2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions ( 5.2 , 5.14 )] . Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. • Start therapy with the Estradiol Transdermal System 0.025 mg per day applied to the skin once-weekly. Dosage adjustment should be guided by the clinical response ( 2.1 ) • The Estradiol Transdermal System should be placed on a clean, dry area of the lower abdomen (below the umbilicus) or upper quadrant of the buttock. The Estradiol Transdermal System should not be applied to the breasts ( 2.5 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. 2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. 2.3 Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure Start therapy with 0.025 mg per day applied to the skin once weekly. The dose should be adjusted as necessary to control symptoms. Clinical responses (relief of symptoms) at the lowest effective dose should be the guide for establishing administration of the Estradiol Transdermal System, especially in women with an intact uterus. 2.4 Prevention of Postmenopausal Osteoporosis Start therapy with 0.025 mg per day applied to the skin once weekly. 2.5 Application of the Estradiol Transdermal System Site Selection • The adhesive side of the Estradiol Transdermal System should be placed on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. • The Estradiol Transdermal System should not be applied to or near the breasts. • The sites of application must be rotated, with an interval of at least 1-week allowed between applications to the same site. • The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the transdermal system off. • Application to areas where sitting would dislodge the Estradiol Transdermal System should also be avoided. Application • The Estradiol Transdermal System should be applied immediately after opening the pouch and removing the protective liner. • The Estradiol Transdermal System should be pressed firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges. • If the system lifts, apply pressure to maintain adhesion. • In the event that a system should fall off reapply it to a different location. If the system cannot be reapplied, a new system should be applied for the remainder of the 7-day dosing interval. • Only one system should be worn at any one time during the 7-day dosing interval. • Swimming, bathing, or using a sauna while using the Estradiol Transdermal System has not been studied, and these activities may decrease the adhesion of the system and the delivery of estradiol. 2.6 Removal of the Estradiol Transdermal System • Removal of the Estradiol Transdermal System should be done carefully and slowly to avoid irritation of the skin. • Should any adhesive remain on the skin after removal of the Estradiol Transdermal System, allow the area to dry for 15 minutes. Then gently rubbing the area with an oil-based cream or lotion should remove the adhesive residue. • Used patches still contain some active hormones. Each patch should be carefully folded in half so that it sticks to itself before throwing it away.