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ACOG Pub Review > PB#141: Management of Menopausal Symptoms > Flashcards

PB#141: Management of Menopausal Symptoms Flashcards

1
Q

Clinical definition of menopause

A

1 year since LMP, representing permanent cessation of menstruation that occurs after loss of ovarian activity

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2
Q

Median age of menopause

A

51 y/o

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3
Q

Terms referring to years preceding FMP associated w/ physiologic changes and clinical sxs (3)

A

Perimenopause, climacteric, menopausal transition

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4
Q

Physiologic process of menopausal transition

A

Fluctuations in hormone levels as ovarian function begins to slow down > serum levels of estradiol and progesterone decreasing and FSH increasing > physiologic changes/clinical sxs

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5
Q

Definition of hot flush

A

Sudden sensation of extreme heat in upper body (particularly face/neck/chest), typically lasting 1-5 mins

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6
Q

Associated characteristics of a hot flush (6)

A

Perspiration, flushing, chills, clamminess, anxiety, (occasionally) heart palpitations

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7
Q

Possible association of vasomotor sxs on sleep

A

Chronic sleep disruption

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8
Q

Percentage of pts who experience hot flushes on daily basis; percentage of pts who experience >10 episodes per day

A

87%; ~33%

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9
Q

Reported median duration of hot flush sxs

A

4-10.2 years

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10
Q

Why do hot flushes occur in perimenopause?

A

Thermoregulatory zone is narrowed and becomes more sensitive to subtle changes in core body temp > small increases in temp trigger themoregulatory mechanisms > sensation of hot flush (vasodilation, sweating, decreased skin resistance)

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11
Q

Central physiologic mechanisms that play a role in vasomotor sxs (5)

A

Serotonergic, noradrenergic, opioid, adrenal, autonomic

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12
Q

Has a genetic predisposition to vasomotor sxs been identified?

A

Yes, based on several polymorphisms related to sex steroid metabolism

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13
Q

General frequency of reported vasomotor sxs by race

A

Black pts reported most vasomotor sxs, Asian pts reported fewest vasomotor sxs

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14
Q

Theories for racial variations in vasomotor sx reporting (4)

A

Genetic factors, physiologic differences, diets varying in soy products, cultural perceptions/reporting differences

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15
Q

Do vasomotor sx frequency vary by BMI?

A

Yes, more common in obese pts

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16
Q

Environmental factors related to vasomotor sxs (3)

A

Mood sxs (ie depression/anxiety), low SES, smoking

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17
Q

General cause of vaginal atrophy

A

Direct consequence of hypoestrogenic state associated w/ menopause > anatomic/physiologic changes in genitourinary tract

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18
Q

Percentage of pts who will experience at least 1 sx of vaginal atrophy

A

10-40%

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19
Q

Sxs associated w/ vaginal atrophy (4)

A

Vaginal/vulvar dryness, discharge, itching, dyspareunia

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20
Q

Histologic/Physiologic changes that lead to vaginal atrophy (4)

A

Loss of superficial epithelial cells in genitourinary tract (causing thinning of tissue), loss of vaginal rugae and elasticity (causing narrowing/shortening of vagina), increased fragility of epithelial tissue (which may cause tearing/bleeding/fissures), loss of subQ fat in labia major

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21
Q

Anatomic changes that occur w/ vaginal atrophy (3)

A

Narrowing of introitus, fusion of labia minora, shrinking of clitoral prepuce/urethra

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22
Q

Changes to vaginal pH associated w/ menopause; clinical result

A

Vaginal pH becomes more alkaline, altered vaginal flora and increased risk of urogenital infection

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23
Q

What happens to vaginal secretions during menopause?

A

Secretions (largely transudate from vaginal vasculature) may decrease

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24
Q

Effects of vaginal atrophy on sexual function

A

Measures of sexual dysfunction seen at higher rates in pts w/ vaginal atrophy

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25
Q

Most effective tx for vasomotor sxs related to menopause

A

Systemic HRT (w/ estrogen alone or in combo w/ progesterone)

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26
Q

Standard dose of conjugated estrogen (+/- progestin), is evidence of benefit demonstrated, is it FDA approved; low dose of conjugated estrogen (+/- progestin), is evidence of benefit demonstrated, is it FDA approved?

