Endocrine 2 Exam 2: Stewart-Lynch Menopause Therapeutics

Menopause: permanent cessation of menses (for __ ____ _____) due to a ___ _____of ____ ____

12 consecutive months, permanent loss, ovarian function

Menopause

-median age in the US is ____ ___

-physiological symptoms may be present up to ___ ____ ____ (____)

52 years, 4 years prior, perimenopause

Menopause

-symptoms are related to a lack of ___

estrogen

Menopause Symptoms - Symptoms Related to Lack of Estrogen

-____ symptoms (VMS; ____ symptoms)

vasomotor, VMS, systemic

Menopause Symptoms - Symptoms Related to Lack of Estrogen

-vasomotor symptoms include __ ____ and __ ____

hot flashes, night sweats

Menopause Symptoms - Symptoms Related to Lack of Estrogen

-____ symptoms of menopause (GSM; ____ symptoms)

genitourinary, local

Menopause Symptoms - Symptoms Related to Lack of Estrogen

-GSM includes:

vulvovaginal atrophy, VVA, dryness, dyspareunia, incontinence, recurrent UTIs

Menopause Goals of Treatment

1. Reduce or eliminate ___ to improve ___

2. Minimize risk of ___ __ from drug therapy

symptoms, QOL, adverse effects

Menopause Treatment

-highly individualized based on _____ ____ ____ (does patient still have ___?) and _____ ______ (are the patient's symptoms __ or ___?)

past medical history, uterus, clinical presentation, VMS, GSM

Menopause Treatment

-lifestyle changes

-___ ______ _____ (most effective)

-misc. agents

hormone replacement therapy

Menopause Non-Pharm Treatment for Vasomotor Symptoms include:

maintain cool environment, measures that aid in heat dissipation (layers of clothing), avoid caffeine, alcohol, spicy foods, smoking cessation, relaxation

Menopause Non-Pharm Treatment for GSM include:

-personal ___ (OTC products that are water or silicone based including Replens)

personal lubricants (OTC products that are water or silicone based, ex. Replens)

Menopause Herbal Treatment

-___ ___ (in product ____; but has _____ _____)

-____ (_____, ____ ____; has ____ _____ ____)

Black Cohesh, Remifemin, limited benefit, Phytoestogens soy, red clover, even less benefit

Key Point: Phytoestogens increase ___ effects (so be careful in patients _______ for _____ ______)

estrogenic, contraindicated, estrogen therapy

Hormone Replacement Therapy

-_____ is given to treat the ___ of menopause

-_______ may be given to __ the uterus

estrogen, symptoms, progesterone, protect

____ _____ is the most effective treatment for _____ and _____ symptoms (hormone replacement therapy)

estrogen therapy, vasomotor, genitourinary

Hormone Replacement Therapy Contraindications for Menopause

estrogen sensitive cancers (ex. breast, endometrial, etc), coronary artery disease, TIA/stroke, history of DVT or PE, personal history or inherited high risk of thromboembolic disease (ex. Factor V Leidan, etc), active liver/gall bladder disease, unexplained vaginal bleeding

difference between contraceptives is that for menopause, there is ____ _____ that can be dealt with in ______ _____

more risk, treating symptoms

symptoms of menopause are due to lack of ___, which is why we give estrogen to ____ ____

estrogen, treat symptoms

menopause = ___

contraceptive = ___

treat, prevent

Hormone Replacement Therapy

-the ___ ___ ___ (WHI) was a large randomized controlled trial of women aged __-__ years studying ____ ± _____ therapy

Women's Health Initiative, 50-79, estrogen, progestin

Women's Health Initiative Limitations

1. only ___ route of administration at set dose/duration (_____ ____)

2. limited enrollment of the women that HRT is actually ___ for (which are women with bothersome vasomotor symptoms)

1, oral estrogen, indicated

Women's Health Initiative

-Takeaway: benefits likely outweigh risks if hormone therapy is initiated at age ___ ___ or within ___ ____ of ____ _____

<60 years, 10 years,, menopause onset

Hormone Replacement Therapy

-use ___ effective dose for ___ duration possible

lowest, shortest

if woman has vasomotor symptoms and GSM → use __ products

if woman has GSM only → use __ products

systemic, local

Hormone Replacement Therapy-Systemic

-for women with intact uterus → use product with ___ + ___

estrogen, progesterone

Hormone Replacement Therapy-Systemic

-for women with no uterus (hysterectomy) → use product with ___ ____

estrogen only

for women needing systemic therapy who has no estrogen contraindications and has intact uterus → use one of the following:

1st line =

2nd line =

oral, transdermal, systemic vaginal estrogen PLUS progesterone, Bazedoxifene/CEE

for women needing systemic therapy with no uterus (hysterectomy), use the following:

oral, transdermal, systemic vaginal estrogen alone

for women needing systemic therapy that are CONTRAINDICATED for estrogen therapy use one of the following:

