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Human Reproduction > Week 3: Menopause > Flashcards

Week 3: Menopause Flashcards

1
Q

Question 1

A
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2
Q

How is menopause defined?

A
  • 12 months of amenorrhea following the final menstrual period
  • w/ no obvious pathologic cause
  • Secondary to loss of ovarian follicular activity
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3
Q

Average age of menopause

A

51.4 years

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4
Q

What is perimenopause?

A

The transition from reproductive age to menopause

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5
Q

Perimenopause AKA

A

Menopausal transition

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6
Q

How long is perimenopause and when does it start?

A

On average, occurs ~4 years prior to the last menstrual period

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7
Q

Describe the hypothalamic-pituitary-ovarian axis in reproductive age women

A

Hypothalamus -GnRH-> anterior pituitary -LH & FSH-> Ovarian follicles -Estrogen & Inhibin-> increasing levels of Estrogen & Inhibin cause negative feeback to both the hypothalamus and the anterior pituitary

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8
Q

Describe the hypothalamic-pituitary-ovarian axis in perimenopause

A

Hypothalamus -GnRH-> Anterior Pituitary -LH & FSH-> Ovarian follicles -Estrogen & Inhibin-> increasing levels of Estrogen & Inhibin cause negative feeback to both the hypothalamus and the anterior pituitary

However, in perimenopause, the ability of the aging ovarian follicles granulosa cells of developing follicles to secrete inhibin decreases and so there is a decrease in negative feedback to the anterior pituitary resulting in an increase in FSH and Estrogen levels are maintained

The increase in FSH causes the follicular phase to shorten which causes the increase in Anovulatory cycles (abnormal uterine bleeding).

This causes accelerated loss of remaining ovarian follicles until depletion

With diminished ovarian follicles this results in depleted Estrogen production which further decreases negative feedback resulting in even higher GnRH, FSH and LH levels

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9
Q

How common are hot flashes in perimenopausal women

A

occurs in ~80%

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10
Q

Clinical presentation of hot flashes

A
  • Sudden wave of heat that spreads over the body, particularly the upper body and face lasting 1-5 minutes

associated with:

  • sweating
  • palpitations
  • anxiety
  • sleep disturbances
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11
Q

Describe the role of menopause and cardiovascular disease

A

Decreased estrogen can affect the lipid profile which can increase LDL cholesterol and lead to cardiovascular disease

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12
Q

Etiology of hot flashes

A

secondary to dysfunction of the thermoregulatory nucleus of the hypothalamus which regulates sweating and vasodilatation to maintain body temperature within the thermal regulatory zone.

With women with hot flashes they have a narrower thermal regulatory zone due to changes in Estrogen, this means that minimal changes in body temperature can result in activation of the thermoregulatory nucleus of the hypothalamus

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13
Q

Explain how Estrogen levels influence body temperature regulation

A

It is hypothesized that a drop in estrogen increases neurotransmitter concentrations in the hypothalamus which creates a narrower thermoregulatory zone

In particular, NE and Serotonin have been shown to lower the thermoregulatory setpoint due to rapid fluctuations in estrogen levels or rapid estrogen withdrawal and not chronically low estrogen levels

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14
Q

Explain the mechanism of bone density changes in menopause

A

high risk within the first 10 years of menopause

Osteoblasts constanly lay down new bone while osteoclasts constantly resorb bone

Osteoblasts produce RANKL and OPG

RANKL binds to RANK on the surface Osteoclast progenitor cells leading to osteoclast development and bone resorption

OPG binds to RANKL which prevents it from binding with RANK and preventing osteoclast development and bone resorption

In menopause, with lower Estrogen RANKL production is greater than OPG production eading to increased bone resorption and is favored over bone deposition leading to long-term bone loss

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15
Q

Symptoms of perimenopause/menopause

A
  • Hot flashes
  • Bone loss
  • Risk of cardiocascular disease
  • vulvovaginal atrophy
  • +++ more
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16
Q

Describe the mechanism of vulvovaginal atrophy in menopause

A

Symptoms of dryness, itching anddyspareunia

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17
Q

How does a drop in estrogen change the thermoregulatory zone to increase hot flashes?

A

It is hypothesized that a drop in estrogen increases neurotransmitter concentrations in the hypothalamus which creates a narrower thermoregulatory zone

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18
Q

What to expect with menopause?

A
  • Hot flashes
  • Bone density loss
  • increased risk of cardiovascular disease
  • vulvovaginal atrophy (dryness, itching, dysparenia)
  • Incontinence & risk of recurrent UTIs
  • Risk of mood distrubances including (new onset depression in the menopausal transition and sleep distrubances)
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19
Q

What is dyspareunia?

