Ex 4 L2. MHT 2 (36)

Question 1

Current recommendations for MHT onset:

Answer 1

Initiation of tx should be limited to women Age <60 or Within 10 years of last period
**does not mean women under 60 HAVE to start MHT

Question 2

Methods of admin for combined estrogen and progestin

Answer 2

Continuous cyclic therapy
Continuous long cycle
Continuous combined

Question 3

E + P: Continuous Cyclic therapy

Answer 3

“Sequential treatment”
Estrogen administered daily
Progesterone administered at least 12-14 days of a 28 day cycle
Scheduled withdrawal bleeding ~90%
Preferred in recently menopausal women

Question 4

E + P Continuous Cyclic Therapy drugs

Answer 4

Premphase - Oral
Conjugated estrogens, medroxyprogesterone acetate
Combipatch - Transdermal, estradiol, norethindrone acetate

Question 5

E + P Continuous Long Cycle (Rare)

Answer 5

“Cyclic withdrawal”
Estrogen administered daily
Progesterone co-administered with estrogen for at least 12 to 14 days every other month
Results in 6 scheduled bleeding times per year
Limited safety data: endometrial protection unclear

Question 6

E + P continuous Combined:

Answer 6

Daily E + P
Results in endometrial atrophy and absence of vaginal bleeding
Initial unpredictable spotting or bleeding which usually resolves within 6-12 months
Drug free period of 1-2 weeks may help stop bleeding
Recommended for women >2 years post-final menstrual period
Long-term endometrial protection: Best

Question 7

E + P Continuous Combined drugs

Answer 7

-Prempro:
Oral
E - conjugated estrogens
P - Medroxyprogesterone acetate
-Fyalov Jinteli
Oral
E: Ethinyl Estradiol
P: Norethindrone acetate
-Angeliq:
Oral
E: Estradiol
P: Drospirenone
-Activella
Amabelz
Mimvey:
Oral
E: estradiol
P: Norethindrone acetate
-Bijuva:
Oral
E: Estradiol
P: Progesterone
-ClimaraPro:
Transdermal
E: Estradiol
P: Levonorgestrel
-Combipatch
Transdermal
E: Estradiol
P: Norethindrone acetate

Question 8

Progestin for Endometrial protection drugs: Medroxyprogesterone

Answer 8

Route: Oral
Brand: Provera
Minimal dose for continuous: 2.5 mg
Minimal dose for Cyclic: 5mg

Question 9

Progestin for Endometrial protection drugs: Norethindrone acetate

Answer 9

Route: Oral
Brand: Aygestin
Minimal dose for continuous: 5mg
Minimal dose for cyclic: 5mg

Question 10

Progestin for Endometrial protection drugs: Micronized Progestin

Answer 10

PREFERRED:
-Has potential to be given as IUD
More localized, less systemic
Route: Oral
Brand: Prometrium
Minimal dose for continuous: 100mg
Minimal dose for cyclic: 200mg

Question 11

Progestin for Endometrial protection drugs: Levonorgestrel

Answer 11

Route: Vaginal/Intrauterine
Brand: Mirena IUD
Minimal continuous: 0.20 mcg
Minimal cyclic: N/a

Question 12

Progestin for Endometrial protection drugs: Progesterone Gel

Answer 12

Route: Vaginal/Intrauterine
Brand: Crinone
Minimal continuous: 45mg
Minimal cyclic: 45 mg

Question 13

Estrogen and SERM

Answer 13

AKA: “Tissue-selective estrogen complex; (TSEC)
SERM:
-Non-hormonal agent
Agonist: Bone
Antagonist: Breast, uterus
Decrease risk of endometrial cancer
VTE, DVT, stroke risks?
Overweight women (BMI .27kg/m^2)
To treat both menopausal symptoms and prevent bone loss in women with an intact uterus
Side effects: GI track disorders, muscle spasm, neck pain , dizziness, oropharyngeal pain

Question 14

Estrogen and SERM drug

Answer 14

Duavee
route: oral
Estrogen: Conjugated estrogen 0.45mg
SERM component: Bazedoxifene 20 mg
80% of women have aches

Question 15

Deciding regimen: Preferred: Transdermal Estrogen +/- Progestin

Answer 15

Less thromboembolic risk, stroke, and heart attack
Less headache, breast tenderness
Consider in hypertriglyceridemia, liver disease, gallbladder disease
Gi intolerance (nausea/vomiting from oral product)
SE:
Skin irritation
Skin transfer possible (topical)

Question 16

Deciding regimen: Alternative 1: Bazedoxifene (SERM) + Estrogen

Answer 16

Avoid vaginal bleeding
Less breast tenderness
Less altered mood

Question 17

Deciding regimen: Alternative 2:

Answer 17

Oral Estrogen +/-
Systemic Vaginal Estrogen +/- Progestin

Question 18

Recommended Treatment Duration:

Answer 18

No set duration of hormone therapy for menopausal symptoms
BEERS - use of MHT in women over 65 is best avoided
Balance an individuals ongoing benefits with personal risks that may be increasing with age and longer duration of hormone therapy
Evaluate patient annually
Consider periodic trials of tapering stopping or changing to safer lower-dose transdermal routes
Hormone therapy for 5.6 to 7.3 years did not affect all-cause mortality at 18 years

