Aetna considers ospemifene medically necessary for the treatment of dyspareunia associated with vulvo-vaginal atrophy in post-menopausal women with female sexual dysfunction (FSD).
Aetna considers biothesiometry experimental and investigational for the diagnosis of female sexual dysfunction (FSD).
Aetna considers the following interventions for the treatment of FSD experimental and investigational becasue of insufficient evidence (not an all-inclusive list):
Note: 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.Background
Female sexual dysfunction (FSD) entails many facets in the sexual process in women including vaginal dryness, arousal disorder, painful intercourse, an inability to achieve orgasm, and lack of clitoral sensation.
Despite significant anatomical and embryological parallels between women and men, the multi-faceted nature of FSD clearly is different from that of the man. Clinicians can not approach female patients or their sexual function problems in the same fashion as in male patients. The context in which a woman experiences her sexuality is equally if not more important than the physiological outcome she experiences, and these issues should be determined before beginning medical therapy or determining treatment effectiveness.
Biothesiometry is a technique that can be used for evaluating genital neurological function in women. It entails the use of a small cylindrical instrument employed to evaluate the sensitivity of the clitoris and labia to pressure and temperature. However, there is insufficient evidnce regarding its clinical use for the diagnosis of FSD.
Erol et al (2003) evaluated genital and extra-genital somatic sensory system in diabetic women using biothesiometry and investigated the relation 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 Index of Female Sexual Function (IFSF) questionnaire. Somatic sensory system of all women enrolled to the study was assessed by biothesiometry and threshold sensory values of 9 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 sites, the mean biothesiometric values were significantly higher in diabetics. The sensation of 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, somatic sensory system is affected by diabetes however sexual dysfunction does not always manifest.
If a specific etiology for FSD is discovered on history, physical, and laboratory examination, the suspected etiology may be treated. If no specific etiology for FSD is discovered, basic treatment strategies are applied. These include educational interventions, enhancement of stimulation and elimination of routine (e.g., use of erotic books or videos, varying positions, use of vibrators, etc.), provision of distraction techniques (e.g., background music, encourage fantasies, etc.), encouragement of non-coital behaviors (e.g., sensate focus exercises, sensual massage), and techniques to minimize dyspareunia (e.g., change in position, topical lidocaine, lubricants, etc.).
Female erectile devices such as the Eros clitoral stimulation device (UroMetrics, Inc., St. Paul, MN) are used to obtain greater clitoral engorgement, which increases lubrication, and enhances the ability to achieve an orgasm. However, more studies are needed to ascertain the medical necessity and long-term effects of clitoral stimulation devices as compared with 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 was 43.5 years and 2 years, respectively. These 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.
An UpToDate review on “Sexual dysfunction in women: Management” (Shifren, 2014) states that “A clitoral suction vacuum device, EROS-Clitoral Therapy Device, is approved by the US Food and Drug Association (FDA) for female sexual dysfunction. Its design is similar to vacuum devices used for male erectile dysfunction. It may improve local arousal and response by improving clitoral blood flow. The device is expensive and likely no more effective than less costly devices available without a prescription, such as vibrators”.
Silverstein et al (2011) stated that treatments of FSD have been largely unsuccessful because they do not address the psychological factors that underlie female sexuality. Negative self-evaluative processes interfere with the ability to attend and register physiological changes (interoceptive awareness). These researchers examined the effect of mindfulness meditation training on interoceptive awareness and the 3 categories of known barriers to healthy sexual functioning: attention, self-judgment, and clinical symptoms. A total of 44 college students (30 women) participated in either a 12-week course containing a "meditation laboratory" or an active control course with similar content or laboratory format. Interoceptive awareness was measured by reaction time in rating physiological response to sexual stimuli. Psychological barriers were assessed with self-reported measures of mindfulness and psychological well-being. Women who participated in the meditation training became significantly faster at registering their physiological responses (interoceptive awareness) to sexual stimuli compared with active controls (F(1,28) = 5.45, p = 0.03, η(p)(2) = 0.15). Female meditators also improved their scores on attention (t = 4.42, df = 11, p = 0.001), self-judgment, (t = 3.1, df = 11, p = 0.01), and symptoms of anxiety (t = -3.17, df = 11, p = 0.009) and depression (t = -2.13, df = 11, p < 0.05). Improvements in interoceptive awareness were correlated with improvements in the psychological barriers to healthy sexual functioning (r = -0.44 for attention, r = -0.42 for self-judgment, and r = 0.49 for anxiety; all p < 0.05). The authors concluded that mindfulness-based improvements in interoceptive awareness highlight the potential of mindfulness training as a treatment of FSD.