1st line =

2nd line =

SSRI/SNRI, Gabapentin, Pregabalin, Clonidine, Fezolinetant (Veozah)

note that __ is an SSRI FDA approved for vasomotor symptom treatment

paroxetine

note that paroxetine is an SSRI FDA approved for vasomotor symptom treatment, but INTERACTS WITH ___ (used in estrogen-dependent cancers)

tamoxifen

note that fezolinetant (Veozah) should not be used in ___

cirrhosis

why should fezolinetant (vezoah) not be used in cirrhosis?

liver disease and estrogen is a NO NO! should not be used if post-menopausal

remember if patient has GSM only → use ___ estrogen products

local

for women needing local estrogen therapy, use the following:

1. _____ ___ or ___

2. _____ _____ ___

2nd line = _____ or ____

vaginal creams or tablets, non-systemic vaginal ring, ospemifene or prasterone

when would you used the 2nd line (ospemifene and prasterone)

pts. who has not used or chooses not to use vaginal estrogen

for women needing local estrogen therapy that is CONTRAINDICATED for estrogen therapy, use the following:

1. _____ ___ (if these are ineffective, then use regular ______ _____ _____ agent; if _____ is due to _____ ___, ____ _____ to assess benefit vs risk)

personal lubricant, estrogen-containing local, contraindication, breast cancer, consult oncologist

Hormone Replacement Therapy Bleeding Considerations

If patient does not have menses → use product that does NOT cause a __ ____

withdrawal bleed

what are products that do not cause withdrawl bleed?

Hormone Replacement Therapy Bleeding Considerations

If patient does have menses (ex. they are perimenopausal) → need to determine treatment based on patient ___ for more ____ ______ or _____

preference, regular bleeding, amenorrhea

What are 3 types of HRT Regimens?

Continuous-Cyclic, Continuous-Combined, Continuous Long Cycle

ALL Regimens involve ____ being dosed ___ to achieve adequate ___ ____

estrogen, daily, symptom control

Continuous-Cyclic Regimen (sequential)

-estrogen is administered ____ with a _____ co-administered for at least __-___ ____ of a 28 day cycle

daily, progestin, 12-14 days

Continuous-Cyclic Regimen (sequential)

-with this regimen, _____ and ______ ______ ___ occurs __-__ days ____ last _____ ____

scheduled, predictable withdrawal bleed, 1-2 days, after, progestin dose

Continuous-Cyclic Regimen

-this regimen is preferred for _____, ___ woman who desires a ______ and _____ _____

younger, perimenopausal, scheduled, withdrawal bleed

Continuous-Combined Regimen

-estrogen and _____ are co-administered ___

progestin, daily

Continuous-Combined Regimen

-eventually will cause ___ (bc ______ is given every day; ____ _____ _____)

amenorrhea, progestin, no withdrawal bleed

Continuous-Combined Regimen

-eventually will cause amenorrhea, BUT can cause ______ bleeding for first __-__ ____

unpredictable, 6-12 months

Continuous-Combined Regimen

-this regimen is preferred in women __ _____ of ______

>2 years, menopause

Continuous Long Cycle (cyclic withdrawal)

-estrogen is given daily, and _____ is given ___ times a year (____ ____ ___) for ___-__ days

progestin, 6, every other month, 12-14 days

Continuous Long Cycle (cyclic withdrawal)

-patient will have __ periods a year

6

Continuous Long Cycle

-patient will have 6 periods a year (less frequent), but patient bleeding episodes may be __ and ___ than ____ ____ on continuous-cyclic regimen

heavier, longer, withdrawal bleeding

Continuous Long Cycle

the downside of progesterone use in this regimen is that we are not sure if this regimen provides enough progestin to ___ the uterus; bleeding episodes may last ____ than with _____ ______

protect, longer, continuous cycle

Continuous Long Cycle

the advantage of progesterone use in this regimen is that it ___ ____ _____

helps with tolerability

______, _____, and _____ are oral estrogen only containing products

Premarin, Menest, Estrace

Estrogen Only Containing Products-ORAL

-should be taken ___ by _____

daily

Estrogen Only Containing Products-ORAL

-generally well __ among patients

accepted

Estrogen Only Containing Products-ORAL

-undergo significant first pass metabolism, which ___ triglycerides, SHBG, Cortisol Binding Globulin, CRP, and Angiotensinogen

increases

Dotti, Lyllana, Minivelle, Vivelle DOT, Climara, and Menostar are ___ ___ estrogen only containing products

transdermal patch

Estrogen only containing products-PATCH

-also well accepted

-do ___ undergo first pass metabolism (advantage)

not

Estrogen only containing products-PATCH

-___ rate of delivery

-less nausea, headache, breast pain, DVT than oral

continuous

Estrogen only containing products-PATCH

-___, ___, ___, and ___ ___ are administered twice a week to buttocks or abdomen

Dotti, Lylanna, Minivelle, Vivelle DOT

Estrogen only containing products-PATCH

-___ and ___ are administered once a week to lower abdomen or upper buttocks

Climara, Menostar

Divigel, Estrogel, Elestrin, and Evamist are ___/__ estrogen only containing products

gels/sprays

Estrogen only containing products-GELS/SPRAYS

-do not undergo first pass metabolism, but more variability in ___ and causes ___ effects

absorption, systemic

Estrogen only containing products-GELS/SPRAYS

-___ is applied to upper thigh daily

Divigel

Estrogen only containing products-GELS/SPRAYS

-___ and ___ are applied topically to arm daily (avoid breast tissue)

