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Endo/Repro II Test 1 > 1. MHT > Flashcards

1. MHT Flashcards

1
Q

What are symptoms of menopause (body is not making enough estrogen)?

A
  1. Hot flashes
  2. Night sweats
  3. Vaginal dryness/painful intercourse/sexual DYS
  4. Sleep problems
  5. Mood/cognitive problems
  6. Urinary incontinence
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2
Q

During menopause, ________ and __________ are also affected.

A
  1. Bones (osteopenia, -porosis, fractures)
  2. CV (ACS/ MI, CVD)
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3
Q

What is the primary therapy for menopausal symptoms?

A

Estrogen

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4
Q

Tx for menopause in:

    1. Women with intact uterus
    1. Women without an intact uterus
A
  1. WITH uterus: estrogen + progestin
  2. WITHOUT uterus: estrogen
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5
Q

Why must a woman with an intact uterus be treated with [estrogen + progestin]?

A
    • Estrogen alone will cause endometrial proliferation, which can lead to hyperplasia and endometrial carcinoma.
    • Progestin’s oppose effects of estrogen’s.
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6
Q

What are the 4 estrogens available for use in menopausal hormone therapy?

A

1) Estradiol
2) Conjugated estrogens (CE)
3) Esterified estrogens (EE)
4) Estropipate: Crystallized estrone solubilized w/ sulfate and then stabilized w/ piperazne

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7
Q

What are the 3 progestin drugs available for menopausal hormone therapy?

A
  • 1) Medroxyprogesterone (MPA alone or with CE)
  • 2) Methyltestosterone (alone or with EE)
  • 3) Progesterone (alone)
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8
Q

MOA of Estrogen?

A
  1. Estrogen binds to a/B- estrogen receptors on the cell membrane.
  2. Transferred to nucleus => increased gene and protein expression
  3. Physiological response.
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9
Q

Estrogen causes a ↓ production/activity of?

A
  1. Cholesterol (TC/LDL-C)
  2. Anti-thrombin III
  3. Osteoclast activity (bone turnover)
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10
Q

Estrogen causes a ↑ production/activity of?

A
  1. TAG’s and HDL-C
  2. Clotting factors
  3. Platelet aggregation
  4. Na+ and fluid retention
  5. Thyroid Binding Globulin (TBG)
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11
Q

We do NOT want to give Estrogen to who?

A

Those at-risk of clotting.

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12
Q

List 7 potential AE’s associated with a combo of estrogen + progestin used for treatment of postmenopausal women with a uterus.

A
  1. Breast cancer
  2. CHD
  3. Dementia (aged 65 y/o +)
  4. GB disease
  5. Stroke
  6. Venous thromboembolism
  7. Urinary incontinence ***
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13
Q

List 3 potential benefits associated with a combo of estrogen + progestin used for treatment of postmenopausal women.

A
  1. Improvement of diabetes
  2. Less incidence of all fractures
  3. Less incidence of colorectal cancer
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14
Q

List 5 potential AE’s associated with estrogen used for treatment of postmenopausal women.

A
  1. Dementia (aged 65 y/o +)
  2. GB disease
  3. Stroke
  4. Venous thromboembolism
  5. Urinary incontinence
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15
Q

List 3 potential benefits associated with estrogen thrapy used for treatment of postmenopausal women.

A
  1. ↓ incidence of breast cancer (invasive)
  2. ↓ incidence of all fractures
  3. Improvement of diabetes
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16
Q

The Women’s Health Initiative (WHI) study found that MHT is very effective for what?

A
    • ↓/treat vasomotor sx’s and vaginal changes (and their associated complications)
    • But do NOT use to prevent CVD or dementia and to help bones or prevent colorectal cancer
17
Q

What is the recommendation/agreement for using MHT therapy in younger women?

A

Can be used to tx moderate-severe menopausal sx’s in relatively young (up to age 59 or within 10 years of menopause)

18
Q

What is the recommendation/agreement for MHT therapy in women with vaginal sx’s only?

A

Treat with low-dose topical vaginal estrogen.

19
Q

Which age group has less risk of blood clots/stroke from MHT therapy?

A

Both estrogen and estrogen + progestin increase risk of blood clots, however risk is lowest in 50-59YO.

20
Q

There is an increased risk of breast cancer with MHT when treated for how long?

How does this alter how we treat?

A
  • 3-5 years of continous estrogen + progestin
  • Use it at the lowest dose possible for the shortest amount of time.
21
Q

Do the risk and benefits of MHT continue even when MHT is stopped?

A

No. Risks and benfits are attenuated/eliminated.