In a pilot study, Millheiser et al (2010) evaluated the safety and tolerability of non-surgical radiofrequency (RF) thermal therapy for treatment of laxity of the vaginal introitus after vaginal delivery. They also explored the utility of self-report questionnaires in assessing subjective effectiveness of this device. A total of 24 women (25 to 44 years) once using reverse gradient RF energy (75 to 90 joules/cm(2) ), delivered through the vaginal mucosa were include in this study. Post-treatment assessments were at 10 days, 1, 3, and 6 months. Main outcome measures included pelvic examinations and adverse event reports to assess safety. The author modified Female Sexual Function Index (mv-FSFI) and Female Sexual Distress Scale-Revised (FSDS-R), Vaginal Laxity and Sexual Satisfaction Questionnaires (designed for this study) to evaluate both safety and effectiveness, and the Global Response Assessment to assess treatment responses. No adverse events were reported; no topical anesthetics were required. Self-reported vaginal tightness improved in 67 % of subjects at 1 month post-treatment; in 87 % at 6 months (p < 0.001). Mean sexual function scores improved: mv-FSFI total score before treatment was 27.6 +/- 3.6, increasing to 32.0 +/- 3.0 at 6 months (p < 0.001); FSDS-R score before treatment was 13.6 +/- 8.7, declining to 4.3 +/- 5.0 at month 6 post-treatment (p < 0.001). Twelve of 24 women who expressed diminished sexual satisfaction following their delivery; all reported sustained improvements on SSQ at 6 months after treatment (p = 0.002). The authors concluded that the RF treatment was well-tolerated and showed 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 in 24 women aged 25 to 44 years, reverse-gradient RF (energy range 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, and FSDS-R score before treatment was 13.6 +/- 8.7, declining to 4.3 +/- 5.0 at month 6 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 (2103) reported the long-term effectiveness of a single non-surgical procedure with RF energy for laxity at the vaginal introitus. A total of 30 pre-menopausal women (age of 21 to 52 years) with one 30-min office procedure using RF applied to the vaginal introitus; 12-month outcome assessments included the linguistic validated Japanese versions of the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) and the Vaginal Laxity and Sexual Satisfaction Questionnaires. Sexual function improved significantly throughout 6 months (30 subjects); mean FSFI total score was 22.4 ± 6.7 before treatment and then improved to mean 26.0 ± 5.8 at month 6 (p = 0.002), inclusive of 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; 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 1st 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.
In a randomized, placebo-controlled, phase III clinical trial, Portman and colleagues (2014) evaluated the safety and effectiveness of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vaginal dryness in post-menopausal women with vulvo-vaginal atrophy (VVA). This was a 12 week, multi-center, randomized, double-blind, parallel-group phase III study of post-menopausal women (40 to 80 years) with VVA and self-reported vaginal dryness as their most bothersome symptom. The co-primary efficacy end-points were the change from baseline to week 12 in (i) percentage of parabasal cells in the maturation index (MI), (ii) percentage of superficial cells in the MI, (iii) vaginal pH, and (iv) severity of vaginal dryness. Safety assessments included physical examination, cervical Papanicolaou test and clinical laboratory analyses. Endometrial thickness and histology was also assessed. A total of 314 women were randomized to once-daily ospemifene 60 mg/day (n = 160) or placebo (n = 154). Significant improvements in the percentages of parabasal and superficial cells in the MI and vaginal pH were observed with ospemifene compared with placebo (p < 0.001 for all parameters). The mean change from baseline in severity score of vaginal dryness reported by women receiving ospemifene compared with those receiving placebo approached statistical significance (p = 0.080). Improvements in each of the 4 co-primary end-points with ospemifene were statistically significant compared to placebo in the per protocol population. The majority of treatment-emergent adverse events were considered mild-to-moderate in severity. The authors concluded that once-daily oral ospemifene 60 mg was effective for the treatment of VVA in post-menopausal women with vaginal dryness.
Wurz and co-workers (2014) stated that during the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and VVA. Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60 % of post-menopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment or other factors. After 20+ years in development, ospemifene (Osphena) was approved by the FDA in 2013 for treatment of moderate-to-severe dyspareunia associated with VVA due to menopause. As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in post-menopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), from the same chemical class as the breast cancer drugs tamoxifen and toremifene. Unlike other selective estrogen receptor modulators, ospemifene exerts a strong, nearly full estrogen agonist effect in the vaginal epithelium, making it well suited for the treatment of dyspareunia in post-menopausal women. Results of phase III clinical trials showed that ospemifene significantly improved the vaginal maturation index (decreased parabasal cells and increased superficial cells), decreased vaginal pH, and decreased severity of the self-identified most bothersome symptom (dyspareunia or vaginal dryness) compared to placebo. Long-term safety studies revealed that 60 mg ospemifene given daily for 52 weeks was well-tolerated and was not associated with any endometrium or breast-related safety concerns. This review discussed the pre-clinical and clinical data supporting the use of ospemifene for the treatment of dyspareunia associated with VVA due to menopause and provided an overview of its clinical safety.
