Menopause Flashcards
Natural menopause is defined by…
Permanent cessation of menses (periods) for more than 1 year - secondary to lack of estrogen production via the ovaries
Perimenopause is defined by…
The time period prior to menopause, characterized by menstrual cycle irregularity, increased frequency of anovulatory cycles, and symptoms similar to menopause
Early natural menopause simply refers to…
Loss of ovarian function at a young age
Premature menopause is defined by patients experiencing symptoms under the age of…
40
Early menopause is defined in age via…
40-45
Patients experiencing premature or early menopause are at risk of symptoms from…
Estrogen deficiency
Restoring estrogen levels until natural age of menopause is recommended to help…
Prevent complications
Some factors that may precipitate earlier onset of menopause include…
Smoking
Exposure to toxins
Chemotherapy
Hysterectomy
Menopause is related to ovarian follicles because…
There is an age related decrease in number and quality of ovarian follicles - by menopause, few/none remain
The end result of hormonal changes in menopause is that…
Ovarian secretion of estradiol ceases - ovulation does not occur, progestin concentrations remain low (pituitary tries to increase FSH and LH to initiate follicle development, but ovary cannot respond)
Estradiol and progesterone secretion is stopped
Menopause course over time can be…
Slow and progressive
OR
Fast onset all at once
Post-menopause, estrogen production decreases to ____ of pre-menopausal levels. Primary estrogen becomes ____, which has ____ estrogenic potency of estradiol.
¬10% of pre-menopausal levels
Primary estrogen = estrone, 1/3 estrogenic potency of estradiol
Symptoms of menopause include…
Vasomotor symptoms
Sleep pattern changes
Mood and cognition changes
Genitourinary changes
Bleeding changes
Classic sign + major complaint of menopause is…
Hot flashes
Hot flashes are characterized by…
Sudden onset of intense warmth starting in chest that may progress to neck and face, often accompanied by visible red flushing (and possible sweating, palpitations, anxiety)
Typically episodic and last ¬4 minutes
Unfortunately associated with diminished sleep quality, irritability, difficulty concentrating, decreased QoL
Vasomotor symptoms (VMS) appears to be caused by…
Narrowing of thermoregulatory system, caused by changes in estrogen levels
Risk factors for experiencing VMS may include…
Less physical activity
Family hx/genetics
Age of onset
Induced menopause
Some lifestyle modifications that could help with VMS include…
Cooling techniques
Avoidance of triggers
Exercise, yoga, relaxation training
Weight loss in those who have extra weight
Smoking cessation
Limited to no evidence, but reasonable to suggest
This appears to be beneficial in reducing frequency + severity of VMS, as well as sleep:
Non-pharm related
CBT
The main pharmacotherapy for VMS symptoms revolves around…
Hormone therapy
The most effective pharmacotherapy treatment options for VMS is…
Estrogen +/- progesterone
Recall that estrogen provides protection for BMD as well
If the patient has had a hysterectomy, estrogen therapy can be…
NO UTERUS
Used alone
In patients with a uterus, estrogen therapy needs to be…
Combined with a progestin
Estrogen needs to be combined with progestins in people with uteruses because…
Estrogen alone is associated with increased risk of endometrial hyperplasia or cancer - risk related to dose and duration of estrogen therapy
Progestins decrease risk in a dose and duration fashion
When taken together, risk of endometrial hyperplasia is no higher than in untreated women
Progestin should be used for a minimum of ____, and dose should be matched to…
12-14 days per month - match dose of progestin to dose of estrogen
All sources of estrogen are equally effective, however some individuals may…
Switch between products based on response
Dosage of estrogen is based on…
Clinical appropriateness - often lowest, effective dose
Titrated based on symptom relief
Onset of symptom control with estrogen may vary…
As little as 2 weeks, up to 8 weeks:
We should assess for response for symptom control at…
Timing?
4 weeks at standard dose
6-12 weeks for lower doses
Some potential benefits to use transdermal estrogen over oral include…
Less risk of DVT - better if high CV risk
Avoids first pass effect: less nausea, headache, effect on TG’s
Increased sex drive
Decreased risk of gallbladder dysfunction
Different progestin products include…
Medroxyprogesterone
Micronized progesterone
IUD - levonorgestrel (ok for any dose of estrogen)
Micronized progesterone may have an advtanage over medroxyprogesterione by…
Lower risk of VTE + breast cancer (observational data)
Prometrium and its generic are made with ____ - this may be important due to…
Sunflower/peanut oil - potential allergy
Bazedoxifene is a ____ that acts as…
Selective estrogen receptor modulator (SERM) - antagonist of estrogen receptors on endometrial + breast tissue and an agonist at receptors in bone.
