Ex 4 L2. MHT 2 (36) Flashcards
Current recommendations for MHT onset:
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
Methods of admin for combined estrogen and progestin
Continuous cyclic therapy
Continuous long cycle
Continuous combined
E + P: Continuous Cyclic therapy
“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
E + P Continuous Cyclic Therapy drugs
Premphase - Oral
Conjugated estrogens, medroxyprogesterone acetate
Combipatch - Transdermal, estradiol, norethindrone acetate
E + P Continuous Long Cycle (Rare)
“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
E + P continuous Combined:
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
E + P Continuous Combined drugs
-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
Progestin for Endometrial protection drugs: Medroxyprogesterone
Route: Oral
Brand: Provera
Minimal dose for continuous: 2.5 mg
Minimal dose for Cyclic: 5mg
Progestin for Endometrial protection drugs: Norethindrone acetate
Route: Oral
Brand: Aygestin
Minimal dose for continuous: 5mg
Minimal dose for cyclic: 5mg
Progestin for Endometrial protection drugs: Micronized Progestin
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
Progestin for Endometrial protection drugs: Levonorgestrel
Route: Vaginal/Intrauterine
Brand: Mirena IUD
Minimal continuous: 0.20 mcg
Minimal cyclic: N/a
Progestin for Endometrial protection drugs: Progesterone Gel
Route: Vaginal/Intrauterine
Brand: Crinone
Minimal continuous: 45mg
Minimal cyclic: 45 mg
Estrogen and SERM
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
Estrogen and SERM drug
Duavee
route: oral
Estrogen: Conjugated estrogen 0.45mg
SERM component: Bazedoxifene 20 mg
80% of women have aches
Deciding regimen: Preferred: Transdermal Estrogen +/- Progestin
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)
Deciding regimen: Alternative 1: Bazedoxifene (SERM) + Estrogen
Avoid vaginal bleeding
Less breast tenderness
Less altered mood
Deciding regimen: Alternative 2:
Oral Estrogen +/-
Systemic Vaginal Estrogen +/- Progestin
Recommended Treatment Duration:
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
What to avoid for vasomotor symptoms
Black Cohosh
Dong Quai
-Liver toxicity
What to take for vasomotor symptoms
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
Non-Hormonal Therapy SSRIs/SNRIs for Hot flashes
Drug of choice if no estrogen
Selective Serotonin Reuptake inhibitors (SSRIs)
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
Avoid Paroxetine with_ strong CYP2D^ inhibitors reduce efficacy of __
Tamoxifen; Tamoxifen
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Venlafaxine (Effexor) 37.5-150mg/day
Desvenlafaxine (Pristiq) 50-100mg/day
Duloxetine (Cymbalta) (60mg/day)
SE: Dry mouth, anorexia, nausea, constipation
Fezolinetant (Veozah)
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
Bio-identical hormone replacement therapy
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
Bio-identical hormone replacement therapy drug
Bijuva
Route: Oral
Estrogen: Estradiol 0.5mg or 1 mg
Progestin: Micronized progestin 100mg
Menopausal Decision Support management
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
First line Tx of Genitourinary Syndrome of menopause
Non-hormonal
Lubricants
-Short duration of action
-Frequent applications needed
-Vaginal moisturizers
-2-3 applications
Second lineTx of Genitourinary Syndrome of menopause
Estrogen
Topical
Cream*
Tablet*
Ring
-low dose oral contraceptive
*low-dose do not require progestin for endometrial protection
Ospemifene (Osphena)
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
Prasterone (Intrarosa)
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
MHT principles
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