In a phase-III, randomized, double-blind, 12-week trial (n = 919), Constantine and associates (2015) compared the safety and effectiveness of oral ospemifene 60 mg/day versus placebo in post-menopausal women with VVA in 2 strata based on self-reported, most bothersome symptom of either dyspareunia or dryness. Primary data were published previously. These investigators reported herein pre-specified secondary efficacy end-points analyses, including changes from baseline to weeks 4 and 12 for FSFI total and domain scores as well as serum hormone levels. Ospemifene 60 mg/day demonstrated a significantly greater FSFI total score improvement versus placebo at week 4 (p < 0.001). Improvement in FSFI scores continued to week 12 (p < 0.001). At week 4, the FSFI domains of Sexual Pain, Arousal, and Desire were significantly improved with ospemifene versus placebo; at week 12, improvements in all domains were significant (p < 0.05). Changes in serum hormones were minor and uncorrelated with changes in sexual functioning. The authors concluded that in a large, randomized, double-blind, placebo-controlled trial, ospemifene 60 mg/day significantly improved FSD in women with VVA; consistent effects across FSFI domains were observed.
Kingsberg and Woodard (2015) stated that low or absent sexual desire is the most common sexual dysfunction in women, and its prevalence peaks during midlife. Its etiology is complex and may include biological, psychological, and social elements. Major risk factors for its development include poor health status, depression, certain medications, dissatisfaction with partner relationship, and history of physical abuse, sexual abuse, or both. Diagnosis is based on criteria set by the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) and requires that a woman experience personal distress. Clinical evaluation should include medical history, sexual history, and, sometimes, a physical examination. Laboratory data are of limited value, except when warranted by history or physical examination. Treatment options include non-pharmacologic interventions such as education, office-based counseling, and psychotherapy. Although there are no UFDA-approved treatments for low desire, pharmacologic agents have been used off-label for this purpose. Bupropion is an anti-depressant that has been shown to improve desire in some women with and without depression. Systemic estrogen therapy is not recommended in the absence of vasomotor symptoms and is not directly associated with desire. However, vaginal estrogen is useful in patients presenting with concomitant vaginal atrophy and dyspareunia. Ospemifene is a selective estrogen receptor modulator that can be used as an alternative to vaginal estrogen. Exogenous testosterone (e.g., gel, implant, injection, patch and oral formulations) has demonstrated efficacy in treating loss of desire in post-menopausal women. However, patients should be counseled that it is not FDA-approved for this purpose and there are limited published long-term safety data. Several agents for the treatment of low desire are currently in development.
Furthermore, an UpToDate review on “Sexual dysfunction in women: Management” (Shifren, 2015) states that “Ospemifene -- A new selective estrogen receptor modulator, ospemifene, was recently introduced for the treatment of dyspareunia associated with vulvovaginal atrophy”.
Belkin et al (2015) stated that there is growing recognition of FSD as an important women's health concern. Despite an increased awareness of the pathophysiologic components to FSD, currently, there are no drugs approved for the most common sexual complaint in women-decreased sexual desire. In response to an overwhelming demand for therapy for FSD, several drugs are undergoing development and testing. These investigators provided the latest data on pharmacological treatments for FSD currently in phase I and II clinical trials. These include topical alprostadil, bremelanotide (BMT), intra-nasal testosterone (TBS-2), intra-vaginal dehydroepiandrosterone (DHEA), sublingual testosterone with sildenafil, apomorphine (APO), bupropion and trazodone. It should be noted that the definitions of FSD have recently been revised in the diagnostic and statistical manual for mental disorders (DSM) 5, with merging of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder (FSAD) into female sexual interest/arousal disorder (FSIAD). However, it is noted that the majority of clinical trials discussed in this paper used the DSM IV-R diagnoses of HSDD and FSAD. The authors concluded that medications in early phase trials showed promise for the treatment of FSD. These therapies focus on treating many possible causes of FSD.
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.
Furthermore, an UpToDate review on “Sexual dysfunction in women: Management” (Shifren, 2015) does not mention electrical stimulation as a therapeutic option.
