Ch10: Prescription Therapies

Question 1

depo provera

Conditions when risks outweigh benefits (4)

Answer 1

BP >160/95
Vascular disease
DM with vascular disease or DM >20 year duration
Stroke
Ischemic heart disease
Multiple risk factors for CVD

Question 2

Most biologically active estrogen

Answer 2

Estradiol

primary source from ovarian follicle

Question 3

Most abundant circulating endogenous estrogen in postmenopausal women

Answer 3

Estrone

converted from androstenedione secreted by adrenal cortex

Question 4

Major estrogen in pregnancy

Answer 4

Estriol

Question 5

Vaginal estradiol that exerts systemic effects

Answer 5

Femring

Question 6

Marketed conjugated equine estrogens (CEE)

Answer 6

Prempro
Premphase
in combination with synthetic medroxyprogesterone acetate

Question 7

Marketed synthetic conjugated estrogens

Answer 7

Cenestin (CE-A)
Enjuvia (CE-B)
no synthetic CE product is approved for osteoporosis

Question 8

Marketed estradiol

Answer 8

Oral: Estrace, Gynodiol, Innofem
Transdermal: (gels)Divigel, Estrogel, Elestrin, (spray)Evamist, (emulsion)Estrasorb, (matrix patch)Alora, Climara, Estradot, Menostar, Minivelle, Vitelli, (reservoir patch)Estraderm
Vaginal: Estrace, Estring, Femring, Vagifem, Yuvafem, Imvexxy
considered bio identical

Question 9

Marketed esterified estrogen

Answer 9

Menest, mixture containing 75-85% estrone

not indicated for osteoporosis

Question 10

Marketed estropiprate

Answer 10

Ogen, oral form of estrone sulfate, solubility day and stabilized by piperazine
approved for prevention of osteoporosis

Question 11

Marketed ethinyl estradiol

Answer 11

Femhrt

Question 12

Tamoxifen

Indicated treatment and antagonist/agonist effect on tissue

Answer 12

Primary prevention of breast ca in high-risk premenopausal and postmenopausal women (49% reduction in invasive ER pos breast ca)
Antagonist: breast
Agonist: bone, liver, uterus
Liver: decreases LDL, increases HDL
VMS: 50% women report hot flashes
VTE/PE: increased risk

Question 13

Raloxifene

Indicated treatment and antagonist/agonist effect on tissue

Answer 13

Osteoporosis retention and treatment and prevention of invasive breast ca in high-risk postmenopausal women
Agonist: bone
Antagonist: breast (76% breast ca reduction after 3y use)
Neutral: uterus, vagina
VTE/PE risk: increased
VMS: hot flashes less intense than seen with tamoxifen

Question 14

Bazedoxifene

Indicated treatment and antagonist/agonist effect on tissue

Answer 14

Treatment of osteoporosis 
Agonist: bone
Antagonist: breast, uterus
Neutral: vagina
VMS: mild hot flashes
VTE: increased

Question 15

Ospemifene

Indicated treatment and antagonist/agonist effect on tissue

Answer 15

Treatment of dyspareunia
Agonist: vagina, uterus
VTE: increased

Question 16

Toremifene

Indicated treatment and antagonist/agonist effect on tissue

Answer 16

Treatment of advanced estrogen sensitive breast ca, adjuvant treatment of early breast ca
Agonist: weaker on uterus than tamoxifen, liver, bone
Antagonist: breast
Prolonged QT interval which may lead to ventricular arrythmia

Question 17

Lasofoxifene

Answer 17

Treatment of osteoporosis

Agonist: bone, vagina, uterus

Question 18

USPSTF recommends use of low to moderate dose statin therapy for primary preventions where all (3) these criteria are met:

Answer 18

1. Age 40-75 years
2. Presence of one or more CVD risk factors: dyslipidemia, DM, HTN, smoking
3. Calculated 10-year risk of a CV event of 10% or greater

Question 19

AEs of statins (4)

Answer 19

Myalgias 3-5%
Myopathies 0.2-.2%
New-onset DM 9-27%
Hepatoxicity <1%

Question 20

Myalgias

Answer 20

Muscle pain
Flu-like symptoms
NL CK levels

Question 21

Myopathy

Answer 21

Muscle weakness

+/- elevated CK levels

Question 22

Myositis

Answer 22

Muscle tenderness due to inflammation
Elevated CK
Leukocytosis

Question 23

Myonecrosis

Answer 23

Muscle injury

Elevated CK levels

Question 24

Rate

Answer 24

Number of events per number of participants per time interval

Question 25

Relative risk

Answer 25

Rate of disease/outcome of interest in exposed group divided by rate of disease/outcome of interest in unexposed group

Question 26

Absolute risk or attributable risk

Answer 26

Risk difference between exposed and unexposed groups | “How many additional cases per year?"