A

0.625mg daily, evidence of benefit demonstrated, FDA approved; 0.3-0.45mg daily, evidence of benefit demonstrated, FDA approved

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27
Q

Standard dose of micronized estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved; low dose of micronized estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved; ultra-low dose of micronized estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved?

A

1mg daily, evidence of benefit demonstrated, FDA approved; 0.5mg daily, evidence of benefit demonstrated, FDA approved; 0.25mg daily, evidence of benefit mixed, not FDA approved

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28
Q

Standard dose of transdermal estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved; low dose of transdermal estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved; ultra-low dose of transdermal estradiol-17beta (+/- progestin), is evidence of benefit demonstrated, is it FDA approved?

A

0.0375-0.05mg daily, evidence of benefit demonstrated, FDA approved; 0.025mg daily, evidence of benefit demonstrated, FDA approved; 0.014mg daily, evidence of benefit mixed, not FDA approved

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29
Q

Dose of conjugated estrogen + bazedoxefine, is evidence of benefit demonstrated, is it FDA approved?

A

Conjugated estrogen 0.45mg daily + bazedoxefine 20mg daily, evidence of benefit demonstrated, FDA approved

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30
Q

Percent reduction in frequency of weekly hot flushes associated w/ PO estrogen +/- progestin; OR reduction in severity of hot flushes associated w/ PO estrogen +/- progestin

A

75%; OR = 0.13

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31
Q

OR reduction in severity of self-reported vasomotor sxs associated w/ estrogen alone; OR reduction in severity of self-reported vasomotor sxs associated w/ estrogen + progestin

A

OR = 0.42; OR = 0.38

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32
Q

Routes that estrogen +/- progestin can be administered (2)

A

PO, transdermally (via patch/gel/spray)

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33
Q

Potential adverse effects associated w/ standard doses of HRT (4)

A

Breast tenderness, VB, bloating, HAs

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34
Q

General HRT regimens associated w/ better adverse effect profiles

A

Low dose and ultra-low dose regimens

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35
Q

Lowest dosage of PO estradiol found to be effective in treating hot flushes

A

0.5mg daily

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36
Q

General principle for treating vasomotor sxs w/ HRT

A

Lowest effective dose for shortest duration needed to relieve sxs

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37
Q

Longterm risks of systemic combo HRT (2)

A

VTE, breast cancer

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38
Q

Adverse outcomes w/ slightly increased risks associated w/ 5 years of combined HRT, per WHI (4)

A

Breast cancer, coronary heart disease, stroke, VTE

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39
Q

Improved outcomes associated w/ 5 years of combined HRT, per WHI (2)

A

Decreased risk of fractures, decreased risk of colon cancer

40
Q

Adverse outcome w/ increased risk associated w/ 5 years of estrogen only, per WHI

A

VTE (no increased risk of CV events or breast cancer seen)

41
Q

Poss improved outcome associated w/ HRT in pts <60 y/o and within 10 years of menopause, per WHI reanalysis

A

Cardioprotective effects (though HRT should not be used for primary/secondary heart disease prevention)

42
Q

Route of estrogen that has lower risk of VTE

A

Transdermal

43
Q

Percentage of pts who experience sx recurrence following discontinuation of HRT

A

50% (regardless of age and duration of use)

44
Q

Is routine discontinuation of HRT at 65 y/o recommended?

A

No

45
Q

Is abrupt discontinuation or tapered discontinuation recommended for HRT?

A

No evidence available to recommend one over the other

46
Q

Pts in whom PO conjugated estrogen + bazedoxefine should be considered

A

For pts requiring tx of vasomotor sxs and to prevent osteoporosis in postmenopausal pts w/ a uterus

47
Q

Progestin-only regimen that may help w/ vasomotor sxs, is evidence of benefit demonstrated, is it FDA approved?

