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Flashcards in Ovarian failure/menopause Deck (45):
1

Natural menopause definition

permanent loss of ovarian follicular activity
12 consecutive mo of amenorrhea
no other obvious pathologic/physiologic cause
avg age 51

2

Perimenopause definition

time prior to menopause and 1st year after menopause

3

Induced menopause definition

cessation of menstruation due to surgical removal of ovaries
OR iatrogenic ablation (chemo/radio)

4

Premature menopause/POI definition

menopause occurs >2 SD below mean age
FSH > 30 mIU/mL x 2 at least 1 mo apart
amenorrhea > 4 mo
preceded with a duration of disordered menses

5

Pathophysiology of menopause

depletion of ovarian follicles
reduced inhibin due to low FSH
increased activin - increases with reduced inhibin, tries to increase FSH
high FSH/LH
low Estrogen - dysfunctional granulosa cells
low progesterone
low androgen levels

6

Menopause symptoms

headaches/hot flashes
teeth loosen, gums recede
nipples become smaller and flatten
breasts droop and flatten
skin becomes drier, develops rougher texture
backaches
risk of CV disease
abdomen loses muscle tone
vaginal dryness, itching, shrinking
stress/urge incontinence

7

Issues involved in ovarian failure

menstrual changes
vasomotor symptoms
urogenital changes
mood changes
sexual changes
CVD
bone health

8

Menopause - menstrual changes

Cycles initially get shorter before longer
- rapid follicular recruitment
- initially loop cycle: Luteal Out Of Phase follicular event (short)
- then lag cycles (long)
AUB
Depletion in primordial follicles
amenorrhea eventually occurs

9

LOOP cycle

Luteal Out Of Phase follicular event
premature formation of a follicle due to major surge in FSH during luteal phase

10

Lag cycles

Long follicular phase with aberrant folliculogenesis
high E2, low P4

11

Vasomotor symptoms during menopause

Hot flashes/night sweats
sudden onset - begins in chest, may progress to neck/face
often associated with anxiety, palpitations and sweating
can interfere significantly with life
75-80% of women experience them
generally from 6 mo - 5 y, but can last as long as 15 years
can occur in perimenopause

12

Etiology of vasomotor symptoms during menopause

Estrogen withdrawal
-->
Dysregulation of firing rate of thermosensitive neurons in preoptic hypothalamus
decreased alpha2 activity
significantly smaller thermoneutral zone

13

Management of vasomotor symptoms during menopause

Lifestyle - cool rooms, regular exercise, stop smoking
HT: estrogen alone or with progestin - lowest dose for shortest duration
Non-hormonal therapy: clonidine alpha 2 agonist
gabapentin
SSRI
Stellate ganglion block
Non-Rx - controversial, vitamin E??

14

Urogenical consequences of menopause

vaginal atrophy
UTI
incontinence
pelvic prolapse

Atrophy of urogenital epithelium and subepithelial tissues
Degeneration of collagen, elastin, sm
decreased blood flow to tissues

15

Estrogen-sensitive pelvic tissues

receptors found in:
Introitus
vagina
bladder
urethra
pelvic floor musculature

16

Vaginal atrophy (menopause)

DYspareunia
vaginal dryness
itching
irritation

17

Pathophysiology of vaginal atrophy

thinning of epithelium
less blood flow
vaginal length/diameter shrink
nerve endings exposed
increased trauma

18

UTI during menopause pathophys

mucosa is thinner
glycogen production declines
decreasing level of lactobacilli
reduced lactic acid production

19

Urinary incontinence during menopause pathophys

reduction in mean uretrhal closure pressure
thinning of bladder mucosa and increased irritation
increased likelihood of urinary incontinence

20

Mood changes during menopause

some evidence for increased irritability, tearfulness, anxiety, poor concentration
secondary to - ??
- fluctuating E levels (E has positive effects on serotonin activity, upregulation of 5-HT1 receptors, decreased MOA activity)
- sleep disturbance

21

Depression during menopause

Risk factors:
- Hx of depressive disorders
- poor physical health
- Life stressors
- Hx of surgical menopause
- Long transition

22

Sexual concerns during menopause

Lack of E: dyspareunia, decreased vaginal blood flow, altered sesation
Reduction in ovarian testosterone
AUB is problematic
depressive symptoms

23

Managing sexual concerns during menopause

Address interpersonal/contextual components
Address biologic factors (AUB, vaginal atrophy, mood/anxiety)
Routine evaluation of hormone - limited value
testosterone therapy by experienced physicians

24

CVD during menopause

women who have had oophorectomy: higher age adjusted risk than those with intact ovaries
Adjusting for age, postmenopaulsa women - 2x risk seen in premenopausal
Less favourable lipid profiles
increased insulin resistance
increased likelihood of thrombosis
HT no longer indicated

25

Bones - menopause

Higher rates of fracture in postmenopausal women
loss of bone density
preservation of bone mineral density/fewer fractures with HT

26

Tx of osteoporosis in women

recommended for:
T-score =3% for risk of hip fracture
- FRAX >=20% for risk of a major osteoporotic fracture (forearm/hip/shoulder/clinical spine fracture) in next 10 years

Raloxifene, bisphosphonates, PTH, denosumab, calcitonin

27

POI - HT

premature menopause/ POI - associated with lower risk of breast ca and earlier onset of osteoporosis, CHD
HT recommended for them at least until median age of normal menopause

28

Considerations with HT use - cognition

WHI: no improvement in cognitive function
prospective study on women with mild-moderate AD: no effect for 1 yr on disease progression/cognitive function/global outcome

29

HT and breast cancer

HT use 1-4 y: no added risk
5 or more: RR 1.35, risk increased by 2.3% per year of use
elevated risk disappeared by 5 y after stopping
greater risk is still family history

30

HT and colon cancer

WHI observational
no protective effect on colorectal cancer mortality

31

HT and lung cancer

WHI: no significant increase in incidence
significant increase in death from lung ca in women who took EPT

32

HT and ovarian ca

current/recent use of MHT - RR 1.37 for serious endometriod ovarian cancer

33

HT and endometrial ca

only progestin / continuous combined reduces risk of endomterial ca

34

HT and stroke

EPT - no increase in stroke risk or an increased risk (HERS, WHI)
oral route higher RR than transdermal

35

HT and venous thromboembolism

no consistently observed procoagulant effect of HT in prospective studies
oral E mor econsistently affects coagulation and fibrinolysis and transdermal

36

HT and CHD

CV risks improve on HT in those >70 y (but not symptomatic for menopause)

37

HT conclusions

ET does NOT increase risk of CVD in early postmenopausal years, but increases it if begun some time after menopause

38

HT and gallbladder disease

increased risk

39

EPT risks

venous thromboembolism
stroke (inconsistent data)
breast ca for use beyond 5 y
ovarian cancer
gallbladder disease

40

EPT benefits

QOL
bone density
colon ca

41

ET in women with previous hysterectomy - risks

venous thromboembolism
storke (inconsistent)
ovarian ca
gallbladder disease

42

ET in women with previous hysterectomy - benefits

QOL
bone density

43

Causes of POI

Accelerated follicle depletion
Primary hypogonadism
Common causes:
Turner
Fragile X
Somatic and X chromosome gene defects
AI ovarian failure
Toxins

44

Polyglandular autoimmune syndrome

adrenal, thyroid, pancreatic failure

45

Estrogen supplementation for depression

Not effective