Appeal type: Formulary Exception
Decision: Overturned

Diagnosis: Vaginal Dryness
Treatment: Intrarosa 6.5mg INSERT, Pre-service
The insurer denied the Intrarosa 6.5mg INSERT, Pre-service.
The denial is overturned.

The patient is a female with vaginal atrophy and dyspareunia.  She has a history of breast pain and a biopsy revealed ductal hyperplasia.  She tried and failed Premarin vaginal cream. The request is for Intrarosa.

Yes the health plan should cover the proposed treatment.
Vaginal dehydroepiandosterone (DHEA), also referred to as prasterone, is a treatment option for dyspareunia associated with genitourinary syndrome of menopause (GSM). The Food and Drug Administration (FDA) approved the use of prasterone 6.5 milligrams (mg) (0.5% formulation) as a daily vaginal suppository for the treatment of dyspareunia in the setting of vulvar or vaginal atrophy due to menopause.

The mechanism of action of prasterone on the vagina is likely due to the aromatization of androstenedione and testosterone locally to estrone and estradiol through a process referred to by some investigators as intracrinology. In one study, weeks of vaginal dehydroepiandosterone (DHEA) (6.5 milligrams) caused estrone to rise from 15 to 18 picograms per milliliter (pg/mL) and estradiol from two to three picograms per milliliter (pg/mL). 

Prasterone was found to be an effective treatment for dyspareunia in a randomized trial that assigned postmenopausal patients with dyspareunia to prasterone or placebo for 12 weeks and found improved Female Sexual Function Index (FSFI) overall scores and in the pain and satisfaction domains. At 12 weeks, treatment with vaginal dehydroepiandosterone (DHEA) resulted in a significant increase from baseline in serum dehydroepiandosterone (DHEA), testosterone, and estrone but not estradiol levels, although dehydroepiandosterone (DHEA), estradiol, estrone, and testosterone remained within the range of an average postmenopausal patient.

Dehydroepiandosterone (DHEA) has been studied as a potential medication to increase libido in postmenopausal patients, but its efficacy is uncertain, and the serum dehydroepiandosterone (DHEA) levels with this dose of vaginal prasterone are unlikely to have an impact. Also, libido often improves with any adequate treatment of dyspareunia.

The formulary options include estradiol cream, estradiol vaginal inserts, estring, premarin cream, and yuvafem.  These are all estrogen containing products.  The patient has tried and failed premarin.  She also has a history of ductal hyperplasia of the breast so the use of estrogen containing products increases the risk of progression of hyperplasia.  Therefore this would potentially cause an adverse effect for the patient.

In review of the medical record and the literature, the use of intrarosa is Food and Drug Administration (FDA) approved for the treatment of dyspareunia secondary to vaginal atrophy from menopause.  There are randomized controlled trials demonstrating safety and efficacy and improvement in dyspareunia.  This is also a safe medication to use in the setting of breast disease.  Given the patient has failed alternative options of premarin and estrogen products pose a risk for adverse health events, Intrarosa would be an effective alternative.  The literature supports that this is a medically appropriate option for the treatment of dyspareunia.  Therefore the plan should cover the proposed treatment.