IE 4: Menopause

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42 Terms

1

What is the definition of peri-menopause?

  • Time from which menopause becomes irregular to Final Menstrual Period

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2

What is menopause?

  • Cessation of menstrual bleeding for continuous 12 month period

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3

What are factors that affect the age of onset for menopause?

  • Smoking

  • Genetics

  • Body Size

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4

What are different causes of menopause?

  • Premature (prior to age of 40)

  • Surgical

  • Primary ovarian insufficiency (genetic, metabolic, med related, immune related, related disorders)

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5

What are primary hormones associated for menopause?

  • Estrogen, progesterone, testosterone (ovaries)

  • FSH, LH (pituitary gland which is controlled by hypothalamus)

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6

Aging leads to what?

  • Aging leads to atresia (diminished oocytes) which leads to decreased estradiol concentrations which is detected by pituitary/hypothalamus

    • Significant increase in FSH and LH concentrations are seen as a result

    • Lack of corpus luteum leads to lack of progesterone activity

    • Testosterone productions drops to about half of that of young women in her 20s


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7

What are hallmark symptoms of menopause?

  • Menstrual irregularity (earliest sign)

  • Vasomotor symptoms

    • Hot flushes, night sweats (average duration 7 years, highest in 2 year post-menopause)

  • Breast tenderness/swelling

  • Heavy or irregular bleeding

  • Genitourinary Symptoms of Menopause (GSM)

    • Urogenital atrophy (vaginal dryness, dyspareunia, recurrent UTI, urge/stress incontinence)


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8

What is the other symptoms of Menopause?

  • Sleep disruption (higher in those with VMS)

  • Depressive symptoms

  • Memory loss, difficulty in concentration, decline in cognitive performance

  • Arthralgia


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9

For the diagnosis, what is the STRAW staging system? When is it not useful?

  • Identify a change in bleed pattern and amenorrhea

  • NOT useful if no uterus, hormonal contraceptive use or IUD, or other prior procedures which affect menstrual function

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10

What are alternative methods of diagnosing menopause?

  • Lab testing (FSH, estradiol) – very erratic during transition and limited efficacy in those using contraception

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11

What is the treatment for menopause?

  • Menopausal Hormone Therapy (MHT)

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12

What is the benefit of MHT? What risk-benefit ratio do you consider?

  • Most effective option for VMS and GSM management

  • Women < 60 years of age or within 10 years of menopause onset benefits of treating bothersome symptoms outweigh risks of MHT

  • Risk is greater for heart disease, stroke, VTE, dementia in women not meeting this criteria

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13

During MHT, what therapy is done during the menopause transition?

  • Estrogen alone or estrogen + progestogen therapy during the menopause transition to improve QOL

    • Primary focus on alleviation of VMS and GSM

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14

In MHT, women with an intact uterus should use what?

  • Women with an intact uterus – should use BOTH estrogen and progestogen therapy to prevent unopposed estrogen activity which causes overstimulation of uterine lining and can progress to endometrial hyperplasia and cancer

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15

In MHT, what formulations are available?

  • Multiple formulations and sources available

    • Some patients prefer bioidentical options (estradiol, micronized progesterone)

    • Others appropriate for compounding, allergy considerations, data available


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16

In MHT, estrogen therapy can do what?

  • Estrogen therapy can reduce frequency and severity of VMS (oral agents have been first-line option)

    • Vaginal estrogen formulations are ideal for GSM including prevention of recurrent UTI

    • Vaginal products minimize systemic absorption but provide adequate relief

    • Systemic agents may worsen urinary stress incontinence


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17

Estrogens come in what formulations?

  • Oral, transdermal, vaginal formulations

    • Estradiol (bioidentical) is most common then CEEs (mixtures, NOT bioidentical, but better studied)

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18

What are key considerations of ORAL estrogens?

  • Oral estrogens affected by gut and liver metabolism (possible higher VTE risk due to increased liver clotting factor
    production activity)

  • Oral estrogens may positively impact lipids (lower LDL, increase HDL, but may increase triglycerides)

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19

What are key considerations of transdermal estrogens?

  • Key considerations of transdermal estrogens:

    • Gels, patches, sprays with similar efficacy to oral options

    • First-pass gut/liver metabolism is avoided – decreased VTE risk, less negative impact on triglycerides

    • Consider patient preference when selecting formulation

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20

What are key considerations of vaginal estrogens?

  • Creams, tablets, rings

  • No systemic progestogen needed with typical doses because of lack of systemic absorption of estrogen (except with ring
    because dose is higher) – risk is unknown with high dose usage

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21

What do progestogens do?

  • Protects against endometrial hyperplasia and cancer risk related to unopposed estrogen

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22

What are some key considerations of oral progestogens?

  • Options: MPA, norethindrone, drospirenone, levonorgestrel, micronized progesterone (bioidentical)

  • Consider side effects and risk profile for each agent

    • Drospirenone – anti-aldosterone activity, hyperkalemia risk

    • Micronized progesterone – manufactured in peanut oil

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23

What are key considerations of transdermal progestogens?

  • “OTC” options - lack of evidence, may not meet regulations

  • Combination patches available

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24

What are key considerations of IUD progestogens?

