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Endocrine > Menopause & Hormonal Replacement Therapy > Flashcards

Menopause & Hormonal Replacement Therapy Flashcards

1
Q

What is is Menopause?

A

Menopause is the permanent cessation of menses.

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2
Q

How is Menopause determined?

A
  1. 12 consecutive months of amenorrhea.
  2. Physiologically, it is the cessation of ovarian follicular activity.
    - Ovulation, estrogen & progesterone secretion
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3
Q

What is the median age of onset of Menopause?

A

51
2 yrs earlier than average if hysterectomy.
49 in smokers

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4
Q

What happens in conjunction w/ menopause?

A
  1. Follicular Depletion

- born with 2 million ovulate but ovulate

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5
Q

What happens to the level of circulating androgens as menopause approaches?

A

Levels fall.

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6
Q

What do Post-menopausal ovaries secrete? And why?

A
  1. Primarily androgens.
    - accounts for 50% of circulating androgens.
    - Adrenals and peripheral tissue synthesize rest.
  2. Elevated LH levels at menopause.
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7
Q

What is Perimenopause?

A

The period preceding (2-4yrs) and the year following menopause.

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8
Q

What happens during Perimenopause?

A
  1. Menstrual cycle irregularity, anovulatory cycles.
  2. Vasomotor symptoms
  3. Psychological symptoms
  4. Sleep Disturbances
  5. Sexual issues
  6. 10-15 fold increase in FSH, 4-5 fold increase in LH, 90% decrease in estradiol.
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9
Q

What was the Women’s Health Initiative (WHI)?

A
  1. Set of clinical trials and studies to address health issues in post-menopausal women.
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10
Q

What were the 3 interventions used in the WHI?

A
  1. Hormone Therapy
  2. Dietary Modification
  3. Calcium/Vit D supplementation.
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11
Q

Characteristics of Hormonal therapy in WHI?

A
  1. conjugated equine estrogen + MPA
    -Hysterectomy CEE only.
  2. Expected to decrease CHD
    -Increased stroke
  3. Expected to increase risk of breast cancer.
    -combination EandP did
    halted 5 years in
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12
Q

Characteristics of Dietary Modification in WHI?

A
  1. Low fat diet
  2. Expected to decrease CHD, stroke, CVD
    - modest decrease
  3. Expected to decrease risk of colorectal cancer.
    - possible
  4. Expected to decrease risk of breast cancer.
    - dont know
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13
Q

Characteristics of Calcium/Vit D supplementation in WHI?

A
  1. 1g/d Ca, 400 IU of Vit D
  2. Expected to reduce risk of bone fractures.
  3. Expected to reduce risk of colorectal can
    - NO
  4. Increased risk of kidney stones.
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14
Q

Criticisms of WHI?

A
  1. Low adherence, High attrition
  2. Under reported benefits
  3. Ave age was 63, menopause typically begins 51.
    - Only 3.5% age 50-54
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15
Q

What are the goals of treatment for menopause?

A
  1. Relieve menopausal symptoms
    - hot flashes (short term)
  2. Prevention of osteoporosis (long term)
    - balance against risks
  3. Estrogen + Progestogen is recommended therapy.
    - Estrogen only if hysterectomy
    - Progestogen protects against uterine/endometrial cancer.
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16
Q

What oral estrogens are used to treat Menopausal symptoms?

A
  1. Conjugated Equine Estrogens
    - 50-60% estrone sulfate, remainder equine
    - std. dose = 0.625mg/d
  2. Oral Estradiol (Estrace, micronized estradiol)
    - Estradiols converted to estrones in intestinal mucosa and liver.

Increase hepatic synthesis SHBG

17
Q

What are characteristics of Transdermal Estrogens?

A
  1. Bypass liver/GI, first-pass metabolism
  2. more physiological estradiol/estrone ratio
  3. DONT increase SHBG, lower lipids
  4. once or twice wk 50ug/d equals .625mg CEE.
  5. Gels and creams less consistent.
18
Q

What are characteristics of SQ implants of estrogen?

A

Can last up to a year.

NOT popular in US.

19
Q

What are characteristics of intranasal spray estrogens?

A

once/twice daily

as effective as oral or transdermal.

20
Q

Characteristics of Vaginal rings?

A

Estring, Femring
1. Effective at low doses, lower serum lipids and decrease bone loss.
Last for 3 months

21
Q

What are AE of estrogens?

A

Nausea, HA, breast tenderness, heavy bleeding.
Long term:
-Thromboembolism, CHD, stroke, breast cancer.

22
Q

Drug Drug interactions of estrogens?

A
  1. Anticonvulsive may increase estrogen metabolism. Higher doses needed.
  2. Estrogens increase TBG, CBG
23
Q

What are Phytoestrogens?

A

Soy Isoflavones, popular but not effective.

24
Q

Why are Progestogens always included in HRT?

A

To suppress endometrial hyperplasia/cancer.

NOT in women w/ hysterectomy

25
Q

How do Progestogens oppose Estrogen?

A
  1. By decreasing nuclear ER concentrations.

- Promote estradiol conversion to estrone in endometrium.

26
Q

What are the 4 Estrogen-Progestogen regimens?

A
  1. Continuous cyclic
  2. Continuous combined
  3. Continuous long cycle
  4. Intermittent combined (continuous pulsed or pulsed progestogen)
27
Q

What are characteristics of the Continuous Cyclic regimen?

A
  1. Estrogen daily, Progestogen lasts 12-14 days of 28d cycle.
  2. Results in withdrawal bleeding in 90% post DC of progestogen.
  3. Oral: .625mg CEE + 5/10 mg MPA
  4. Transdermal: 50ug E2 + .14/.25 mg norethinorone.
28
Q

What are characteristics of the Continuous combined regimen?

A
  1. Estrogen + Progestogen continuously
  2. Oral or Transdermal
  3. Results in endometrial atrophy and absence of bleeding.
  4. Initially causes unpredictable spotting/bleeding.
    - Decrease E or Increase P
29
Q

What are characteristics of the Continuous long-cycle regimen?

A
  1. Estrogen daily
  2. Progestogen every other month for 12-14d
  3. Bleeding may be heavier and last longer than continuous cyclic regimen.
30
Q

What are characteristics of the Intermittent combined regimen?

A
  1. 3 days of estrogen followed by 3 days Estrogen + Progestogen.
    - repeated w/o interruption.
  2. Decrease incidence of bleeding
  3. Allows a lower progestogen dose = low AE
31
Q

What is the quarterly progestin regimen?

A
  1. MPA 14d q 3 months

2. High incidence of endometrial hyperplasia

32
Q

What are advantages of Micronized progesterone?

A
  1. 100-200 mg/d

2. Less bleeding less effect on blood lipids.

33
Q

Can Levonorgestrel IUD be used as HRT?

A

Yes but it is OFF Label

34
Q

What effects does Drospirenone have?

A
  1. Progestogenic
  2. Anti-androgenic
  3. Anti-mineralocorticoid
  4. decreased hyperplasia, no hyperkalemia.
35
Q

What are AE of progestogens?

A
  1. Irritability, HA, sleep disturbance
  2. Depression
  3. Bloating
36
Q

When do androgen levels fall?

A

After age 20

-Levels

37
Q

Where and from what is Testosterone produced in women after age 20?

A

50% of T produced peripherally.

From DHEA and Androstenedione released by adrenals.

38
Q

How much of Testosterone is bound by SHBG and when is there more unbound?

A

99%

After menopause

39
Q

What is the major source of Testosterone post menopause?

A

Ovaries

Endocrine (9 decks)

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