Block 2 Lecture 4 -- Menopause and HRT Flashcards Preview

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Flashcards in Block 2 Lecture 4 -- Menopause and HRT Deck (50):
1

What is the definition of menopause?

12 consecutive months of amenorrhea via cessation of ovarian follicular activity

2

What is the median age of menopause in the US?

51 (2 years earlier if smoker or hysterectomy)

3

What are the hormonal changes in menopause?

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

4

What is perimenopause?

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

5

What are the symptoms of menopause?

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

6

When do menopausal symptoms begin?

perimenopause

7

Describe the enrollment in the WHI '91 study.

160k post-menopausal women aged 50-79

8

How long was the WHI study run?

15 years

9

What are the interventions in the WHI study?

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

10

Describe the drugs given as HRT in the WHI study.

CEE 0.625mg/day
+ MPA 2.5 mg/day if uterus intact

11

Why was the HRT arm halted?

increased stroke risk with no effect on CHD
combo increased risk of breast cancer

12

When was the HRT arm halted?

combo after 5 years
e only after 7 years

13

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

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

14

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

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

15

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

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

16

What were the criticisms of the WHI study?

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

17

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

HRT not harmful if initiated early

18

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

-- decreased total mortality
-- decreased colorectal/endometrial cancer
-- decreased hip and total fx
-- decreased t2dm and PAD

19

What did outside analysis of the WHI study conclude?

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

20

Describe the enrollment in the Danish Osteoporosis Prevention Study

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

21

How long was the Danish Osteoporosis Prevention study conducted?

treated for 10 years
followed for 16

22

What was the conclusion of the Danish Osteoporosis Prevention Study?

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

23

What are the goals of menopause treatment?

1) relieve vasomotor symptoms in the short term (5-years)
2) prevent osteoporosis in the long term

24

What is the standard dose of CEE?

0.625 mg/day

25

Describe the content of CEE

50-60% estrone sulfate
-- remainder = other equine estrogens

26

What is the most popular oral estrogen in the US?

premarin (CEE)

27

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

less than 10%
-- estrones are converted back to estradiol over time

28

Describe the absorption of estradiol?

during absorption, intestinal mucosa and liver convert to estrones

29

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

transdermal estrogen patch

30

How is the IN estrogen spray dosed?

1-2 x/day

31

What are the forms of parenteral estrogen?

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

32

How often do estrogen-containing vaginal rings last?

3 months

33

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

transdermal, vaginal ring

34

Which parenteral estrogen is least likely to have ADRs?

transdermal

35

What are the drug interactions for estrogens?

1) anticonvulsants (induce 3A4)
2) may increase THBG, CBG, SHBG

36

What are the forms of progesterone used in menopause?

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

37

Why are progestogens always included with estrogens?

to prevent endometrial hyperplasia and cancer

38

What are the effects of progesterone on estrogens?

1) decrease nuclear ER concentration
2) promote conversion of estradiol to estrone

39

What are the estrogen-progestogen regimens used in menopause?

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

others
-- lo-dose
-- quarterly progestogen

40

Describe the continuous cyclic regimen.

E daily + P last 12-14 days
-- results in withdrawal bleed 90% of patients
-- oral or TD

41

Describe the continuous combined regimen.

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

How may spotting be stopped in the continuous combined regimen?

increase P or decrease E

43

Describe the continuous long-cycle regimen.

E daily + P q other month x 12-14 days
-- longer heavier bleeding than continuous cycling

44

Describe the intermittent combined regimen.

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

45

Describe low-dose HRT

0.45 mg CEE + 1.5 mg MPA
-- maintains sx relief and BMD

46

Describe quarterly progestogen regimen in HRT.

MPA x 14 days q 3 months
-- higher incidence of endometrial hyperplasia

47

What are the ADRs of progesterone?

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

48

What is drosperinone?

anti-androgenic P with anti-MR effects
-- decreased hyperplasia
-- no hyperkalemia

49

What are the results of levonorgestrel IUD therapy?

off-label HRT use:
-- atrophic endometrium
-- low systemic P levels

50

What are the effects of micronized progesterone therapy?

-- less bleeding
-- does not improve lipids