-pelvic pain disorders.
      

   Note: See Pharmacy Clinical Policy Bulletins for: bremelanotide injection (Vyleesi) and flibanserin tablets (Addyi) for the treatment of pre-menopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), and for ospemiphene tablets (Osphena) for severe vaginal dryness and dyspareunia due to menopause.

2. Experimental, Investigational, or Unproven

   1. Aetna considers biothesiometry experimental, investigational, or unproven for the diagnosis of FSD.
   2. Aetna considers the following interventions for the treatment of FSD experimental, investigational, or unproven (not an all-inclusive list) because of insufficient evidence:
      
      
      • Bibliotherapy
      • Biothesiometry
      • Endo-vaginal and vulvar rejuvenation laser
      • Female erectile devices (e.g., Eros clitoral stimulation device)
      • Gene therapy
      • Growth factor therapy
      • Hyaluronic acid
      • Laser therapy (e.g., Micro-ablative carbon dioxide laser)
      • Methylenedioxymethamphetamine (MDMA)
      • Oxytocin
      • Percutaneous tibial nerve stimulation
      • Photobiomodulation of the vulvar region
      • Platelet-rich fibrin injections
      • Platelet-rich plasma injections
      • Radiofrequency ablation (e.g., by means of the MorpheusV applicator) of the vaginal canal
      • Radiofrequency thermal therapy (e.g., the ThermiVa procedure, and the Viveve procedure)
      • Regenerative medicine
      • Sacral neuromodulation
      • Stem cell-based therapies
      • Transcranial direct current
      • Vaginal electrical stimulation.

3. Policy Limitations and Exclusions

   Some Aetna plans exclude drugs or supplies for sexual dysfunction or inadequacy. Please check benefit plan descriptions for details.

   Aetna does not cover vibrators, which have been used in the treatment of FSD because vibrators do not meet Aetna’s contractual definition of covered durable medical equipment (DME). Please check benefit plan descriptions. Coverage of DME is limited to devices that are not normally of use in the absence of illness or injury. Vibrators are not primarily a medical device, and may be of use in the absence of illness and injury.

4. Related Policies

   • CPB 0113 - Botulinum Toxin
   • CPB 0345 - Implantable Hormone Pellets
   • CPB 0510 - Progestins 
   • CPB 0528 - Testosterone Undecanoate (Aveed) Injection

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
90832	Psychotherapy, 30 minutes with patient
90833	Psychotherapy, 30 minutes with patient when performed with an evaluation and management service (List separately in addition to the code for primary procedure)
90834	Psychotherapy, 45 minutes with patient
90836	Psychotherapy, 45 minutes with patient when performed with an evaluation and management service (List separately in addition to the code for primary procedure)
90837	Psychotherapy, 60 minutes with patient
90838	Psychotherapy, 60 minutes with patient when performed with an evaluation and management service (List separately in addition to the code for primary procedure)
97110	Therapeutic procedure, 1 or more areas, each 15 minutes; therapeutic exercises to develop strength and endurance, range of motion and flexibility
CPT codes not covered for indications listed in the CPB:
Stem cell based therapies for female erectile devices, biothesiometry, Viveve Procedure, vaginal electrical stimulation, ThermaVi, transcranial direct current, bibliotherapy, endo-vaginal and vulvar rejuvenation laser, photobiomodulation of the vulvar region, radiofrequency ablation (e.g., by means of the MorpheusV applicator) of the vaginal canal - no specific code
0232T	Injection(s), platelet rich plasma, any site, including image guidance, harvesting and preparation when performed
0552T	Low-level laser therapy, dynamic photonic and dynamic thermokinetic energies, provided by a physician or other qualified health care professional
0672T	Endovaginal cryogen-cooled, monopolar radiofrequency remodeling of the tissues surrounding the female bladder neck and proximal urethra for urinary incontinence
17110	Destruction (eg, laser surgery, electrosurgery, cryosurgery, chemosurgery, surgical curettement), of benign lesions other than skin tags or cutaneous vascular proliferative lesions; up to 14 lesions [micro-ablative carbon dioxide laser]
17111	15 or more lesions [micro-ablative carbon dioxide laser]
64566	Posterior tibial neurostimulation, percutaneous needle electrode, single treatment, includes programming
Other CPT codes related to the CPB:
11980	Subcutaneous hormone pellet implantation (implantation of estradiol and/or testosterone pellets beneath the skin)
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
HCPCS codes not covered for indications listed in the CPB:
Methylenedioxymethamphetamine (MDMA) - no specific code
J2590	Injection, oxytocin, up to 10 units
J7318	Hyaluronan or derivative, Durolane, for intra-articular injection, 1 mg
J7320	Hyaluronan or derivative, GenVisc 850, for intra-articular injection, 1 mg
J7321	Hyaluronan or derivative, Hyalgan, Supartz or Visco-3, for intra-articular injection, per dose
J7322	Hyaluronan or derivative, Hymovis, for intra-articular injection, 1 mg
J7323	Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose
J7324	Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose
J7325	Hyaluronan or derivative, Synvisc or Synvisc-One, for intra-articular injection, 1 mg
J7326	Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose
J7327	Hyaluronan or derivative, Monovisc, for intra-articular injection, per dose
J7328	Hyaluronan or derivative, GELSYN-3, for intra-articular injection, 0.1 mg
J7329	Hyaluronan or derivative, Trivisc, for intra-articular injection, 1 mg
J7331	Hyaluronan or derivative, SYNOJOYNT, for intra-articular injection, 1 mg
J7332	Hyaluronan or derivative, Triluron, for intra-articular injection, 1 mg
P9020	Platelet rich plasma, each unit
ICD-10 codes covered if selection criteria are met:
F52.0 - F52.1, F52.22 - F52.31, F52.5 - F52.9	Sexual dysfunction not due to a substance or known physiological condition, female
N90.5	Atrophy of vulva
N94.10 - N94.19	Dyspareunia
N94.2	Vaginismus
N94.89	Other specified conditions associated with female genital organs and menstrual cycle
N95.2	Postmenopausal atrophic vaginitis
R10.20 – R10.23	Pelvic and perineal pain
R37	Sexual dysfunction, unspecified

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Background

Female sexual dysfunction (FSD) encompasses a heterogeneous group of disorders characterized by persistent disturbances in sexual desire, arousal, orgasm, or pain that result in clinically significant personal distress and impaired quality of life. FSD is multifactorial in etiology, reflecting complex interactions among biological, psychological, interpersonal, and sociocultural factors; as such, evaluation and management require a comprehensive, multimodal approach. Non‑pharmacologic interventions are foundational and include cognitive behavioral therapy (CBT), mindfulness‑based therapy, and structured sex therapy, which target maladaptive cognitions, performance anxiety, relational dynamics, and body awareness, with evidence demonstrating improvements in validated sexual function and distress outcomes (Mestre‑Bach, 2022; Toledo, 2026). Pelvic floor physical therapy may be indicated in select individuals, particularly when pelvic floor dysfunction contributes to dyspareunia or impaired sexual response. Pharmacologic options remain limited and are generally associated with modest clinical benefit; these include centrally acting agents such as flibanserin and bremelanotide, which have demonstrated improvements in sexual desire and related distress in appropriately selected premenopausal women, as well as ospemiphene tablets, a selective estrogen receptor modulator indicated for dyspareunia associated with vulvovaginal atrophy (Nappi, 2022; Toledo, 2026). Overall, current evidence supports an integrated treatment strategy that combines behavioral, physical, and pharmacologic modalities, tailored to the underlying contributors and patient-specific factors.

