Menopause Flashcards

Question

Describe the estrogen formulations for use in menopause? Effectiveness of the options?

Answer 1

Guidelines – Recommend transdermal estrogen for individuals with CV risks – Lower VTE risk (studies

Answer 2

Use the most appropriate, often lowest, effective dose E.g. 0.3mg Premarin or 0.5mg Estrace or 25ug 17β-estradiol Titrate dose based upon symptom relief

Answer 3

Generally, start with low doses and titrate up based on symptom response Lower doses may take longer to see a response – may take as long as 12 weeks For standard doses check for a response after 4 weeks.

Answer 4

As little as 2 weeks for some, up to 8 weeks for others Assess for response at 4 weeks at standard dose and 6-12 weeks for lower doses

Answer 5

Estrace – Generics available Premarin – Only brand name Patch – Differnece in dosing frequency Estardot, Oesclim - Twice Weekly Climara - weekly Application Site s- Clean, dry, intact skin – Butt is preferred place, lower abdomen, lower back, or hip - Rotate from left to right side each time Gels are used daily

Answer 6

Are similarly effective for vasomotor sx’s Appear to provide same protection on BMD

Answer 7

Avoids the FPE, so less nausea, less h/a, less of an effect on TG’s ↑ sex drive? (some studies) ↓ risk of DVT ↓ risk of gallbladder dx ** BAsed on observational data**

Answer 8

Food allergies Prometrium - Some generics made with peanut oil and sunflower oil – Allergy Concerns Mirena IUD – Off label when used for menopause - good option for those wanting contraception, convenience of IUD, irregular menses still – Useful for any doses of estrogen - Used for up to 5 years

Answer 9

May cause drowsiness, especially when taken with food Advantages vs. MPA: Observational data shows it has a lower risk of VTE and breast cancer Of note… Prometrium made with sunflower oil, some generics made with peanut oil, some with sunflower oil Educate to take at bedtime – IMPORTANT

Answer 10

Duavive® (0.45mg CE and 20mg bazedoxifene) Conjugated Estrogen and SERM

Answer 11

Bazedoxifene: is a selective estrogen receptor modulator (SERM) that acts as an antagonist of estrogen receptors on endometrial and breast tissue and an agonist at receptors in bone CE + bazedoxifene is called a tissue selective estrogen complex (TSEC) provides endometrial protection without the need for a progestogen --> Protection of BMD – Avoids side effects of progestin (do not need to take a progestin here) avoids bothersome adverse effects of progestogens such as breast tenderness and uterine bleeding

Answer 12

Take 1 tablet daily

Answer 13

(17β estradiol (estradiol hemihydrate) and progesterone (micronized) A bioidentical formulation of HRT in combination format Evidence shows ↓ in moderate-to-severe VMS, ↑ QOL and sleep quality Dose: 0.5 mg/100 mg and 1 mg/100 mg capsules once daily with food

Answer 14

Indicated for short-term tx of VMS in menopausal women with an intact uterus

Answer 15

A synthetic steroid analogue of norethynodrel (a progestogen), which is metabolized in the body to make 3 substances that act like E, P, and A (androgen) – it has weak activity Weak activity compared to natural hormones - DOES NOT CONTAIN ACTUAL HORMONES

Answer 16

Cochrane review: more effective than placebo, but slightly less effective than EPT Similar to EPT products, consider risks before using Has the same CI’s and AE’s as E and P

Answer 17

Dose: 2.5mg tab (po) once daily Tx of VMS in menopause – atleast 1 2months from last menstrual people - Indicated for short term use – Studied for 3 years (not much real world data)

Answer 18

Black Box Warning: Endometrial cancer risk, breast cancer risk

Answer 19

– Endometrial cancer. Risk, breast cancer risk – Does not contain actual estrogen, but leads to asubstance that mimics estrogen

Answer 20

HS DROWSINESSSSS

Answer 21

Pregnancy can still occur in perimenopause

Answer 22

If date of last menses was <1yr ago, contraception may be desired Options to provide VMS relief and contraception: Low dose CHC (pill, patch, or ring) Estrogen + LNG-IUS (contraception) MHT + barrier Nonhormonal tx option + progestogen-only contraceptive

Answer 23

Safe to use in the perimenopausal period when contraception is required, but do not use once in menopause as the daily dose of ethinyl estradiol (e.g. 20 µg) is 4-5x times higher than the low-standard dose of estradiol required for symptom relief and bone benefit (e.g. 1mg estradiol)

