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Menopause Flashcards

1
Q

Define natural menopause

A

The permanent cessation of menses of 1 year’s duration secondary to lack of estrogen production by the ovaries

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2
Q

Define perimenopause (menopause transition)

A

The time period prior to menopause which is characterized by menstrual cycle irregularity, increased frequency of anovulatory cycles, & symptoms similar to menopause

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3
Q

What age is early menopause?

A

Early menopause = before age 45

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4
Q

What age is premature menopause?

A

Premature = before age 40

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5
Q

What age is primary ovarian insufficiency (POI)?

A

POI = before 40, but can still have irregular or transient menstruation

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6
Q

True or False? If menopause is premature/early then it is not recommended to try to restore estrogen levels.

A

False - restoring estrogen levels until natural age of menopause is recommended to help prevent some complications - may require higher doses of estrogen (also Ca, Vit D, exercise, follow-ups)

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7
Q

What are some factors which MAY precipitate earlier onset of menopause? (4)

A
  1. Smoking
  2. Exposure to toxins
  3. Chemotherapy
  4. Hysterectomy
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8
Q

Go through the hormonal changes seen throughout the years that leads to menopause.

A
  1. During the reproductive years, E and P levels rise & fall with cycles, as FSH promotes follicle development and ovum release.
  2. There is an age related decrease in # and quality of ovarian follicles; by menopause few/none remain.
  3. As a result, ovarian secretion of estradiol ceases & ovulation does not occur, so P concentrations also remain low.
  4. The pituitary increases FSH and LH in an attempt to initiate follicle development, but the ovaries cannot respond.
  5. End result: the ovaries cease to secrete estradiol & progesterone.
  6. This can be a slow, progressive decline over years, or a dramatic drop at once.
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9
Q

How is estrogen produced pre-menopause?

A

Mainly by the ovaries (as 17 beta-estradiol). However, other sites can produce smaller amounts of estrogen through the conversion of androgens.

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10
Q

How is estrogen produced post-menopause?

A
  • Estrogen production decreases to ~10% of premenopausal levels.
  • The primary estrogen is estrone, which has ~ 1/3 estrogenic potency of estradiol.
  • It is produced in adipose tissue via conversion of androstenedione.
    – Androstenedione –> estrone –> estradiol
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11
Q

What are the main symptoms/groups of symptoms of menopause? (5)

A
  1. Vasomotor symptoms
  2. Sleep pattern changes
  3. Mood and cognition changes
  4. Genitourinary changes
  5. Bleeding changes
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12
Q

How do vasomotor symptoms mainly present? When and how long?

A
  • Hot flashes and night sweats.
  • Begin pre-menopause, max prevalence in 1st 2 years post-menopause.
  • On average, VMS persist for 7-8 years.
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13
Q

How are hot flashes characterized?

A
  1. The sudden onset of intense warmth that begins in the chest and may progress to the neck and face.
  2. Often accompanied by visible red flushing.
  3. May also be accompanied by anxiety, palpitations, and profuse sweating.
  4. Are typically episodic and last, on average, for 4 minutes.
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14
Q

What (might) be some causes for hot flashes?

A
  1. Appears to be due to a narrowing of the thermoregulatory system caused by changes in estrogen levels.
  2. Postmenopausal women are thought to have narrowing of their “thermoneutral zone” - small changes in temp can stimulate the regulatory response of sweating or shivering.
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15
Q

What are some risk factors for hot flashes?

A
  1. Less physical activity
  2. Family history/genetics
  3. Age of onset
  4. Induced menopause
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16
Q

What are the 3 groups of treatment options for vasomotor symptoms (VMS)?

A
  1. CBT
  2. Menopausal Hormonal Therapy (MHT)
    - Estrogen
    - Estrogen + progestogen
    - Estrogen + bazedoxifene
    - Tibolone
  3. Nonhormonal therapy (Lifestyle management in there too)
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17
Q

While lifestyle modifications don’t have a whole lot of evidence for VMS, they are still okay to try. What are some examples to try/suggest?