The American College of Obstetricians and Gynecologists (ACOG) recommends cognitive behavioral therapy, mindfulness-based therapy, and sex therapy for female sexual dysfunction, all of which are supported by randomized controlled trials (RCTs) and a network meta-analysis for desire/arousal and orgasmic disorders (ACOG, 2019; Dalrymple et al., 2025; Toledo et al., 2025). Vaginal estrogen and intravaginal prasterone (DHEA) have level A evidence according to ACOG for dyspareunia due to genitourinary syndrome of menopause (ACOG, 2019). Additionally, ACOG recommendations include pelvic floor physical therapy as a first-line treatment for genito-pelvic pain disorders, which is supported by a 2024 systematic review and meta-analysis (ACOG, 2019; Dalrymple et al., 2025; Jorge et al., 2024).

A wide range of additional interventions has been proposed for the management of female sexual dysfunction; however, many of these modalities lack sufficient high-quality evidence demonstrating clinically meaningful benefits or have not been well studied in rigorous, controlled trials. These interventions include behavioral and adjunctive approaches such as bibliotherapy and biothesiometry; device-based or mechanical interventions, including female erectile devices (e.g., clitoral stimulation) and vaginal electrical stimulation; pharmacologic and hormonal therapies such as oxytocin; neuromodulation techniques, including percutaneous tibial nerve stimulation, sacral neuromodulation, and transcranial direct current stimulation; and endovaginal or vulvar laser therapy (including micro-ablative carbon dioxide laser), radiofrequency-based therapies, photobiomodulation, platelet-rich plasma or fibrin injections, hyaluronic acid injections, and other regenerative medicine or stem cell-based approaches. Additionally, emerging or investigational therapies such as gene therapy, growth factor therapy, and agents like methylenedioxymethamphetamine (MDMA) have been explored in limited or experimental settings. Overall, the available literature is characterized by small sample sizes, heterogeneous patient populations and outcome measures, a lack of standardized definitions of dysfunction, and limited long-term safety data, resulting in substantial uncertainty regarding effectiveness, durability, and risk–benefit profiles.

Ospemifene

Ospemifene, branded as Osphena (Duchesnay USA, Inc.) is an orally administered selective estrogen receptor modulator (SERM) with tissue-selective estrogen agonist and antagonist activity, exerting estrogenic effects on the vaginal epithelium. It was approved by the U.S. Food and Drug Administration (FDA) in 2013 for the treatment of moderate to severe dyspareunia, and subsequently for moderate to severe vaginal dryness, both of which are symptoms of vulvar and vaginal atrophy (VVA) associated with menopause. VVA is a component of genitourinary syndrome of menopause and is a recognized contributor to female sexual dysfunction, particularly due to pain with intercourse and impaired vaginal lubrication. By binding to estrogen receptors in vaginal tissue, ospemifene promotes epithelial maturation, improves vaginal pH, and increases mucosal thickness and lubrication, thereby reducing symptom burden. Although it is administered systemically, ospemifene is considered an alternative to local estrogen therapy due to its selective receptor activity; however, its pharmacologic profile includes estrogenic effects on the endometrium and is associated with potential risks such as thromboembolic events, necessitating careful patient selection and monitoring (Duchesnay USA, 2025; Palacios, 2020).

Vyleesi (Bremelanotide Injection) for the Treatment of Hypoactive Sexual Desire Disorder

Bremelanotide, branded as Vyleesi (Cosette Pharmaceuticals, Inc.) is a melanocortin receptor agonist administered as subcutaneous injection for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems with the relationship, or the effects of a medication or drug substance. Per the Prescribing Information, Vyleesi is not indicated for treatment of HSDD in postmenopausal women or in men, or indicated to enhance sexual performance.

Bibliotherapy for the Treatment of Female Sexual Dysfunction

van Lankveld and colleagues (2021) examined the efficacy of bibliotherapy for sexual dysfunctions, when compared with no treatment and compared with other interventions. Medline, Embase, and PsycINFO were searched from 1970 to January 2020. Selection criteria were RCTs examining assisted or unassisted bibliotherapy for all types of sexual dysfunctions compared with no treatment (waitlist or placebo) or with other psychological interventions. Bibliotherapy is defined as psychological treatment using printed instruction to be used by the individual or couple suffering from sexual dysfunction. Primary outcome measures were male and female sexual functioning level and continuation/remission of sexual dysfunction. Secondary outcomes were sexual satisfaction and drop-out rate. Sexual functioning and sexual satisfaction were self-reported by subjects using validated questionnaires. A total of 15 RCTs (1,113 subjects—781 women; 332 men) met inclusion criteria. Compared with no treatment, unassisted bibliotherapy resulted in larger proportions of female subjects reporting remission of sexual dysfunction, and sexual satisfaction was higher in treated subjects, both female and male participants. Compared with no treatment, assisted bibliotherapy had significant positive effects on female sexual functioning; no effects on male sexual functioning were found. Results of unassisted and assisted bibliotherapy did not differ from those of other intervention types on any outcome. Overall, no differences between study conditions were found regarding drop-out rates. The certainty of the evidence for all outcomes was rated as very low. The authors found indications of positive effects of bibliotherapy for sexual dysfunctions. Across studies, more significant effects were found for women than for men. However, owing to drawbacks in the study designs as well as imprecision of the findings, these investigators were unable to draw firm conclusions regarding the use of bibliotherapy for the treatment of sexual dysfunction. These researchers stated that more high quality and larger trials are needed. Relevant outcome measures for future studies should be defined as well as unified grading systems to measure these endpoints. Furthermore, future studies should report on treatment acceptability and adherence.

Biothesiometry

Biothesiometry is a technique that can be used to evaluate genital neurological function in women. It involves the use of a small cylindrical instrument to assess the sensitivity of the clitoris and labia to pressure and temperature. However, there is insufficient evidence regarding its clinical use for the diagnosis of FSD.

Erol et al. (2003) evaluated the genital and extra-genital somatic sensory systems in diabetic women using biothesiometry and investigated the relationship with sexual dysfunction. A total of 30 diabetic women and 20 normal sexually active women as a control group were evaluated with a detailed medical and sexual history, including the Index of Female Sexual Function (IFSF) questionnaire. The somatic sensory system of all women enrolled in the study was assessed by biothesiometry, and threshold sensory values of nine genital sites and 14 extra-genital sites were analyzed. The IFSF score in diabetic women was 23.6, while it was 38.3 in the control group (p < 0.0005). For each genital as well as extra-genital site, the mean biothesiometric values were significantly higher in diabetics. The sensation of the introitus vagina, labium minora, and clitoris were found to be the most deteriorated genital sites in diabetic women. The difference between diabetic women with or without FSD was not significant for biothesiometric values. These findings indicate that the somatic sensory system is affected by diabetes; however, sexual dysfunction does not always manifest.

Botulinum Toxin Therapy

Botulinum toxin (BoNT) is a neurotoxin derived from Clostridium botulinum that exerts its effect through inhibition of acetylcholine release at the neuromuscular junction, resulting in temporary chemodenervation and reduction of muscle activity. Its clinical use has expanded beyond neuromuscular disorders to include a variety of pain and functional conditions. In the context of female sexual dysfunction, BoNT has been investigated as a potential intervention for conditions characterized by pelvic floor muscle hypertonicity or pain—such as genito-pelvic pain/penetration disorders, vulvodynia, and chronic pelvic pain—which may contribute to impaired sexual function. Proposed mechanisms include reduction of involuntary muscle spasm, modulation of peripheral nociceptive signaling, and secondary improvement in pain-related avoidance behaviors. However, as of June 2026, there are no botulinum toxin products that are FDA-approved for the treatment of female sexual dysfunction. See CPB 0113 - Botulinum Toxin.