Estrogel, Elestrin

Estrogen only containing products-GELS/SPRAYS

-___ is applied to inner forearm daily

Evamist

Premarin vaginal cream, Estrace vaginal cream, Vagifem, Imvexxy, Estring, and Femring are _____ estrogen only containing products

vaginal

Estrogen only containing products-VAGINAL

-does not undergo first pass metabolism

-local and systemic effects (formulation dependent); tablets and local rings have relatively less systemic effects than __

creams

Estrogen only containing products-VAGINAL

-the vaginal creams (Premarin and Estrace) are dosed ___ x 2 weeks, then at a maintenance dose 1-3x per week

daily

Estrogen only containing products-VAGINAL

-the vaginal tablets (Vagifem and Imvexxy) are inserted once __ for 2 weeks, then 1 tablet twice a week

daily

Estrogen only containing products-VAGINAL

-products that are administered locally to vagina typically have low systemic effects, with the exception of ___ which is ___-soluble and therefore has systemic effects

Femring, water

Estrogen only containing products-VAGINAL

-Estring does NOT have systemic effects, because the vaginal ring is blended in ___ (not water soluble)

silicone

Estrogen only containing products-VAGINAL

-the vaginal rings (Estring and Femring) dosing is 1 ring every ___ days

90

Prometrium and Provera are _____ progestin only containing products

oral

Progestin only containing products-ORAL

-Note that Prometrium contains ___ oil (so make sure patient is not allergic)

peanut

Premphase, Prempro, Activella, Mimvey, FemHRT, and Angeliq are _____ estrogen progestin combination products

oral

Estrogen progestin combination products-ORAL

-Prempro is conjugated equine ___ combined with ____

estrogen, medroxyprogesterone

Estrogen progestin combination products-ORAL

-Premphase is ___ packaged with ___

Premarin, Prempro

Estrogen progestin combination products-ORAL

-with Premphase, the CEE is taken daily x __ days, then the combination of CEE + MPA (ie prempro) daily x __ days

14, 14

Estrogen progestin combination products-ORAL

-Premphase regimen is ___-__

continuous cyclic

Estrogen progestin combination products-ORAL

-Prempro, Activella, Mimvey, FemHRT, Angeliq are taken ___ by mouth, and therefore result in a ___-__ regimen

daily, continuous combination

Estrogen progestin combination products-ORAL

-Angeliq is unique becuase it contains ___ as the progesterone

drospirenone

Combipatch and ClimaraPro are _____ ____ estrogen progestin combination products

transdermal patch

Estrogen progestin combination products-TRANSDERMAL PATCH

-Combipatch is applied twice weekly to lower abdomen. Can be used for __-__ regimen (when used alone) or ___-__ regimen (when using estrogen only therapy x 14 days then combipatch only x 14 days)

continuous combined, continuous cyclic

Estrogen progestin combination products-TRANSDERMAL PATCH

-ClimaraPro is applied once weekly to lower abdomen. Used for ___-___ regimen

continuous combined

Vaginal Cream Applicators

-used for 2 vaginal creams (___ vaginal cream and ___ vaginal cream)

-calibrated to measure the amount of __ (not amount of API)

Premarin, Estrace, cream

Vaginal Tablet Applicator

-used for ___

Vagifem

Vaginal Ring Applicator

-used for ____ and ___

Estring, Femring

2nd line therapy for VMS

-____/_____ ___ (Duavee)

Bazedoxifene, conjugated estrogens

2nd line therapy for VMS

-Bazedoxifene/Conjugated estrogens is used for patient with a uterus

-bazedoxifene is an endometrial estrogen ___

-dosed daily

antagonist

2nd line therapy for VMS

-____ (Veozah)

Fezolinetant

2nd line therapy for VMS

-Fezolinetant is a _____ NK3 Antagonist dosed ___

nonhormonal, daily

2nd line therapy for VMS

-remember CANNOT use Fezolinetant with ___

cirrhosis

2nd line therapy for Dyspareunia from VVA

-____ (Osphena)

Ospemifene

2nd line therapy for Dyspareunia from VVA

-Ospemifene is a ___ (has estrogen antagonist activity in vaginal mucosa) that is dosed ___

SERM, daily

2nd line therapy for Dyspareunia from VVA

-Ospemifene does not require added ___ to protect the patient's uterus (bc it is local)

progestin

2nd line therapy for Dyspareunia from VVA

-____ (DHEA) (Intrarosa)

Prasterone