Transcript Clinical Slide Set. Perimenopause

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© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
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© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
in the clinic
Perimenopause
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What is perimenopause?
 Transitional time late in a woman’s reproductive life
 Time of hormonal flux
 Also called “menopause transition”
 Duration = 5 years
 Symptoms may begin 8 yrs before final menstrual period
 Average age at onset: 47.5 yrs
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
How is it diagnosed?
 Early perimenopause: variable cycle length (>7 days
different from normal cycle)
 Late perimenopause: >2 missed cycles or >60 days
amenorrhea
 During both phases
 Ovarian function progressively decreases
 Follicle-stimulating hormone, luteinizing hormone increase
 No diagnosis required unless symptoms are present
 Irregular menstrual bleeding, hot flashes, night sweats
 Mood changes, sleep disturbances, sexual dysfunction
 Lab tests not usually needed to make treatment decisions
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Diagnosis is based on characteristic symptoms
 Abnormal uterine bleeding
 Hot flashes
 Night sweats
 Symptoms occur up to 8 years before final menstrual period
 Laboratory testing not helpful for establishing diagnosis
 Including FSH and estradiol levels
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What types of menstrual changes occur
during perimenopause?
 Abnormal uterine bleeding associated with anovulatory
cycles
 Light and infrequent bleeding
 Unpredictable and heavy menstrual bleeding
 Prolonged menses
 Spotting
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What is the differential diagnosis of AUB in
perimenopausal women?
 PALM-COEIN Classification for Causes of AUB
 Structural
 Polyp
 Adenomyosis
 Leiomyoma
 Malignancy and hyperplasia
 Nonstructural
 Coagulopathy
 Ovulatory dysfunction
 Endometrial
 Iatrogenic
 Not yet classified
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What type of evaluation should be performed
in perimenopausal women experiencing AUB?
 History
 Bleeding severity, associated pain, family history bleeding
 Possible underlying coagulopathy
 HMB since menarche
 Significant bleeding with dental work, surgery, parturition
 Easy bruising, gum bleeding, or epistaxis
 Medications
 Associated with AUB: anticoagulants; HT; herbal products
 Physical exam
 Assess for structural lesions involving the vagina or cervix
 Assess for palpable abnormalities of the uterus
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
Suggested Tests for Evaluation of AUB
 All women should have the following tests:
 Pregnancy test (urine or serum)
 Complete blood count, Thyroid stimulating hormone
 Cervical cancer screening with pap test
 Endometrial biopsy if age > 45 years
 Selected tests to consider during the initial evaluation:
 Chlamydia
 Prolactin level
 Prothrombin time and partial thromboplastin time
 Transvaginal ultrasonography
 Saline infusion sonohysterography
 If symptoms persist or structural abnormalities are present:
 Saline-infused sonohysterography
 Hysteroscopy
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What therapies should be offered to
perimenopausal women with AUB?
 Contraceptive-dose hormones often preferred
 Suppress ovulation + control menstrual patterns + protect
against pregnancy more than postmenopausal-dose HT
 Levonorgestrel intrauterine system
 More effective than low-dose combined oral contraceptives
for reducing menstrual blood loss
 Surgical options (endometrial ablation, hysterectomy)
 Option when medical therapy failed or is contraindicated +
childbearing is completed
 Therapy should be dictated by patient’s goals
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are the prevalence and associated
risk factors for VMS?
 Prevalence
 60%–80% in late perimenopause, early postmenopause
 Some women may experience VMS even earlier
 Risk factors
 Obesity
 African American race
 Lower education
 Anxiety
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What effective hormonal and nonhormonal
therapies are available to treat moderate to
severe VMS?