Endo-Vaginal and Vulvar Rejuvenation Laser

Meyer et al. (2025) stated that pelvic floor dysfunctions in women can lead to problems of urinary and/or anorectal incontinence, prolapse, as well as sexual dysfunction. Treatment approach is physiotherapeutic to begin with and then, possibly, surgical: colposuspension, sub-urethral sling placement, intra-urethral injections of a bulking agent, cystorectocele cure, sacrospinal fixation or laparoscopic promontofixation. Moreover, these researchers stated that the results using an endo-vaginal and vulvar rejuvenation laser need to be confirmed.

Female Clitoral Erectile Devices

Female clitoral erectile devices, such as the Eros clitoral stimulation device (UroMetrics, Inc.), are used to achieve greater clitoral engorgement, which increases lubrication and enhances the ability to achieve orgasm. However, more studies are needed to ascertain the medical necessity and long-term effects of clitoral stimulation devices compared to established approaches such as lubricants, manual stimulation, and over-the-counter devices.

In a pilot study, Schroder et al. (2005) assessed the effectiveness of Eros therapy in alleviating sexual dysfunction in irradiated cervical cancer patients. A total of 15 women were enrolled, and 13 completed the study. The median patient age and radiotherapy enrollment interval were 43.5 years and 2 years, respectively. The investigators concluded that the clitoral stimulation device may alleviate sexual dysfunction in irradiated cervical cancer patients, and a randomized controlled study is needed to evaluate the full benefits of this approach.

Gene/Growth Factor/Stem Cell-Based Therapies and Regenerative Medicine

Farmer and colleagues (2016) developed an evidence-based state-of-the-art consensus report that critically integrates current knowledge of the therapeutic potential for known molecular and cellular targets to facilitate the physiologic processes underlying female sexual function. Expert opinion was established by grading the evidence-based medical literature, intensive internal committee discussion, public presentation, and debate. Scientific investigation is urgently needed to expand knowledge and foster development of future treatments that maintain genital tissue integrity, enhance genital physiologic responsiveness, and optimize positive subjective appraisal of internal and external sexual cues. The authors concluded that future treatment targets include pharmacologic modulation of emotional learning circuits, restoration of normal tactile sensation, growth factor therapy, gene therapy, stem cell-based therapies, and regenerative medicine. Concurrent use of centrally and peripherally acting therapies could optimize treatment response.

Hyaluronic Acid for the Treatment of Female Sexual Dysfunction

Dos Santos and colleagues (2021) stated that the decline in post-menopausal serum estrogen concentration results in several changes in the vulvovaginal and vesicourethral areas, leading to the genitourinary syndrome of menopause, including symptoms such as vaginal atrophy. In a systematic review, these investigators examined the effects of hyaluronic acid (HA) in the treatment of vaginal atrophy. The search strategy was developed using the following terms: "hyaluronic acid vaginal gel," "vaginal estrogens," "vaginitis, atrophic," and "post-menopause." This strategy was used in major databases such as Medline, Embase, Scopus, Cochrane Library, Web of Science, Virtual Health Library (BVS), Congress Abstracts, and Gray Literature (Google Scholar and British Library) for studies published until June 2020. The systematic review was performed to evaluate the results of atrophic vaginitis/vaginal dryness, dyspareunia, vaginal pH, and cell maturation of the studies found by the search strategy. A total of 833 studies were identified; 528 studies were directed for reading titles and abstracts, and 515 were excluded for not meeting the selection criteria. A total of 13 studies were selected for reading the full text; 5 primary studies involving 335 women met the criteria and were included. The studies were published between the years 2011 and 2017. It was not possible to perform a meta-analysis due to the substantial heterogeneity present in the studies. The findings suggested that treatment with HA, when compared with the use of estrogens, did not present a significant difference in the results obtained for the outcomes: epithelial atrophy, vaginal pH, dyspareunia, and cell maturation. The authors concluded that the findings suggested that HA has a profile of efficacy, safety, and tolerability comparable with vaginal estrogens for the treatment of symptoms of vaginal atrophy; it was a possible alternative for women who could not use hormonal treatment. These researchers stated that the analysis of the studies in this systematic review suggested that HA exhibited efficacy similar to vaginal estrogens for the treatment of the signs of vaginal atrophy and dyspareunia; however, the included studies measured the data in different ways, causing the performance of meta-analysis to be impaired.

In a systematic review, Wierzbicka and associates (2021) examined the available treatments that reduce symptoms of vaginitis and vaginal atrophy by improving dyspareunia, mucosal inflammation, vaginal pH, and vaginal dryness in women who have undergone brachytherapy or radiotherapy due to uterine or cervical malignancies. These investigators carried out a comprehensive literature search following PRISMA guidelines. The systematic search was performed using electronic databases, namely Scopus, Web of Science, and PubMed, between October and November 2020 to identify randomized controlled trials (RCTs) and prospective randomized studies (PRS). The analyzed population consisted of 376 patients with uterine or cervical cancer, treated with HA, vitamin A, vitamin E, alpha-tocopherol acetate, and dienestrol. Treatment with HA along with vitamin A and vitamin E revealed advantages in endpoints such as reduced dyspareunia, vaginal mucosal inflammation, vaginal dryness, bleeding, fibrosis, and cellular atypia. Administration of alpha-tocopherol acetate reduced vaginal mucosal inflammation and improved vaginal acanthosis, whereas dienestrol resulted in reduced dyspareunia, vaginal caliber, and bleeding. The authors concluded that vaginal suppositories were found to be clinically effective in managing late-onset vulvovaginal side effects following radiotherapy.

These researchers noted that the use of HA, vitamin A, vitamin E, or dienestrol can be considered a positive supplement for gynecological cancer survivors; therefore, a significant improvement in sexual function, vaginal health, and self-pleasure could be observed. The aforementioned suppositories reduced the symptoms of long-term vulvovaginal lesions such as dyspareunia, mucosal inflammation, dryness, and fibrosis. Moreover, research has established a positive correlation between the vaginal suppositories and decreased vaginal bleeding, fibrosis, and cellular atypia. As such, it appeared that enhancing the cancer survivors’ quality of life (QoL) as well as their sexual activity provided them with a heightened sense of identity along with enhanced femininity, value, self-perception, and purpose. Unfortunately, the data available in the literature are not sufficient, and large, randomized, placebo-controlled trials are needed to prove their effect before introducing these treatments as standard therapy.

Methylenedioxymethamphetamine (MDMA)

Wexler et al. (2023) noted that sexual health, an integral component of overall well-being, is often compromised by common yet under-diagnosed sexual dysfunctions. Traditional interventions encompass pharmacotherapies and psychotherapies. Unconventional therapies, such as methylenedioxymethamphetamine (MDMA), offer hope for sexual dysfunction. In a systematic review, these investigators discussed MDMA's effects on sexual responsiveness and its potential role in the treatment of sexual dysfunction. They examined the effects of MDMA on different domains of the female and male sexual response cycles. These researchers carried out a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, Medline, and Embase were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were "MDMA" or "ecstasy" in combination with "desire," "arousal," "lubrication," "orgasm," "pleasure," "libido," "erection," and "ejaculation." Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least one domain of the female and/or male sexual response cycles that were described and measured. Randomized controlled trials (RCTs), cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis. These investigators identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle, and 8 met criteria for assessment of the male sexual response cycle; 4 of the 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of the 4 studies; however, they were not affected in 1 RCT. In men, 7 studies examined the effects of MDMA on desire and/or arousal, 5 studies measured the impact on erection, 3 on orgasm, and 2 on ejaculation; 60% of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies examining orgasm reported a delay in achieving orgasm, but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative. The authors concluded that the findings of this review suggested that MDMA generally increased sexual desire and intensified orgasm when achieved. These researchers stated that while producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile function as well as ejaculatory function in men.