Very good for BMD
Advantages of bazedoxifene + CE is that it provides…
Endometrial protection without the need for a progestin, as well as avoiding bothersome AE’s of progestins (breast tenderness, uterine bleeding)
Bijuva is on the formulary and is a combination of…
Estradiol and progesterone
Evidence of Bijuva showed…
Decrease in moderate-severe VMS, increased QoL and sleep quality
Bijuva should be given with ____ to…
Food to increase absorption
Tibolone is a unique option indicated for short-term treatment of VMS in menopausal women in that it does not…
Contain actual hormones
Tibolone MOA is that it is a…
Synthetic steroid analogue of norethynodrel (progestin) that gets metabolized to make 3 substances that act like estrogen, progesterone, and androgens - do have weaker activity
Efficacy of tibolone showed that…
It was more effective than placebo
Slightly less effective than estrogen/progesterone therapy
Precautions and CI’s with tibolone are…
Similar to estrogen/progesterone - consider risks before using
Contraception may be desired if date of last menses…
Was less than 1 year ago
Pregnancy can still occur in perimenopause
Options to provide VMS relief with contraception include…
Low dose CHC (pill, patch, or ring)
Estrogen + LNG-IUD
MHT + barrier
Nonhormonal tx option + progestogen-only contraceptive
Hormonal contraceptives are safe to use in the perimenopausal period when contraception is required, however in menopause…
Hormonal contraceptive should be avoided since daily dose of estradiol is 4-5x higher than low-standard dose required for symptom relief and bone benefit
Perimenopausal women who should NOT use OCP’s include…
Who would we avoid CHC’s in normally?
Smokers
History of: estrogen-dependent cancer, heart disease, HTN, diabetes, or blood clots
CHC usage can mask signs of…
VMS, menstrual irregularities
Ifa patient taking CHC’s is over 50, we should…
STOP and use non-hormonal contraceptive until amenorrhea for 12 months
If a patient taking CHC’s is over 55, we should…
STOP - spontaneous conception is very rare
To be conservative menopause society suggested 58+
Bioidentical hormones are…
Plant-derived hormones structurally identical to what is naturally produced in the body
Compounded bioidentical hormone therapy (BHT) products may contain a mix of…
Estradiol, estrone, estriol, DHEA, testosterone, progesterone
Pros of compounded BHT include…
“safe and natural”
“Custom-made” based on salivary, serum, urine hormone levels
Can be compounded in many different delivery routes
Potential cons of BHT include…
Hormone testing is unreliable and not necessary (not TI meds)
Desired level of hormones not established, may not correlate with symptoms
Products have variable potency = under/over-dosing
Lack of safety/efficacy data
In an EPT dosing regimen, estrogen is taken ____ and progestin can be taken _____
Estrogen continuously every day - progestin continuously every day or cyclically for 12-14 days a month
Main advantages of taking both estrogen and progestin include…
Easier to remember
Avoids withdrawal bleeding
Less risk of endometrial hyperplasia
Continuous progestin use may cause this to occur…
Unpredictable bleeding
If bleeding continues after first 6 months, see Dr - may indicated need for higher dose or re-evaluation
Cyclic progesterone may be preferred if a patient
Wants fewer pills
Has recently experienced menopause + do not want breakthrough bleeding
Cyclic allows for predictable, withdrawal bleeding
Estrogen common AE’s include…
Nausea
Breast tenderness
Headache
Bloating
Progestin common AE’s include…
Sedation, especially with food
Irritability
Bloating
Headache
PMS-like symptoms (mood swings, bloating, fluid retention, sleep disturbance, decreased libido, weight gain)
Vaginal bleeding is common with MRT, for the first…
3-6 months of therapy initiation
Estrogen and progestin AE’s are often ____. A reasonable course of action if they are intolerable is to…
Dose-related: change products, since different HT’s can have different individual effects
Contraindications with MHT include…
Unexplained vaginal bleeding
Active liver disease
Pregnancy
Estrogen-dependent cancer - ovarian, endometrial (caution if high cancer risk)
Active thromboembolic disease
Untreated/uncontrolled CVD
Non-oral forms of estrogen should be considered if a patient presents with…
