Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Menopausal symptoms.
Treatment: Vivelle-DOT 0.5MG/ 24HR TD PTTW, Pre-service.
The insurer denied the Vivelle-DOT 0.5MG/ 24HR TD PTTW, Pre-service.
The denial is overturned.

The patient is a female who has menopausal symptoms.  She has been on Vivelle-DOT for several years with stable symptoms.  She has had intolerance to generics in the past. The request is for continuance.  This was denied because the Plan states the patient has not tried and failed the formulary option.

Yes, the proposed treatment is medically necessary.
According to the American College of Obstetrics and Gynecology (ACOG), studies of the efficacy of hormone therapy (HT) for the treatment of vasomotor symptoms have principally investigated standard doses of hormone therapy (HT). Although hormone therapy is well tolerated by most women, standard doses may cause adverse effects, such as breast tenderness, vaginal bleeding, bloating, and headaches. Low-dose and ultra-low systemic doses of estrogen may be associated with a better adverse effect profile than standard doses and may reduce vasomotor symptoms in some women.  Examples of low-dose systemic estrogen therapy formulations include 0.30.45 milligrams per day (mg/d) of oral conjugated equine estrogen, 0.5 milligrams per day (mg/d) of oral micronized estradiol, 5.0 micrograms per day of ethinyl estradiol, and 0.0250.0375 milligrams per week (mg/wk) of transdermal estradiol (patch). There also are low-dose formulations of estradiol available in topical gels, creams, and sprays that are approved by the U.S. Food and Drug Administration (FDA). There is good evidence that oral and transdermal low-dose estrogen regimens effectively alleviate vasomotor symptoms in women. 

The Heart Outcomes Prevention Evaluation, a large trial that assessed the efficacy of different doses of hormone therapy on vasomotor symptoms in more than 2,500 postmenopausal women, found a similar reduction in vasomotor symptoms with a conjugated equine estrogen dosage of 0.625 milligrams per day (mg/d) and all lower combination doses. Another study of 333 women randomized to receive various doses of estradiol or placebo found that a dosage as low as 0.5 milligrams per day (mg/d) of oral estradiol is effective in treating hot flushes.

The results of studies that assessed the efficacy of ultra-low doses of estrogen (0.25 milligrams of oral micronized estradiol and 0.014 milligrams of transdermal estradiol) to treat vasomotor symptoms have been mixed, and currently these doses are not Food and Drug Administration (FDA) approved for this indication. Some studies have shown improvement in vasomotor symptoms with ultra-low dose estrogen alone or in combination with progestin. For example, an randomized controlled trial (RCT) of 425 women demonstrated that 41% of women experienced a reduction in moderate and severe hot flushes with ultra-low dose estradiol therapy (0.014 milligrams per day estradiol patch) compared with placebo. However, other studies have not shown a benefit for the treatment of vasomotor symptoms. In a randomized controlled clinical trial (RCT) of 333 women, a 0.25 milligram dose of oral estradiol was not more effective than placebo in treating hot flushes.

The degree of improvement of vasomotor symptoms from low-dose and ultra-low dose preparations has not been as extensively studied as with standard-dose preparations. Although women will experience improvement in symptoms with low and ultra-low doses of hormone therapy, lower doses may not be as effective as traditional doses of hormone therapy in alleviating vasomotor symptoms. Nonetheless, given the variable response to hormone therapy and the associated risks, it is recommended that health care providers individualize care and treat women with the lowest effective dose for the shortest duration that is needed to relieve vasomotor symptoms.

The risks of systemic combined hormone therapy include thromboembolic disease and breast cancer. The majority of trials that analyzed the safety of hormone therapy 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 five years of combined hormone therapy. Among women receiving estrogen only, there was an increased risk of thromboembolic events, but not an increased risk of cardiovascular events or breast cancer. It is difficult to generalize these findings to younger women who are recently menopausal because the Women's Health Initiative was aimed at assessing hormone therapy for primary coronary heart disease prevention in women, many of whom were past the menopausal transition.

A reanalysis of the Women's Health Initiative results in women younger than 60 years and within ten years of menopause has suggested a possible cardioprotective effect of hormone therapy for women in this group. However, a follow-up study of the Women's Health Initiative with 13 years of cumulative follow-up data confirmed that the risk of conjugated equine estrogen and medroxprogesterone acetate outweighed the benefits. Similarly, a Cochrane review of hormone therapy that included 23 studies and more than 42,000 participants concluded that hormone therapy should not be used for primary or secondary disease prevention because the risks of use outweigh the benefits.

The use of alternative forms of estrogen and progestin may be associated with a different risk profile. For example, observational studies suggest that transdermal estrogen may have a lower risk of venous thromboembolism compared with oral regimens. Additional data from randomized controlled trials (RCTs) are needed to compare the safety and efficacy of various regimens.

In review of the medical record and current literature the goal of treatment is to individualize care and to treat with the lowest effective dose for the shortest duration that is needed to relieve symptoms.  There is no evidence that one form of treatment is superior over another.  The patient has been stable on Vivelle-DOT for years.  She failed generic versions which is also the recommended formulary alternative.  The transdermal formulation also has a lower risk of venous thromboembolism.  There is a concern that a change in formulation would cause adverse events.  Therefore, it would be necessary to continue since the medication has worked well for this patient and a change could jeopardize her health.

No, the plan did not reasonably provide the correct determination that would be in the best interest of the patient.
Denial of Vivelle-DOT could jeopardize this patient's health.  She has also failed the formulary alternative in the past.