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What is the definition of peri-menopause?
Time from which menopause becomes irregular to Final Menstrual Period
What is menopause?
Cessation of menstrual bleeding for continuous 12 month period
What are factors that affect the age of onset for menopause?
Smoking
Genetics
Body Size
What are different causes of menopause?
Premature (prior to age of 40)
Surgical
Primary ovarian insufficiency (genetic, metabolic, med related, immune related, related disorders)
What are primary hormones associated for menopause?
Estrogen, progesterone, testosterone (ovaries)
FSH, LH (pituitary gland which is controlled by hypothalamus)
Aging leads to what?
Aging leads to atresia (diminished oocytes) which leads to decreased estradiol concentrations which is detected by pituitary/hypothalamus
Significant increase in FSH and LH concentrations are seen as a result
Lack of corpus luteum leads to lack of progesterone activity
Testosterone productions drops to about half of that of young women in her 20s
What are hallmark symptoms of menopause?
Menstrual irregularity (earliest sign)
Vasomotor symptoms
Hot flushes, night sweats (average duration 7 years, highest in 2 year post-menopause)
Breast tenderness/swelling
Heavy or irregular bleeding
Genitourinary Symptoms of Menopause (GSM)
Urogenital atrophy (vaginal dryness, dyspareunia, recurrent UTI, urge/stress incontinence)
What is the other symptoms of Menopause?
Sleep disruption (higher in those with VMS)
Depressive symptoms
Memory loss, difficulty in concentration, decline in cognitive performance
Arthralgia
For the diagnosis, what is the STRAW staging system? When is it not useful?
Identify a change in bleed pattern and amenorrhea
NOT useful if no uterus, hormonal contraceptive use or IUD, or other prior procedures which affect menstrual function
What are alternative methods of diagnosing menopause?
Lab testing (FSH, estradiol) – very erratic during transition and limited efficacy in those using contraception
What is the treatment for menopause?
Menopausal Hormone Therapy (MHT)
What is the benefit of MHT? What risk-benefit ratio do you consider?
Most effective option for VMS and GSM management
Women < 60 years of age or within 10 years of menopause onset benefits of treating bothersome symptoms outweigh risks of MHT
Risk is greater for heart disease, stroke, VTE, dementia in women not meeting this criteria
During MHT, what therapy is done during the menopause transition?
Estrogen alone or estrogen + progestogen therapy during the menopause transition to improve QOL
Primary focus on alleviation of VMS and GSM
In MHT, women with an intact uterus should use what?
Women with an intact uterus – should use BOTH estrogen and progestogen therapy to prevent unopposed estrogen activity which causes overstimulation of uterine lining and can progress to endometrial hyperplasia and cancer
In MHT, what formulations are available?
Multiple formulations and sources available
Some patients prefer bioidentical options (estradiol, micronized progesterone)
Others appropriate for compounding, allergy considerations, data available
In MHT, estrogen therapy can do what?
Estrogen therapy can reduce frequency and severity of VMS (oral agents have been first-line option)
Vaginal estrogen formulations are ideal for GSM including prevention of recurrent UTI
Vaginal products minimize systemic absorption but provide adequate relief
Systemic agents may worsen urinary stress incontinence
Estrogens come in what formulations?
Oral, transdermal, vaginal formulations
Estradiol (bioidentical) is most common then CEEs (mixtures, NOT bioidentical, but better studied)
What are key considerations of ORAL estrogens?
Oral estrogens affected by gut and liver metabolism (possible higher VTE risk due to increased liver clotting factor
production activity)
Oral estrogens may positively impact lipids (lower LDL, increase HDL, but may increase triglycerides)
What are key considerations of transdermal estrogens?
Key considerations of transdermal estrogens:
Gels, patches, sprays with similar efficacy to oral options
First-pass gut/liver metabolism is avoided – decreased VTE risk, less negative impact on triglycerides
Consider patient preference when selecting formulation
What are key considerations of vaginal estrogens?
Creams, tablets, rings
No systemic progestogen needed with typical doses because of lack of systemic absorption of estrogen (except with ring
because dose is higher) – risk is unknown with high dose usage
What do progestogens do?
Protects against endometrial hyperplasia and cancer risk related to unopposed estrogen
What are some key considerations of oral progestogens?
Options: MPA, norethindrone, drospirenone, levonorgestrel, micronized progesterone (bioidentical)
Consider side effects and risk profile for each agent
Drospirenone – anti-aldosterone activity, hyperkalemia risk
Micronized progesterone – manufactured in peanut oil
What are key considerations of transdermal progestogens?
“OTC” options - lack of evidence, may not meet regulations
Combination patches available
What are key considerations of IUD progestogens?
LNG-IUD is effective in providing endometrial protection but not an FDA approved option
Ideal for those with contraceptive needs or do not tolerate oral or transdermal options
What are alternate options to progestogens and estrogens?
