ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER.
Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. (See WARNINGS, Malignant Neoplasms, Endometrial Cancer.)
CARDIOVASCULAR AND OTHER RISKS
Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. (See WARNINGS, Cardiovascular Disorders and Dementia.)
The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies).
The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies.)
Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estraderm® (estradiol transdermal system) is designed to release estradiol through a rate-limiting membrane continuously upon application to intact skin.
Two systems are available to provide nominal in vivo delivery of 0.05 or 0.1 mg of estradiol per day via skin of average permeability (interindividual variation in skin permeability is approximately 20%). Each corresponding system having an active surface area of 10 or 20 cm2 contains 4 or 8 mg of estradiol USP and 0.3 or 0.6 mL of alcohol USP, respectively. The composition of the systems per unit area is identical.
Estraderm® (estradiol transdermal system) is indicated in:
- Treatment of moderate to severe vasomotor symptoms associated with the menopause.
- Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
- Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
- Prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.
The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 IU/day may also be required to ensure adequate daily intake in postmenopausal women.
Published Studies Related to Estraderm (Estradiol Transdermal)
Pharmacokinetics of testosterone and estradiol gel preparations in healthy young
The paucity of pharmacokinetic data on testosterone gel formulations and absence
of such data on estradiol administration in healthy young men constitutes a
fundamental gap of knowledge in behavioral endocrinological research. We
addressed this issue in a double-blind and placebo controlled study in which we
applied a topical gel containing either 150mg of testosterone (N=10), 2mg of
estradiol (N=8) or a respective placebo (N=10) to 28 healthy young men...
Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial. [2011.11.29]
BACKGROUND: This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg... CONCLUSIONS: EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated. Copyright (c) 2011 Elsevier Inc. All rights reserved.
Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial. [2011.09.24]
OBJECTIVE: The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system... CONCLUSION: The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright A(c) 2011 Mosby, Inc. All rights reserved.
Prevention of menstrual migraine with perimenstrual transdermal 17-beta-estradiol: a randomized, placebo-controlled, double-blind crossover study. [2011.08]
The effect of treatment with percutaneous E(2) (100 mug/24 h) during 2 weeks perimenstrually on the number and severity of menstrual migraine attacks was studied in 27 women in a randomized, placebo-controlled, double-blind, crossover trial. We were not able to demonstrate any difference between E(2) supplementation and placebo on the number or severity of migraine attacks, but both regimens showed significant effects compared with before treatment.
Increased estradiol and improved sleep, but not hot flashes, predict enhanced mood during the menopausal transition. [2011.07]
BACKGROUND: The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression... CONCLUSIONS: For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression.
Reports of Suspected Estraderm (Estradiol Transdermal) Side Effects
Breast Cancer (13),
Abdominal Pain (11),
Hot Flush (11), more >>
Page last updated: 2014-11-30