A
  1. Cooling techniques - Fans, A/C, cool drinks
  2. Avoidance of triggers - Caffeine, alcohol, spicy foods
  3. Exercise, yoga, relaxation training - May improve overall well-being
  4. Weight loss in those who have extra weight
  5. Smoking cessation
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18
Q

When is estrogen therapy (ET) used alone for VMS? When is ET used in combination with a progestogen (EPT)?

A
  1. Estrogen therapy (ET) is used alone for VMS if women have had a hysterectomy.
  2. In those who have a uterus, it is used in combination with a progestogen (EPT).
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19
Q

The most effective treatment options for VMS are?

A

Estrogen therapy and EPT

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20
Q

Why must estrogen be combined with progestogen in women with a uterus? How should P be dosed?

A
  1. Unopposed ET for 3 years is associated with a 5-fold increased risk of endometrial hyperplasia or cancer.
  2. Use P for a minimum of 12-14 days/month, & match the dose of the P to the dose of the E.
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21
Q

What are the 2 main estrogen (and combo products) dosage forms for VMS?

A
  1. Oral
  2. Transdermal - patch or gel
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22
Q

How long is onset of symptom control of VMS when on ET/EPT?

A
  • As little as 2 weeks for some, up to 8 weeks for others.
  • Assess for response at 4 weeks at standard dose and 6-12 weeks for lower doses.
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23
Q

Estrogen: transdermal vs. oral. What are the differences to be aware of in terms of efficacy and ADEs/benefits (if any)?

A
  • Are similarly effective for vasomotor sx’s.
  • Appear to provide same protection on BMD.
  • There are some potential benefits to use of a transdermal estrogen:
    – Avoids first pass effect, so less nausea, less headache, less of an effect on TGs.
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24
Q

What is the potential ADE of micronized progesterone?

A

May cause drowsiness, especially when taken with food

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25
Q

What are the advantages of micronized progesterone vs. medroxyprogesterone acetate (MPA)?

A

Observational data shows it has a lower risk of VTE and breast cancer

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26
Q

What is tibolone?

A

A synthetic steroid analogue of norethynodrel (a progestogen), which is metabolized in the body to make 3 substances that act like E, P, and A (androgen) – it has weak activity (DOES NOT CONTAIN ACTUAL HORMONES)

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27
Q

When is tibolone indicated?

A

Indicated for short-term tx of VMS in menopausal women with an intact uterus

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28
Q

What if contraception is desired in women experiencing VMS?

A
  1. Low dose CHC (pill, patch, or ring)
  2. Estrogen + LNG-IUS
  3. MHT + barrier
  4. Nonhormonal treatment option + progestogen-only contraceptive
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29
Q

When can hormonal contraceptives be used in menopause?

A

Safe to use in the perimenopausal period when contraception is required, but do not use once in menopause as the daily dose of ethinyl estradiol (e.g. 20 μg) is 4-5x times higher than the low-standard dose required for symptom relief and bone benefit (e.g. 1mg estradiol)

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30
Q

What are bioidentical hormones?

A
  1. Plant-derived hormones structurally identical to what is naturally produced in the body.
    Examples:
    - Oral and transdermal 17 B-estradiol & micronized progesterone (commercially available pharma products)
    - Biest (20% estradiol/80% estriol) – compounded product
  2. Compounded products may contain a mix of estradiol, estrone, estriol, DHEA, testosterone, progesterone.
  3. Neither is more ‘natural’ than the other – they still need to be converted through a synthetic process to mimic body’s hormones.
  4. Bioidentical hormones – whether from pharma or compounded pharmacist – contain the same ingredients.
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31
Q

What do those in favour of compounded BHT say?

A
  1. ‘Safe and natural’ (generally a marketing advantage)
  2. ‘Custom-made’ based on salivary, serum, urine hormone level testing
  3. Can compound in many different delivery routes (e.g. troches, subdermal implants)
  4. Still require a written Rx.
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32
Q

What do the detractors of compounded BHT say?