 Mild and infrequent VMS
 Use conservative measures
 Dress in layers, avoid hot and spicy foods, lower room temp
 Moderate to severe VMS in frequency and intensity
 Negatively affects sleep, mood, and QOL
 Hormonal and nonhormonal therapies can restore
thermoregulatory dysfunction
 Low-dose combination contraceptive methods relieve hot
flashes, control menstrual cycles, prevent pregnancy
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
Effective Nonhormonal Therapies for VMS
 SSRIs
 Reduce hot flashes by about 1/d
 Escitalopram may be more efficacious than other SSRIs
 Avoid tamoxifen + paroxetine in breast cancer survivors
 AEs: Nausea, fatigue, palpitations, dry mouth, rash, sleep
disturbance, sweating, dizziness, headache, low libido
 Venlafaxine (SNRI)
 Reduces hot flashes by about 1/d
 AEs: Possible small increases in systolic and diastolic BP
 Gabapentin
 Less reduction in hot flashes than with SSRIs, venlafaxine
 Optimal dosing unclear; likely between 900–2400 mg/d
 AEs: Dizziness, unsteadiness, fatigue, and somnolence
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
Which complementary and alternative
therapies are effective for treating VMS?
 Ineffective
 Yoga, paced respiration
 Cognitive behavioral therapy
 Ginseng root, Dong quai
 Phytoestrogens
 Data insufficient
 Black cohosh
 Vitamin E
 Acupuncture
 Exercise
 Possibly beneficial
 Red clover for hot flashes
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are the prevalence and risk factors
for sleep and mood disorders?
 Sleep problems
 Affect at least one-third
 Sleep difficulties highest risk in late perimenopause
 Risk factors: lower inhibin B levels, stress, depression,
nocturia, hx sleep disorders, number of physical conditions,
use of prescription sleep medications
 Depression
 Risk is higher during perimenopause
 Risk factors: history of depression, higher BMI, use of
psychotropic medications, major life stressors
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What treatments are available for
management of sleep disorders?
 Nonpharmacologic therapies
 Consistent recreational physical activity
 Pharmacologic therapies
 Antidepressants and hypnotics
 May reduce insomnia for those with both sleep
disturbances and VMS
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are the concerns regarding sexual
dysfunction?
 Sexual interest/arousal disorder
 β-blockers, SSRIs, SNRIs, HT: may contribute to sexual
dysfunction
 Oral combination hormonal contraceptives decrease free
testosterone but have unclear effect on libido
 Nonoral contraceptives may be associated with better
sexual function
 Painful sexual intercourse
 Due to vaginal atrophy or inadequate lubrication
 Exam showing pale vaginal mucosa, petechiae, and loss of
ruggae helps confirm Dx and direct appropriate treatment
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
How is sexual dysfunction managed?
 Direct treatment to the underlying diagnosis
 For low desire
 Flibanserin
 Transdermal testosterone therapy (off-label; use adequate
contraception)
 For discomfort due to vaginal atrophy or inadequate
lubrication
 Vaginal moisturizers and lubricants
 Vaginal estrogen treatment usually reserved for
postmenopausal women
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
CLINICAL BOTTOM LINE: Evaluation
and Treatment...
 AUB caused by structural and nonstructural abnormalities
 PALM-COEIN classification system guides evaluation
 Endometrial biopsy to r/o hyperplasia or cancer
 For all women older than 45 years with AUB
 Multiple medical therapies can improve bleeding patterns
 Once AUB classified as anovulatory
 Hormonal contraceptives reduce AUB, control VMS,
prevent pregnancy
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What types of hormonal contraceptive
options are available for perimenopausal
women?
 CHCs
 Contain both estrogen and progestin
 Available in pill, patch, and ring formulations
 Oral CHCs with low doses of ethinyl estradiol often
sufficient to control hormonal fluctuations
 Progestins only
 Later generations created to decrease androgenic activity
 Can be safely used in many of women with
contraindications to CHCs
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
Contraindications to CHC
 Migraine headache with aura at any age
 Cigarette smokers > 35 y
 History of VTE/pulmonary embolism, stroke, MI
 Uncontrolled hypertension: >160mmHg systolic or >100mgHg diastolic
 Systemic lupus erythematosus with positive antiphospholipids
 Postpartum <21 d
 History of bariatric surgery (malabsorptive type)
 Diabetes (retinopathy, nephropathy, or neuropathy or >20 y duration)
 Current breast cancer
 Hepatocellular adenoma, malignant hepatoma, severe decompensated
cirrhosis, acute or flare of viral hepatitis
 Undiagnosed abnormal uterine bleeding
 Complicated valvular heart disease, known thrombotic mutations
 Organ transplantation only if complicated
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are the cardiovascular risks of CHCs
in perimenopausal women?
