L14- perimenopause, menopause, and post menopausal disorders

menopause

• permanent cessation of menstrual periods; 12 months of amenorrhea without any other obvious pathologic or physiologic cause

• complete or near complete ovarian follicular depletion with resulting

  • low estrogen

  • high FSH

perimenopause transition

• menopausal transition being on average 4 years before final menstrual period (FMP)

• irregular menstrual cycles and marked hormonal fluctuations often accompanied by

  • hot flashes

  • sleep disturbances

  • mood sx

  • vaginal dryness

  • changes in lipid and bone loss begin

• transition is generally characterized by a gradual decrease in menstrual bleeding

perimenopause

• early

  • change ≥7days in the intermenstrual interval

    • 25-35days to 40-50days

  • FSH levels variable, but typically high

• late

  • skipped sycles, episodes of amenorrhea

  • hot flashes=common

perimenopause- eval

• women >45

  • irregular menstrual cycles adn menopausal sx such as hot flashes, mood changes, or sleep

  • no further dx evaluation needed

    • FSH offers no additional information and may be misleading

    • if amenorrhea, rule out preg!!

• women 40-45

  • irregular cycles ± menopause sx:

    • eval fro other causes

      • serum hCG, prolactin, TSH, FSH

• women <40

  • complete eval for primary ovarian insufficiency

    • FSH, estradiol TSH, serum hCG, prolactin, testosterone

perimenopause- dx

• women >45

  • made based upon change in intermenstrual interval (less freq menses ) ± menopausal sx

  • dx from perimenopause to menopause only once 12months of amenorrhea

• women 40-45

  • as above, except ruel out other causes of menstrual dysfunction first

• women <40

  • do not dx as perimenopause or early menopause

  • requires full eval and it notable fro elevated FSHm low estradiol, then dx is POI

perimenopause and early menopausal sx

• hot flashes

• depression/sleep disturbance

  • SIGNIFICANT risk new onset depression

  • risk decreases by early post-menopause

• cognitive changes

  • forgetfulness, difficulty with word retrieval, brain fog

  • actual consequence of hormonal change remain uncertain

• genitourinary syndrome of menopause

  • vulvovaginal atrophy: decreased estrogen→ decreased blood flow to vagina/vulva→ decreased vaginal lubrication= vaginal dryness, dyspareunia, sexual dysfunction

  • urinary sx

• sleep disturbance

  • can occur in presence or absence of hot flashes

hot flashes

• MOST COMMON sx

• sudden sensation of heat centered on the upper chest and face that rapidly becomes generalized

  • ± profuse perspiration, palpitations, anxiety

  • occurs several times/day

• sig impact on function

  • sleep, concentration, mood, energy, sexual desire

ddx- hot flashes

• menopause

• thyroid disorder

• malignancy

• medication induced

• endocrine disorder

• neuro disoder

• anxiety

• substance use

long term consequences of estrogen def

• boen loss

• CV disease

• osteoarthritis

• body comp

  • gain mat and lose lean mass

• skin changes

• impaired balance

perimenopause- non hormonal tx

• SSRIs/SNRIs

  • start wirh SSRI liek citalopram or escitalopram (fewer SE and withdrawal sx)

  • paroxetine (avpid on tamoxifen)

• antiepileptics

  • gabapentin

  • pregabalin

• clonidine

• anticholinergic

  • oxybutynin (risk cog impairment in older adults)

• nerokinin 1,3 receptor antagonist

  • elinzanetant (risk for liver issues)

• nerokinin 3 receptor antagonist

  • fezolinetant (boxed warning for baseline and serial LFTs)

perimenopause tx options

• hormonal replacement therapy (HRT) or menopausal hormonal therapy (MHT)

  • combined estrogen- progestin therapy

    • any women with an intact uterus to prevent endometrial hyperplasia

  • unopposed estrogen therapy

    • women without intact uterus

• non hormonal

OCP role in perimenopause

• viable option for healthy sx perimenopausal women and those that wish to AVOID preg or have heavy bleeding

• combo low estrogrn and progestin conraceptives (pill, ring, patch)

• tx individualized

• consider stop at 50

  • can transition to MHT is still sx

OCP and perimenopause- CIs

• >35yr and smoking

• HTN

• DM

• hx VTE/stroke

• migraine with aura

• obesity

non contraceptive benefits of OCPS in perimenopause

• suppress vasomotor sx

• restore predictable bleeding

• decreased dysmenorrhea

• enhance BMD

• lower risk endometrial/ovarian cancer

MHT contraindications

• hc breast CA

• CHD

• previous venous thrombosis event or stroke

• acute liver disease

• unexplained vaginal bleeding

• high risk endometrial cancer (not absolute CI)