Answer 24

“Perimenopausal women with contraindications to OCP shoulod not nuse them

Answer 25

Taking CHC’s can mask signs of VMS & menstrual irregularities. This can make it difficult to know when ‘it is safe to stop taking’ If ≥50yo, stop and use non-hormonal contraceptive until amenorrhea for >12 months If ≥55yo, stop. Spontaneous conception very rare (to be conservative the menopause society recently suggested >58yo)

Answer 26

What are bioidentical hormones? Plant-derived hormones structurally identical to what is naturally produced in the body Compounded products may contain a mix of estradiol, estrone, estriol, DHEA, testosterone, progesterone --> Whether from pharma or compounded pharmacist – contain the same ingredients Neither is more ‘natural’ than the other– they still need to be converted through a synthetic process to mimic body’s hormones

Answer 27

‘Safe and natural’ (generally a marketing advantage) ‘Custom-made’ based on salivary, serum, urine hormone level testing Can compound in many different delivery routes (e.g. troches, subdermal implants) Still require a written Rx…

Answer 28

Individualized testing not necessary as not narrow TI meds. Hormone testing is unreliable The desired levels of hormones have not been established and may not correlate with symptoms Products have variable potency which could result in under/over-dosing – don’t adhere to strict FDA-mandated potency tests that Rx products do (PK/PD testing) Lack safety / efficacy data

Answer 29

Patient takes both E and P daily

Answer 30

easy to remember avoids the withdrawal bleeding Decreases risk the most for endometrial hyperplasia

Answer 31

However, unpredictable bleeding may occur: 40% have irregular breakthrough bleeding in 1st 6 months; 20% by 1 yr If bleeding continues after first 6 months – see Dr. AUB after 6 months may indicate a need for a higher dose or something more serious

Answer 32

The E is taken daily and the P is taken for 12-14 continuous days per cycle Withdrawal bleeding typically begins after last P dose (within 1-2 days) Recommended starting dose differs for continuous vs cyclic dosing

Answer 33

Prefer fewer pills Recent menopausal who do not want breakthrough bleeding (predictable bleeding vs breakthorough)

Answer 34

Nausea Breast tenderness Headache Bloating Management: Often dose related Change products

Answer 35

Irritability Breast tenderness Bloating Headache “PMS-like symptoms”: mood swings, bloating, fluid retention, sleep disturbance, decreased libido, weight gain

Answer 36

Vaginal bleeding is common in 1st 3-6 months Different HT’s can have different effects; individualize tx and periodically reassess

Answer 37

Unexplained vaginal bleeding Active liver dx Estrogen-dependent cancer (breast, endometrial, cervical) Pregnancy Active thromboembolic dx (e.g. DVT, PE, stroke, MI) Untreated / uncontrolled CVD

Answer 38

High cancer risk

Answer 39

Hypertriglyceridemia Hepatobiliary disease Migraine Established CVD Past VTE Diabetes Advanced age and no previous MHT

Answer 40

SSRIs and SNRIs Veozah (fezolinetant) Clonidine Oxybutynin gabapentin pregabalin

Answer 41

Alternatives to tx vasomotor sx’s when HT is CI or not desired Less effective than HT, but still efficacious (reduce VMS 25-69%) – Varibale response

Answer 42

Paroxetine 10-20mg od or 12.5mgCR to 25mgCR od Citalopram 10-20mg od Escitalopram 10-20mg od Venlafaxine 37.5 – 75mg od Desvenlafaxine 100mg od

Answer 43

Low dose often effective. Quicker onset vs. depression: allow 2-4 weeks for effect

Answer 44

Must be cognizant of their associated AE’s and DI’s Consider use in those with co-morbidities

Answer 45

Duloxetine

Answer 46

Indicated for treatment of moderate to severe VMS associated with menopause

Answer 47

MOA: nonhormonal selective neurokinin 3 receptor antagonist

Answer 48

Dose: 45mg po once daily (do not crush/chew tablets)

Answer 49

Common adverse effects – headache (9.7%), liver enzyme elevation (5.4%) [MONITOR], abdominal pain (4.4%), diarrhea (3.9%), insomnia (3.9%), nausea (3.1%)