A

Depo Provera, evidence of benefit demonstrated, not FDA approved

48
Q

Is there evidence of benefit demonstrated, and is there FDA approval for testosterone?

A

Evidence of benefit not demonstrated, not FDA approved

49
Q

Potential adverse effects associated w/ testosterone tx (4)

A

Lipid derangements, clitoromegaly, hirsutism, acne

50
Q

Clinical benefits to adding testosterone to HRT (2)

A

Improved sexual function scores, increased number of satisfying sexual episodes

51
Q

Tibolone med class

A

Synthetic steroid w/ tissue-specific estrogenic and progestogenic effects

52
Q

Benefits of tibolone (3)

A

Improved bone density, vasomotor sxs, vaginal sxs (w/o estrogenic effects on uterus/breasts)

53
Q

Tibolone dosing, is evidence of benefit demonstrated, is it FDA approved?

A

2.5mg daily, evidence of benefit demonstrated, not FDA approved (and not available in US)

54
Q

What are bioidenticals?

A

Plant-derived hormones that are chemically similar or structurally identical to those produced by the body

55
Q

Concerns re bioidenticals

A

Do not undergo clinical testing > purity/potency/ quality are not verified > both underdosage and overdosage are possible 2/2 variable bioavailability/bioactivity

56
Q

Dosing, evidence for desvenlafaxine in tx of vasomotor sxs

A

100mg daily, showed significant reduction in mod-to-severe hot flushes per day

57
Q

Reported adverse effects associated w/ desvenlafaxine (8)

A

Nausea, dizziness, dry mouth, nervousness, constipation, somnolence, sweating, sexual dysfunction (side effects typically resolve w/ time and/or dose adjustment)

58
Q

Paroxetine dosing, is evidence of benefit demonstrated, is it FDA approved?

A

7.5mg daily, evidence of benefit demonstrated, FDA approved (only nonhormonal therapy approved by FDA for tx of vasomotor sxs)

59
Q

Clonidine med class

A

Central acting alpha2-agonist antihypertensive agent

60
Q

Clonidine dosing, is evidence of benefit demonstrated, is it FDA approved?

A

0.1mg daily, evidence of benefit demonstrated (though not as much as HRT), not FDA approved

61
Q

Common adverse effects associated w/ clonidine (3)

A

Dry mouth, insomnia, drowsiness (BP not adversely affected)

62
Q

Gabapentin med class

A

Gamma-aminobutyric acid analog

63
Q

Gabapentin dosing, is evidence of benefit demonstrated, is it FDA approved?

A

600-900mg daily, evidence of benefit demonstrated (though not as much as HRT), not FDA approved

64
Q

Common adverse effects associated w/ gabapentin (3)

A

Dizziness, somnolence, peripheral edema

65
Q

Which meds have better efficacy between gabapentin, SSRIs, and SNRIs in management of vasomotor sxs?

A

Similar efficacy

66
Q

Which med did pts prefer in crossover trial between venlafaxine and gabapentin in tx of vasomotor sxs?

A

Venlafaxine

67
Q

What are phytoestrogens (w/ two examples)?

A

Plant-derived substances w/ estrogenic biological activity (isoflavones genistein and daidzein)

68
Q

Food products containing high amounts of isoflavones (3)

A

Soybeans, soy products, red clover

69
Q

Has any significant difference in frequency of hot flushes been demonstrated w/ phytoestrogens?