Established CVD (high lipids, TG), past VTE
Hepatobiliary disease
Migraine
Diabetes
Advanced age and no previous MHT
An alternative to vasomotor symptoms when MHT is CI or not desired are…
Serotonergic antidepressants - SSRI, SNRI
Efficacy of serotonergic agents for VMS are…
Less effective than HT, but still efficacious
The specific SSRI’s that have been studied for VMS are these 3…
Paroxetine
Citalopram
Escitalopram
The specific SNRI’s that have been studied for VMS are these 2…
Venlafaxine
Desvenlafaxine
SSRI/SNRI is a good option to consider in those with…
Co-morbid mood symptoms
Fezolinetant (veozah) is a new medication indicated for tx of moderate-severe VMS associated with menopause. Its MOA is…
Nonhormonal - selective neurokinin 3 receptor antagonist
Modulates thermal activity in the hypothalamus
Common AE’s that were noted with fezolinetant included…
Headache
Liver enzyme elevation
Abdominal pain, diarrhea
Insomnia
Nausea
Note CYP metabolized
Other non-hormonal treatment options for VMS includes…
Clonidine
Oxybutynin
Gabapentin
Pregabalin
Note indiviudal medication AE’s
Evidence for herbal products in VMS…
Points to conflicting results, or no better than placebo
Osteoporosis is related to menopause in that…
Post-menopause, estrogen deficiency causes accelerated bone loss via increasing bone turnover + resorption
Estrogen enhances osteoblastic production of osteoprotegerin which has antiosteoclastic properties
Estrogen therapy has been shown to reduce fracture risk in postmenopausal women. However, it is only indicated…
For prevention of osteoporosis only, not treatment - a patient should also have indication for another condition (VMS)
Estrogen therapy should NOT be only for osteoporosis prevention alone
Effects of estrogen on bone protection are ____ related. Standard dose HT ____, while low dose HT _____.
Dose related; standard dose HT reduces risk of osteoporotic fracture, low dose HT beneficially increases BMD
The benefits of fracture risk ____ when HT is discontinued.
Dissipate - return to pre-treatment levels in 1-2 years
Estrogen and progestin appears to have these effects on lipids…
Estrogen decreases LDL, increase HDL. Oral increases TG.
MPA blunts good lipid effects of estrogen. Micronized progesterone is lipid friendly
However consider estrogen effects on inflammation + markers of thrombosis… Not exactly CV protective
Multiple observational studies + meta-analysis have shown that use of HT in younger women under 60, within 10 years of menopause…
May have a beneficial effect on reducing CVD, or at least does NOT increase CHD risk
Use of HT in patients older than 60 or 10 years post menopause…
May increase risk of CHD, VTE and stroke vs. earlier initiation
MHT may increase risk of ____ regardless of age of initiation. We should address risk factors for…
VTE - address risk factors for stroke + DVT before initiating, and choose appropriate dose/formulation
Low dose HT or transdermal ET may have less DVT risk
HT and breast cancer risk…
Increases with longer duration
In women with prior breast cancer history, systemic HT…
Is generally not advised - joint decision with oncologist.
Low dose vaginal therapy = minimal systemic absorption
In order to attain benefit while minimizing risk while using HT, we should be using appropriate…
Dose, duration, regimen, and route of administration
Duration of treatment for HT is…
Individualized - appropriate dose to control symptoms. Assess yearly to see if treatment is still required
Sleep difficulty is a hallmark symptom of menopause transition. Management can include…
General insomnia recommendations: CBT, hypnotics antidepressants
MHT may help in those experiencing VMS
Some women may be more vulnerable to depressive symptoms, anxiety, and irritability - this may be due to…
Estrogen depletion, deficiency, or changing levels
Estrogen has multiple effects on brain function
Does estrogen therapy help with mood?
Recall that moderate-severe VMS are more likely to have moderate-severe depressive symptoms
Some studies show ET improving depressive sx’s in perimenopausal women, and may augment clinical response to SSRI’s
Use of antidepressants + psychotherapy remain mainstsay of tx for mood disorders and anxiety
How does HT connect with cognitive function and dementia?
As of today - HT is not recommended to preserve cognitive function, or prevent/treat dementia.