A

Painful intercourse

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20
Q

What is the mechanism of vulvovaginal atrophy in menopause?

A
  • decreased estrogen results in thinning of the vaginal epithelium and loss of vaginal collagen in adipose tissue
  • Loss of sebaceous glands on the vulva leads to increased dryness
  • Vulva is also affected by narrowing of the vaginal introitus
  • thinning of the epithelium of the lower urinary tract including the bladder and urethra increase risk of incontinence and can contribute to recurrent UTIs
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21
Q

Mechanism of mood disturbances in menopause

A

Increased risk of new onset depression and sleep distrubances

this is unclear if it is secondary to a decrease in estrogen or if it is 2o to menopausal symptoms

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22
Q

Options for treatment of menopause

A

Menopause hormone therapy

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23
Q

Benefits of menopausal hormone therapy

A
  • The most efficacious treatment for hot flashes (75% reduction in hot flashes)
  • Improves fracture rates
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24
Q

Considerations with menopausal hormone therapy

A

Be on the minimal dose for the shortest amount of time possible due to the increased risk associated with its use

For healthy women in their 50s the overall risk of complications is low

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25
Q

Why do women taking menopausal hormone therapy with an intact uterus need progestin therapy in addition to estrogen therapy?

A

For women with an intact uterus, progestin therapy must be added to prevent endometrial hyperplasia and cancer

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26
Q

Risks for women receiving Estrogen & Progestin

A

Increased risk for:

  • Breast cancer
  • Stroke
  • Cardiovascular events
  • Venous thromboembolism
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27
Q

Risks for women without a uterus receiving Estrogen ONLY

A

NO increased risk:

  • Breast cancer
  • Cardiovascular events

There still is increased risk for:

  • Stroke
  • Venous thromboembolism
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28
Q

Alternatives to Menopausal hormone therapy

4 listed

A
  • Gabapentin
  • Clonidine
  • SSRI/SNRIs
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29
Q

MOA of Gabapentin as an alternative to Menopausal hormone therapy

A

Mechanism Unknown

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30
Q

MOA of Clonidine as an alternative to Menopausal hormone therapy

A
  • α-2 adrenergic agonist
  • decreases sympathetic outflow by inhibiting the release of NE
  • With decreased NE, the thermoregulatory zone is returned closer to normal
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31
Q

MOA of SSRIs/SNRIs as an alternative to Menopausal hormone therapy

A

decrease the uptake of serotonin and norepinephrine returning the thermoregulatory setpoint to turn closer to normal

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32
Q

Efficacy of SSRIs/SNRIs as an alternative to Menopausal hormone therapy for hot flashes

A

Reducing hot flashes by 50-62%

33
Q

Herbal medication alternatives

A
  • Black cohosh
  • Phyto-estrogens such as (Soy)

There is inconsistent evidence of efficacy

34
Q

Vaginal estrogen as a treatment option for menopause

A
  • Vaginal estrogen is an option for vulvovaginal or urinary menopausal symptoms
  • It is used locally with minimal systemic absorption but still improves the urogenital symptoms of menopause
35
Q

How is menopause diagnosed?

A

It is a clinical diagnosis, 12 months of amenorrhea

36
Q

What is premature ovarian insufficiency?

A

Loss of ovarian function before age 40 (basically premature menopause before the age of 40)

37
Q

Average age of menopause

A

51 years old in North America, rest of world 51-55

38
Q

Perimenopause starts when?

A

can occur up to 5 years prior to menopause

39
Q

Factors that can influence the age of menopause

A
  • Genetics
    • Variation in estrogen receptor gene
    • FHx early menopause
  • Ethnicity
    • Hispanic earlier menopause
    • Japanese-American later menopause
  • Smoking
    • Average 2 years earlier
  • Reproductive history
    • Earlier if nulliparous
40
Q

Straw Stages of Reproductive Aging

A
41
Q

Discuss the endocrinology of menopause

A
  • First oocytes are developed in 15 weeks of gestation
  • Primordial follicles 20 weeks gestation
  • Follicular growth and oocyte atresia
  • Decrease of oocyte number continues until menopause
42
Q