 Perimenopausal women have a higher baseline risk for
MI and stroke than younger women
 Consider risks for these events in association with CHC
use
 Absolute rates of stroke and MI with oral CHCs are low
 Nonoral CHCs (vaginal ring, patch) may carry increased
stroke risk compared with oral CHCs
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are the risks for VTE associated with
CHC use among perimenopausal women?
 VTE events in perimenopausal women are more common
 Baseline risk for VTE increases with age
 Type of progestin may affect this risk
 If concern for VTE risk is high (family history, obesity), then
first- or second-generation progestins may be preferred
 Third-generation progestin norgestimate not associated
with increased risk for VTE —may be a good option for
women with refractory hirsutism
 Unclear whether nonoral CHCs have an increased risk for
VTE as compared with oral CHCs
 Fourth generation progestin drospirenone has not been
clearly associated with increased risk for VTE —may
improve premenstrual dysphoric disorder.
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What are special considerations in
perimenopausal women at risk for bone loss?
 Increased risk for osteopenia and osteoporosis
 Due to increasing age and declining estrogen levels
 DMPA use increases bone loss
 Provides contraception and regulates menstrual cycles
 But suppresses endogenous estrogen levels
 Bone loss may not be completely reversible
 Consider use of CHCs or the levonorgestrel IUS instead
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
What other medical conditions affect
decisions when prescribing CHCs?
 Obesity, hypertension, diabetes, hyperlipidemia
 CV and VTE risk increased when combined with CHCs
 DMPA not favored due to metabolic effects
 If CVD risk factors: progestin-only method often prescribed
 Cancer
 Even in those at highest risk for breast cancer, risk-benefit
ratio seems to favor benefit of CHC use, when appropriate
 Menstrual migraines
 CDC: don’t use estrogen-containing products in women >35
years who have migraine (and at any age if aura present)
 Progestin-only methods may relieve symptoms
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
When and how should women transition
from CHCs to HT?
 Women can continue on CHCs until age 55
 With yearly evaluation of safety and symptoms
 FSH levels help guide decisions to transition off CHCs
 No hormonal contraception for 14 days before FSH test
 Suggested transitions off hormonal contraception
 Depo-Provera: Continue until age 50-51, if signs of
hypoestrogen, offer estrogen therapy until age 55; in
women >50, 2 consecutive FSH levels >35 IU/L drawn at
injection visit at least 90 days apart suggest menopause
 Mirena IUD: 12 months amenorrhea + 2 FSH levels > 35 IU/L
 Copper IUD: 12 months amenorrhea + 2 FSH levels >35 IU/L
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
 CHCs and HT differ in formulation and potency
 Oral and nonoral CHCs: ethinyl estradiol typically used
 Systemic HT: 17 β-estradiol or conjugated equine estrogen
most commonly used
 Standard-dose oral CHCs: 20-35 mcg ethinyl estradiol
(ultra-low-dose: 10 mcg)
 Standard oral HT: ≤5 mcg ethinyl estradiol, 17 β-estradiol
≤1 mg, or 0.625 mg conjugated equine estrogen
 No indication to start HT after discontinuation of CHCs
unless bothersome symptoms occur / persist
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.
CLINICAL BOTTOM LINE: Treatment...
 Hormonal contraception preferred for managing AUB & VMS
 Symptom relief
 Improved cycle control
 Protection against unintended pregnancy
 Both CHC and progestin-only hormonal contraceptives can be
used safely in most women
 HT is used once menopause occurs
© Copyright Annals of Internal Medicine, 2015
Ann Int Med. 162 (2): ITC2-1.