Question 27

Number Needed to Treat (NNT)

Answer 27

Reciprocal of AR (absolute risk) | “How many people need to be treated to result in one less negative outcome?"

Question 28

Potential adverse events of estrogen therapy and estrogen-progesterone therapy (list 11)

Answer 28

``` Uterine bleeding Breast tenderness, sometimes enlargement Nausea Abdominal bloating Fluid retention in extremities Changes in the shape of the cornea, contact lens intolerance Headache, sometimes migraine Dizziness Mood changes, particularly with progestin Angioedema Gallstones, pancreatitis ```

Question 29

``` Coping strategies for ET or EPT adverse events: Fluid retention (4) ```

Answer 29

Restrict salt Maintain adequate water intake Exercise Try mild prescription diuretic

Question 30

Coping strategies for ET or EPT adverse events: | Bloating (3)

Answer 30

Switch to low dose non-oral continuous estrogen Lower progestogen Switch to another progestin or to micronized progesterone

Question 31

``` Coping strategies for ET or EPT adverse events: Breast tenderness (5) ```

Answer 31

``` Lower estrogen dose Switch to another estrogen Restrict salt Switch to another progestin Cut down on caffeine and chocolate ```

Question 32

Coping strategies for ET or EPT adverse events: | Headaches (6)

Answer 32

Switch to non-oral continuous estrogen Lower dose of estrogen or progestogen or both Switch to continuous-combined regimen Switch to progesterone or a 9-norpregnane derivative Ensure adequate water intake Restrict salt, caffeine and alcohol

Question 33

``` Coping strategies for ET or EPT adverse events: Mood changes (7) ```

Answer 33

Investigate pre-existing depression or anxiety Lower progestogen dose Switch progestogen Switch from systemic progestin to progestin intrauterine system Change to continuous-combined EPT regimen Ensure adequate water intake Restrict salt, caffeine, and alcohol

Question 34

Coping strategies for ET or EPT adverse events: | Nausea (4)

Answer 34

Advise taking oral estrogen tablets with meals or before bed Switch to another oral estrogen Switch to non-oral estrogen Lower estrogen or progestogen dose

Question 35

Coping strategies for ET or EPT adverse events: | Bleeding (2)

Answer 35

Lower dose of estrogen or progestogen | Switch to a non-progestogen combined therapy (bazedoxifene SERM)

Question 36

contraindications for ET or EPT (9)

Answer 36

Undiagnosed abnormal genital bleeding Known, suspected, or history of breast ca, except in appropriately selected patients being treated for metastatic disease or with oncology involvement Known or suspected estrogen-dependent neoplasia Active or history of DVT, PE Active or recent (<1y) arterial thromboembolic disease (CVA, MI) Liver dysfunction or disease Known or suspected pregnancy Known hypersensitivity to ET or EPT Porphyria cutaneous tardis

Question 37

List 6 main types of estrogen

Answer 37

Human estrogen (17beta estradiol, estrone, estriol) Animal-derived estrogen (conjugated equine estrogen) Synthetic estrogen (CE-A, CE-B) Synthetic estrogen analogs with steroid molecular structure (ethinyl estradiol) Synthetic estrogen analogs without a steroid molecular structure (stilbesterol derivatives, not used for menopause-related therapy) Plant-based estrogens without a steroid skeleton (phytoestrogens, not prescription products)

Question 38

Compare and contrast 4 human estrogens

Answer 38

Estradiol: 17 beta estradiol, most biologically active, secreted in ovaries, converts to estrone Estrone: weaker, 50-70% less active, most abundant circulating endogenous estrogen in postmenopause, conversion of androstenedione secreted by adrenal cortex to estrone by peripheral tissues, converts to estriol Estriol: weakest, only 10% as active as estradiol, major estrogen in pregnancy Estetrol: synthesized exclusively during pregnancy by human fetal liver, very weak estrogen, not FDA approved for use in the US

Question 39

Bazedoxifene and CEE combination, good alternative for:

Answer 39

Women who do not tolerate progesterone therapy, history of irregular bleeding associated with a thickened endometrial stripe