Micro-Ablative Carbon Dioxide Laser

In a retrospective case-control study, Pitsouni and associates (2017) compared 30 W versus 40 W power of carbon dioxide (CO2) laser for the therapy of genitourinary syndrome of menopause (GSM). Post-menopausal women with severe intensity of dyspareunia and dryness were eligible to be included in this study. Primary outcomes were dyspareunia and dryness; secondary outcomes were itching/burning, dysuria, frequency and urgency, the Female Sexual Function Index (FSFI), vaginal maturation value (VMV), and vaginal health index score (VHIS). One laser therapy was applied every month for three months. Outcomes were evaluated at baseline and one month following the third therapy. A total of 50 women (25 per group) were included in this study. In the 30 W group, the mean improvement of dyspareunia, dryness, itching/burning, FSFI, VMV, and VHIS was 6.1 ± 1.7, 6.0 ± 1.9, 5.9 ± 2.0, 16.6 ± 6.7, 29.9 ± 13.0, and 11.0 ± 2.9, respectively (within-group comparisons all p < 0.001). In the 40 W group, the mean improvement of dyspareunia, dryness, itching/burning, FSFI, VMV, and VHIS was 6.1 ± 1.7, 6.5 ± 2.0, 5.2 ± 2.5, 14.8 ± 7.1, 25.0 ± 13.4, and 10.5 ± 4.1, respectively (within-group comparisons, all p ≤ 0.001). Comparison between 30 W and 40 W revealed that the mean improvement or presence of all GSM symptoms and clinical signs was not statistically significantly different. The authors concluded that CO2 laser therapy may improve GSM symptoms and clinical signs, and this improvement did not appear to be associated with the power of 30 W or 40 W.

In a systematic review, Weinberger and colleagues (2019) examined what treatments are effective across the various symptom complexes of female sexual dysfunction (FSD). Utilizing Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, these researchers conducted a systematic review of PubMed, Embase, clinicaltrials.gov, and the Cochrane Review databases. A total of 11 search strings, encompassing the terms "female sexual dysfunction" and "treatment" in combination with "vulvovaginal atrophy," "vaginismus," "vaginal atrophy," "vulvodynia," "vestibulitis," "hypoactive sexual desire," "arousal disorder," "sexual pain disorder," "genitourinary syndrome of menopause," and "orgasmic disorder," were utilized. A total of 605 relevant articles were retrieved, and 103 original studies met inclusion criteria. A total of 42 treatment modalities were utilized, including 26 different classes of medications. Although outcome measures varied, the most substantial improvement across multiple studies was noted with various hormonal regimens. The most common treatments included hormonal therapy (25 studies), phosphodiesterase type-5 inhibitors (9 studies), botulinum toxin A (5 studies), and flibanserin (5 studies). The psychotherapeutic approach was detailed in 36 articles, while three studies utilized homeopathic treatments. Numerous treatments showed efficacy in a single case series, including the promising results associated with the micro-ablative carbon dioxide laser. Despite the marked improvement in specific FSD domains, neither pharmacologic treatments nor psychotherapeutic interventions demonstrated consistent disease resolution. The authors concluded that the treatment of FSD is multifactorial; medications alone do not resolve FSD. The wide variability of treatment and outcome measures across the literature attests to the complexity of FSD and the need for a treatment algorithm that addresses all four domains of FSD.

Febrina et al. (2022) noted that cancer and its treatment negatively affect female sexual health and function. The prevalence of FSD after cancer is between 33% and 43%. Numerous studies have addressed therapeutic options for sexual dysfunction in women with cancer; however, it still remains a challenge to select the most effective option for patients. These investigators compiled and appraised recent evidence of any interventions for managing sexual dysfunction in female cancer survivors. They carried out a literature search of the electronic databases Medline, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) using general search terms of "women," "cancer," "intervention," and "sexual dysfunction." They included randomized controlled trials (RCTs) and uncontrolled before-after studies that examined the effectiveness of interventions for FSD in women with a history of cancer. The methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies. A total of 36 studies were included for qualitative synthesis (14 RCTs [n = 1,284], 17 uncontrolled trials [n = 589], and 5 cohort studies [n = 497]). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intra-vaginal DHEA (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements in sexual function. Both laser therapy (fractional CO2 and erbium) and multi-modal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function. The authors concluded that the most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multi-modal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10 to 70 participants), with moderate to high risk of bias. Moreover, these researchers stated that large-scale, double-blind RCTs with long-term follow-up and at low risk of bias are needed to demonstrate the clinical effectiveness of these interventions.

Miscellaneous Investigational Therapies

Kershaw and co-workers (2019) stated that percutaneous tibial nerve stimulation (PTNS) is now an established treatment for pelvic floor dysfunction, such as overactive bladder, fecal incontinence, or voiding dysfunction. The prevalence of female sexual dysfunction is high in this group. These researchers examined the effect of PTNS on sexual function in this patient group by systematically reviewing the literature and pooling the data in a meta-analysis. The literature search was conducted using the Medline, Embase, and CINAHL databases. Initial results yielded 74 citations. From these, 9 articles met the inclusion criteria; 2 articles were doubly reported, leaving 7 studies in the systematic review. Only 4 studies reported sufficient information to be included in the meta-analysis. A total of 3 studies were randomized controlled trials (RCTs), and 5 were before-after studies. The number of subjects in each study ranged from 11 to 220. Four of the 7 studies reported a positive effect of PTNS on sexual function. In the meta-analysis of 4 studies, there was a significant improvement in general sexual function with PTNS (p = 0.04, standardized mean difference [SMD] = -0.41, confidence intervals [CI]: -0.79 to -0.03, I² = 0%). In a subgroup analysis of the bowel domain of sexual function, there was a significant improvement with PTNS (p = 0.03, mean difference [MD] = 17.7, CI: 1.92 to 33.47, I² = 0%). The authors concluded that although the studies were of small size, the results were promising in terms of a positive effect of PTNS on sexual function, and these researchers recommended further research in this area.

Khunda and associates (2019) noted that sexual function is being increasingly recognized as an important patient-reported outcome. Sacral neuromodulation (SNM) is a treatment with an expanding list of indications. The effect of SNM on sexual function has been examined in a number of studies with variable results. In a systematic review and meta-analysis, these investigators evaluated the literature and pooled the data if appropriate. The literature search was carried out primarily on the Healthcare Databases Advanced Search (HDAS) platform using the Medline, Embase, and CINAHL search engines. Of 196 initial citations, 17 articles met the pre-defined inclusion criteria; 13 studies reported enough information to be included in the meta-analysis. RevMan 5 software was used for analysis; 8 of the 17 studies reported a positive effect of SNM on sexual function. Pooled analysis of data from 11 studies involving 573 patients before SNM and 438 patients after SNM showed significant improvement in sexual function (SMD = -0.39; 95% CI: -0.58 to -0.19; p = 0.0001). The results remained significant in most subgroup analyses except in patients suffering from fecal incontinence. The authors concluded that SNM in women with pelvic floor disorders, especially bladder dysfunction, appeared to have a positive effect on sexual function. These researchers stated that these findings need to be verified in adequately powered primary research using sexual function as the primary outcome.

In a systematic review, Perez-Lopez and colleagues (2019) examined the effects of available treatments for vestibulodynia. Using six search engines, these investigators searched for RCTs that compared any intervention versus placebo or sham in women with vestibulodynia until December 2018. The primary outcome was dyspareunia assessed with visual analog scale (VAS) or numeric rating scales (NRS). Secondary outcomes were daily vestibular symptoms (DVS), the McGill Pain Questionnaire (MPQ), and the Female Sexual Function Index (FSFI). Effects were described as mean differences (MDs) with their 95% confidence intervals (CIs). Traditional and frequentist network meta-analyses (NMA) were performed using random effect models. A total of 4 RCTs (n = 275) were included, evaluating vaginal cream of conjugated estrogens, oral desipramine with or without topical lidocaine, topical lidocaine, laser therapy, and transcranial direct current stimulation. In traditional meta-analysis, interventions did not reduce dyspareunia (MD = 0.08; 95% CI: -0.49 to 0.64), DVS (MD = -0.04; 95% CI: -0.31 to 0.24; 4 interventions), or MPQ (MD = -0.17; 95% CI: -2.16 to 1.81; 4 interventions). The FSFI score was significantly improved (MD = -5.14; 95% CI: -9.52 to -0.75). In NMA, oral desipramine with or without lidocaine significantly improved FSFI scores versus other treatments. The authors concluded that several existing interventions were not associated with improvements in vestibulodynia; there was only improvement in sexual function with oral desipramine with or without lidocaine.