  • do cont estrogen AND progestin therapy

• TIA

calculating risk

• calculate CV and breast cancer risk before initiating MHT

• avoid in high risk CVD (>10% 10yr risk) or mod-high risk breast cancer (>1.67% 5yr risk)

risks of MHT

• individualized risk assessment needed

  • age 60-69yrs

  • overall risk age 50-59= considerable lower

• ± heart disease: mostly in older menopausal women

• stroke: very low for 50-59

• venous theomboembolism

  • lower absolue risk 50-59

  • lower risk with transdermal compared with oral estrogen

• breast cancer

• endometrial hyperplasia and cancer

  • no sig risk if cont with progestogen with intact uterus

• gallbladder disease

preferred tx - late perimenopausal/early menopausal

• transdermal estradiol OR oral estradiol + cyclic micronized progesterone first 12 days of each calendar month

  • withdrawal bleeding common with cyclic combined hormone regimens

preferred tx- perimenopausal mood disorders

• individualized: MHT and/or SSRI

preferred tx- women >2-3 yrs post-final menstrual period

• continuous combined regimens (for ammenohhrea)

• transdermal estradiol PR oral estradiol + continuous micronized progesterone

preferred tx- surgical menopause

• hysterectomy: unopposed estrogen

monitoring parameters

• dose adjustments

  • start low and titrate up

• endometrial monitoring

  • postmenopausal and irregualr bleeding: endometrial biopsy PRIOR to starting MHT

  • continuous combined therapy: monitor vaginal bleeding x6 months, if continues→ endometrial biopsy

  • cyclic progestin or ET- TVUS can be used to monitor endometrium, but not as reliable as biopsy

    • persistent bleeding always requires endometrial biopsy regardless of US findings

• routine mammography and breast exams

MHT duration of use

• individualized based on ongoign sx burden, risk assessment and shared decision making

• extended use (60-65) may be reasonable when clinician and pt agree that benefits of sx relief outweigh risks

• varying results on tapering vs abrupt stop

implications of stopping MHT tx

• retue of estrogen deficiency sx

• resumption of bone loss

• decrease in breast CA risk

• effect on CAD unclear

other disorders of menopause

• lichen sclerosus

• genitourinary syndrome of menopause

• pelvic organ prolapse

• incontinence

• sexual dysfunction

• osteoporosis

lichen sclerosus

• benign, chronic, progressive, dermatologic condition characterized by marked inflammation, epithelial thinning, and distinctive dermal changes ± pruritis

lichen sclerosus- eti and epi

• eti: unknown, ± genetic and hormonal factors, common with autoimmune disease

• epi: l=peak onset prepubertal and peri-or postmenopausal period

lichen sclerosus- sx

• vulvar pruritis

• anal discomfort

• dyspareunia

• dysuria

lichen sclerosus- physical exam findings

• shiny white, atrophic papules and mcaules that may coalesce into plaques

  • can also be hemorrhagic, purpuric, hyperkeratotic, bullousm eroded, or ulcerated

  • MC affects labia minora and majora

• loss of vulvar architecture

  • clitoral phimosis

lichen sclerosus- dx

• clinical sx base don exam findings/hx IF classic presentations

• punch biopsy recommended if:

  • uncertain dx

  • concern for neoplasia

  • pt presenting with atypical features or during reproductive yrs

    • vulvar dermatitis more likely

  • if initial tx fails

• assess fro underlying autoimmune disease

• remain alert to coexisting bacterial or fungal vulvar infections or extragenital LS

lichen sclerosus- mgmt

• pt edu

  • discuss disease course, potential for recurrences, importance of tx adhereance, adn malignancy risk

    • ass with risk vulvar squam cell carcinoma if untreated/treate dinadequately

• topical therapy

  • super potent steroids (clobetasol propionate 0.05% x12 weeks)

• adverse effects

  • risk of cutaneous atrophy, telangiectasia, adn striae, but modified mucous membranes of labia and clitoris are relatively resistant to SE of topical steroids

• psychosocial support

  • address impact on sexual health and quality of life, consider sexual counseling

• maintenance therapy

  • taper 2-3times/week application after remission to prevent recurrence

• response monitoring

  • if no response after 12 weeks, reassess tx approach and dx

• sx mgmgt

  • emollients- daily use

  • lubricants- helpful for dyspareunia

genitourinary syndrome of menopause (vulvovaginal atrophy)

• a/sx caused by hypestrogenic changes to labia majora and minora, clitoris, vestibule, urethra, adn bladder