A

No (though no evidence of detrimental effects seen either)

70
Q

Examples of herbal txs for vasomotor sxs (6)

A

Dong quai (Angelica sinensis), dang gui bu xue tang, black cohosh (Actaea racemosa or Cimicifuga racemosa), ginseng, St. John’s wort, ginkgo biloba

71
Q

One situation in which herbal tx regimen was found to be as effective as HRT in relieving menopausal sxs

A

Chinese herbal medicine + acupuncture

72
Q

Risk associated with/ black cohosh

A

Liver toxicity

73
Q

Vitamin regimen associated w/ marginal reduction (one fewer hot flush per day) in vasomotor sxs

A

Vit E 800IU daily

74
Q

Alternative technique that may be effective in pts w/ vasomotor sxs w/ contraindications to HRT

A

Local injection of anesthetic into stellate ganglion

75
Q

Common sense lifestyle changes for managing vasomotor sxs (3)

A

Layering clothing, maintaining lower ambient temp, consuming cool drinks

76
Q

Ingredients associated w/ increased severity/frequency of vasomotor sxs (2)

A

Alcohol, caffeine

77
Q

Lifestyle modification that improves tolerance to vasomotor sxs indirectly

A

Aerobic exercise (by improving quality of life)

78
Q

Recommended tx modality for pts w/ only vaginal sxs

A

Local estrogen

79
Q

Estradiol-17beta vaginal ring dosing, is evidence of benefit demonstrated, is it FDA approved?

A

7.5mcg daily, evidence of benefit demonstrated, FDA approved

80
Q

Estradiol vaginal tablet dosing, is evidence of benefit demonstrated, is it FDA approved?

A

25mcg daily, evidence of benefit demonstrated, FDA approved

81
Q

Estradiol vaginal ring dosing, is evidence of benefit demonstrated?

A

0.05mg daily, evidence of benefit demonstrated

82
Q

Estradiol-17beta vaginal cream dosing, is evidence of benefit demonstrated?

A

2g daily, evidence of benefit demonstrated

83
Q

Conjugated estrogen vaginal cream dosing, is evidence of benefit demonstrated?

A

0.5-2g daily, evidence of benefit demonstrated

84
Q

Typical administration for vaginal estrogen formulations

A

Administered daily x1-2 weeks > indefinitely at low doses for maintenance thereafter

85
Q

Is local estrogen therapy associated w/ increased risk of endometrial hyperplasia?

A

No (so neither progestin add-on nor endometrial surveillance is needed unless PMB occurs)

86
Q

First-line tx recs for vaginal atrophy in pts w/ hx of hormone-sensitive breast cancer

A

Nonhormonal methods (though short-term use of hormonal methods can be considered for pts w/ severe/refractory sxs when other options have failed)

87
Q

Are low-dose systemic estrogen formulations appropriate for pts w/ vaginal atrophy in addition to vasomotor sxs?

A

Yes (all systemic formulations of conjugated estrogen, micronized estradiol-17beta, transdermal estradiol-17beta that are available for vasomotor sxs also have evidence of benefit demonstrated and are FDA approved for use in vaginal atrophy)

88
Q

Lowest PO dosage of CEE shown to improve vaginal atrophy; lowest transdermal dosage of estradiol-17beta shown to improve vaginal atrophy

A

0.3mg daily; 12.5mcg daily

89
Q

Ospemifene med class

A

SERM (estrogen agonist at vagina, antagonist at endometrium)

90
Q

Ospemifene dosing, is evidence of benefit demonstrated, is it FDA approved?

A

60mg daily, evidence of benefit demonstrated, FDA approved

91
Q

Common adverse effects of ospemifene (5)

A

Hot flushes, vaginal discharge, muscle spasms, genital discharge, excessive sweating

92
Q

Other FDA-approved use for ospemifene besides vaginal atrophy

A

Mod-to-severe dyspareunia in postmenopausal pts

93
Q

First-line nonhormonal options for tx of vaginal atrophy sxs

A

Water-based or silicone-based vaginal lubricants (evidence of benefit demonstrated, not FDA approved)

94
Q

MoA of vaginal moisturizers

A

Trap moisture > provide long-term relief of vaginal dryness (evidence of benefit demonstrated, not FDA approved)

95
Q

Measures shown to improve w/ use of vaginal moisturizers (4)

A

Vaginal dryness, pH balance, elasticity, vaginal itching/irritation/ dyspareunia sxs

96
Q

Are herbal remedies/soy products recommended as tx of vaginal atrophy sxs?

A

Insufficient evidence

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