In a single-center RCT, Huang et al. (2025) compared the effectiveness of PTNS with a validated sham control in the treatment of female sexual dysfunction (FSD). Women with FSD were recruited and randomly assigned at a 1:1 allocation ratio to either PTNS or a validated sham control using transcutaneous nerve stimulation (TENS). Treatment was carried out through weekly 30-minute sessions for a total of 12 weeks. Sexual function was assessed at baseline, 6 weeks, and 12 weeks primarily using the FSFI questionnaire; the Urogenital Distress Inventory (UDI-6) was recorded to assess for any baseline urinary incontinence/voiding dysfunction. Linear mixed-effect models for longitudinal data were employed to compare FSFI scores across different time points. A total of 34 PTNS and 31 TENS subjects were included in the final analysis. Overall, 48% (16/34) of PTNS subjects versus 29% (11/33) of TENS subjects were no longer at risk for FSD (FSFI greater than 26.55) after 12 weekly treatments. Both PTNS and TENS subjects showed similar improvements in FSFI total scores after 12 weeks of treatments. Interestingly, subjects who did not present with baseline urogenital distress symptoms reported a statistically significant larger improvement in sexual satisfaction following PTNS treatments compared to placebo (p = 0.017). The authors concluded that this trial showed sustained effectiveness of PTNS in improving sexual function. Specifically, patients who did not have co-existing urinary dysfunction reported significant improvement in sexual satisfaction following PTNS. These researchers stated that the findings of this trial suggested that PTNS may have a direct neuromodulation effect on sexual dysfunction and may hold promise as a treatment modality for FSD.

Oxytocin and Progesterone

Progesterone is an endogenous steroid hormone produced primarily by the ovaries that regulates the menstrual cycle, supports endometrial preparation for implantation, and maintains pregnancy. Although it is sometimes included in combination hormone therapy for gynecologic or menopausal indications, progesterone is not a primary mediator of sexual desire or arousal. As of June 2026, there are no U.S. FDA-approved progesterone-only therapies indicated for the treatment of female sexual dysfunction, and available evidence does not support its use as a targeted treatment for disorders of sexual desire, arousal, or orgasm. See CPB 0510 - Progestins.

Oxytocin is an endogenous cyclic nonapeptide hormone synthesized in the hypothalamus and released from the posterior pituitary, with established physiologic roles in uterine contractility and lactation, as well as central effects on social, emotional, and reproductive behaviors (Osilla, 2025). As a pharmacologic agent, synthetic oxytocin is approved by the U.S. FDA for limited obstetric indications, including induction or augmentation of labor and control of postpartum hemorrhage (Par Health USA, 2026; Osilla, 2025). In the context of female sexual function, endogenous oxytocin levels have been observed to increase during sexual arousal and orgasm, suggesting a physiologic role in modulation of sexual response (Cera, 2021). Off-label uses of exogenous oxytocin have included sexual arousal and orgasm; however, these applications remain poorly characterized and lack robust clinical evidence of efficacy (Osilla, 2025). Clinical studies evaluating exogenous administration (e.g., intranasal or topical formulations) for female sexual dysfunction have demonstrated inconsistent or no significant improvements in sexual desire, arousal, or orgasmic function (Kruger, 2018; Mesbahi, 2022). Accordingly, the use of oxytocin for the treatment of female sexual dysfunction is not supported by current evidence and is considered experimental, with no established therapeutic role or regulatory approval for this indication.

Worsley and colleagues (2016) reviewed the contribution of hormones, other than estrogens and androgens, to female sexual functioning and the evidence that specific endocrinopathies in women are associated with female sexual dysfunction (FSD). They updated the previously published International Society of Sexual Medicine Consensus on this topic. The literature was searched using several online databases, with an emphasis on studies examining the physiologic role of oxytocin, prolactin, and progesterone in female sexual function and any potential therapeutic effect of these hormones. The association between common endocrine disorders, such as polycystic ovary syndrome, pituitary disorders, and obesity, and FSD was also examined. The quality of data published in the literature and recommendations were based on the Grading of Recommendations Assessment, Development, and Education (GRADE) system. There is no evidence to support the use of oxytocin or progesterone for FSD. Treating hyperprolactinemia might lessen FSD. Polycystic ovary syndrome, obesity, and metabolic syndrome could be associated with FSD, but data are limited. There is a strong association between diabetes mellitus and FSD. The authors concluded that further research is needed, particularly high-quality, large-scale studies of women with common endocrinopathies, to determine the impact of these prevalent disorders on female sexual function.

Farahat et al. (2023) stated that genitourinary syndrome of menopause (GSM) is a common and disturbing issue for post-menopausal women. Unlike vasomotor symptoms, it has a progressive trend. In a systematic review and meta-analysis, these investigators examined the safety and effectiveness of oxytocin gel versus placebo gel in the management of post-menopausal women with GSM. They searched for randomized controlled trials (RCTs) from Web of Science, SCOPUS, PubMed, and Cochrane Central Register of Controlled Trials databases on January 18, 2023. Keywords such as "oxytocin," "intravaginal," "vaginal," "atrophic," and "atrophy" were used. They used Review Manager (RevMan) version 5.4 in the analysis. These researchers employed the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes; both were presented with the corresponding 95% confidence interval (CI) and were calculated with the Mantel-Haenszel or inverse variance statistical method. Cochrane's Q test and the I² statistic were used as measures of statistical inconsistency and heterogeneity. The Cochrane Risk of Bias Tool for RCTs was used for the quality assessment of the included studies. A total of seven studies with 631 patients were included. Regarding the maturation index, there was a statistically insignificant increase in the oxytocin arm (MD = 12.34, 95% CI: -12.52 to 37.19, p = 0.33). Clinically assessed vaginal atrophy showed a statistically significant reduction in the oxytocin group (RR = 0.32, 95% CI: 0.23 to 0.10, p < 0.00001). For dyspareunia, vaginal pH, and histological evaluation of vaginal atrophy, there was a statistically insignificant difference between the two groups (RR = 1.02, 95% CI: 0.82 to 1.27, p = 0.84), (MD = -0.74, 95% CI: -1.58 to 0.10, p = 0.08), and (MD = -0.38, 95% CI: -0.82 to 0.06, p = 0.09), respectively. There was no significant difference in the safety profile between the two groups as measured by endometrial thickness (MD = 0.00, 95% CI: -0.23 to 0.23, p = 0.99). The authors concluded that although oxytocin has been proposed as a viable alternative to estrogen in the treatment of GSM, the findings of this review showed the opposite. These researchers stated that larger, high-quality RCTs are needed to confirm or refute these findings. These studies should aim to provide clearer evidence regarding the impact of oxytocin on different parameters of GSM.

The authors stated that the drawbacks of this review included the small sample size and limited number of studies included in this analysis, short and different follow-up periods, the use of various tools in each study to evaluate vaginal atrophy, and the use of different drug dosages. Due to data limitations, these researchers were unable to carry out subgroup analyses to examine the impact of the aforementioned variations. Furthermore, there was variation in the eligibility criteria of the clinical trials, where some studies employed subjective methods such as patient-reported symptoms, whereas other studies used clinical and laboratory-based criteria for the enrollment of patients.

