Clinician's Guide Chapter 3

Question 1

What are vasomotor symptoms (VMS)?

Answer 1

Hot flashes and night sweats experienced during menopause transition

VMS are the most commonly reported symptoms of menopause.

Question 2

By 2025, how many women are expected to experience menopause-related VMS in the US?

Answer 2

21 million women

Globally, this number is projected to be 1.1 billion.

Question 3

What characterizes a hot flash?

Answer 3

A sudden intense sensation of heat in the upper body

Typically affects the face, neck, and chest.

Question 4

What is a night sweat?

Answer 4

A hot flash that occurs during sleep

Question 5

What are the typical durations of hot flash episodes?

Answer 5

Between 1 and 5 minutes

Question 6

What are some common methods used to assess VMS?

Answer 6

Subjective questionnaire-based symptom scales and physiological measures

Examples include the Greene Climacteric Scale.

Question 7

What factors can affect the prevalence of reported VMS?

Answer 7

Variations in questions on frequency and severity of symptoms

Also affected by the time frame covered in assessments.

Question 8

How are hot flash severity levels classified by the FDA?

Answer 8

• Mild: sensation of heat without sweating
• Moderate: sensation of heat with sweating, able to continue activity
• Severe: sensation of heat with sweating, causing cessation of activity

Question 9

What percentage of women experience VMS during menopause according to the SWAN study?

Answer 9

60% to 80%

Question 10

Which racial/ethnic group reported the highest prevalence of VMS in the SWAN study?

Answer 10

Black women (46%)

Question 11

What is the median duration of VMS experienced by women in the Penn Ovarian Aging Study?

Answer 11

10 years

Question 12

What are the four distinct groups of VMS trajectories identified in a major Australian longitudinal study?

Answer 12

• Mild
• Moderate
• Early severe
• Late severe

Question 13

What socioeconomic factors are associated with VMS prevalence?

Answer 13

• Lower educational attainment
• Lower socioeconomic position

Question 14

What is the relationship between obesity and VMS?

Answer 14

Higher body mass index (BMI) is associated with increased likelihood of reporting VMS

Question 15

How does smoking affect the risk of VMS?

Answer 15

Current smokers are almost twice as likely to report VMS compared to never smokers

Question 16

What impact do vasomotor symptoms have on quality of life?

Answer 16

Negative effects on sleep, mood, and cognitive function

Question 17

What physical health outcomes are linked to VMS?

Answer 17

• Cardiovascular disease (CVD)
• Poor bone health

Question 18

What is the role of ovarian estrogen in VMS?

Answer 18

Declines in ovarian estradiol are likely important but do not fully explain VMS

Question 19

What is the thermoregulatory model of VMS?

Answer 19

Postulates that VMS are acute heat-dissipation events due to altered thermoregulation

Question 20

What are KNDy neurons?

Answer 20

A network of neurons that regulates GnRH secretion and is involved in thermoregulation

KNDy stands for kisspeptin-neurokinin B-dynorphin.

Question 21

What changes occur in KNDy neurons in postmenopausal women?

Answer 21

Hypertrophy and increased neurokinin B and kisspeptin gene expression

Question 22

True or False: Higher adiposity is consistently linked to increased VMS across all ages.

Answer 22

False

Higher adiposity in younger women or those early in menopause is linked to increased VMS, but the opposite is true for older women.

Question 23

What messenger RNA is not expressed in KNDy neurons?

Answer 23

GnRH messenger RNA

KNDy neurons are involved in reproductive hormone regulation.

Question 24

What gene expressions are increased in KNDy neurons due to estrogen withdrawal?

Answer 24

• Neurokinin B
• Kisspeptin

This increase occurs without neuron loss in the hypothalamus.

Question 25

What effect does estrogen have on neurokinin B and kisspeptin expression in monkeys?

Answer 25

Estrogen suppresses neurokinin B and kisspeptin expression ## Footnote This suggests a regulatory role of estrogen on these neuropeptides.

