Lecture 35: Menopausal Hormone Therapy Flashcards
Menopause
-final menstrual period
Menopause diagnosis confirmed after ___
-12 months of amenorrhea
Premenopause
-period of endocrine changes BEFORE menstruation stops
Perimenopause (climacteric)
-endocrine changes surrounding the menopause
postmenopause
-endocrine changes AFTER menstruation stops
Menopause onset age
-51 years (40-58)
-40% of woman’s life is postmenopausal
Premature menopause
-premature ovarian insufficiency (POI)
-before age 40
-hysterectomy, radiation therapy, chemo
-1%
-inc risk of mortality and morbidity
Worst symptoms of menopause occur
within first 1-2 years
menopause symptoms last how long
7+ years
Causes of menopause
-physiologic
-oophorectomy
-breast cancer chemo
-radiation therapy
Physiologic cause of menopause
-deterioration of follicular cells and ova w aging
-dec estrogen and progesterone levels = inc FSH and LH
Clinical presentation of menopause
-hot flashes
-night sweats
-irregular menses
-episodic amenorrhea
-sleep disturbance
-mood changes
-fatigue
-vulvovaginal atrophy
-UTI
-dec sex drive
-urinary freq, urgency
Long term consequences of menopause
-CV disease (#1 killer of women)
-bone loss
-osteoarthritis
-body comp
-skin changes
-balance
Treatment of Menopausal symptoms
-nonpharmacologic therapy
-MHT
-nonhormonal alterntatives
vasomotor symptoms
-hot flashes
-night sweats
Recomended nonpharmacologic treatment of menopause
-weight loss
-CBT
-clinical hypnosis
-stellate ganglion block (pain management injection)
Scam therapies for menopause
-lifestyle changes
-????
this slide ??? 12
Indications for Menopausal Hormone Therapy
-Vasomotor symptoms
-Vulvovaginal atrophy
-osteoporosis prevention
ABSOLUTE contraindications to MHT
-random vaginal bleeding
-pregnany
-endometrial/breast cancer
-stroke
-thromboembolic disorder
-active liver disease
RELATIVE contraindications to MHT
-uterine leiomyoma
-migraine w aura
-seizure disorders
-diabetes
-hypertriglyceridemia
-active gallbladder disease
-high heart disease risk
-family history of breast cancer
Estrogen monotherapy is only to be used on
women WITHOUT a uterus
Estrogen monotherapy dosage forms
-oral
-transdermal
-topical
-intravaginal
-IM injections
Oral estrogen monotherapy products
-more side effects
-Premarin (conjugated)
-Menest (esterified)
-Estrace (micronized)
Transdermal Estrogen monotherapy produts
-preferred
-Climara
-Lyllana
-Menostar
-Minivelle
-Vivelle-dot
-Dotti
Topical estrogen monotherapy products
-less used bc absorption varies and kids can get into it
-Estrogel
-Divigel
-Elestrin
-Evamist (spray)
Vaginal estrogen monotherapy products
-cream (estrace, premarin)
-insert (Imvexxy)
-tablet (vagifem, yuvafem)
-ring (estring, femring)
IM estrogen monotherapy injections
-more used for gender care
-try the other ones first
-estradiol cypionate (depo-estradiol)
-estradiol valerate (deletrogen)
Topical ESTROGEN vaginal products should be prescribed for:
-women EXCLUSIVELY experiencing vulvovaginal atrophy
PROGESTIN should be prescribed to
-women WITH uterus
-in addition to estrogen to dec risk of endometrial cancer
Concerns w hormone use
-women’s health initiative study
WHI purpose
-address common causes of death and poor quality of life for postmenopausal women
-15 year trials and studies
-effects of hormone therapy, diet, and calcium/vit D
WHI estrogen and progesterone therapy effects
-inc CV disease (esp thromboembolism)
-inc some cancer
-dec colorectal cancer
-dec hip fractures
WHI estrogen monotherapy effects
-inc CV but not really CHD
-no difference in cancer
-dec in hip fractures
Critical factors in determining whether hormone therapy reduces or inc risk of CHD
-time since menopause
-age of initiation
-no effect on cancer risk tho
risk of estrogen monotherapy for women <60 within 10 years of menopause
-no evidence of CHD
risk of estrogen monotherapy for women >10 years of menopause
-inc risk of CHD within the first 2 years
Highest risk group for CHD from estrogen monotherapy
-women 70-79 and >20 years of menopause
Risk of estrogen monotherapy on women w CHD
-no additional benefits
estrogen w progestin therapy age group risks
-lowkey same as estrogen monotherapy?
