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. (See WARNINGS, Cardiovascular disorders.)
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 CLININAL 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 or to women taking estrogen alone therapy. (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.
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DELESTROGEN SUMMARY
DELESTROGEN® (estradiol valerate injection, USP) contains estradiol valerate, a long-acting estrogen in sterile oil solutions for intramuscular use. These solutions are clear, colorless to pale yellow. Formulations (per mL): 10 mg estradiol valerate in a vehicle containing 5 mg chlorobutanol (chloral derivative/preservative) and sesame oil; 20 mg estradiol valerate in a vehicle containing 224 mg benzyl benzoate, 20 mg benzyl alcohol (preservative), and castor oil; 40 mg estradiol valerate in a vehicle containing 447 mg benzyl benzoate, 20 mg benzyl alcohol, and castor oil.
DELESTROGEN (estradiol valerate injection, USP) is indicated in the:
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Treatment of moderate to severe vasomotor symptoms associated with the menopause. There is no adequate evidence that estrogens are effective for nervous symptoms or depression which might occur during menopause and they should not be used to treat these conditions.
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Treatment of vulval and vaginal atrophy.
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Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
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Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).
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NEWS HIGHLIGHTS
Published Studies Related to Delestrogen (Estradiol)
The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART'MUS) trial: rationale, objectives and state of advancement. [2009.11.15]
Multiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system, which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss... Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum.
A randomized controlled trial of a low-dose combined oral contraceptive containing 3 mg drospirenone plus 20 microg ethinylestradiol in the treatment of acne vulgaris: lesion counts, investigator ratings and subject self-assessment. [2009.09]
OBJECTIVE: To assess the efficacy of a combined oral contraceptive (COC) containing 3 mg drospirenone (drsp) plus 20 microg ethinylestradiol (EE) administered in 24 days of active treatment followed by a four-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris... CONCLUSION: The 3 mg drsp/20 microg EE COC administered in a 24/4 regimen significantly reduced acne lesions.
Steady-state pharmacokinetics following application of a novel transdermal estradiol spray in healthy postmenopausal women. [2009.09]
This study was designed to evaluate the steady-state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1-, 2-, or 3-spray doses (24 participants/dose level) of a 1.7% estradiol metered-dose transdermal spray (1.53 mg/spray) once daily for 14 days...
Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. [2009.08.19]
CONTEXT: Estrogen deprivation therapy with aromatase inhibitors has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy. OBJECTIVE: To determine whether 6 mg of estradiol (daily) is a viable therapy for postmenopausal women with advanced aromatase inhibitor-resistant hormone receptor-positive breast cancer... CONCLUSIONS: In women with advanced breast cancer and acquired resistance to aromatase inhibitors, a daily dose of 6 mg of estradiol provided a similar clinical benefit rate as 30 mg, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined in phase 3 clinical trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00324259.
Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder. [2009.08]
OBJECTIVE: The aim of this study was to investigate which add-back hormone replacement therapy would be most beneficial in terms of mood effects for patients with premenstrual dysphoric disorder who are receiving gonadotropin-releasing hormone agonist therapy... CONCLUSION: Based on the findings of the present study, long-cycle add-back treatment to avoid frequent progestagen use appears to be most beneficial for patients with premenstrual dysphoric disorder.
Clinical Trials Related to Delestrogen (Estradiol)
Effect of Angeliq on Blood Pressure (BP) in Postmenopausal Hypertensive Women [Completed]
The objective of the study is to evaluate the effects of Angeliq on BP over a period of 8
weeks in postmenopausal women who may benefit from hormone replacement therapy (HRT) for the
relief of vasomotor symptoms and who have hypertension.
Evaluation of Adhesion Quality of a New Formulation of the Mylan Estradiol Transdermal System 0.025 mg/Day and Climara® Transdermal System 0.025 mg/Day [Completed]
The primary objective of this study was to compare the adhesive quality of a new formulation
of the Mylan Estradiol Transdermal System with that of Climara® Transdermal System following
a single system application in 80 healthy postmenopausal female volunteers. As a secondary
objective, primary dermal irritation was assessed after removal of each transdermal system.
Treatment of Hot Flushes in Asian Women With Ultra-Low Dose Estradiol Patch [Completed]
150 postmenopausal Asian women with vasomotor symptoms, after fulfilling the inclusion and
exclusion criteria will be enrolled in the study. The women will be randomly assigned to one
of two treatment groups (Menostar® or placebo), after which they will be asked to use a patch
once a week for 12 weeks.
Vasomotoric Symptoms Study of a 0.5 mg Estradiol and 2.5 mg Dydrogesterone Combination [Completed]
Neoadjuvant Estradiol or Androgen Deprivation in Clinically Localized Prostate Cancer [Completed]
Prostate cancer is the most commonly diagnosed cancer among males in the U. S. More than
220,000 men will be diagnosed with prostate cancer in the USA this year and more that 31,000
will die of this disease.
Androgen deprivation, the elimination of testosterone and its active metabolites, remains the
single most effective intervention available for the treatment of advanced prostate
carcinoma. Androgen deprivation induces an immune response to normal prostate and prostate
cancer, which is usually short-lived. Estradiol induces activation of many arms of the
immune system and may be a more effective and long lasting means of inducing immunity to
prostate tissue.
This study will treat clinically localized prostate cancer patients with either estrogens, or
standard androgen deprivation without estrogens, prior to prostatectomy in order more
completely to describe immune regulation by estradiol in men. Control tissue from patients
who have not been treated with androgen deprivation will be procured from the Northwest
Special Projects in Oncology Research Excellence (SPORE) tissue core and used as comparisons
against the cancers treated before prostatectomy. Tumors removed at prostatectomy, tissue
samples and blood samples will be assessed for immune system changes.
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Page last updated: 2009-10-20
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