Question 26

In rodent studies, what physiological changes are observed in ovariectomized rats without estrogen replacement?

Answer 26

A shift in the thermoneutral zone ## Footnote This shift parallels the thermoregulatory changes seen in postmenopausal women.

Question 27

What is the role of serotonin in vasomotor symptoms (VMS)?

Answer 27

Serotonin may help reduce the number and severity of VMS ## Footnote SSRIs, which increase serotonin, have shown efficacy in trials.

Question 28

What receptor subtypes are important for thermoregulation in relation to serotonin?

Answer 28

* 5-HT1A * 5-HT2A ## Footnote These receptors have distinct roles in regulating body temperature.

Question 29

What effect does direct stimulation of the 5-HT2A receptor have in rodents?

Answer 29

Induces hyperthermia ## Footnote This demonstrates the receptor's role in temperature regulation.

Question 30

True or False: The precise involvement of serotonin in the physiology of VMS is well understood.

Answer 30

False ## Footnote The role of serotonin and its receptors in VMS physiology requires further study.

Question 31

What is the role of the autonomic nervous system in VMS?

Answer 31

It includes sympathetic and parasympathetic branches that regulate thermoregulation ## Footnote Norepinephrine has been implicated in central thermoregulatory function.

Question 32

What is the effect of norepinephrine on thermoregulation?

Answer 32

Narrowing of the thermoregulatory zone ## Footnote This effect has been observed in animal studies.

Question 33

What physiological response was observed during hot flashes in women with VMS?

Answer 33

Increased blood flow to the forearm and hand ## Footnote This response demonstrates altered cutaneous circulation during VMS.

Question 34

What is the relationship between cardiac vagal control and VMS?

Answer 34

Significant decreases in cardiac vagal control during VMS ## Footnote This has been observed in both laboratory and ambulatory studies.

Question 35

What brain regions show increased activity preceding the onset of a hot flash?

Answer 35

* Brainstem * Insula * Prefrontal cortices ## Footnote Increased activity in these areas suggests their role in VMS.

Question 36

What is the default mode network associated with?

Answer 36

Active during rest in the absence of external stimuli ## Footnote Hyperactivity is linked to major depressive disorder and other psychiatric conditions.

Question 37

What is the hypothalamic-pituitary-adrenal axis associated with in relation to VMS?

Answer 37

Cortisol and dysregulated function ## Footnote Dysregulation is common in stress conditions.

Question 38

What does endothelial dysfunction predict?

Answer 38

Cardiovascular events ## Footnote It is a significant predictor of cardiovascular health.

Question 39

What proinflammatory profile alterations have been linked to VMS?

Answer 39

Higher IL-8 and tumor necrosis factor-a ## Footnote These alterations indicate a more pro-inflammatory state.

Question 40

What is the FDA-approved first-line therapy for relief of VMS?

Answer 40

Hormone therapy ## Footnote This includes estrogen therapy and estrogen-progestogen therapy.

Question 41

What is the effect of estrogen therapy on VMS frequency?

Answer 41

Reduces frequency by 75% ## Footnote Estrogen therapy is effective for managing VMS symptoms.

Question 42

What medication is FDA approved for reducing VMS and is commonly used for depression?

Answer 42

Paroxetine ## Footnote It is an SSRI with sustained benefits for VMS.

Question 43

Fill in the blank: The lowest, most-effective dose of hormone therapy should be used and may take _______ to take effect.

Answer 43

6 weeks ## Footnote This timeframe is important for assessing the therapy's effectiveness.

Question 44

What medication significantly reduced VMS frequency and severity in gynecologic cancer survivors after 4 and 16 weeks of treatment?

Answer 44

Paroxetine ## Footnote Paroxetine was well tolerated with no serious adverse events reported.

Question 45

What is the effect of paroxetine on sleep problems associated with VMS?

