Vaginal Estradiol and Appetite & Cravings Changes: What the Evidence Actually Shows

What does the vaginal estradiol label list?

Estradiol Vaginal Cream, 0.01% is FDA-approved for moderate to severe symptoms of vulvar and vaginal atrophy due to menopause [1]. Its adverse reactions section gives no frequencies and lists, among other things, nausea, vomiting, abdominal cramps and bloating; increase or decrease in weight; edema; breast tenderness, enlargement and pain; headache, migraine and dizziness; mood disturbances; and changes in libido [1]. Appetite and food cravings are not in that list [1].

The same label states that systemic absorption may occur with the cream and that the warnings, precautions and adverse reactions associated with oral estrogen treatment should be taken into account [1].

Does the oral estradiol label say anything different?

The oral estradiol tablet label lists increase or decrease in weight and reduced carbohydrate tolerance among the reactions reported with estrogen and/or progestin therapy, again without frequencies [3]. That list also includes nausea, vomiting, abdominal cramps and bloating, and mood disturbances [3]. It does not name appetite or cravings either [3].

The cream, the vaginal tablet and the vaginal ring are separate products with separate prescribing information; the label described here covers the cream only [1].

What did the trials measure?

The 2016 Cochrane review of local estrogen for vaginal atrophy included randomized comparisons of intravaginal estrogenic preparations used for at least 12 weeks [2]. Its two primary outcomes were participant-assessed symptom improvement and endometrial thickness [2]. Secondary outcomes were clinician-assessed symptom improvement, other adverse events including breast disorders, total adverse events excluding breast disorders, and adherence to treatment [2]. Appetite is not among the outcomes it lists [2].

The 2022 position statement of the North American Menopause Society recommends low-dose vaginal estrogen, vaginal dehydroepiandrosterone or oral ospemifene for bothersome genitourinary syndrome of menopause symptoms not relieved by over-the-counter therapies in women without indications for systemic hormone therapy. It also notes that hormone therapy risks differ by type, dose, duration, route of administration, timing of initiation and whether a progestogen is used [4].

Where weight change fits

Increase or decrease in weight appears in the cream's adverse reactions section with no rate attached [1]. The oral tablet label lists weight change and reduced carbohydrate tolerance the same way, without frequencies [3]. The Climara patch label, a different product and route, lists weight increase as a postmarketing reaction [5].