risk of breast cancer in women with a uterus
-increase
-no difference in mortality
risk of breast cancer in women w hysterectomy
-decreased
-no change in mortality
MHT current recommendations
-women UNDER 60
-OR
-within 10 years of last period
Methods of estrogen/progestin admin
-continuous cyclic therapy
-continuous long cycle
-continuous combined
Continuous CYCLIC therapy (e+p)
-sequential treatment
-estrogen daily
-progesterone 12-14 days out of a 28 day cycle
-mimic cycle
-scheduled withdrawal bleeding
Continuous CYCLIC therapy preferred in
-recently menopausal women
Continuous CYCLIC therapy products (e+p)
-Premphase
-Combipatch
Premphase
-Continuous CYCLIC
-oral
-conjugated ESTROGENS
-medroxyPROGESTERONE acetate
Combipatch
-continuous CYCLIC
-Transdermal
-Estradiol
-norethindrone acetate (progestin)
Continuous LONG cycle therapy (e+p)
-RARE
-“cyclic withdrawal”
-estrogen daily
-progesterone + estrogen for 12-14 days every OTHER month
-6 bleedings per year
-limited safety data
Continuous COMBINED therapy (e+p)
-estrogen AND progesterone daily
-endometrial atrophy = no bleeding
-unpredictable spotting that goes away 6-12 months
-drug free period of 1-2 weeks may help stop bleeding
Continuous COMBINED therapy recommended for
-women >2 years post-final menstrual period
-best long term endometrial protection
Continuous Combined products
-slide 32
Progestin for endometrial protection
-medroxyprogesterone (oral) Provera
-norethindrone acetate (oral) Aygestin
-micronized progestin (oral) (preferred) PROmetrium (peanut oil warning)
-levonorgestrel (vaginal) Mirena IUD
-progesterone gel (vaginal) Crinone
Estrogen and SERM
-tissue-selective estrogen complex (TSEC)
-treat menopausal symptoms
-prevent bone loss in women w uterus
Selective estrogen receptor modulator (SERM)
-non-hormonal
-bone agonist
-breast and uterus antagonist
-dec risk of endometrial cancer
-stroke risk?
-overweight women might not work on
Estrogen and SERM side effects
-GI disorders
-muscle spasm
-neck pain
-dizzines
-oropharyngeal pain
Estrogen and SERM product
-Duavee
-oral
-conjugated estrogen
-bazedoxifene (SERM)
Preferred MHT regimen
-transdermal estrogen +/- progestin
Why is transdermal estrogen +/- progetin preferred
-less thromboembolic risk, stroke, heart attack
-less headache
-less breast tenderness
-good for GI intolerance bc it not oral
transdermal estrogen +/- progestin considerations
-hypertiglyceridemia
-liver disease
-gall bladder disease
side effects of transdermal estrogen
-skin irritation
-skin transfer possible (topical)
Alternative MHT regimen
-bazedoxifene + estrogen
bazedoxifene + estrogen pros
-avoid vaginal bleeding
-less breast tenderness
-less altered mood
Alternative MHT regimen
-oral estrogen +/- progestin
-systemic vaginal estrogen +/- progestin
Recommended treatment duration of MHT
-no set duration
-suggest to avoid in women over 65
-weigh cost vs benefits
-evaluate annually
-consider periodic trials of tapering ot changing to lower dose/transdermal route
-MHT for 5-7 years did not affect mortality
Alternatives for vasomotor symptoms that are NOT recommended
-black cohosh (liver toxicity)
-dong quai (inc risk of bleed w warfarin)
Recommended alternatives for vasomotor symptoms
-gabapentin
-oxybutynin
-SSRI/SNRI
-fezolinetant
SSRI/SSNRI use for
-hot flashes (vasomotor)
-drug of choice if NO estrogen treatment
Avoid paroxetine with