Answer 45

Paroxetine helps reduce VMS-associated sleep problems and increases sleep duration ## Footnote Benefits for nighttime awakenings were sustained through 12 or 24 weeks of treatment.

Question 46

List some SSRIs and SNRIs that have shown efficacy in reducing VMS.

Answer 46

* Citalopram (10-20 mg) * Escitalopram (10-20 mg) * Desvenlafaxine (100-150 mg) * Venlafaxine (37.5-150 mg) ## Footnote These have been shown to reduce hot flash frequency and severity in large RCTs.

Question 47

What was the outcome of a pooled analysis of symptomatic women treated with escitalopram and venlafaxine?

Answer 47

All were effective and comparable in reducing hot flash frequency ## Footnote The reductions were 1.4 VMS/d for escitalopram, 1.8 VMS/d for venlafaxine, and 2.4 VMS/d for low-dose 17-β estradiol.

Question 48

What is the role of gabapentin in treating VMS?

Answer 48

Gabapentin (600-2400 mg) reduces VMS ## Footnote An RCT showed greater reductions in hot flash severity compared to fluoxetine.

Question 49

What adverse events are associated with clonidine?

Answer 49

* Hypertension when abruptly stopped * Hypotension with consistent use * Lightheadedness * Headaches * Dry mouth * Dizziness * Sedation * Constipation ## Footnote Clonidine is the only non-hormone medication approved for VMS in the UK.

Question 50

What is the FDA-approved use of oxybutynin?

Answer 50

Treatment of overactive bladder ## Footnote It has also shown efficacy in reducing VMS frequency and severity.

Question 51

True or False: Neurokinin B antagonists are widely available for clinical use.

Answer 51

False ## Footnote They are still in experimental stages.

Question 52

What mind-body technique has evidence for efficacy in alleviating VMS?

Answer 52

Cognitive-behavioral therapy ## Footnote It has been shown effective for breast cancer survivors and perimenopausal/postmenopausal women.

Question 53

What is the effect of clinical hypnosis on VMS?

Answer 53

It has been shown to reduce VMS ## Footnote Results indicate it is comparable to venlafaxine alone.

Question 54

What does mindfulness-based stress reduction focus on?

Answer 54

Decreasing stress through nonreactive acceptance and mindfulness ## Footnote It showed initial efficacy in reducing bother associated with hot flashes, but findings were weak.

Question 55

Has weight loss been conclusively demonstrated to reduce VMS?

Answer 55

No ## Footnote Evidence suggests some benefit, particularly in women early in menopause transition.

Question 56

What did randomized controlled trials find regarding exercise for VMS?

Answer 56

No evidence supports the use of exercise for VMS ## Footnote However, exercise has many other health benefits.

Question 57

Fill in the blank: Acupuncture has not been shown to be effective in reducing _______.

Answer 57

VMS ## Footnote A meta-analysis concluded that acupuncture was no more effective than sham acupuncture.

Question 58

What is the efficacy of s-equol derivatives of soy isoflavones for VMS?

Answer 58

Mixed evidence ## Footnote Studies suggest that soy products may require long durations to reach full effect.

Question 59

Name some therapies unlikely to alleviate VMS.

Answer 59

* Black cohosh * Crinum * Dioscorea * Dong quai * Evening primrose * Flaxseed * Ginseng * Siberian ginseng * Hops * Maca * Omega-3s * Pine bark * Pollen extract * Puerperia * Vitamin supplementation ## Footnote A Cochrane review noted insufficient evidence for Chinese herbal medicine for VMS.

Question 60

What is stellate ganglion block used for?

Answer 60

Treatment of VMS ## Footnote Evidence suggests it may have some efficacy, but further trials are needed.

Question 61

What approaches do women often attempt to manage hot flashes?

Answer 61

* Avoiding triggers * Cooling techniques (e.g., breathable clothing, fans) ## Footnote There is no empirical evidence for the efficacy of these approaches.