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Hormonal Replacement Therapy (HRT) for Menopause and Perimenopause

General Information

eneral Informationeneral Information


  • natural menopause is a physiologic event characterized by loss of ovarian activity and permanent cessation of menses, diagnosed after 12 consecutive months of amenorrhea without a pathological cause
  • menopause may also be induced by surgery, chemotherapy, or radiation, with sudden onset in these circumstances (18313505Lancet 2008 Mar 1;371(9614):760)
  • perimenopause (the menopausal transition) defined as the beginning of the physiologic changes leading to ovarian failure in the years preceding the final menstrual period2

Menopausal symptoms

  • symptoms associated with menopausal transition may vary in duration and severity, and include vasomotor symptoms and urogenital symptoms1,2
  • vasomotor symptoms2
    • reported in 50%-82% of women with natural menopause in United States
    • symptoms include
      • hot flashes, characterized by
        • sudden sensation of heat in the upper body
        • perspiration
        • flushing
        • chills
        • clamminess
        • anxiety
        • heart palpitations
      • night sweats
      • sleep disturbances
    • risk factors for vasomotor symptoms1,2
      • lack of exercise
      • maternal history of vasomotor symptoms
      • menopause at < 52 years old
      • induced menopause
    • Study Summary
      hot flashes and night sweats in > 50% of perimenopausal women
      • based on cross-sectional study Cross-Sectional Study
      • 342 women aged 40-55 years completed self-reported survey
        • 133 women were premenopausal
        • 72 were perimenopausal
        • 46 were postmenopausal
      • hot flashes in
        • 28.6% of premenopausal women
        • 58.8% of perimenopausal women
        • 60.5% of postmenopausal women
      • night sweats in
        • 18.2% premenopausal women
        • 54.4% perimenopausal women
        • 32.6% postmenopausal women
      • PubMed16148247The Journal of the American Board of Family Practice20050901J Am Board Fam Pract185374374 Reference - 16148247J Am Board Fam Pract 2005 Sep-Oct;18(5):374full-text
    • symptom severity
      • Study Summary
        sedentary lifestyle associated with more severe menopausal symptoms
        • based on cohort study Cohort Study
        • 6,079 women aged 40-59 years were evaluated by Menopause Rating Scale (MRS), Goldberg Anxiety and Depression Scale, and Athens Insomnia Scale
        • sedentary lifestyle defined as < 3 weekly 30-minute periods of physical activity
        • compared to nonsedentary women, sedentary women had more severe menopausal symptoms as indicated by higher
          • MRS scores
            • total (p = 0.0001)
            • somatic subscale, including hot flushes/sweating, heart discomfort, sleep problems, and muscle and joint problems (p = 0.0001 for all)
            • psychological subscale, including depression, irritability, anxiety, and mental and physical exhaustion (p = 0.0001 for all)
            • urogenital subscale, including sexual and bladder problems, and vaginal dryness (p = 0.0001 for all)
          • Goldberg depression scores (p = 0.001)
          • Goldberg anxiety scores (p = 0.007)
          • Athens Insomnia scores (p = 0.001)
        • PubMed26818013Menopause (New York, N.Y.)20160501Menopause235488488 Reference - 26818013Menopause 2016 May;23(5):488
      • Study Summary
        current smoking associated with increased risk of moderate-to-severe hot flashes
        • based on cross-sectional study Cross-Sectional Study
        • 1,087 women aged 40-60 years were evaluated by questionnaire
        • 56% of women reported having hot flashes
        • current smoking associated with
          • increased risk for moderate-to-severe hot flashes (adjusted odds ratio [OR] 1.9, 95% CI 1.3-2.9)
          • increased risk for daily hot flashes (adjusted OR 2.2, 95% CI 1.4-3.7)
        • PubMed12576249Obstetrics and gynecology20030201Obstet Gynecol1012264264 Reference - 12576249Obstet Gynecol 2003 Feb;101(2):264
      • factors associated with persistence of vasomotor symptoms over time in cohort study
        • 1,449 women with frequent vasomotor symptoms (≥ 6 days in the previous 2 weeks) during the menopause transition evaluated
        • median total vasomotor symptom duration 7.4 years
        • factors associated with longer duration of vasomotor symptoms included
          • African American ethnicity
          • being pre- or perimenopausal at first report of vasomotor symptom onset
          • having greater perceived stress and symptom sensitivity, or higher depressive symptoms and anxiety at first report of vasomotor symptom onset
        • Reference - cxh102028875pmdc25686030pJAMA Intern Med 2015 Apr 1;175(4):531, editorial can be found in cxh102028876pmdc25686269pJAMA Intern Med 2015 Apr 1;175(4):540
  • urogenital symptoms2
    • reported in 10%-40% of women
    • symptoms include
      • atrophic vaginitis, characterized by
        • vaginal dryness
        • discharge
        • itching
        • dyspareunia
      • sexual dysfunction