Tamoxifen (breast cancer drug)
Strong CYP2D6 (paroxetine) inhibitors reduce efficacy of
Tamoxifen (breast cancer drug)
SSRIs
-Paroxetine (Brisdelle, Paxil, Pexeva) (7-15mg) (FDA) approved for menopause)
-Citalopram (10-30mg)
-Escitalopram (10-20mg)
SNRIs (serotonin and norepinephrine reuptake inhibitors)
-venlafaxine (Effexor) 37.5mg-150mg/day
-desvenlafaxine (Pristiq) 50-100
-duloxetine (Cymbalta) 60
side effects of SNRIs
-dry mouth
-anorexia
-nausea
-constipation
Fezolinetant (Veozah)
-NK3R ANTAgonist
-mod-severe vasomotor symptoms
-take w CYP1A2 inhibitors
-45mg PO qd
KDNY neurons
-innervate thermoreg center in hypothalamus
-stimulated by neurokinin B (NKB)
-inhibited by estrogen
Inc vasomotor symptoms caused by
-dec estrogen in menopause leads to unopposed NKB stimulation
Fezolinetant (Veozah) contraindications
-known cirrhosis
-severe renal probs
-must check liver function before starting at 3/6/9 months
Fezolinetant (veozah) side effects
-inc LFT
-ab pain
-diarrhea
-insomnia
-back pain
-hot flash
-expensive
Fezolinetant (veozah) contraindicated if LFT is greater than or equal to
2
-checked annually
Bio-identical hormone replacement therapy
-compounds w unique mix of estradiol, estrone, estriol, progesterone
-minimal insurance coverage
-only 1 FDA approved
-lack of data
Bio-identical hormone replacement therapy product
-Bijuva
-oral
-estradiol 0.5-1mg
-micronized progestin 100mg
Recommended menopausal symptom management for women within 10 years of menopause and low CVD
-may use MHT
-oral or transdermal
Recommended menopausal symptom management for women within 10 years of menopause w moderate CVD risk
-transdermal estrogen
-avoid oral
Recommended menopausal symptom management for women w high CVD risk
-avoid oral MHT
-if genitourinary symptoms: low dose vaginal estrogen
AVOID systemic MHT for women with
-high CV risk
-mod-high risk breast cancer risk
Genitourinary Syndrome of Menopause (GSM) first line treatments (nonhormonal)
-lubricants
-vaginal moisturizers (2-3/week)
Genitourinary Syndrome of Menopause (GSM) second line treatments (estrogen)
-topical cream/ring/tablet
-low dose oral contraceptive
Drugs for mod-severe Dyspareunia (painful intercourse)
-Ospemifene (oral)
-Prasterone (vaginal)
Ospemifene (osphena)
-treat dyspareunia
-SERM
-vagina and uterus agonist
-60mg PO wf
Ospemifene (osphena) recommended for
-POSTmenopausal women
Ospemifene (osphena) black box warning
-endometrial cancer
-stroke
-VTE
Ospemifene (Osphena) side effects
-vaginal discharge
-endometrial hyperplasia
-hot flashes (7-12%)
-similar precautions to estrogen therapies
Prasterone (Intrarosa)
-inactive Dehydroepiandrosterone (DHEA) converted to active estrogens and androgens
-intravaginal qd at bedtime
-no black box warning
-POST menopausal women
Prasterone (intrarosa) contraindications
-undiagnosed vaginal bleeding
-avoid if history of breast cancer
Which is first line for GSM??
idk man
Genitourinary syndrome of menopause
-vulvovaginal atrophy
-urinary tract dysfunction
-sexual dysfunction
-urinary freq/urgency
USPSTF graded estrogen D in PREVENTION of chronic conditions in postmenopausal women
-NO BENEFIT of estrogen + progesterone in women w INTACT uterus
-NO BENEFIT of estrogen alone in hysterectomy
eSTRING vs femRING***
-RING is bigger than STRING
-femRING has bigger systemic absorption
=can relieve vasomotor symptoms
-gotta put a girlie on progesterone w this one