  • spectrum of genital, sexual, and urinary sx

genitourinary syndrome of menopause- epi and eti

• epi: most menopausal pts effected, prevalance not well est

• eti: hypoestrogenic state

genitourinary syndrome of menopause- sx

• vulvovaginal dryness

• decreased vaginal lubrication during sexual activity

• dyspareunia, including vulvar or vaginal pain

• vulvar or vaginal bleeding

• decreased arousal, orgasm, or sexual desire

• vulvovaginal burning, irritation, or itching

• vaginal discharge (leukorrhea); thick yellow, or malodorous vaginal discharge may be sign of infection and requires eval (wet mount or NAAT)

• levator spasm

• UT sx

• urethral prolapse

genitourinary syndrome of menopause- PE findings

• labia minora resorption or fusion

• tissue fragility, thinning/fissures/petechiae

• introital retraction

• loss of hymen remnants

• prominence of urethral meatus

• urethral eversion or prolapse

• vulvovagonal pallor/erythema

• loss of vaginal rugae

• decreased vulvovagonal secretions/lubrication

• decreased elasticity

• vaginal discharge that is thin, white, and non odorous

• spasm of levator muscle on palpation

genitourinary syndrome of menopause- dx

• clinical made in pts in hypoestrogenic state + characteristic sx ± findings on pelvic exam

• s/sx must be bothersome and should not be better accounted fro by another dx

genitourinary syndrome of menopause- initial tx

• non hormonal vaginal moisturizers (daily) and lubricants (for sexual activities)

• pelvic floor muscle exercises (kegels)

genitourinary syndrome of menopause- tx of persistent sx

• low dose vaginal estrogen therapy

  • conjugated estrogen (premarin) of cream intravaginally x2weeks then reduce to twice weekly

  • estradiol vaginal cream: estrace of cream intravaginally admin x2weeks then reduce to twice weekly

• other meds: vaginal DHEA (prasterone) or oral SERM (ospemifene)

pelvic organ prolapse

• herniation of pelvic organs to or beyond vaginal walls

• occurs in up tp 50% of parous women

  • cystocele

  • rectocele

  • enterocele

  • uterine

• RF:

  • parity

  • advancing age

  • menopause

  • obesity

  • hysterectomy

  • race.ethnicity

pelvic organ prolapse- sx

• bulge/pressure sx

• urinary

  • stress incontinence

  • difficulty voiding

• defactory sx

  • constipation

  • incomplete emptying

• sexual dysfunction, dyspareunia

pelvic organ prolapse- ddx

• pelvic mass: ovarian or vaginal cyst, cancer, fibroids

• chronic inversion of uterus

• hypertrophy of cervix

• UTI

pelvic organ prolapse- dx

• pelvic exam

  • determine staging: baden walker halfway system

    • grades 0-4

  • pelvic organ prolapse quanificatio system (POP-Q)

• medical hx

pelvic organ prolapse- mgmt

• individualized and indicated if sx

• conservative options

  • vaginal pessary

  • pelvic floor PT

  • estrogen not found to be helpful for prolapse, but can help reduce pessary related complications

• surgical

  • for pts who fail or decline conservative tx

pelvic organ prolapse prevention

avoid pregnancies in quick succession

urinary incontinence

• low estrogen→ atrophy of urethral mucosal epithelium → urethritis, diminished urethral mucosal eal, loss of compliance, and possible irritation→ all contributing to incontinence

types of urinary incontinence

• stress: involuntary leakage of urine that occurs with increases in intra- abdominal pressures (exertion, sneezing, coughing, laughing) in the absence of a bladder contraction

• urge: urge to void immediately preceding or accompanied by involuntary leakage of urine

• mixed: both

• overflow: continuous urinary leakage or dribbling in setting of incomplete bladder emptying

urinary incontinence- epi

• affects 50% adult women, increases with age

• RF:

  • advancing age

  • obesity

  • multiparity

  • vaginal birth

  • fhx

urinary incontinence- impact of health

• quality of life

• sexual dysfunction

• morbidity

• increased caregiver burden

urinary incontinence- eval and dx

• thorough history

  • sx and clinical classification

  • systemic sx

  • acute/subacute/chronic onset

  • meds

  • alcohol/caffiene

• physical exam bases on hx

  • abdominal/pelvic exam, ± euro exam

  • consider stress test

• Ua on ALL pts

  • culture if concerned of UTI

  • if hematuria→ culture, if neg→ cystoscopy/imaging usually warranted if persistnet

urinary incontinence- urodynamic testing

• NO ROLE in initial eval and tx of straight forward stress, urge or mixed incontinence: defer to GU

