WARNING: 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 currently no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. (See WARNINGS, Malignant Neoplasms, Endrometrial cancer.)
CARDIOVASCULAR AND OTHER RISKS
Estrogens with and without 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 and WARNINGS, Cardiovascular
Disorders and Malignant Neoplasms, Breast cancer.)
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 and WARNINGS, Dementia and CLINICAL STUDIES and WARNINGS, Dementia and PRECAUTIONS, Geriatric Use.)
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.
Alora (Estradiol Transdermal System, USP) is designed to deliver estradiol continuously and consistently over a 3 or 4-day interval upon application to intact skin. Four strengths of Alora are available, having nominal in vivo delivery rates of 0.025, 0.05, 0.075, and 0.1 mg estradiol per day through skin of average permeability (inter-individual variation in skin permeability is approximately 20%). Alora has contact surface areas of 9 cm2, 18 cm2, 27 cm2, and 36 cm2 and contains 0.77, 1.5, 2.3, and 3.1 mg of estradiol, USP, respectively. The composition of the estradiol transdermal systems per unit area is identical.
Alora 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 to remain in neutral calcium balance. 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 Alora (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.
Clinical Trials Related to Alora (Estradiol Transdermal)
Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients [Recruiting]
The purpose of this clinical research study is to determine whether the ESTRING or a special
preparation of a testosterone cream inserted vaginally are safe for use in breast cancer
patients. This study will also evaluate if either of these treatments can improve symptoms
of vaginal dryness or decreased sexual interest that are related to your treatment for
Serum Estradiol Levels In Postmenopausal Women With Breast Cancer Receiving Adjuvant Aromatase Inhibitors and Vaginal Estrogen [Recruiting]
The purpose of this study is to see if Vagifem« 10mcg is safe for women who have had breast
cancer. Vagifem is an estrogen product. It is a tiny tablet that is inserted into the
vagina. It relieves vaginal dryness. Women who have had breast cancer are usually told not
to take estrogen. This is because estrogen use can lead to a breast cancer recurrence or a
new primary breast cancer. It is unclear if the estrogen in Vagifem is only absorbed in the
vagina. It may be absorbed into the blood stream for a short time and may cause a brief rise
in your estrogen level. However, there is no clear evidence that this would cause any bad
effects in patients with breast cancer. How much, if any, of these topical estrogens are
absorbed through the vagina is not known. We also do not know what the impact is of low
dose estrogen absorption on breast cancer outcomes. Also, the absorption should decrease as
the mucus membranes are restored after estrogen exposure.
Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function [Recruiting]
This study compares the effects of two common hormone medications on the heart and blood
vessels of healthy post-menopausal women over the age of 45.
The study will take place over the course of about 5 months. Each subject will take two
different medications over two six-week periods. They will be randomized at the beginning of
the study to either estradiol+medroxyprogesterone acetate or estradiol+drospirenone for the
first period, and will receive the other medication the second six-weeks of the study. At
the very beginning of the study and at the end of each six-week treatment period, subjects
will come to the hospital various tests including non-invasive blood vessel imaging tests,
blood draws to test the levels of certain hormones in the body, an oral glucose tolerance
test, a test to monitor renal blood flow, and 24-hour blood pressure monitoring. Between
treatment periods, there will be a four-week medication-free washout period.
Comparative Efficacy of Low-Dose Estradiol and Venlafaxine XR for Treatment of Menopausal Symptoms [Recruiting]
The primary objective of this study is to determine the efficacy of both low-dose oral (by
mouth) 17-▀-estradiol and the non-hormonal drug venlafaxine XR compared to placebo in
reducing hot flashes. Included in this objective is the intention to compare venlafaxine XR
to estradiol therapy, to provide evidence of the relative efficacy of venlafaxine to what is
currently considered the most established but also a controversial therapy. 17-├č-estradiol
is a type of estrogen. Venlafaxine XR is the extended release (XR) version of venlafaxine.
Venlafaxine XR is an serotonin-norepinephrine reuptake inhibitor (SNRI). A placebo is a
substance containing no medication.
Initiating Transdermal Estradiol Therapy in Turner's Syndrome [Recruiting]
This is a multicenter, randomized, controlled, semi-blinded study to compare two low doses
of estradiol administered by recently available transdermal patches for the initiation of
puberty in Turner syndrome girls 11. 5-13. 0 years old in conjunction with growth hormone (GH)
The specific hypotheses to be tested are: when combined with growth hormone (GH) treatment,
low dose transdermal estradiol (LTE2) replacement will be more effective in stimulating
feminization, height velocity, and bone mineral density without compromising growth
potential than very low dose transdermal estradiol (VLTE2), which will in turn be superior
to GH alone in effects on feminization, height velocity, and bone mineral density.
Page last updated: 2014-11-30