Botulinum Toxin Therapy:
In a prospective, open-label, pilot study, Morrissey and colleagues (2015) examined the effectiveness of electromyography (EMG)-guided onabotulinumtoxinA (Botox; Allergan, Irvine, CA) injections in treating patient's perception of pelvic pain and improving quality of life (QoL) measurement scores. Women with chronic pelvic pain and high-tone pelvic floor dysfunction (HTPFD) who have failed conventional therapy between January 2011 and August 2013 were enrolled in this study. Botox injections (up to 300 U) were done using needle EMG guidance, from a trans-perineal approach, to localize spastic pelvic floor muscles (PFMs). Data were collected at baseline, 4, 8, 12, and 24 weeks after injections. This included demographics; visual analog scale (VAS) scores for pain and dyspareunia; validated questionnaires for symptoms, QoL, and sexual function; Global Response Assessment scale for pelvic pain; digital examination of PFM for tone and tenderness; and vaginal manometry. Side effects were also recorded. Out of 28 women who enrolled in the study, 21 completed the 6-month follow-up and qualified for analysis. The mean (SD) age was 35.1 (9.4) years (range of 22 to 50 years), and the mean (SD) body mass index was 25 (4.4). Co-morbidities included interstitial cystitis/bladder pain syndrome (42.9 %) and vulvodynia (66.7 %). Overall, 61.9 % of subjects reported improvement on Global Response Assessment at 4 weeks and 80.9 % at 8, 12, and 24 weeks post-injection, compared with baseline. Of the subjects who were sexually active at baseline, 58.8 % (10/17), 68.8 % (11/16), 80 % (12/15), and 83.3 % (15/18) reported less dyspareunia at 4, 8, 12, and 24 weeks, respectively. Dyspareunia VAS score significantly improved at weeks 12 (5.6, p = 0.011) and 24 (5.4, p = 0.004) compared with baseline (7.8). Two of the 4 patients who avoided sexual activity at baseline secondary to dyspareunia resumed and tolerated intercourse after Botox. Sexual dysfunction as measured by the Female Sexual Distress Scale significantly improved at 8 weeks (27.6, p = 0.005), 12 weeks (27.9, p = 0.006), and 24 weeks (22.6, p < 0.001) compared with baseline (34.5). The Short-Form 12 Health Survey (SF-12) showed improved QoL in the physical composite score at all post-injections visits (42.9, 44, 43.1, and 45.5 versus 40 at baseline; p < 0.05), and in the mental composite score at both 12 and 24 weeks (44.3 and 47.8 versus 38.5, p = 0.012). Vaginal manometry demonstrated significant decrease in resting pressures and in maximum contraction pressures at all follow-up visits (p < 0.05). Digital assessment of PFM (on a scale from 0 to 4) showed decreased tenderness on all visits (mean of 1.9, 1.7, 1.8, 1.9; p < 0.001) compared with baseline (2.8). Reported post-injection adverse effects included worsening of the following pre-existing conditions: constipation (28.6 %), stress urinary incontinence (4.8 %), fecal incontinence (4.8 %), and new onset stress urinary incontinence (4.8 %). The authors concluded that EMG-guided Botox injection into PFM could be beneficial for women with refractory HTPFD who have failed conservative therapy. This was a small (n = 21) pilot study with short-term follow-up (24 weeks). The role of botulinum toxin in the treatment of FSD associated with pelvic floor dysfunction need to be ascertained in well-designed studies.
|CPT Codes / HCPCS Codes / ICD-10 Codes|
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":|
|ICD-10 codes will become effective as of October 1, 2015:|
|There are no specific codes for ospemifene, female erectile devices, biothesiometry, mindfulness meditation training or the Viveve Procedure,vaginal electrical stimulation:|
|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:|
|J0585||Injection, onabotulinumtoxinA, 1 unit|
|J0586||Injection, abobotulinumtoxinA, 5 units|
|J0587||Injection, rimabotulinumtoxinB, 100 units|
|J0588||Injection, incobotulinumtoxinA, 1 unit|
|J1071||Injection, testosterone cypionate, 1 mg|
|J2320||Injection, nandrolone decanoate, up to 50 mg|
|J3121||Injection, testosterone enanthate, 1 mg|
|J3145||Injection, testosterone undecanoate, 1 mg|
|S0189||Testosterone pellet, 75 mg|
|ICD-10 codes not covered for indications listed in the CPB:|
|F52.0 - F52.1
F52.22 - F52.31
F52.5 - F52.9
|Sexual dysfunction not due to a substance or known physiological condition, female|
|N94.89||Other specified conditions associated with female genital organs and menstrual cycle|
|R37||Sexual dysfunction, unspecified|