Ospemifene (Osphena®)
(SERM with selective tissue activity, so no progesterone needed?) – approved for dyspareunia and vaginal dryness and atrophy
Intravaginal DHEA – consider if non-estrogen therapy is needed
For other options, what is Tissue-selective estrogen complex (TSEC)+estrogen agonist antagonist (SERM) good for?
Good for those who cannot tolerate progestogen therapy but need to oppose estrogen effects to obtain endometrial protection
CEE + bazedoxifene (Duavee®)
What is testosterone for in “other options”?
Testosterone: interest in low-libido management or sexual dysfunction (patches, creams – no FDA approval, dosing unclear)
For MHT, risk of endometrial cancer is minimized with what?
Combo estrogen and progestogen
Progestogens can be continuous or cyclic but what is preferred?
Progestogens can be continuous or cyclic, with cyclic preferred if 12 months of amenorrhea have not yet occurred
What is the contraindications to MHT?
Undiagnosed vaginal bleeding, treatment of hormone-dependent malignancy, history of estrogen-dependent malignancy, MI, stroke, VTE, dementia, severe liver disease
What is a significant issue in post menopausal women? How can MHT help and what is its place in therapy?
Osteoporosis is a significant issue for post-menopausal women
MHT reduces bone turnover, increases BMD, and decreases hip fracture rates
Despite benefits, these are NOT considered first line therapy for osteoporosis treatment or prevention due to other risks
of MHT
Sleep improvements is based on reduction of what?
VMS and GSM
Mood data is mixed but studies show slight effects of what on those on MHT?
Mood data is mixed but some studies show slight anti-depressant and anti-anxiety effects in those on MHT
Oral estrogen therapy is associated with what risk increase? Transdermal estrogen is what risk compared to oral
VTE and stroke – oral estrogen therapy associated with two fold increase in risk of VTE (compounds further with additional risk factors)
Transdermal estrogen VTE risk is lower than that of oral, but should generally avoid estrogen therapy in high risk patients
Breast cancer risk is driven by what?
Breast cancer – primarily driven by progestogen use based on data, but risk for individual women is still low overall.
Limit use/duration of MHT and stick to lowest doses possible to manage symptoms
How often should treatment be reassessed for MHT?
Treatment should be individualized and risk-benefits should be reassessed annually (regardless of age)
Recurrence of sx may occur to how many people with MHT d/c?
Recurrence of symptoms may occur in up to 50% of women with MHT discontinuation
No ideal regimen for discontinuation (abrupt or tapered)
VMS improvements is seen when after initiating MHT? What time range is needed for full impact assessment? How long does it take to follow up?
VMS improvement seen often after 2-6 weeks of initiating MHT, but 8-12 weeks needed for full impact assessment
Follow-up every 1-2 months and annual evaluation is strongly encouraged
When do you consider non-hormonal treatment? What are they?
Pts with contraindications to MHT
SSRI/SNRI – effective alternatives for reduction of hot flushes and improve mood disorders
Best data for citalopram, escitalopram, desvenlafaxine, paroxetine (FDA approval)
Avoid paroxetine with tamoxifen due to DDI which prevents conversion of tamoxifen to active metabolite (CYP2D6 inhibition)
Gabapentin and pregabalin
Small studies, some efficacy in VMS reduction
Clonidine
Elevates the “flush threshold” and can reduce symptoms, but less effective than previous options
What are the non-pharm and complementary options?
40-50% of women in western countries use herbs, supplements, acupuncture, relaxation, massage, etc. to address menopausal symptoms
Phytoestrogens (isoflavones) – theoretically an option
Black cohosh – evaluate liver function first, data is mixed
Avoidance of triggers (spicy foods, alcohol, hot foods/liquids)
Recommend cooling techniques for hot flushes or lubrication for painful intercourse or vaginal dryness
Yoga – good data for overall reduction compared to no intervention
Aerobic exercise – mixed data
For management of perimenopause, contraceptive management can be used if what?
If contraceptive efficacy is needed
MHT alone is not effective for pregnancy prevention
Can transition patient to MHT once contraception no longer needed
Preferred option is CHC or LNG-IUD
Sx can continue to be managed by adding low dose supplemental estrogen during “pill-free week” or extended cycle dosing
What are key patient education points?
Patients should understand the goal of treatment of menopausal symptoms is to improve quality of life
choice to treat or not to treat symptoms is an individual one
Women should be informed of the evidence-based benefits and risks of MHT so that they can make a decision
based on factual data
An overview of multiple MHT options and formulations should be given so that therapy plan can be customized
based on patient characteristics, comorbidities, and preferences
Patients should also be informed of non-hormonal and non-pharmacologic treatment options for menopausal
symptoms