  • post void residual (PVR) by bladder scan/US

    • stress or urgency: incertain dx, initial therapy fails, or if concern for urinary retention or overflowing incontience

urinary incontinence- initial first line tx

• modify contributing factors (meds)

• weight reduction of obese/overweight

• lifestyle mod

• pelvic floor PT

• supervised pelvic floor therapy ± biofeedback

• vaginal weighted cones

• bladder training

• topical vaginal estrogen (peri or post menopausal)

stress urinary incontinence tx

• if conservative tx not suff

• continence pessaries

• no pharm agents approved by FDA

• surgery

  • mid urethral sling

urge/overactive urinary incontinence

• if conservative tx not sufficient

• beta 3 adrenergic agonists (mirabegron ER preferred)

• antimuscarinic agents/anticholinergics (oxybutynin. darifenacin, fesoterodone, etc)

  • safety warning for dementia risk

• tibial nerve stimulatio, botox, sacral nerve stimulation, laser therapy

sexual dysfunction

• lack of sexual desire, impaired arousal, inability to achieve orgasm, pain with sexual activity, or a combo

• eti= multifactorial

• eval= physical and pelvic exam

sexual dysfunction- non pharm mgmt

• vaginal lubricats/moisturizers

• lifestyle changes

• couples and or sex therapy

• pelvic floor PT

sexual dysfunction- pharm therapy

• MHT
  low dose vaginal estrogen

• transdermal testosterone therapy (post menopausal only)

• bremelanotide

  • premenopausal

  • avoid if CVD, uncontrolled HTN

• flibanserin

  • premen, also postmen <65

• bupropion/wellbutrin

osteoporosis

• low bone mass, microacrchitectural disruption, skeletal fragility

  • → decreased bone strength and increased risk of fracture
    

• RF:

  • advancign age

  • female

  • previous fracture

  • low body weight

  • steroid use

  • paretnal hx hip fracture

  • diet

  • smoking

  • excessive alcohol

  • sedentary

osteoporosis- prevention

• postmenopausal women need 1200mg Ca2+ daily + VIt D 800 IU daily

• weightbearing exercise at least 30min most days + muscle strengthening 2-3days/week

• adequate caloric intake

• smoking cessation

• avoid heavy alcohol

osteoporosis- clinical manifestations

• NONE until there is fracture

  • vertebral body fracture=MC

  • often incidental

• other fractures

  • hip

  • distal radius (colles)

osteoporosis- eval

• assess for RF for fracture and to eval for other conditions that can contribute to bone loss

• las eval:

  • biochem profile

  • 25-hydroxyvitamin D

  • complete blood count

  • DXA to assess BMD

osteoporosis- dx

any of the following:

• fragility fracture (spine, hip, distal radius, humerus, pelvis)

• T score≤2.5 at ANY site

• high fracture risk- FRAX 10 year prob of major osteoporotic fracture ≥20% or 10year probability of hip fracute ≥3%

osteoporosis- mgmt

• pharm tx recommended for most postmenopausal women with prior fragility fracture , T score ≤-2.5, or t score -1.0—2.5 + 1- year probability major osteoporotic fracture >20% or 10 year probability of hip fracture ≥3%

• oral bisphophonate

  • alendronate = typical first choice

  • admin in AM ≥30min before first food/drink adn must stay UPRIGHT fro 30-60min

  • avoid in esophageal disorders, inability to follow dosign req, or CKD with eGFR<30

  • repeat DXA in 1-2yrs

  • drug holoday considered after 3-5 years (osteonecrosis of jaw risk)

osteoporosis- additional tx

• if very high fracture risk, anabolic agents ate recommended

  • triparatide

  • abaloparatide

  • romosozumab

• if cannot tolerate bisphosphonates:

  • IV bisphos recommended - zoledronic acid

  • if not tolerated at all: anabolic agents above

osteoporosis- monitoring and duration of tx

• repeat dxa after 1-2 years of tx

  • if MBD stable-improved: continue tx, reasses in 2-5yrs

  • if MBD decreased >5percent or least sig change or new fracture→ eval and adjust contributign factors adn adjust therapy as needed

• all pts with progressive BMD loss despite osteoporosis pharm therapy should be referred to specialist

• duration:

  • individualized adn depends on agent used, response, and reassessment of fracture risk

osteoporosis- screening

• recommended in:

  • women ≥65

  • women <65 + one or more RF

    • previous fragility fracture, steroid therapy, parental hx hip fracture, low BMI, cigarette smoking, alcoholism, RA

  • men with clinical manifestation for low bone mass (radiographic osteopenia, hx low trauma fraction, loss of more than 1.5” height) or with risk factors for fracture