Photobiomodulation the Vulvar Region

Pereira et al. (2024) noted that GSM defines a set of symptoms associated with an estrogen deficit involving alterations in organs genitourinary and that results in several urinary, genital, as well as sexual alterations. Brazilian women live about 1/3 of their life after menopause, where hormonal changes occur along with clinical manifestations, characterized by vaginal and vulvar dryness, burning sensation, discomfort, vulvo-vaginal irritation, lack of lubrication, dyspareunia and UI. Fractionated photo-thermolysis and radiofrequency systems, alone or in combination were tested to improve GSM. These researchers stated that the objective of this trial is to present a clinical protocol to examine the clinical response of patients with symptoms of GSM after the application of photobiomodulation in the vulvar region. In this randomized, double-blind, placebo-controlled study protocol, women over 50 years of age who are in the post-menopausal period (amenorrhea for at least 12 months, with no pathology involved) with 1 or more symptoms of GSM will be randomly divided into 2 groups. The treatment group (n = 30) will receive 4 consecutive applications, weekly, using DMC laser diode (λ = 808 nm), 4J per point, 100 mW of power, 1,016W/cm2, 8 sites in the vulvar region. The placebo group (n = 30) will be handled as the treatment group, but with the laser turned off. The QoL will be evaluated using female sexual functioning index (FSFI-6), urinary incontinence questionnaire (ICIQ-SF), Quality of life will be analyzed using the female sexual functioning index (FSFI-6). The intensity of menopausal symptoms will be evaluated using VAS; and the vulvo vaginal atrophy will be measured by the VHIS. In addition, the vaginal temperature will be measured using a thermal camera, the pressure of the pelvic floor force (vaginal dynamometer) and a 1-hour Pad Test will be carried out to quantify the urinary loss. With this procedure, these investigators intend to obtain an overall better QoL and diminished symptoms in women with GSM. All assessments will be conducted before the 1st irradiation and after the last one. This clinical protocol is registered at ClinicalTrials.gov under the number NCT05557799.

Platelet-Rich Fibrin Injections

Oyardı and Ural (2025) examined the effectiveness of injectable platelet-rich fibrin (PRF) for the treatment of vaginal atrophy, also known as genitourinary syndrome of menopause (GSM), which may affect one-third of a woman's lifespan. This trial enrolled post-menopausal women who had symptoms of GSM, such as vaginal burning, dryness, itching, and sexual dysfunction. Injectable PRF (i-PRF) was applied to three areas on the posterior vaginal wall twice, one month apart. The genitourinary symptoms of the subjects were assessed by means of the Female Sexual Function Index (FSFI) and the sexual quality of life (QoL) questionnaire before, one month, and six months after the procedure. A total of 35 patients were recruited, with a mean age of 54.1 ± 5.5 years. The analysis of the desire, arousal, lubrication, orgasm, satisfaction, pain, and total scores of the pre-procedural and post-procedural FSFI and sexual QoL questionnaire scores showed significant improvements (p < 0.001). The authors concluded that i-PRF treatment provided advantages such as safe and easy application, autologous material nature, absence of procedure-related complications or side effects, short procedure time, absence of the need for hospitalization, low cost, and a non-hormonal nature. These investigators stated that the findings of this study suggested that i-PRF may be a promising therapeutic option for patients with symptoms of GSM; however, prospective, larger, longer-term randomized controlled trials (RCTs) are needed to confirm and validate these findings. These studies should also examine the effects after more and/or larger doses of i-PRF, potentially monitoring the changes in the vaginal wall with biopsy and using different indices, such as the vaginal health index.

The authors stated that the drawbacks of this trial included the lack of a standardized application procedure for the dose, application frequency, injection site, and number of injections of i-PRF. Furthermore, the number of cases was low (n = 35), and there was no control group. Lastly, the follow-up period was relatively short at six months, and one of the questionnaires used indicated a continued improvement at six months, although not significantly better than at three months follow-up. The fact that more than 77% of the patients included in the study had a vaginal birth and the average body mass index (BMI) of the patients was 29 were factors that may affect the interpretation of the study results.

Platelet-Rich Plasma Injections

Dankova et al. (2023) noted that there is no clear evidence in the literature that platelet-rich plasma (PRP) injections improve female sexual dysfunction (FSD) and female stress urinary incontinence (SUI). In a systematic review, these investigators examined the safety and effectiveness of PRP injections in women with the above pathologies and studied the optimal dosing, frequency, and area of injections, as well as the duration of treatment. They conducted a systematic search on PubMed, Embase, and the Cochrane Library database, and sources of grey literature from the date of database or source creation to January 2023. After title/abstract and full-text screening, clinical studies on humans examining the effectiveness of PRP in gynecological disorders using standardized tools were included. Risk of bias was assessed using RoB-2 for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for observational studies. A total of 4 prospective and 1 retrospective study examined FSD, while 6 prospective and 1 RCT evaluated female SUI. A total of 327 women with a mean age of 51 ± 12 years were included. For FSD, PRP significantly improved the Female Sexual Function Index (FSFI), the Vaginal Health Index (VHI), and the Female Sexual Distress Scale (FSDS). For SUI, PRP resulted in a significant improvement in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the Urogenital Distress Inventory (UDI-6). The identified RCT reported a significantly higher mean score of ICIQ-SF (p < 0.05) and UDI-6 (p < 0.01) in the mid-urethral sling group compared to the PRP injections group. Regarding the risk of bias, the RCT was characterized by high risk, whereas the observational studies were of moderate risk. The protocol for PRP injections for FSD was the injection of 2 ml of PRP into the distal anterior vaginal wall once monthly for 3 months. For female SUI, 5 to 6 ml of PRP should be injected into the peri-urethral area once monthly for 3 months. The authors concluded that despite the promising initial results of PRP injections, the level of current evidence is low due to methodological issues in the available studies. These researchers stated that it became clear that there is an emerging need for high-quality RCTs examining PRP injections for the treatment of FSD and female SUI.

The authors stated that this study had several drawbacks. First, the included studies displayed significant heterogeneity in terms of PRP preparation technique, dose, injected area, and duration of treatment; thus, a meta-analysis could not be carried out. Of interest, most included studies raised methodological concerns. This problem predominantly stemmed from the small number of included subjects, the sub-optimal methods of reporting randomization, the relatively short follow-up, the restricted number of events, and the implementation of non-recognized scales. Accordingly, some important parameters, such as PRP preparation technique, dose of PRP, injected area, and the percentage of patients with improvement in underlying disease symptoms, remained unreported in some of the included studies.

Radiofrequency Ablation (e.g., the MorpheusV Applicator) of the Vaginal Canal

Rothenberger et al. (2025) stated that GSM is a prevalent condition with various symptoms including burning, dryness, dyspareunia, and irritative lower urinary tract symptoms (LUTS) that result from vulvo-vaginal atrophic changes. Although hormonal therapy is a key therapy for patients with in GSM, some may choose non-hormonal therapies. In a prospective, unblinded, multi-center, case-series study, these researchers examined the effectiveness of radiofrequency ablation (RFA) of the vaginal canal with the MorpheusV applicator in reducing symptoms of GSM. This trial included women with GSM as confirmed by VHIS. Participants received 3 sessions of RFA approximately 4 weeks apart with follow-up to 6-month post-treatment. The primary outcome was VHIS at 6-month post-treatment; and secondary outcomes included VHIS at 3 months, VAS pain score with each treatment, 3- and 6- UDI-6, as well as FSFI questionnaires. From 2021 to 2023, a total of 71 women were enrolled in this trial with 51 followed to the 6-month follow-up time-point. Treatments were found to be low in VAS pain score with mean values of 2.13 ± 2.1, 2.55 ± 2.38, and 2.18 ± 2.14 at treatments 1, 2, and 3 respectively. An improvement in VHIS score was observed from baseline to 3 months after the last treatment (15.00 ± 5.37 versus 19.62 ± 4.44) and sustained at 6 months (20.23 ± 4.12) (p < 0.001). Significant improvements in both UDI-6 and FSFI were also observed. Between baseline and 6 months after treatment (FSFI: 18.81 ± 9.57 versus 22.81 ± 10.34, p < 0.001; UDI-6: 39.58 ± 15.98 versus 22.42 ± 14.03, p < 0.001). No AEs were encountered by any subject during this study. The authors concluded that the findings of this study suggested that RFA of the vaginal canal by the MorpheusV applicator was a safe and effective approach for the treatment of GSM. It also demonstrated subjective improvements in SUI, urge UI, and sexual function. Moreover, these researchers stated that drawbacks of this trial included the unblinded nature of the study and the lack of a comparator group.