Answer 50

CYP metabolism – watch for interactions

Answer 51

Clonidine 0.05mg bid Modestly effective: 38% ↓ sx’s vs. 30% placebo SE’s: orthostasis, drowsiness, dry mouth, constipation D/c if no benefits after 2-4 weeks

Answer 52

Oxybutynin 2.5-5mg bid Can reduce hot flash frequency by up to 77% SE: anticholinergic side effects

Answer 53

Gabapentin 300mg hs up to 900mg hs Meta analysis: ↓ hot flashes by 20-30% SE’s: dizziness, light-headed, fatigue

Answer 54

Pregabalin 75mg BID up to 300mg hs Limited data; one study showed ↓hot flashes by 65% vs. 50% placebo SE’s: dizziness, somnolence

Answer 55

Bone Loss After Menopause Incraesed risk of bone fracture

Answer 56

Post-menopause, estrogen deficiency causes accelerated bone loss by increasing ’ing bone turnover & resorption Estrogen enhances osteoblasts to produce more OPG, which binds to RANKL. This blocks the RANKL-RANK interaction, thereby preventing osteoclast activation and bone resorption.

Answer 57

Estrogen therapy can reduce fracture risk at various sites by 24% to 39% in postmenopausal women Indicated for prevention of osteoporosis only – not treatment – Ca2+, Vit D, exercise Effects on bone protection are dose-related ** Shoud not be on HT for osteoporosis if not othe rindications for it (e.g. VMS)*

Answer 58

Standard dose HT reduces the risk of osteoporotic fracture--> hip & vertebral Low dose HT beneficially increases BMD (less data for reducing fracture risk) The benefits on fracture risk dissipate upon d/c of HT – return to pre-treatment levels in 1-2yrs “In the absence of CI, systemic HT is an appropriate therapy to protect against bone loss in women <60yo or within 10yrs of menopause onset”

Answer 59

It causes vasodilation with short-term use With long-term use it: ↓ LDL, ↑ HDL Lowers fibrinogen Lowers plasminogen-activator inhibitor type 1 Countering this is its effect on inflammation (measured by C-reactive protein) and on markers of thrombosis

Answer 60

Found negative CV outcomes. More recent studies found that the use of estrogen in women under 60 and within 10 years of menopause actually have a neutral to decreased CVD risk. **Older women starting HT and women who are further away from their final menstrual period appear to be at greater risk of a cardiac event vs. those who are younger and those who initiate HT closer to their menopause**

Answer 61

No increased risk with MHT if initiated <10yrs since menstrual cycles and <60yo Higher incidence if initiated later

Answer 62

Cochrane review: increased risk regardless of <10yrs or >10yrs (although higher in older starters) Address risk factors for stroke and DVT before deciding to initiate HT: - Those at high risk should avoid HT and use non-hormonal - Those at medium risk may want to consider lower dose E, transdermal products, or non-hormonal - Low dose HT may confer less stroke & DVT risk (observational studies) - Transdermal ET may confer less DVT risk (observational) Micronized Progesterone may be less thrombogenic than MPA

Answer 63

Risk ↑ with longer duration Risk persists for those on EPT but no effect on breast cancer mortality Trends persist for those on ET Studies are lacking with regard to breast cancer risk with long term use Observational data is mixed; risk may depend on a variety of factors

Answer 64

In women with prior breast cancer history, systemic HT is not is generally not advised – joint decision with oncologist Low dose vaginal therapy provides minimal systemic absorption for GSM symptoms in breast cancer survivors – joint decision with oncologist

Answer 65

Duration of treatment: (unknown) Individualized – used to say 5 years. Now, the safest regimen at the appropriate dose to control symptoms - periodically (~yearly) assess to see if still require treatment e.g. no sx for the last year – taper or come off altogether

Answer 66

Sleep difficulty is a hallmark symptom of the menopause transition Both sleep onset and maintenance insomnia are ↑’ed during (peri-)menopause Can interfere with QOL, and cause daytime fatigue, irritability, and impaired cognition

Answer 67

General insomnia recommendations: CBT, valerian, hypnotics, antidepressants MHT may help in those also experiencing VMS Hormone tx may improve night sweats – Only used if VMS

Answer 68

Some women may be more vulnerable to depressive symptoms during menopause transition, or experience anxiety & irritability May be due to estrogen depletion, deficiency, or changing levels