  • LNG-IUD is effective in providing endometrial protection but not an FDA approved option

  • Ideal for those with contraceptive needs or do not tolerate oral or transdermal options


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25

What are alternate options to progestogens and estrogens?

  • Ospemifene (Osphena®)

    • (SERM with selective tissue activity, so no progesterone needed?) – approved for dyspareunia and vaginal dryness and atrophy

    • Intravaginal DHEA – consider if non-estrogen therapy is needed

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26

For other options, what is Tissue-selective estrogen complex (TSEC)+estrogen agonist antagonist (SERM) good for?

  • Good for those who cannot tolerate progestogen therapy but need to oppose estrogen effects to obtain endometrial protection

  • CEE + bazedoxifene (Duavee®)

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27

What is testosterone for in “other options”?

  • Testosterone: interest in low-libido management or sexual dysfunction (patches, creams – no FDA approval, dosing unclear)

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28

For MHT, risk of endometrial cancer is minimized with what?

  • Combo estrogen and progestogen

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29

Progestogens can be continuous or cyclic but what is preferred?

  • Progestogens can be continuous or cyclic, with cyclic preferred if 12 months of amenorrhea have not yet occurred

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30

What is the contraindications to MHT?

  • Undiagnosed vaginal bleeding, treatment of hormone-dependent malignancy, history of estrogen-dependent malignancy, MI, stroke, VTE, dementia, severe liver disease

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31

What is a significant issue in post menopausal women? How can MHT help and what is its place in therapy?

  • Osteoporosis is a significant issue for post-menopausal women

  • MHT reduces bone turnover, increases BMD, and decreases hip fracture rates

  • Despite benefits, these are NOT considered first line therapy for osteoporosis treatment or prevention due to other risks
    of MHT

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32

Sleep improvements is based on reduction of what?

  • VMS and GSM

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33

Mood data is mixed but studies show slight effects of what on those on MHT?

  • Mood data is mixed but some studies show slight anti-depressant and anti-anxiety effects in those on MHT


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34

Oral estrogen therapy is associated with what risk increase? Transdermal estrogen is what risk compared to oral

  • VTE and stroke – oral estrogen therapy associated with two fold increase in risk of VTE (compounds further with additional risk factors)

    • Transdermal estrogen VTE risk is lower than that of oral, but should generally avoid estrogen therapy in high risk patients

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35

Breast cancer risk is driven by what?

  • Breast cancer – primarily driven by progestogen use based on data, but risk for individual women is still low overall.

    • Limit use/duration of MHT and stick to lowest doses possible to manage symptoms


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36

How often should treatment be reassessed for MHT?

  • Treatment should be individualized and risk-benefits should be reassessed annually (regardless of age)

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37

Recurrence of sx may occur to how many people with MHT d/c?

  • Recurrence of symptoms may occur in up to 50% of women with MHT discontinuation

    • No ideal regimen for discontinuation (abrupt or tapered)

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38

VMS improvements is seen when after initiating MHT? What time range is needed for full impact assessment? How long does it take to follow up?

  • VMS improvement seen often after 2-6 weeks of initiating MHT, but 8-12 weeks needed for full impact assessment

  • Follow-up every 1-2 months and annual evaluation is strongly encouraged


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39

When do you consider non-hormonal treatment? What are they?

  • Pts with contraindications to MHT

    • SSRI/SNRI – effective alternatives for reduction of hot flushes and improve mood disorders

      • Best data for citalopram, escitalopram, desvenlafaxine, paroxetine (FDA approval)

      • Avoid paroxetine with tamoxifen due to DDI which prevents conversion of tamoxifen to active metabolite (CYP2D6 inhibition)

    • Gabapentin and pregabalin

      • Small studies, some efficacy in VMS reduction

    • Clonidine

      • Elevates the “flush threshold” and can reduce symptoms, but less effective than previous options


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40

What are the non-pharm and complementary options?

  • 40-50% of women in western countries use herbs, supplements, acupuncture, relaxation, massage, etc. to address menopausal symptoms

    • Phytoestrogens (isoflavones) – theoretically an option

    • Black cohosh – evaluate liver function first, data is mixed

  • Avoidance of triggers (spicy foods, alcohol, hot foods/liquids)

  • Recommend cooling techniques for hot flushes or lubrication for painful intercourse or vaginal dryness

  • Yoga – good data for overall reduction compared to no intervention

  • Aerobic exercise – mixed data


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41

For management of perimenopause, contraceptive management can be used if what?

  • If contraceptive efficacy is needed

    • MHT alone is not effective for pregnancy prevention

    • Can transition patient to MHT once contraception no longer needed

    • Preferred option is CHC or LNG-IUD

      • Sx can continue to be managed by adding low dose supplemental estrogen during “pill-free week” or extended cycle dosing

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42

What are key patient education points?

  • Patients should understand the goal of treatment of menopausal symptoms is to improve quality of life

    • choice to treat or not to treat symptoms is an individual one

  • Women should be informed of the evidence-based benefits and risks of MHT so that they can make a decision
    based on factual data

  • An overview of multiple MHT options and formulations should be given so that therapy plan can be customized
    based on patient characteristics, comorbidities, and preferences

  • Patients should also be informed of non-hormonal and non-pharmacologic treatment options for menopausal
    symptoms


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