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Hormone Therapy for Menopause Reviewed

  • Authors: News Author: Laurie Barclay, MD
    CME Author: Penny Murata, MD
  • CME/CE Released: 4/8/2010
  • Valid for credit through: 4/8/2011
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Target Audience and Goal Statement

This article is intended for primary care clinicians, gynecologists, oncologists, and other specialists who provide care to menopausal women.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  1. Report the indications for hormone therapy in menopausal women.
  2. Report the contraindications to hormone therapy in menopausal women.


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  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


  • Brande Nicole Martin

    CME Clinical Editor, Medscape, LLC


    Disclosure: Brande Nicole Martin has disclosed no relevant financial relationships.

CME Author(s)

  • Penny Murata, MD

    Clinical Professor, Pediatrics, University of California, Irvine, California
    Pediatric Clerkship Director, University of California, Irvine, California


    Disclosure: Penny Murata, MD, has disclosed no relevant financial relationships.

CME Reviewer/Nurse Planner

  • Laurie E. Scudder, MS, NP

    Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland


    Disclosure: Laurie E. Scudder, MS, NP, has disclosed no relevant financial relationships.

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Hormone Therapy for Menopause Reviewed

Authors: News Author: Laurie Barclay, MD CME Author: Penny Murata, MDFaculty and Disclosures

CME/CE Released: 4/8/2010

Valid for credit through: 4/8/2011


April 8, 2010 — Women must be informed of the potential benefits and risks of all treatment options for menopausal symptoms and concerns and should receive individualized care, according to a review of the role of perimenopausal hormone therapy published in the April issue of Obstetrics & Gynecology.

"With the first publication of the results of the Women's Health Initiative (WHI) trial in 2002, the use of HT [hormone therapy] declined dramatically," write Jan L. Shifren, MD, and Isaac Schiff, MD, from Harvard Medical School and Massachusetts General Hospital in Boston. "Major health concerns of menopausal women include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognition, and mood.... Given recent findings, specifically regarding the effect of the timing of HT initiation on coronary heart disease [CHD] risk, it seems appropriate to reassess the clinician's approach to menopause in the wake of the recent reanalysis of the WHI."

Many therapeutic options are currently available for management of quality of life and health concerns in menopausal women. Treatment of vasomotor hot flushes and associated symptoms is the main indication for hormone therapy, which is still the most effective treatment of these symptoms and is currently the only US Food and Drug Administration–approved option. For healthy women with troublesome vasomotor symptoms who begin hormone therapy at the time of menopause, the benefits of hormone therapy generally outweigh the risks.

However, hormone therapy is associated with a heightened risk for coronary heart disease. Based on recent analyses, this higher risk is attributable primarily to older women and to those who reached menopause several years previously. Hormone therapy should not be used to prevent heart disease, based on these analyses. However, this evidence does offer reassurance that hormone therapy can be used safely in otherwise healthy women at the menopausal transition to manage hot flushes and night sweats.

Although hormone therapy may help prevent and treat osteoporosis, it is seldom used solely for this indication alone, particularly if other effective options are well tolerated.

Short-term treatment with hormone therapy is preferred to long-term treatment, in part because of the increased risk for breast cancer associated with extended use. The lowest effective estrogen dose should be given for the shortest duration required because risks for hormone therapy increase with advancing age, time since menopause, and duration of use.

Low-dose, local estrogen therapy is recommended vs systemic hormone therapy when only vaginal symptoms are present.

Alternatives to hormone therapy should be recommended for women with or at increased risk for disorders that are contraindications to hormone therapy use. These include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active hepatic or gallbladder disease.

In addition to estrogen therapy, progestin alone, and combination estrogen-progestin therapy, there are several nonhormonal options for the treatment of vasomotor symptoms. Lifestyle interventions include reducing body temperature, maintaining a healthy weight, stopping smoking, practicing relaxation response techniques, and receiving acupuncture.

Although efficacy greater than placebo is unproven, nonprescription medications that are sometimes used for treatment of vasomotor symptoms include isoflavone supplements, soy products, black cohosh, and vitamin E.

There are several nonhormonal prescription medications sometimes used off-label for treatment of vasomotor symptoms, but they are not approved by the Food and Drug Administration for this purpose. These drugs, and their accompanying potential adverse effects, include the following:

  • Clonidine, 0.1-mg weekly transdermal patch, with potential adverse effects including dry mouth, insomnia, and drowsiness.
  • Paroxetine (10 - 20 mg/day, controlled release 12.5 - 25 mg/day), which may cause headache, nausea, insomnia, drowsiness, or sexual dysfunction.
  • Venlafaxine (extended release 37.5 - 75 mg/day), which is associated with dry mouth, nausea, constipation, and sleeplessness.
  • Gabapentin (300 mg/day to 300 mg 3 times daily), with possible adverse effects of somnolence, fatigue, dizziness, rash, palpitations, and peripheral edema.

"Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences," the review authors write. "For women experiencing an early menopause, especially before the age of 45 years, the benefits of using HT until the average age of natural menopause likely will significantly outweigh risks. The large body of evidence on the overall safety of oral contraceptives in younger women should be reassuring for those experiencing an early menopause, especially given the much lower estrogen and progestin doses provided by HT formulations."