A
  1. Individualized testing not necessary as not narrow TI meds. Hormone testing is unreliable.
  2. The desired levels of hormones have not been established and may not correlate with symptoms.
  3. Products have variable potency which could result in under/over-dosing – don’t adhere to strict FDA-mandated potency tests that Rx products do (PK/PD testing).
  4. Lack safety / efficacy data.
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33
Q

What are the EPT dosing regimens?

A
  1. Estrogen is taken continuously every day.
  2. Progestogens can be taken:
    - Continuously every day, or…
    - Cyclically for 12-14 days per month
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34
Q

What are the main advantages of continuous combined EPT?

A
  1. Easy to remember
  2. Avoids the withdrawal bleeding
  3. Decreases risk the most for endometrial hyperplasia
35
Q

What are the potential side effects of continuous combined EPT?

A

Unpredictable bleeding may occur; 40% have irregular breakthrough bleeding in 1st 6 months; 20% by 1 year

36
Q

In what situation might continuous E + cyclic P be preferred?

A
  1. Prefer fewer pills
  2. Recent menopausal who do not want breakthrough bleeding
37
Q

What are the common ADEs of estrogen?

A
  1. Nausea
  2. Breast tenderness
  3. Headache
  4. Bloating
  5. Vaginal bleeding is common in 1st 3-6 months
38
Q

What are the common ADEs of progestins?

A
  1. Irritability
  2. Breast tenderness
  3. Bloating
  4. Headache
  5. ‘PMS-like symptoms’: mood swings, bloating, fluid retention, sleep disturbance, decreased libido, weight gain
  6. Vaginal bleeding is common in 1st 3-6 months
39
Q

How to manage common ADEs of estrogen and/or progestins?

A
  1. Often dose-related
  2. Change products
40
Q

What are the contraindications of MHT?

A
  1. Unexplained vaginal bleeding
  2. Active liver dx
  3. Estrogen-dependent cancer
  4. Pregnancy
  5. Active thromboembolic dx (e.g. DVT, PE, stroke, MI)
  6. Untreated / uncontrolled CVD
41
Q

What is the caution for using MHT?

A

High cancer risk

42
Q

When to consider non-oral estrogen?

A
  1. Hypertriglyceridemia
  2. Hepatobiliary disease
  3. Migraine
  4. Established CVD
  5. Past VTE
  6. Diabetes
  7. Advanced age and no previous MHT
43
Q

What are the SSRIs and SNRIs that can be used for VMS symptoms?

A
  1. Paroxetine
  2. Citalopram
  3. Escitalopram
  4. Venlafaxine
  5. Desvenlafaxine
44
Q

True or False? SSRIs/SNRIs used for VMSs act quicker than they would for depression.

A

True (2-4 weeks)

45
Q

Veozah (fezolinetant) is a new non-hormonal drug for VMS. What is the MOA?

A

Nonhormonal selective neurokinin 3 receptor antagonist

46
Q

What are some ‘other’ nonhormonal drugs that can be used for VMS?

A
  1. Clonidine
  2. Oxybutynin
  3. Gabapentin
  4. Pregabalin
47
Q

What are 2 herbal products that might have some decent evidence for VMS?

A
  1. Black cohosh
  2. Isoflavones
48
Q

What to know about osteoporosis and menopause?

A

Post-menopause, estrogen deficiency causes accelerated bone loss by increasing bone turnover & resorption

49
Q

Estrogen therapy, menopause, and osteoporosis. When should hormone therapy be used if at all?

A
  1. Estrogen therapy can reduce fracture risk at various sites by 24% to 39% in postmenopausal women.
  2. Indicated for prevention of osteoporosis only – not treatment.
  3. Effects on bone protection are dose-related BUT IF NO VMS THEN SHOULD NOT BE ON HORMONE THERAPY FOR OSTEOPOROSIS ONLY.
50
Q

What effects on LDL, HDL, and triglycerides do the following have:
1. Estrogen oral
2. Estrogen topical
3. MPA daily or cyclical
4. Micronized progesterone daily or cyclical

A

Estrogen Oral:
- Decrease LDL
- Increase HDL
- Increase TG
Estrogen Topical
- Decrease LDL
- Increase HDL
- Neutral TG
MPA daily or cyclical
- Blunt good lipid effects of estrogen
Micronized
- Lipid friendly

51
Q

What effects on LDL, HDL, and triglycerides do the following have: Estrogen topical?