Radiofrequency Thermal Therapy (e.g., ThermiVa Procedure and the Viveve Procedure)

In a pilot study, Millheiser et al. (2010) evaluated the safety and tolerability of non-surgical radiofrequency (RF) thermal therapy for the treatment of laxity of the vaginal introitus after vaginal delivery. They also explored the utility of self-report questionnaires in assessing the subjective effectiveness of this device. A total of 24 women (aged 25 to 44 years) underwent treatment using reverse gradient RF energy (75 to 90 joules/cm²) delivered through the vaginal mucosa. Post-treatment assessments were conducted at 10 days, 1 month, 3 months, and 6 months. Main outcome measures included pelvic examinations and adverse event reports to assess safety. The authors modified the Female Sexual Function Index (mv-FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), as well as the Vaginal Laxity and Sexual Satisfaction Questionnaires (designed for this study), to evaluate both safety and effectiveness, along with the Global Response Assessment to assess treatment responses. No adverse events were reported, and no topical anesthetics were required. Self-reported vaginal tightness improved in 67% of subjects at 1 month post-treatment and in 87% at 6 months (p < 0.001). Mean sexual function scores improved: the mv-FSFI total score before treatment was 27.6 ± 3.6, increasing to 32.0 ± 3.0 at 6 months (p < 0.001); the FSDS-R score before treatment was 13.6 ± 8.7, declining to 4.3 ± 5.0 at 6 months post-treatment (p < 0.001). Twelve of the 24 women who expressed diminished sexual satisfaction following their delivery all reported sustained improvements on the Sexual Satisfaction Questionnaire at 6 months after treatment (p = 0.002). The authors concluded that the RF treatment was well-tolerated and demonstrated an excellent 6-month safety profile in this pilot study. Responses to the questionnaires suggested subjective improvement in self-reported vaginal tightness, sexual function, and decreased sexual distress. They stated that these findings warrant further study.

In a review on “Female sexual disorders: Treatment options in the pipeline,” Krychman (2013) noted that Viveve (Sunnyvale, CA) has developed a monopolar RF thermal therapy to improve laxity of the vaginal introitus and sexual satisfaction in women after vaginal deliveries. In a pilot study involving 24 women aged 25 to 44 years, reverse-gradient RF (with energy levels of 60 joules [n = 3], 75 joules [n = 3], and 90 joules [n = 18]) was delivered through the vaginal mucosa. No adverse events were reported, and no topical anesthetics were required. Self-reported vaginal tightness improved in 67% of patients at 1 month post-treatment and in 87% at 6 months (p < 0.001). Mean sexual function scores improved, with the FSDS-R score before treatment being 13.6 ± 8.7, declining to 4.3 ± 5.0 at 6 months post-treatment (p < 0.001). The author concluded that this office-based procedure is well-tolerated and has shown excellent preliminary results. These findings need to be validated by well-designed studies.

In a prospective single-arm study, Sekiguchi and colleagues (2013) reported the long-term effectiveness of a single non-surgical procedure using RF energy for laxity at the vaginal introitus. A total of 30 pre-menopausal women (aged 21 to 52 years) underwent one 30-minute office procedure using RF applied to the vaginal introitus. Twelve-month outcome assessments included the linguistically validated Japanese versions of the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), as well as the Vaginal Laxity and Sexual Satisfaction Questionnaires. Sexual function improved significantly over 6 months (30 subjects); the mean FSFI total score was 22.4 ± 6.7 before treatment and improved to a mean of 26.0 ± 5.8 at 6 months (p = 0.002), including improved scores in 5 of 6 FSFI domains except desire (p < 0.001 - <0.01). In the 22 of 30 subjects remaining evaluable at 12 months, the mean was 26.0 ± 5.2 (p = 0.08). Distress related to sexual activity decreased significantly; the baseline FSDS-R mean score of 15.8 ± 11.7 improved to 9.8 ± 8.0 at 1 month and was sustained throughout 12 months (p < 0.001 - 0.002). Subjects reported decreased vaginal laxity within the first month after the procedure (p < 0.001); responses peaked, and effectiveness was sustained through 12 months (p < 0.001). The authors concluded that a single non-surgical office-based RF procedure for vaginal introital laxity achieved significant and sustainable 12-month effectiveness with respect to improved integrity at the vaginal introitus and improved sexual satisfaction. Treatment was well-tolerated with no adverse events. The main drawbacks of this study were the lack of a control group, small sample size, and relatively short follow-up. These preliminary findings need to be validated by well-designed studies.

Lalji and Lozanova (2017) evaluated the safety and efficacy of a non-invasive radiofrequency device when used to treat stress urinary incontinence (SUI) and vulvo-vaginal laxity through its heating effect that stimulates collagen and elastin fibers. A total of 27 women (average age of 44.78 ± 10.04 years) with indications of mild to moderate SUI as well as vulvo-vaginal laxity were treated with a monopolar RF device. The treatment course consisted of three once-weekly sessions. Each session included intra-vaginal treatment followed by treatment of the labia majora and the perineum. Improvement in the SUI condition was evaluated by applying the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF). Data were collected at baseline, after the last treatment, and at the 1-month follow-up visit. Vaginal laxity was assessed by a subjective vulvo-vaginal laxity questionnaire (VVLQ). Data were collected before the first treatment and during the 1-month follow-up visit. Patient satisfaction was recorded using a satisfaction questionnaire. Data were collected after the last treatment and at the 1-month follow-up visit. Any adverse events (AEs) related to the treatments were monitored. On a scale of 0 to 5, the average frequency of urine leak improved from "2 to 3 times a week" (2.15 ± 1.03 points prior to treatment) to "once a week" (1.00 ± 0.78 points post-treatment), and on to "never" (0.44 ± 0.51 points at the 1-month follow-up visit). Sixteen subjects (59.3%) reported a decrease in the amount of leakage, with 15 women (55.6%) becoming completely leak-free at the 1-month follow-up. At the 1-month follow-up visit, 24 subjects (88.9%) expressed that their condition's interference with everyday life decreased, and 17 patients (62.9%) said the condition did not interfere with their everyday life at all as a result of the treatment. All results were statistically significant (p < 0.05). No AEs were recorded. All subjects reported improvement in vaginal laxity, from an average perception of "very loose" (2.19 ± 1.08 points prior to treatment) to "moderately tight" (5.74 ± 0.76 points at the 1-month follow-up visit). During the follow-up visit, 89% of the patients "agreed" or "strongly agreed" that their SUI condition improved, and 93% of the patients "agreed" or "strongly agreed" that their gratification during intercourse improved. None of the subjects reported dissatisfaction. The authors concluded that the findings of this study confirmed the monopolar RF method as a safe and effective treatment for SUI and vulvo-vaginal laxity. The treatments were well-tolerated by all subjects with no AEs. Moreover, these investigators stated that a further controlled study is needed to confirm the data and evaluate the long-term effects of the endo-vaginal treatment.

