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PHS 933 > Block 2 Lecture 4 -- Menopause and HRT > Flashcards

Block 2 Lecture 4 -- Menopause and HRT Flashcards

1
Q

What is the definition of menopause?

A

12 consecutive months of amenorrhea via cessation of ovarian follicular activity

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2
Q

What is the median age of menopause in the US?

A

51 (2 years earlier if smoker or hysterectomy)

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3
Q

What are the hormonal changes in menopause?

A

1) estrogen, progesterone decrease
2) FSH and LH increase
3) ovaries primarily produce androgens
4) SHBG decreases, generating increased free T, but overall less total T

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4
Q

What is perimenopause?

A

the period preceding menopause by 2-4 years and the year following menopause

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5
Q

What are the symptoms of menopause?

A

1) vasomotor
2) mood changes, anxiety
3) sleep disturbances
4) vaginal dryness

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6
Q

When do menopausal symptoms begin?

A

perimenopause

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7
Q

Describe the enrollment in the WHI ‘91 study.

A

160k post-menopausal women aged 50-79

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8
Q

How long was the WHI study run?

A

15 years

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9
Q

What are the interventions in the WHI study?

A

1) HRT
2) d-mod
3) D + Ca

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10
Q

Describe the drugs given as HRT in the WHI study.

A

CEE 0.625mg/day

+ MPA 2.5 mg/day if uterus intact

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11
Q

Why was the HRT arm halted?

A

increased stroke risk with no effect on CHD

combo increased risk of breast cancer

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12
Q

When was the HRT arm halted?

A

combo after 5 years

e only after 7 years

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13
Q

Describe the interventions in the d-mod arm of WHI?

A

1 g/day Ca + 400 IU/day Vit. D

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14
Q

What were the expectations in the Ca/D arm of the WHI study?

A

1) decreased bone fx
2) decreased colorectal cancer risk
3) increase kidney stones

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15
Q

Describe the interventions in the d-mod arm of WHI.

A

low-fat diet (less than 20% of calories) resulting in a 10% fat reduction vs. control

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16
Q

What were the criticisms of the WHI study?

A

1) low adherence, high attrition
2) under-reported benefits
3) average as was 63

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17
Q

What did sub-group analysis of the WHI study conclude?

A

HRT not harmful if initiated early

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18
Q

What were the under-reported benefits of the WHI study?

A
    • decreased total mortality
    • decreased colorectal/endometrial cancer
    • decreased hip and total fx
    • decreased t2dm and PAD
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19
Q

What did outside analysis of the WHI study conclude?

A

window of opportunity for max effect of HRT on total mortality and CHD:

    • within 6 years of menopause and/or before age 60
    • continue for 5+ years
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20
Q

Describe the enrollment in the Danish Osteoporosis Prevention Study

A

1006 peri-menopausal women (u-60 yo) randomized to combined HRT (or estrogen only)

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21
Q

How long was the Danish Osteoporosis Prevention study conducted?

A

treated for 10 years

followed for 16

22
Q

What was the conclusion of the Danish Osteoporosis Prevention Study?

A 
significantly reduced risk of:
-- mortality,
-- heart failure
-- MI
without increased risk of:
-- cancer
-- thromboembolism
-- stroke
23
Q

What are the goals of menopause treatment?

A

1) relieve vasomotor symptoms in the short term (5-years)

2) prevent osteoporosis in the long term

24
Q

What is the standard dose of CEE?

A

0.625 mg/day

25
Q

Describe the content of CEE

A

50-60% estrone sulfate

– remainder = other equine estrogens

26
Q

What is the most popular oral estrogen in the US?

A

premarin (CEE)

27
Q

How much of the oral estrogen forms reach circulation as free estradiol?

A

less than 10%

– estrones are converted back to estradiol over time

28
Q

Describe the absorption of estradiol?

A

during absorption, intestinal mucosa and liver convert to estrones

29
Q

What estrogen form gives the most physiologic (pre-menopause) E2:E1 ratio?

A

transdermal estrogen patch

30
Q

How is the IN estrogen spray dosed?

A

1-2 x/day

31
Q

What are the forms of parenteral estrogen?

A

1) patch/gels/creams
2) sq implant
3) intranasal spray
4) vaginal rings

32
Q

How often do estrogen-containing vaginal rings last?

A

3 months

33
Q

Which parenteral estrogens are effective (increase BMD and relieve vasomotor sxs) at low doses?

A

transdermal, vaginal ring

34
Q

Which parenteral estrogen is least likely to have ADRs?

A

transdermal

35
Q

What are the drug interactions for estrogens?

A

1) anticonvulsants (induce 3A4)

2) may increase THBG, CBG, SHBG

36
Q

What are the forms of progesterone used in menopause?

A

1) micronized (prometrium)
2) levonorgestrel IUD (mirena, skyla)
3) drosperinone

37
Q

Why are progestogens always included with estrogens?

A

to prevent endometrial hyperplasia and cancer

38
Q

What are the effects of progesterone on estrogens?

A

1) decrease nuclear ER concentration

2) promote conversion of estradiol to estrone

39
Q

What are the estrogen-progestogen regimens used in menopause?

A

1) continuous cyclic
2) continuous combined
3) continuous long-cycle
4) intermittent combined

others

    • lo-dose
    • quarterly progestogen
40
Q

Describe the continuous cyclic regimen.

A

E daily + P last 12-14 days

    • results in withdrawal bleed 90% of patients
    • oral or TD
41
Q

Describe the continuous combined regimen.

A

E + P continuously

    • oral or TD
    • endometrial atrophy and amenorrhea
    • unpredictable spotting/bleeding initially, resolved within 6-12 months
    • usually reserved for recent menopause (2 years past)
42
Q

How may spotting be stopped in the continuous combined regimen?

A

increase P or decrease E

43
Q

Describe the continuous long-cycle regimen.

A

E daily + P q other month x 12-14 days

– longer heavier bleeding than continuous cycling

44
Q

Describe the intermittent combined regimen.

A

– 3 days E
– then 3 days E+P
– repeat
results in decreased incidence of bleeding
lower P dose = fewer ADRs

45
Q

Describe low-dose HRT

A
  1. 45 mg CEE + 1.5 mg MPA

- - maintains sx relief and BMD

46
Q

Describe quarterly progestogen regimen in HRT.

A

MPA x 14 days q 3 months

– higher incidence of endometrial hyperplasia

47
Q

What are the ADRs of progesterone?

A

1) irritability
2) depression
3) HA
4) sleep disturbance
5) bloating

48
Q

What is drosperinone?

A

anti-androgenic P with anti-MR effects

    • decreased hyperplasia
    • no hyperkalemia
49
Q

What are the results of levonorgestrel IUD therapy?

A

off-label HRT use:

    • atrophic endometrium
    • low systemic P levels
50
Q

What are the effects of micronized progesterone therapy?

A
    • less bleeding

- - does not improve lipids

PHS 933 (14 decks)

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