PHRM 825 Lecture 35&36 - Menopausal Hormone Therapy

when is menopause diagnosed

12 consecutive months of amenorrhea

the time period of endocrine changes BEFORE cessation of menstruation

pre menopause

the period of endocrine changes SURROUND the menopause

perimenopause

the time period of endocrine changes AFTER cessation of menstruation

postmenopause

occur before age 40

hysterectomy, radiation therapy, chemotherapy can be causes

premature menopause (premature ovarian insufficiency)

physiologic cause of menopause

deterioration of the follicular cells and ova with aging

decreased estrogen and progesterone, increased FSH and LH level

surgery cause of menopause

removal of ovaries (oophorectomy)

other causes of menopause

breast cancer chemotherapy and radiation therapy

vasomotor menopause symptoms

hot flashes and night sweats

genitourinary symptoms of menopause

vulvovaginal atrophy, urinary tract dysfunction, sexual dysfunction, urinary frequency

long term consequence of menopause

CV disease, bone loss, osteoarthritis, body composition, skin changes, balance

recommend non pharm therapies for menopause

weight loss

cognitive behavioral therapy

clinical hypnosis

stellate ganglion block

indications of MHT

vasomotor symptoms

genitourinary symptoms

premature hypoestrogenism

osteoporosis prevention

absolute contraindications to MHT

unexplained vaginal bleeding

pregnancy

endometrial/ breast cancer

stroke

thromboembolic disorders

active liver disease

who is estrogen mono therapy indicated for

women without a uterus

oral estrogen mono therapy

premarin (conjugated estrogens)

menest (esterified estrogen)

Estrace (micronized estradiol)

transdermal estrogen mono therapy

climara

lyllana

menostar

minivelle

vivelle dot

dotti

other topical mono therapies

topical gel (Estrogel, divigel, elestrin)

topical spray (evamist)

intravaginal mono therapy products

vaginal cream (Estrace, Premarin)

vaginal insert (imvexxy)

vaginal tablet (vagifem, yuvafem)

vaginal ring (estring, femring)

intramuscular injection mono therapies

estradiol cypionate (depo-estradiol)

estradiol valerate (delestrogen)

what is different between Estring and Femring

Femring requires a progesterone combo because it is absorbed systemically

also helps with vasomotor symptoms

what type of therapy should be used for women with an intact uterus and why

progestin in combination with estrogen

decreases risk of endometrial hyperplasia and cancer

estrogen only use effects of women <60 within 10 years of menopause

no evidence of CHD or breast cancer risk

favorable risk- benefit profile

estrogen only use effects on women >10 years of menopause or ages 60-69

increase risk of CHD and stroke

estrogen only use effects on women 70-79 years with >20 years of menopause

highest risk of CHD and stroke

the women's health initiative (WHI) showed estrogen plus progestin increased the risk of all of the following except:

stroke

fracture

heart attack

venous thromboembolism

breast cancer

fracture

initiation of menopause treatment should be limited to women who:

are age <60 OR within 10 years of last period

what are the three methods of administration for combined therapy

continuous cyclic therapy

continuous long cycle

continuous combined

sequential treatment

estrogen administered daily, progesterone administered at least 12-14 days of a 28 day cycle

scheduled withdrawal bleeding

continuous cyclic therapy

continuous cyclic therapy

oral route

conjugated estrogen + medroxyprogesterone acetate

Premphase

continuous cyclic therapy

transdermal

estradiol + norethindone acetate

Combipatch

cyclic withdrawal

estrogen administered daily

progesterone co-administerd with estrogen every other month

6 bleedings per year

continuous long cycle (rare)

daily estrogen + progesterone

results in endometrial atrophy and no bleeding

best long term endometrial protection

continuous combined

who is continuous combined therapy recommended for

women >2 years post-final menstrual period

continuous combined

oral

conjugated estrogen + medroxyprogesterone acetate

Prempro

continuous combined

oral

ethinyl estradiol + norethindrone acetate

Fyavolv + Jinteli

continuous combined

oral

estradiol + drospirenone

Angeliq

continuous combined

oral

estradiol + norethinedrone acetate

Activella + Mimvey

continuous combined

oral

estradiol + progesterone

Bijuva

continuous combined

transdermal

estradiol + levonorgestrel

ClimaraPro

continuous combined

transdermal

estradiol + norethindrone acetate

Combipatch

oral progestins for endometrial protection

medroxyprogesterone

norethindrone acetate

micronized progestin

vaginal/ intrauterine progestin for endometrial protection

levonorgestrel

progesterone gel

non hormonal agent

decreases risk of endometrial cancer

SERM

agonist and antagonist effects of SERMS

agonist: bone

antagonist: breast, uterus

side effects of estrogen + SERM

GI track disorders, muscle spasm, neck pain, dizziness

estrogen + SERM

oral

conjugated estrogen + bazedoxifene

Duavee

preferred regimen for MHT and why

transdermal estrogen +/- progestin

less DVT, stroke, MI

recommended treatment duration

no set duration

based on individual ongoing benefits

evaluate patient annually and attempt to taper

non recommended alternatives for vasomotor symptoms

Black Cohosh

Dong Quai

recommended alternatives (non hormonal) for vasomotor symptoms

gabapentin

oxybutynin

SSRI/SNRI

fezolinetant

what menopause symptom does SSRIs treat

hot flashes

paroxetine (Brisdelle, Paxil, Pexeva) -diff doses

paroxetine CR (Paxil CR)

citalopram (celexa)

escitalopram (lexapro)

SSRI

Venlafaxine (Effexor)

Desvenlafaxine (Pristiq)

SNRI (serotonin and norepinephrine reuptake inhibitors)

what should patients avoid taking with paroxetine and why

Tamoxifen because strong CYP2D6 inhibitors reduce efficacy of tamoxifen

neruokinin 3 receptor antagonist (NK3R)

Fezolinetant (Veozah)

how does veozah work

blocks NKB that stimulates thermoregulatory center in hypothalamus to help with hot flashes

contraindications of veozah

known cirrhosis

severe renal impairment

concomitant use with CYP1A2 inhibitors (lots of drug interactions)

downsides of veozah

must check liver function test before start and at 3,6,9 months

increased LFT

$550/ month

compounds with unique mix of estradiol, estrone, estriol, and progesterone

bio-identical hormone replacement therapy

bio-identical hormone replacement therapy (only one FDA approved)

oral

estradiol + micronized progestin

Bijuva

women who may definitely use MHT (oral or transdermal)

women within 10 years since menopause + low 10 year CVD risk <5%

rules of treatment for women within 10 years since menopause but moderate 10 year CVD risk (5-10%)

avoid oral estrogen

prefer transdermal administration

treatment for women with high 10 year CVD risk (>10%)

avoid systemic MHT

may use low dose vaginal estrogen for genitourinary symptoms

avoid systemic MHT use for women with risk of what condition

breast cancer risk

first line treatment for genitourinary symptoms

non hormonal

lubricants and vaginal moisturizers

second line treatment for genitourinary symptoms

estrogen:

topicals

low dose oral contraceptive

treatment of moderate- severe dyspareunia

SERM

ospemifene (osphena)

black box warning of ospemifene

endometrial cancer

stroke

VTE

hot flashes

treatment of moderate-severe dyspareunia

inactive DHEA converted to active estrogens and androgens

prasterone (intrarosa)

benefit of prasterone compared to ospemifene

no black box warning for VTE, endometrial hyperplasia

contraindications for prasterone

undiagnosed vaginal bleeding

history of breast cancer