Appeal type: Formulary Exception
Decision: Upheld

Diagnosis: Dyspareunia
Treatment: Estring
The insurer denied Estring
The determination is upheld.

This is a female patient who is under consideration for Estring for the indication of unspecified dyspareunia. The patient reported that she has been on this for three years with good effects. She has the ability to get this medication by prescription, but it is not covered on the preferred formulary on her insurance plan. A letter from her physician states that she has a history of breast cancer and also has atrophic vaginitis and dyspareunia. She has tried Intrarosa, Vagifem, and Osphena. She had not previously failed Vagifem as a treatment option but rather she wanted to switch to a different treatment. She did not switch due to a failure of them. The criteria in this case require the patient to have filled three formulary alternatives before a non-formula alternative would be an option. Vagifem was previously effective per documentation.  Estring has been successful in resolving her symptoms. There are additional formulary drugs available for use in this case. She has been on Estring 2 milligrams (mg) vaginal ring for therapy. She also appears to have had success in the past with Vagifem. Formulary alternatives include estradiol vaginal cream, Imvexxy, and vagifem. The plan requires a trial of three formulary alternatives prior to approval of Estring. At issue is whether the formulary drug will be or has been ineffective, would not be as effective as the non-formulary drug, or would have adverse effects.

In this case, the preferred formulary drugs inclusive of estradiol vaginal cream, Imvexxy, and vagifem have not been proven to be ineffective or not as effective as the non-formulary drug of Estring for the indication of unspecified dyspareunia and atrophic vaginitis.  The American College of Obstetrics & Gynecology clinical guidelines for the management of postmenopausal atrophic vaginitis and dyspareunia recommend oral, topical, dermal or vaginal estrogen replacement when the patient has atrophic vaginitis.

The risks of systemic combined hormone therapy (HT) include thromboembolic disease and breast cancer. The majority of trials that analyzed the safety of HT have assessed preparations containing conjugated equine estrogen alone or in combination with medroxyprogesterone acetate. The Women's Health Initiative (WHI) study, a large randomized controlled trial (RCT) of healthy menopausal women aged 50-77 years, demonstrated a slightly increased risk of breast cancer, coronary heart disease, stroke, and venous thromboembolic events and a decreased risk of fractures and colon cancer after an average of 5 years of combined HT. Among women receiving estrogen only, there was an increased risk of thromboembolic events, but not an increased risk of cardiovascular events or breast cancer.

There is no literature to support that one method over another is safer for total exposure to estrogen. Thus, counseling is key in this case. Thus, there is no evidence that Estring is superior to the formulary alternative of estradiol vaginal cream, Imvexxy, and vagifem and all may increase risk for cancer to some degree.