Intiation in those 65+ may increase cognitive risk
Urogenital aging may be exacerbated by menopause because…
There are many estrogen receptors located in vagina, vulva, urethra, and bladder.
Decrease in estrogen can cause tissue atrophy, reduced secretions and blood flow, contributing to vaginal symptoms
Genitourinary syndrome of menopause (GSM) refers to signs + symptoms resulting from estrogen deficiency on the genitourinary tract. Common symptoms include…
Vaginal dryness, itching, irritation
Burning
Painful intercourse
Lower urinary tract sx’s (urinary frequency, urgency, UTI’s)
Nocturia, dysuria
Onset can vary - may begin during perimenopause, or commonly a couple years after menopause
Treatment decisions for GSM should be based on…
Medical history and a physical exam (no underlying pathology, correlation with menopause?)
1st line tx for vaginal dryness + dyspareunia are…
Lubricants (use with intercourse)
Moisturizers (use regularly) - goal to reduce daily sx’s and make intercourse more comfortable
If OTC agents for GSM are ineffective, we could try…
Vaginal estrogen
Prasterone
Ospemifene
Safety of vaginal estrogen is…
Less concerning - minimal systemic absorption
Accompanying progestin is not needed (risk of VTE, CVD, endometrial + breast cancer does not seem to be increased)
Vaginal estrogen products come in a variety of dosage forms such as…
Creams (Premarin, Estragyn)
Ring (Estring)
Vaginal tablets/inserts (Vagifem, Imvexxy)
Efficacy similar between all - pt. preference
Common AE’s for all forms of vaginal estrogen include…
Local burning/irritation
Leakage (USE HS)
Onset of benefit for vaginal estrogens is usually…
In a few weeks - up to 12 weeks for maximum benefit
Assessed at 3-6 months, then yearly typically. For low risk women on low dose ET, progestin + endometrial surveillance not reocmmended
If someone is experiencing both VMS and GSM symptoms, we can give…
Oral MHT for treating both symptoms.
If GSM sx’s still present while on systemic MHT, systemic and intravaginal ET may be used together
Prasterone is another ____ product, and its MOA is to…
Local vaginal product - synthetic form of DHEA, that when it is administered vaginally, cells in vagina convert to estrogen and androgens where they act locally
Avoids exposure of other tissues to these hormones; good option for women who do not want to use, or have CI to estrogen
We should assess for response of prasterone…
At 3-4 months then periodically
Tolerability of prasterone is…
Good - melting of hard fact may cause discharge
Consider similar warnings and precautions to topical estrogen products (local irritation, burning, leakage)
Ospemifene is an ____ treatment indicated for…
Oral - GSM (moderate to severe dyspareunia +/- vaginal dryness
Ospemifene MOA is…
Non-hormonal SERM: weak agonist effects in endometrium, activates estrogenic pathways in vulvar, vaginal tissues, and bone, blocks pathways in breast
Does ospemifene require progesterone?
So far, does not need to be co-administered with progesterone
No cases of endometrial cancer observed
Ospemifene should be taken with ____ to…
Food - increase bioavailability
AE’s of ospemifene is primarily…
Hot flashes
If occur, do not administer with estrogen
Monitoring of ospemifene is to…
Report any abnormal uterine bleeding to physician ASAP. Assess response to therapy at 3-6 months, then yearly
Is MHT associated with weight gain?
No - during menopause, it is likely for a patient to see an average weight gain of 1.5 lbs/year due to decreased resting metabolic rate that occurs with aging
Soon after menopause, skin changes occur such as…
Skin collagen content, thickness, and elasticity decline
Abnormal uterine bleeding (AUB) is common during the menopause transition period. However, other potential causes of AUB that need to be ruled out include…
AUB = irregular menstrual cycles
Dysfunctional uterine bleeding (DUB) = anovulation
Endometrial hyperplasia and cancer
Benign lesions
DUB = diagnosis of exclusion; evaluation of DUB in a perimenopausal woman is warranted
Any bleeding after 12 months of amenorrhea is considered ____ and should also be investigated
Post-menopausal bleeding
Treatment of AUB is aimed at regulating bleeding patterns. This may include…
Low dose OCP’s
Intermittent or continuous progestin therapy
Recall that vaginal bleeding is common in MHT for the first 3-6 months.
Any unscheduled bleeding after ____ of hormonal treatment should be investigated
6 months