Describe the HPO axis

A
43
Q

Describe estrogen and progesterone levels over life time

A
44
Q

Question 2

A
45
Q

Question 3

A
46
Q

Describe the endocrine events by menopausal stage: Late reproductive years

A
  • Ovulatory, shortened follicular phase
  • FSH starts rising
47
Q

Describe the endocrine events by menopausal stage: Early menopausal transition

A
  • Menstrual irregularity, decreased ovarian follicles
  • Decreased inhibin and increased FSH
  • Normal estradiol
  • Low luteal progesterone (weak corpus luteum)
48
Q

Describe the endocrine events by menopausal stage: Late menopausal transition

A
  • Significant fluctuations in FSH and estradiol
  • Hot flashes will start
49
Q

Describe the endocrine events by menopausal stage: Menopause

A
  • No estradiol secretion
  • Androgen secretion via LH
50
Q

Describe androgens and menopause

A
  • FSH and LH increases
  • LH stimulates ovarian production of androstenedione and testosterone
  • Overall decrease in androgens but an increase in Androgen/estrogen ratio
  • Can lead to Hirsutism
51
Q

Estrogens and Menopause: Reproductive age

A

Androstenedione -aromatase-> estrone -ovary (granulosa cells)-> estradiol (potent)

52
Q

Estrogens and Menopause: Post-menopausal

A

Androstenedione -Aromatase (adipose tissue) -> Estrone (weak)

53
Q

Estradiol vs Estrone

A
  • Estradiol (potent) -reproductive age
  • Estrone (weak) - post-menopausal
54
Q

Question 4

A
55
Q

What tissues are affected by estrogen?

A
  • Brain
  • Eyes
  • Teeth
  • Vasomotor
  • Heart
  • Breast
  • Colon
  • Urogenital tract
  • Bone
56
Q

What are the symptoms of menopause?

A
  • Irregular menses prior to cessation
  • Vasomotor symptoms
  • Night sweats & insomnia
  • Mood swings
  • Vaginal dryness

Long-term effects of decreased Estrogen

  • Increased risk of
    • CHD
    • Osteoporosis
    • Dementia
57
Q

How long do the hotflashes continue after menopause?

A
58
Q

Hot flash physiology

A
59
Q

Ethnicity and hot flashes

A
60
Q

Vaginal dryness with menopause

A

increases the longer the menopause is occuring

61
Q

Describe histology of vaginal atrophy

A
62
Q

Question 5

A
63
Q

What are the treatments and what treatment is most effective for the vasomotor symptoms of estrogen

A
64
Q

Hormone therapy & vasomotor symptoms

A
  • Treatment of moderate to sever vasomotor symptoms (ie, hot flashes, night sweats) remains primary indication for systemic hormone therapy
  • Every systemic estrogen and estrogen-progesterone product approved for this indication in the US/Canada
65
Q

Hormone therapy and vaginal symptoms

A
  • Estrogen is the most effective treatment for moderate to severe symptoms of vulvar and vaginal atrophy
  • Local vaginal estrogen is generally recommended when hormone therapy is considered solely for this indication
66
Q

Hormone therapy and quality of life

A
  • Hormone therapy can improve health-related QOL through mood elevation and decreased menopause symptoms
  • Hormone therapy is not approved for this indication
67
Q

Forms of systemic estrogen therapy

A

usually in a pill or a patch

68
Q

Forms of vaginal estrogen therapy

A
  • creme
  • rings
  • tablets
69
Q

Hormone therapy and people closer in time to menopausal transition

A
70
Q

Hormone therap and stroke

A

31% increased risk but people aged 50-59 typically don’t have a lot of strokes but transdermal administration seems to be a little bit better

71
Q

Hormone therapy and heart disease risk

A

Does hormone replacement reduce heart disease risk? NO!

72
Q

Hormone therapy and breast cancer risk

A

Estrogen therapy for less than 5 years appears to have little impact on breast cancer risk

73
Q

Hormone therapy and endmetral cancer

A
  • unopposed systemic estrogen causes endometrium to grow and up to 5 fold increased risk
  • However, adequate concomitant progestogen recommended for women with an intact uterus
  • Hormone replacement is not recommended with endometrial cancer history
74
Q
A
75
Q

Menopause conclusion

A
76
Q

How to treat vasomotor symptoms of menopause?

A

systemic hormones

Estrogen alone or estrogen + Progesterone

77
Q

How to treat mood symptoms of menopause?

A

SSRIs/SNRIs

78
Q

How to treat vaginal/urinary symptoms of menopause?

A

Topical estrogens

79
Q

Lab tests for menopause?

A
  • There is no hormone or blood test
  • Menopause is a clinical diagnosis which is 12 months of ammenorrhea

Human Reproduction (40 decks)

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