Answer 69

Estrogen has multiple effects on brain function: Positive effect on serotonergic activity Increases the activity of NA E receptors located in regions of brain responsible for learning and memory Increases cerebral blood flow

Answer 70

Women with moderate to severe VMS up to 3x more likely to have moderate-severe depressive sx’s Some studies show ET improving depressive sx’s in perimenopausal women (but not late menopausal) , and it may augment the clinical response to SSRI’s The use of antidepressants and psychotherapy (CBT) remains the mainstay of treatment for mood disorders and anxiety Depressive Sx – Should still be treated with antidepressants If have VMS and mood sx – Hormone therapy and then add on antidepressants if continued

Answer 71

Anecdotally, women often report experiencing memory changes, ↓in concentration with menopause transition Limited data suggests early use of HT in menopause may be associated with diminished risk of later dementia, whereas later initiation of no benefit or perhaps even harmful Where we stand today: HT is not recommended to preserve cognitive function or prevent/tx dementia. Further, initiation >65yo may ↑ the risk

Answer 72

There are many E receptors located in: vagina, vulva, urethra and bladder A decraese in E levels causes many changes such as: tissue atrophy reduced secretions reduced blood flow vaginal pH increase 6-8 (premenopause 4.5 - 5) A decraese in E in addition to normal tissue aging can result in vaginal symptoms

Answer 73

GSM refers to the signs/sx’s resulting from E deficiency on the genitourinary tract

Answer 74

Vaginal dryness Vaginal itching / irritation Burning Painful intercourse Lower urinary tract sx’s: (urinary frequency, urgency, UTI’s) Nocturia, dysuria

Answer 75

Onset varies; may begin perimenopause or commonly a couple years after menopause

Answer 76

If OTC agents are ineffective → vaginal estrogen / prasterone / ospemifene - Vaginal Estrogen preparations

Answer 77

Effective: ￬ GSM sx’s by 60-80% Safety: minimal systemic absorption, hence less concerns with use At recommended doses (low), an accompanying progestogen is not needed Risk of VTE, CVD does not seem to be increased Rates of endometrial cancer appear to be consistent with general population Does not appear to be associated with increased breast cancer risk There is no clinical data beyond 1 year but continue using as long as necessary. Long term observational data supports safety

Answer 78

In addition to helping with GSM sx’s such as dryness and dyspareunia, intravaginal ET may also be useful in preventing recurrent UTIs and managing incontinence 1) VAgoinal Creams 2) Vaginal RIng 3) Vaginal Tablets Vaginal Softgel Inserts

Answer 79

17-beta estradiol (Estring vaginal ring) Insert 1 ring vaginally q 3 months (delivers 7.5ug/24h)

Answer 80

17-beta estradiol 10 ug tablets (Vagifem 10) Insert 1 tab qd x 2 weeks, then 1 tab 2x/week (with days between)

Answer 81

17-beta estradiol 4ug and 10ug (Imvexxy) For the treatment of moderate to severe dyspareunia due to menopause Insert 1 vaginal insert daily x 2 weeks, then 1 insert twice weekly. Start at 4 mcg dose & adjustment is guided by the clinical response

Answer 82

If someone is also experiencing VMS, then oral MHT would be trialed as in addition to helping the VMS sx’s, it will also help with the GSM sx’s as well ∼10-15% of women will still experience GSM sx’s while on systemic MHT, so systemic and intravaginal ET may be used together

Answer 83

Prasterone (Intrarosa®) Ospemifene (Osphena®)

Answer 84

Weight gain: During menopause transition: avg. weight gain of 1.5lbs/yr– this is due to a decraesed resting metabolic rate that occurs with aging (change in fat-to-lean body mass ratio) – not MHT Skin changes Soon after menopause, skin collagen content, thickness, and elasticity decline Abnormal Uterine Bleeding (AUB)

Answer 85

AUB (irregular menstrual cycles) is common during the menopause transition period Prolonged cycle intervals as well as variable bleeding patterns precede eventual amenorrhea and menopause

Answer 86

Dysfunctional uterine bleeding (DUB) which results from anovulation Endometrial hyperplasia and cancer Benign lesions (endometrial polyps)

Answer 87

Since DUB is a diagnosis of exclusion, evaluation of DUB in a perimenopausal woman is warranted Any bleeding after 12 months of amenorrhea is considered post-menopausal bleeding and should also be investigated