Dr. Shifren serves as a scientific advisory board member for the New England Research Institutes. She has been a research study consultant for Eli Lilly & Co and Boehringer Ingelheim and has received research support from Proctor & Gamble Pharmaceuticals.

Obstet Gynecol. 2010;115:839-855. Abstract

Additional Resources

More information on hormone therapy and menopause is available online from the National Heart, Lung, and Blood Institute.

Clinical Context

In the July 17, 2002, issue of the Journal of the American Medical Association, Rossouw and colleagues reported results from the WHI trial that found combined estrogen and progestin therapy vs placebo was associated with increased risk for coronary heart disease in women between the ages of 50 and 79 years. Subsequently, use of hormone treatment decreased. Rossouw and colleagues reanalyzed the data and noted in the April 4, 2007, issue of the Journal of the American Medical Association that the risk for cardiovascular disease was not increased in women between the ages of 50 to 59 years or within 10 years of menopause.

This article reviews the roles of hormone therapy and alternative treatment on vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognition, and mood in menopausal women.

Study Highlights

  • Health concerns during menopause include vasomotor symptoms, including hot flushes and night sweats; urogenital atrophy; osteoporosis; and depression and disordered mood.
  • Vasomotor symptoms:
    • Associated factors are African American ethnicity, high body mass index, smoking, low physical activity, and surgical menopause.
    • The most effective treatment is systemic estrogen therapy.
    • Progestin alone and combined estrogen-progestin therapy are also effective.
    • Alternative treatments are lifestyle changes (cooling body temperature, weight loss, smoking cessation, relaxation, and acupuncture) and prescription medications not yet approved by the Food and Drug Administration (clonidine, paroxetine, venlafaxine, and gabapentin).
    • Nonprescription medications have not been proven to be more effective than placebo.
  • Urogenital atrophy:
    • The recommended treatment is low-dose vaginal estrogen.
    • Long-term treatment effects are unknown.
    • Alternative treatment is a vaginal moisturizer.
    • Incontinence is increased by systemic estrogen therapy and combined estrogen-progestin therapy, but urinary frequency, urgency, and recurrent urinary tract infection are decreased with vaginal estrogen therapy.
  • Osteoporosis:
    • Risk factors are age, Asian or white race, family history, history of fracture, early menopause, prior oophorectomy, low body weight, low calcium and vitamin D intake, smoking, sedentary lifestyle, anovulatory conditions, hyperthyroidism, hyperparathyroidism, chronic renal disease, and systemic corticosteroid use.
    • Hormone therapy with low-dose estrogen or estrogen/progestin therapy increases bone mineral density and decreases fracture risk during treatment but is not recommended solely for osteoporosis.
    • Alternative treatments include bisphosphonates, raloxifene, parathyroid hormone, calcitonin, and alteration of modifiable risk factors.
  • Depression and disordered mood:
    • Hormone therapy for vasomotor symptoms might improve sleep disruption and mood, but the primary treatments are antidepressant medications, psychotherapy, and counseling.
  • Contraindications of hormone therapy use include cardiovascular disease, breast or endometrial cancer, and impaired cognitive function.
  • Cardiovascular disease:
    • Risk factors are age, family history, smoking, obesity, sedentary lifestyle, diabetes, hypertension, and hypercholesterolemia. Combined estrogen-progestin therapy has increased the risk for coronary heart disease.
    • Estrogen therapy in women without a uterus was linked with an increased risk for stroke and venous thromboembolic events and disorders, but not coronary heart disease.
    • Alternative treatments include alteration of modifiable risk factors and treatment of associated conditions.
  • Breast cancer:
    • More than 5 years of combined estrogen-progestin therapy was linked with increased breast cancer risk.
    • Hormone therapy should not be used in women with a history of breast cancer and should be used with caution in women at high risk for breast cancer.
    • Alternatives for women at high risk for breast cancer are tamoxifen or raloxifene, screening mammography, and self-breast examination.
  • Endometrial cancer:
    • Hormone therapy is generally contraindicated but can be considered in highly symptomatic women with a history of early-stage endometrial cancer.
  • Cognitive function:
    • Hormone therapy was associated with a 2-fold increased risk for dementia, most commonly Alzheimer's disease, adverse cognitive effects, and lower scores on the Modified Mini-Mental State Examination.
  • Other contraindications to hormone therapy include active hepatic and gallbladder disease.
  • Regarding ovarian cancer, hormone therapy was linked with no effect, but a small increased risk was observed. Limited data showed that hormone therapy does not appear to affect survival duration in survivors of ovarian cancer.
  • Regarding colorectal cancer, combined estrogen-progestin therapy was linked with a reduced risk, but estrogen in women with a history of hysterectomy had no effect. Hormone therapy is not recommended for prevention of colorectal cancer because of risks of treatment and effectiveness of screening methods.

Clinical Implications

  • Hormone therapy is primarily indicated for healthy menopausal women with vasomotor symptoms, and local estrogen therapy is recommended if only vaginal symptoms are present.
  • The contraindications to hormone therapy in menopausal women are breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver or gallbladder disease.


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