2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women who have a history of endometriosis may need a progestogen [see Warnings and Precautions (5.2 , 5.14) ] . Use estrogen-alone or in combination with a progestogen at the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. • Start therapy with estradiol transdermal system (twice-weekly) 0.0375 mg/day applied to the skin twice weekly for the treatment of moderate to severe vasomotor symptoms due to menopause or moderate to severe symptoms of vulvar and vaginal atrophy symptoms due to menopause. Dosage adjustment should be guided by the clinical response ( 2.1 , 2.2 , 2.3 ) • Start therapy with estradiol transdermal system (twice-weekly) 0.025 mg/day for the prevention of postmenopausal osteoporosis ( 2.4 ) • Place estradiol transdermal system (twice-weekly) on a clean, dry area of the lower abdomen or buttocks. Do not apply estradiol transdermal system (twice-weekly) to the breasts ( 2.5 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause Start therapy with estradiol transdermal system (twice-weekly) 0.0375 mg per day applied to the skin twice weekly. Make dosage adjustments based on the clinical response. Initiate estradiol transdermal system (twice-weekly) at once in a woman not currently taking oral estrogens or in a woman switching from another estradiol transdermal therapy. In women who are currently taking oral estrogens, initiate treatment with estradiol transdermal system (twice-weekly) 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Attempts to taper or discontinue estradiol transdermal system (twice-weekly) at 3 to 6-month intervals. Give estradiol transdermal system (twice-weekly) continuously in a woman who does not have an intact uterus. In a woman with an intact uterus, give estradiol transdermal system (twice-weekly) on a cyclic schedule (for example, 3 weeks on estradiol transdermal system (twice-weekly) followed by 1 week off estradiol transdermal system (twice-weekly)). 2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy Due to Menopause Start therapy with estradiol transdermal system (twice-weekly) 0.0375 mg per day applied to the skin twice weekly. Dosage adjustment should be guided by the clinical response. Attempts to taper or discontinue estradiol transdermal system (twice-weekly) at 3 to 6-month intervals. In women not currently taking oral estrogens or in women switching from another estradiol transdermal therapy, treatment with estradiol transdermal system (twice-weekly) may be initiated at once. In women who are currently taking oral estrogens, initiate treatment with estradiol transdermal system (twice-weekly) 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Give estradiol transdermal system (twice-weekly) continuously in a woman who does not have an intact uterus. In a woman with an intact uterus, give estradiol transdermal system (twice-weekly) on a cyclic schedule (for example, 3 weeks on estradiol transdermal system (twice-weekly) followed by 1 week off estradiol transdermal system (twice-weekly)). 2.3 Hypoestrogenism Due to Hypogonadism, Castration, or Primary Ovarian Failure 2.4 Prevention of Postmenopausal Osteoporosis Start therapy with estradiol transdermal system (twice-weekly) 0.025 mg per day applied to the skin twice weekly. In women not currently taking oral estrogens or in women switching from another estradiol transdermal therapy, treatment with estradiol transdermal system (twice-weekly) may be initiated at once. In women who are currently taking oral estrogens, initiate treatment with estradiol transdermal system (twice-weekly) 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Estradiol transdermal system (twice-weekly) may be given continuously in a woman who does not have an intact uterus. In a woman with an intact uterus, estradiol transdermal system (twice-weekly) may be given on a cyclic schedule (for example, 3 weeks on estradiol transdermal system (twice-weekly) followed by 1 week off estradiol transdermal system (twice-weekly)). 2.5 Application Instructions Place the adhesive side of estradiol transdermal system (twice-weekly) on a clean, dry area of the trunk of the body (including the abdomen or buttocks). Do not apply estradiol transdermal system (twice-weekly) to the breasts. Replace estradiol transdermal system (twice-weekly) twice weekly. Rotate the sites of application, with an interval of at least 1 week allowed between applications to a particular site. Select an area that is not oily, damaged, or irritated. Avoid the waistline, since tight clothing may rub the system off. Apply the system immediately after opening the pouch and removing the oversized protective liner. Press the system firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact, especially around the edges. In the event that a system falls off, reapply the same system or apply a new system to another location. In either case, continue the original treatment schedule. If a woman has forgotten to apply estradiol transdermal system (twice-weekly), have her apply a new system as soon as possible. Apply the new system on the original treatment schedule. The interruption of treatment in women taking estradiol transdermal system (twice-weekly) might increase the likelihood of breakthrough bleeding, spotting and recurrence of symptoms.