Question 19

What to avoid for vasomotor symptoms

Answer 19

Black Cohosh
Dong Quai
-Liver toxicity

Question 20

What to take for vasomotor symptoms

Answer 20

Gabapentin - neuropathic pain, diabetic
-Symptoms: dizziness
Oxybutynin:
Bid, antimuscarinic, anticholinergic
Treats OAB
Elderly - long term use is associated with cognitive decline and dry mouth
-SSRI/SNRI
-Fezolinetant

Question 21

Non-Hormonal Therapy SSRIs/SNRIs for Hot flashes

Answer 21

Drug of choice if no estrogen

Question 22

Selective Serotonin Reuptake inhibitors (SSRIs)

Answer 22

Paroxetine (brisdelle) 7.5mg QHS
Paroxetine (Paxil, Pexeva) 10-20 mg daily
Paroxetine CR (Paxil, CR) 12.5 or 25mg/day
Citalopram (Celexa) 10-30mg/day
Escitalopram (Lexapro) 10-20mg/day
DO NOT WITHDRAW SUDDENLY

Question 23

Avoid Paroxetine with_ strong CYP2D^ inhibitors reduce efficacy of __

Answer 23

Tamoxifen; Tamoxifen

Question 24

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Answer 24

Venlafaxine (Effexor) 37.5-150mg/day
Desvenlafaxine (Pristiq) 50-100mg/day
Duloxetine (Cymbalta) (60mg/day)
SE: Dry mouth, anorexia, nausea, constipation

Question 25

Fezolinetant (Veozah)

Answer 25

Neurokinin 3 receptor (NK3R) antagonist Thermoregulatroy center in hypothalamus is innervated by KNDY neurons that are stimulated (+) by neurokinin B (NKB) and inhibited (-) by estrogen During menopause, decrease in estrogen disrupts balance lead to unopposed NKB stimulation = Increased vasomotor symptoms -Contraindications: Known cirrhosis Severe renal impairment or end-stage renal disease (eGFR <30ml/min/1.73m^2) **Concomitant use with CYP1A2 inhibitors** Warning and precaution: Increased LFT 45mg po daily **Must check liver function tests (LFT) before initiation and at 3, 6, and 9 months If >2 * ULN - Contraindicated** Common SE: Abdominal pain, diarrhea, insomnia, back pain, hot flash Cost: $550/month

Question 26

Bio-identical hormone replacement therapy

Answer 26

Compounds with unique mix of estradiol, estrone, estriol, and progesterone -Bi-estrogens, tri-estrogens +/- Testosterone -Tablets patches, compounded creams, gels, injectable prescriptions -Wiley protocol Insurance coverage minimal "Dearth" of evidence support use for compounded products Only I FDA- approved bio-identical therapy

Question 27

Bio-identical hormone replacement therapy drug

Answer 27

Bijuva Route: Oral Estrogen: Estradiol 0.5mg or 1 mg Progestin: Micronized progestin 100mg

Question 28

Menopausal Decision Support management

Answer 28

Yes: Women within 10 years since menopause + Low 10 year CVD (<5%) May use MHT (oral or transdermal) Maybe: Women within 10 years since menopause + moderate 10-year CVD (5-105) Avoid oral, prefer transdermal NO: Women with high 10-year CVD (>10%) Avoid systemic MHT for women with **Moderate to high breast cancer risk (1.67 to >5%)** If genitourinary symptoms, may consider low-dose vaginal estrogen or other treatments

Question 29

First line Tx of Genitourinary Syndrome of menopause

Answer 29

**Non-hormonal** Lubricants -Short duration of action -Frequent applications needed -Vaginal moisturizers -2-3 applications

Question 30

Second lineTx of Genitourinary Syndrome of menopause

Answer 30

**Estrogen** Topical Cream* Tablet* Ring -low dose oral contraceptive *low-dose do not require progestin for endometrial protection

Question 31

Ospemifene (Osphena)

Answer 31

Tx of **dyspareunia** **BLACK BOX WARNING Endometrial cancer Stroke VTE** 60mg once daily in **postmenopausal women** Taken with meals SE: Vaginal discharge Endometrial hyperplasia **Hot flashes: 7-12%** Similar precautions to estrogen therapies

Question 32

Prasterone (Intrarosa)

Answer 32

Tx of dyspareunia Inactive DHEA converted to active estrogens and androgens Intravaginal 6.5 mg once daily at bedtime in **postmenopausal women** No black box warning **Contraindications: Undiagnosed vaginal bleeding** **Avoid: History of breast cancer** Common se: vaginal discharge (5.7-14%) Cost: $180/month Do not rely on oral DHEA supplements **Estrogen based regimen remain the first line for moderate-severe symptoms of vulvovaginal atrophy**

Question 33

MHT principles

Answer 33

Tx **should be tailored to the individual** and will vary based on **symptom severity, age, medical profile, personal preference, and estimated benefit/risk ratio (osteoporosis fracture risk, CVD risk, breast cancer risk, and thromboembolic risk) = SHARED DECISION MAKING**