1. MHT

Question 1

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

Answer 1

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

Question 2

During menopause, ________ and __________ are also affected.

Answer 2

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

Question 3

What is the primary therapy for menopausal symptoms?

Answer 3

Estrogen

Question 4

Tx for menopause in:

• 1. Women with intact uterus
• 2. Women without an intact uterus

Answer 4

1. WITH uterus: estrogen + progestin
2. WITHOUT uterus: estrogen

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

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

Answer 7

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

Question 8

MOA of Estrogen?

Answer 8

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

Question 9

Estrogen causes a ↓ production/activity of?

Answer 9

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

Question 10

Estrogen causes a ↑ production/activity of?

Answer 10

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

Question 11

We do NOT want to give Estrogen to who?

Answer 11

Those at-risk of clotting.

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

• • ↓/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

Question 17

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

Answer 17

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

Question 18

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

Answer 18

Treat with low-dose topical vaginal estrogen.

Question 19

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

Answer 19

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

Question 20

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

How does this alter how we treat?

Answer 20

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

Question 21

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

Answer 21

No. Risks and benfits are attenuated/eliminated.

Question 22

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

Answer 22

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

Question 23

What are SERMs and TSECs?

Answer 23

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.

Question 24

2 SERM’s

Answer 24

1. Ospemifene
2. Clomiphene

Question 25

**_1 TSEC_**

Answer 25

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

Question 26

What is the clinical indication for the SERM, **Ospemifene**?

Answer 26

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

Question 27

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

Answer 27

1. **Ospemifine** 2. **Tropical estrogen cream**

Question 28

**MOA** of Ospemifene (SERM) for Dyspareunia.

Answer 28

- 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

Question 29

**AE's** associated with the SERM, **Ospemifene?**

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

What is the MOA of the SERM, **Clomiphene**?

Answer 32

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

Question 33

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

Answer 33

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

Question 34

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

Answer 34

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.

Question 35

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

Answer 35

1. Tx **moderate-to-severe vasomotor sx's i**n menopausal _women with a uterus._ 2. **Prevent post-menopausal osteoporosis** (along w/ Ca2+ and Vit D) in _women with a uterus_

Question 36

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

Answer 36

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

Question 37

**MOA** of the TSEC, Bazedoxifene?

Answer 37

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)

Question 38

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

Answer 38

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]

Question 39

**AE's** and **CI** associated with the TSEC, **Bazedoxifene**?

Answer 39

**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.