A

Estrogen Topical:
- Decrease LDL
- Increase HDL
- Neutral TG

52
Q

What effects on LDL, HDL, and triglycerides do the following have: MPA daily or cyclical?

A

MPA daily or cyclical:
- Blunt good lipid effects of estrogen

53
Q

What effects on LDL, HDL, and triglycerides do the following have: Micronized progesterone daily or cyclical?

A

Micronized:
- Lipid friendly

54
Q

What are the effects of estrogen on the CV system with short-term use?

A

Causes vasodilation

55
Q

What are the effects of estrogen on the CV system with long-term use?

A
  1. Decreases LDL, increases HDL
  2. Lowers fibrinogen
  3. Lowers plasminogen-activator inhibitor type 1
    Countering this is its effect on inflammation (measured by CRP) and on markers of thrombosis
56
Q

What to know about hormone therapy and CVD/CHD risk?

A

Multiple observational studies, meta-analysis suggest that the use of HT in younger women (<60yo) within 10 years since menopause has a beneficial effect on reducing CVD, or at very least does not increase.

57
Q

What are the effects of long-term hormone therapy?

A
  1. Decreases LDL, increases HDL
  2. Lowers fibrinogen
  3. Lowers plasminogen-activator inhibitor type 1
    Countering this is its effect on inflammation (measured by CRP) and on markers of thrombosis.
58
Q

What do multiple studies suggest about hormone therapy (HT) in younger women?

A

HT in younger women (<60yo) within 10 years since menopause has a beneficial effect on reducing CVD, or at very least does not increase CHD risk.

59
Q

What is the timing hypothesis of HT and CHD risk?

A

In younger (<60yo) healthy women & <10yrs since menopause transition, there is no increased CHD risk. If ≥10yrs post menopause or >60yo: increased risk of CHD, VTE, and stroke vs. earlier initiation.

60
Q

Is there a link between MHT and stroke?

A
  • No increased risk with MHT if initiated <10 years and <60yo.
  • Higher incidence if initiated later.
61
Q

What is the link between MHT and VTE?

A
  1. Increased risk regardless of <10 years or >10 years (although higher in older starters).
  2. Address risk factors for stroke and DVT before deciding to initiate HT.
62
Q

What is the relationship between HT and breast cancer?

A

Risk increases with longer duration. Studies are lacking with regard to breast cancer risk with long term use. In women with prior breast cancer history, systemic HT is not generally advised.

63
Q

What is the duration of treatment of HT in VMS?

A

No clear answer, it is highly individualized. Reassess ~yearly to see if the person still requires treatment.

64
Q

How to manage insomnia/sleep disorders due to menopause?

A
  1. General insomnia recommendations: CBT, valerian, hypnotics, antidepressants.
  2. MHT may help in those also experiencing VMS.
65
Q

What effects on brain function does estrogen have?

A
  1. Positive effect on serotonergic activity.
  2. Increases the activity of NA.
  3. E receptors located in regions of brain responsible for learning and memory.
  4. Increases cerebral blood flow.
66
Q

How does estrogen therapy affect mood?

A
  1. Some studies show ET improving depressive symptoms in perimenopausal women (but not late menopausal), and it may augment the clinical response to SSRIs.
  2. The use of antidepressants and psychotherapy (CBT) remains the mainstay of treatment for mood disorders and anxiety.
67
Q

Is hormone therapy recommended for cognition and dementia?

A

HT is not recommended to preserve cognitive function or prevent/treat dementia. Further, initiation >65 years may increase the risk.

68
Q

What changes occur due to decreased estrogen in the vagina, vulva, urethra, and bladder?