In a sub-analysis of the VIVEVE I trial, Krychman and colleagues (2018) evaluated the impact of cryogen-cooled monopolar RF (CMRF) therapy for the treatment of vaginal laxity on the domains of sexual function included in the Female Sexual Function Index (FSFI). The VIVEVE I clinical trial was prospective, randomized, single-blind, and sham-controlled; nine clinical study centers in Canada, Italy, Spain, and Japan were included. This sub-analysis included pre-menopausal women with self-reported vaginal laxity who had greater than or equal to one term vaginal delivery and a baseline FSFI total score less than or equal to 26.5, indicating sexual dysfunction. Enrolled subjects were randomized (2:1) to receive CMRF therapy [active (90 J/cm²) versus sham (less than or equal to 1 J/cm²)] delivered to the vaginal tissue. Independent analyses were conducted for each FSFI domain to evaluate both the mean change as well as the clinically important change for active versus sham-treated subjects at 6 months post-intervention. Subjects randomized to active treatment (n = 73) had greater improvement than sham subjects (n = 35) on all FSFI domains of sexual function at 6 months post-intervention. The analysis of covariance change from baseline analyses showed statistically significant improvements, in favor of active treatment, for sexual arousal (p = 0.004), lubrication (p = 0.04), and orgasm (p = 0.007). In addition, active treatment was associated with clinically important and statistically significant improvements in sexual desire (odds ratio [OR] = 3.01 [1.11 to 8.17]), arousal (OR = 2.73 [1.06 to 7.04]), and orgasm (OR = 2.58 [1.08 to 6.18]). The authors concluded that this sub-analysis of the VIVEVE I trial showed that a single, non-ablative CMRF treatment significantly improved overall sexual function (FSFI total score) in women with female sexual dysfunction (FSD) and self-reported vaginal laxity. Of the six domains of the FSFI, the improvement achieved using CMRF therapy was primarily driven by the statistically significant and/or clinically important improvements in sexual desire, arousal, lubrication, and orgasm in women with vaginal laxity and baseline sexual dysfunction. The findings of sexual function improvement provided evidence for the clinical utility and direction for further evaluation of this novel, single treatment, 30-minute, non-surgical outpatient modality for a highly prevalent and undertreated condition. Furthermore, these results underscored the importance of conducting rigorous research using a randomized sham or placebo comparator arm with adequate follow-up time to permit the estimation of a valid treatment effect.

These investigators stated that this sub-analysis had several drawbacks. No control for multiplicity was implemented for the post-hoc analyses of the VIVEVE I trial; thus, results should be interpreted as exploratory or hypothesis-generating. In addition, the generalizability of the findings was restricted to women with self-reported vaginal laxity and FSD as defined by a baseline FSFI total score less than or equal to 26.5. Women who were sexually functional (i.e., baseline FSFI total score greater than 26.5) were not analyzed as part of this sub-analysis; therefore, a substantial proportion of parous women fell into this category. In the VIVEVE I trial, 66% of included subjects presented with sexual dysfunction at the screening visit. Finally, early system characteristics made double-blinding of treatment assignment difficult to achieve. While all subjects were unaware of their treatment assignment for the entire study duration, the site investigator was aware of treatment assignment. Despite this limitation, similar baseline characteristics and study drop-out rates for subjects in the active and sham groups empirically suggested that bias was not introduced by investigator channeling or differential study conduct by treatment assignment throughout the entire duration of trial follow-up. The robust “sham” effect in the first three months further indicated that study validity was not compromised by single-blinding. To mitigate the potential for investigator channeling bias, subjects assigned to the sham group were permitted to receive the active CMRF therapy upon study completion.

The ThermiVa procedure uses heat therapy delivered via RF waves to promote collagen synthesis, shrinkage, and tightening of female tissues. However, there is a lack of evidence regarding its effectiveness for vaginal rejuvenation, FSD, and other gynecological disorders.

Furthermore, on July 30, 2018, FDA Commissioner Scott Gottlieb stated that, “We’ve recently become aware of a growing number of manufacturers marketing ‘vaginal rejuvenation’ devices to women and claiming these procedures will treat conditions and symptoms related to menopause, urinary incontinence, or sexual function. The procedures use lasers and other energy-based devices to destroy or reshape vaginal tissue. These products have serious risks and don’t have adequate evidence to support their use for these purposes. We are deeply concerned women are being harmed. As part of our efforts to promote women’s health, the FDA has cleared or approved laser and energy-based devices for the treatment of serious conditions like the destruction of abnormal or pre-cancerous cervical or vaginal tissue, as well as condylomas (genital warts). But the safety and effectiveness of these devices hasn’t been evaluated or confirmed by the FDA for ‘vaginal rejuvenation.’ In addition to the deceptive health claims being made with respect to these uses, the ‘vaginal rejuvenation’ procedures have serious risks. In some cases, these devices are being marketed for this use to women who have completed treatment for breast cancer and are experiencing symptoms caused by early menopause. The deceptive marketing of a dangerous procedure with no proven benefit, including to women who’ve been treated for cancer, is egregious. In reviewing adverse event reports and published literature, we have found numerous cases of vaginal burns, scarring, pain during sexual intercourse, and recurring or chronic pain. We haven’t reviewed or approved these devices for use in such procedures. Thus, the full extent of the risks is unknown. But these reports indicate these procedures can cause serious harm. Today, we’re warning women and their healthcare providers that the FDA has serious concerns about the use of these devices to treat gynecological conditions beyond those for which the devices have been approved or cleared. We recently notified seven device manufacturers of our concerns about inappropriate marketing of their devices for ‘vaginal rejuvenation’ procedures. They are: Alma Lasers, BTL Industries, Cynosure, InMode, Sciton, Thermigen, and Venus Concept. We requested that the manufacturers address our concerns within 30 days. If our concerns are not addressed, then the FDA will consider what next actions, including potential enforcement actions, are appropriate. This matter has the full attention of our professional staff.”

Testosterone Therapy

Testosterone therapy refers to the exogenous administration of androgens to supplement endogenous hormone levels, which decline with age and may contribute to aspects of female sexual function, including sexual desire and arousal. Androgens are produced by the ovaries and adrenal glands and play a physiologic role in female sexual health. Reduced androgen activity has been associated with hypoactive sexual desire disorder (HSDD), a subtype of female sexual dysfunction. However, as of June 2026, no testosterone formulations are currently FDA-approved for the treatment of female sexual dysfunction. See CPB 0528 - Testosterone Undecanoate (Aveed) Injection.

Vaginal Electrical Stimulation

In a randomized study, Aydin and colleagues (2015) evaluated the effectiveness of vaginal electrical stimulation (VES) in women with FSD without a predominant pelvic floor disorder or urinary incontinence. A total of 42 women with FSD were randomly allocated to VES and placebo groups. Pelvic floor muscle (PFM) assessment and the FSFI questionnaire were performed at baseline and after the completion of sessions. Vaginal electrical stimulation treatment was administered using a vaginal probe. The probe was inserted, and a medium-frequency (50 Hz) alternating current was administered for a duty cycle of 5 seconds on followed by a 5-second rest. Primary outcome measure was the improvement in FSFI score. Pelvic floor muscle assessments were performed according to the PERFECT scheme. Total FSFI scores improved significantly in both the VES group and the control group. Results showed that in the VES group, there was an improvement in total score and FSFI domains that improved including arousal, desire, orgasm, and satisfaction. Similarly, control group domains that improved were desire, arousal, and orgasm. But there was no significant increase in satisfaction scores in the placebo group. No significant changes in pain or lubrication domains were seen in either group. Power, endurance, fast contractions, and repetitions were significantly improved in the VES group. The authors concluded that the lack of significant differences between the placebo and VES groups, except the satisfaction domain, puts into question the effectiveness of electrical stimulation as a monotherapy in treating primary FSD without pelvic floor disorder.

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References