22
Q

MHT therapy is used for moderate-severe vasomotor symptoms by giving…

A

lowest dose to control sx for the shortest amount of time (by re-evaulating) pt.

23
Q

What are SERMs and TSECs?

A
  1. SERMs (selective-estrogen receptor modulators) bind selectively to receptors in tissues with GOOD pro-estrogenic actions and beneficial (non-harmful) anti-estrogenic (ANT) in other tissues, like bone, brain, breast and endometrium
  2. TSECs (tissue selective estrogen complexes) are SERMS + estrogen compound.
24
Q

2 SERM’s

A
  1. Ospemifene
  2. Clomiphene
25
Q

1 TSEC

A
  1. Bazedoxifene (in US, only used as a combo w/ CE)
26
Q

What is the clinical indication for the SERM, Ospemifene?

A
  1. Tx moderate-to-severe dyspareunia (painful intercourse), a sx of vulvar and vagnal atrophy (VVA) during menopause.
27
Q

If a patient presents with menopause and their CC is dysparenuria?

A
  1. Ospemifine
  2. Tropical estrogen cream
28
Q

MOA of Ospemifene (SERM) for Dyspareunia.

A
  • Acts as a estrogen AGO by binding to ER’s in the vagina and estrogen ANT in breast tissue (anti-estrogenic) –>
  • ↑ superficial cell growth,
  • ↑ vaginal secretions,
  • ↓ vaginal pH,
  • ↓ pain/discomfort during intercourse
29
Q

AE’s associated with the SERM, Ospemifene?

A
  1. Worsening of hot flashes/sweating
  2. Acts similar to estrogen in terms of coagulation (↑ risk of stroke/VTE; but at lower rate than estrogens alone)
  3. Endometrial thickening (proliferation) and hyperplasia/malignancy, but no cases in clinical trials yet
30
Q

What are the contraindications for using the SERM, Ospemifene, which are the same as estrogens.

A
  1. Unusual/abnormal vaginal bleeding
  2. Thromboembolic diseases: CVA or MI or VTE or PE or DVT
  3. Caution with use in smokers
  4. Estrogen-related neoplasia’s: uterine or ovarian or breast
31
Q

What is the clinical indication for using the SERM, Clomiphene?

A

Has purely anti-estrogenic actions to stimulate ovulation in Infertile women.

32
Q

What is the MOA of the SERM, Clomiphene?

A
  1. Blocks inhibitory actions of estrogen on hypothalamus GnRH and pituitary gonadotropin release (anti-estrogen) =>
      • ↑ gonadotropin (FSH, LH) secretion => stimulating the ovaries to develop oocyte follicles
33
Q

Which patients are the most significant effects seen in when treated with the SERM, Clomiphene?

A

Induces ovulation in women w/ amenorrhea, PCOS, and dysfunctional bleeding w/ anovulatory cycles.

34
Q

What are the 4 AE’s associated with the SERM, Clomiphene?

A
  1. Multiple births (99% of times = twins)
  2. Ovarian cysts —> ovarian cancer w/ prolonged use (limit use to 3 cycles)
  3. Hot flashes
  4. Luteal-phase dysfunction –> inadequate progesterone prod.
35
Q

2 clinical indications for the TSEC, Bazedoxifene (w/ CE)?

A
  1. Tx moderate-to-severe vasomotor sx’s in menopausal women with a uterus.
  2. Prevent post-menopausal osteoporosis (along w/ Ca2+ and Vit D) in women with a uterus
36
Q

Can Bazedoxifene (w/CE) be used as a progestin and estrogen in people with uterus?

A

YES. It is usually the 2nd go to in poeple with sx.

37
Q

MOA of the TSEC, Bazedoxifene?

A
  1. ANT activity in endometrium (replaces progestin-concept in women with an intact uterus) and in breast tissue
  2. Has estrogenic AGO effects, especially in bone (CE agent)
38
Q

How does Bazedoxifene differ from the 1st gen. SERMS as far as effects and utility?

A
  1. Does NOT stimulate endometrial proliferation
  2. Destroy HER2 malignant cells (SERDs), including cells resistant to Tamoxifen (similar to anti-estrogen drug Fluvestrant)
  3. Less vaginal bleeding than [CE w/ progestin]
39
Q

AE’s and CI associated with the TSEC, Bazedoxifene?

A

AE

  1. ALL AE are due to estrogen, because it has CE.
  2. Bazedoxifene-specific AE: can worsen flashes/sweating (similar to Tamoxifen, Raloxifene and Ospemifene

CI

  1. CI in all cases estrogens are CI.

Endo/Repro II Test 1 (23 decks)

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