A
  1. Tissue atrophy.
  2. Reduced secretions.
  3. Reduced blood flow.
  4. Vaginal pH increases to 6-8 (premenopause 4.5 - 5).
  5. A decrease in E in addition to normal tissue aging can result in vaginal symptoms.
69
Q

What is genitourinary syndrome of menopause (GSM)?

A

GSM refers to the signs/symptoms resulting from E deficiency on the genitourinary tract.

70
Q

What are the common symptoms of GSM?

A
  1. Vaginal dryness.
  2. Vaginal itching / irritation.
  3. Burning.
  4. Painful intercourse.
  5. Lower urinary tract symptoms: (urinary frequency, urgency, UTIs).
  6. Nocturia, dysuria.
71
Q

What are the first-line treatments for GSM?

A

1st-Line: Non-hormonal lubricants (OTC).
A. Lubricants: Use with intercourse.
- Water-based: Astroglide, K-Y Jelly.
- Silicone-based: Astroglide X, K-Y Intrigue.
- Oil-based: Olive oil.
B. Moisturizers: Use regularly (2-3 times weekly).
- Goal is to reduce daily symptoms and make intercourse comfortable.
- Replens (polycarbophil gel), Gynatrof, RepaGyn (hyaluronic acid), K-Y SILK-E.

72
Q

What is the next option if OTC agents are ineffective for GSM?

A

Vaginal estrogen preparations - Minimal systemic absorption so less concerns with use. Don’t need accompanying progestogen.

73
Q

What are the types of local vaginal estrogen products?

A
  1. Vaginal creams.
  2. Vaginal ring.
  3. Vaginal tablets.
  4. Vaginal softgel inserts.
74
Q

What are the common side effects for all of the local vaginal products?

A
  1. Local burning/irritation.
  2. Leakage.
75
Q

Is there a difference in efficacy between the local vaginal products?

A

Similar for all.

76
Q

When might improvement be seen when using a local vaginal product?

A

See improvement in a few weeks - up to 12 weeks for max benefit. Assessed at 3-6 months, then yearly typically.

77
Q

Might we use systemic estrogen therapy for GSM?

A
  1. If someone is also experiencing VMS, then oral MHT would be trialed as in addition to helping the VMS symptoms, it will also help with the GSM symptoms as well.
  2. ~10-15% of women will still experience GSM symptoms while on systemic MHT, so systemic and intravaginal ET may be used together.
78
Q

What is a non-hormonal agent to treat GSM?

A

Prasterone - Is a synthetic form of DHEA (dehydroepiandrosterone) that has no estrogenic (E) or androgenic (A) activities. However, when administered intravaginally, the cells in the vagina convert it into E and A where they act locally, thus avoiding exposure of other tissues to these hormones.

79
Q

What is the potential oral treatment for GSM and how does it work?

A

Ospemifene - Is a nonhormonal SERM. Has weak agonist effects in the endometrium, activates estrogenic pathways in vulvar and vaginal tissues and bone, and blocks pathways in breast (antagonist). Is not co-administered with a progesterone.

80
Q

What to know about weight gain and menopause and MHT?

A

During menopause transition: avg. weight gain of 1.5lbs/yr – this is due to a decreased resting metabolic rate that occurs with aging (change in fat-to-lean body mass ratio) – not MHT.

81
Q

What to know about skin changes in menopause?

A

Soon after menopause, skin collagen content, thickness, and elasticity decline.

82
Q

What is abnormal uterine bleeding (AUB)?

A
  1. AUB (irregular menstrual cycles) is common during the menopause transition period.
  2. Prolonged cycle intervals as well as variable bleeding patterns precede eventual amenorrhea and menopause.
83
Q

What are some potential causes of abnormal uterine bleeding (AUB)?

A
  1. Dysfunctional uterine bleeding (DUB) which results from anovulation.
  2. Endometrial hyperplasia and cancer.
  3. Benign lesions (endometrial polyps).
84
Q

How is AUB treated?

A
  1. Treatment is aimed at regulating bleeding patterns.
  2. Low dose OCPs (20ug EE).
  3. Progestin therapy - Can be given intermittently or continuously.

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