IE 4: Menopause

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