Why the product labeling for low-dose vaginal estrogen should be changed

Manson, JoAnn E.; Goldstein, Steven R.; Kagan, Risa; Kaunitz, Andrew M.; Liu, James H.; Pinkerton, JoAnn V.; Rebar, Robert W.; Schnatz, Peter F.; Shifren, Jan L.; Stuenkel, Cynthia A.; Gass, Margery; Utian, Wulf H.

doi:10.1097/gme.0000000000000316

Cited by 64 publications

(45 citation statements)

References 36 publications

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“…Because serum estradiol levels during therapy usually fall within the normal postmenopausal range, the risk profile with low-dose vaginal ET is expected to be lower than with systemic ET (288). However, long-term endometrial safety data are lacking, and 1 year is the maximum duration of RCTs of vaginal ET (261).…”

Section: Adverse Eventsmentioning

confidence: 94%

“…This may reflect an actual neutral effect due to the absence of a first-pass hepatic effect by vaginal estrogens, or that studies of women at high CVD or VTE risk are lacking (281). Available evidence does not support the boxed warning on low-dose vaginal estrogen regarding an increased risk of CHD, stroke, VTE, dementia, and breast cancer, and efforts to modify the labeling of these products are in progress (288).…”

Section: Adverse Eventsmentioning

confidence: 96%

See 1 more Smart Citation

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline

Stuenkel

Davis

Gompel

et al. 2015

The Journal of Clinical Endocrinology & Metabolism

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638

419

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Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures.

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Section: Adverse Eventsmentioning

confidence: 94%

Section: Adverse Eventsmentioning

confidence: 96%

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline

Stuenkel

Davis

Gompel

et al. 2015

The Journal of Clinical Endocrinology & Metabolism

Self Cite

638

419

View full text Add to dashboard Cite

show abstract

“…This publication proposes modified-labeling language that would better reflect the safety profile of low-dose vaginal estrogen and potentially enhance safety by focusing on crucial information regarding these formulations that would benefit women and clinicians. 75 At the time of this article’s publication, the FDA is reviewing and considering the proposal.…”

Section: Hormonal Prescription Medicationsmentioning

confidence: 99%

Management of Menopausal Symptoms

Kaunitz

Manson

2015

Obstetrics &Amp; Gynecology

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154

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Most menopausal women experience vasomotor symptoms, with bothersome symptoms often lasting longer than one decade. Hormone therapy (HT) represents the most effective treatment for these symptoms, with oral and transdermal estrogen formulations having comparable efficacy. Findings from the Women’s Health Initiative and other recent randomized clinical trials have helped to clarify the benefits and risks of combination estrogen-progestin and estrogen-alone therapy. Absolute risks observed with HT tended to be small, especially in younger women. Neither regimen affected all-cause mortality rates. Given the lower rates of adverse events on HT among women close to menopause onset and at lower baseline risk of cardiovascular disease, risk stratification and personalized risk assessment appears to represent a sound strategy for optimizing the benefit: risk profile and safety of hormone therapy. Systemic HT should not be arbitrarily stopped at age 65; instead treatment duration should be individualized based on patients’ risk profiles and personal preferences. Genitourinary syndrome of menopause represents a common condition that adversely impacts the quality of life of many menopausal women. Without treatment, symptoms worsen over time. Low-dose vaginal estrogen represents highly effective treatment for this condition. Because custom-compounded hormones have not been tested for efficacy or safety, U.S. Food and Drug Administration (FDA)-approved HT is preferred. A low dose formulation of paroxetine mesylate currently represents the only nonhormonal medication FDA-approved to treat vasomotor symptoms. Gynecologists and other clinicians who remain abreast of data addressing the benefit: risk profile of hormonal and nonhormonal treatments can help menopausal women make sound choices regarding management of menopausal symptoms.

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“…Patients who wish to consider HT after a diagnosis of breast cancer should be informed that definitive evidence on its influence in prognosis of breast cancer is lacking. The results of observational studies (which are fraught with potential biases) [Biglia et al 2010;Manson et al 2014;Santen et al 2002;Cold et al 2015] and a recent phase II RCT (evaluating use of estradiol-releasing vaginal ring 7.5 µg/d for 12 weeks) have been reassuring with respect to safety [Melisko et al 2016]. However, a single RCT suggested that HT in breast cancer survivors may increase breast cancer recurrence or new breast cancers by 2-3-fold [Holmberg and Anderson, 2004].…”

Section: Hormone Therapymentioning

confidence: 99%

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

et al. 2017

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There is increasing attention and concern about managing the adverse effects of adjuvant endocrine therapy for women with early breast cancer as the side effects of therapy influence compliance and can impair quality of life (QoL). Most side effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are directly related to estrogen deprivation, and the symptoms are similar to those experienced during natural menopause but appear to be more severe than that seen in the general population. Prolonged estrogen deprivation may lead to atrophy of the vulva, vagina, lower urinary tract and supporting pelvic structures, resulting in a range of genitourinary symptoms that can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of QoL. The genitourinary side effects may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment. We provide an overview of practical clinical approaches to understanding the pathophysiology and the management of genitourinary symptoms in postmenopausal women receiving adjuvant endocrine therapy for breast cancer.

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Why the product labeling for low-dose vaginal estrogen should be changed

Cited by 64 publications

References 36 publications

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline

Management of Menopausal Symptoms

A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy

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