General references used

  1. Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE; American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause. Endocr Pract. 2011 Nov-Dec;17 Suppl 6:1-25PDF, executive summary can be found in Endocr Pract 2011 Nov 1;17(6):949
  2. American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol. 2014 Jan;123(1):202-16, correction can be found in Obstet Gynecol 2016 Jan;127(1):166
  3. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015 Nov;100(11):3975-4011

Recommendation grading systems used

  • American Association of Clinical Endocrinologists (AACE) guideline grading system
    • grades of recommendation
      • Grade A - best evidence level 1, or best evidence level 2 but adjusted upwards for positive subjective factors
      • Grade B - best evidence level 2, or best evidence level 1 adjusted downwards for negative subjective factors, or best evidence level 3 adjusted upwards for positive subjective factors
      • Grade C - best evidence level 3, or best evidence level 2 adjusted downwards for negative subjective factors, or best evidence level 4 adjusted upwards for positive subjective factors
      • Grade D - best evidence level 4, or best evidence level 3 adjusted downwards for negative subjective factors, or < two-thirds consensus (regardless of evidence level)
    • levels of evidence
      • Level 1 - randomized trials or meta-analysis of randomized trials
      • Level 2 - nonrandomized controlled trial, prospective cohort study, retrospective case-control study, or meta-analysis of these types of studies
      • Level 3 - cross-sectional study, surveillance study, consecutive case series, or single case reports
      • Level 4 - no evidence (theory, opinion, consensus, review, or preclinical study)
  • American College of Obstetricians and Gynecologists (ACOG) levels of recommendation
    • Level A - recommendations based on good and consistent scientific evidence
    • Level B - recommendations based on limited or inconsistent scientific evidence
    • Level C - recommendations based primarily on consensus and expert opinion
    • Reference - ACOG Practice Bulletin 141 on management of menopausal symptoms (24463691Obstet Gynecol 2014 Jan;123(1):202)
  • Endocrine Society uses Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system
    • strength of recommendation
      • Strong recommendation - guideline panel members have high confidence that desirable effects of recommendation outweigh undesirable effects (or vice versa)
      • Weak recommendation - guideline panel members conclude with less confidence that desirable effects of recommendation probably outweigh undesirable effects, or benefits and harms are finely balanced, or appreciable uncertainty
    • quality of evidence
      • High-quality evidence - consistent evidence from well-performed randomized controlled trials, or exceptionally strong evidence from unbiased observational studies
      • Moderate-quality evidence - randomized controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise evidence), or unusually strong evidence from unbiased observational studies
      • Low-quality evidence - ≥ 1 critical outcome from observational studies, randomized controlled trials with serious flaws, or indirect evidence
      • Very low-quality evidence - ≥ 1 of the critical outcomes from unsystematic clinical observations or very indirect evidence

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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T913525, Hormonal Replacement Therapy (HRT) for Menopause and Perimenopause; [updated 2018 Nov 30, cited place cited date here]. Available from Registration and login required.

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