Transcript Menopause MS II - Amazon Web Services

Menopause
MS II
Joanna Wilson, D.O.
Internal Medicine,
HerCare at Amarillo Diagnostic Clinic
Community Associate Professor of Internal Medicine
Texas Tech, Amarillo
Proportion of average female lifespan
spent in menopause years: 1/3 to 1/2
•
•
•
•
Objectives:
To recognize the physiology of the menopause
To review the natural experiences of menopause
To appreciate the challenges of symptom treatment
STRAW¥ Staging System
Final Menstrual Period
(FMP)
-5
-4
-3
-2
-1
0
Stages:
+1
+2
Terminology:
Reproductive
Early
Peak
Menopausal Transition
Late
Postmenopause
Late*
Early
Early*
Late
Perimenopause
Duration of
Stage:
Menstrual Cycles:
Endocrine:
variable
variable
to
regular
normal FSH
variable
variable cycle
length
regular
(>7 days
different from
normal)
FSH
2 skipped
cycles and an
interval of
amenorrhea
FSH
* Stages
1
yr
Amen x
12 mos
until
demise
4 yrs
none
FSH
most likely to be characterized by vasomotor symptoms
¥ STages of Reproductive Aging Workshop
Adapted from Soules et al., Fertility and Sterility, VOL. 76, NO. 5,
November 2001, p. 875
Determinants of Age at Menopause
(Average Age =51 years)
Unaffected by:
–
–
–
–
–
–
–
–
Race
Socioeconomic status
Number of pregnancies
Oral contraceptive use
Education
Physical characteristics
Age of menarche
Age of last pregnancy
Affected by:
–
–
–
–
–
–
Smoking
Family pattern
Chemotherapy
Nulliparity
Hysterectomy*
Excessive alcohol intake*
– *=possible assn
Can We Predict Menopause? No
• Antimullerian hormone
• Synthesized in the granulosa cells of preantral and small
antral follicles
• Inhibits the transition from primordial into primary follicles
preventing excessive follicular recruitment by FSH
– Correlates strongly to antral follicle count =
“functional ovarian reserve”
• Peak level at age 30
• Undetectable about 5 years prior to final menstrual period
– Potential predictor of menopause
• Less useful for younger (<41 years) and older (>57 years)
FSH >30 Suggests Cessation of
Ovulation
Hypothalamic-Pituitary Circulation:
Prior to Menopause
Hypothalamus
Hypothalamic-Pituitary
Circulation
Anterior Pituitary Gland
GnRH
LH
FSH
Estrogen
Progesterone
Hypothalamic-Pituitary Circulation:
Peri-Menopause (anovulatory cycle)
Hypothalamus
Hypothalamic-Pituitary
Circulation
Anterior Pituitary Gland
GnRH
LH
FSH
Estrogen
X
Progesterone
Perimenopause: Intermittent
Ovulation and Irregular Cycles
Estradiol
(pg/mL)
Progesterone
(ng/mL)
300
200
20
100
10
0
0
Cycle 1
Cycle 2
Cycle 3
Anovulation
Anovulation
Ovulation
Irregular
Bleeding
Irregular
Bleeding
Short
Follicular Phase
Clinical Issues of Menopause:
Change in Uterine Bleeding
• Most common symptom of menopause
• Irregular bleeding occurs from 10 years prior
to final menstrual period (FMP)
– Decreased frequency of ovulation (anovulatory
cycles)
• Pregnancy is possible until ALL ovulation ceases
• Uterine bleeding after menopause is always
cause for concern if the patient is not taking
hormones
Estrogen Receptors Are In Almost
Every Cell!
Clinical Issues of Menopause:
Vasomotor Symptoms
• Second most common symptom of menopause
• Primary reason women seek medical
treatment
• 1-5 minutes with increased skin temp. 1-7˚C
• More frequent and severe after
premenopausal oophorectomy
Prevalence of Vasomotor Symptoms
• > 75% of women report hot flashes within the
2-year period surrounding their menopause
• 25% remain symptomatic for > 5 years
• 5% of women have hot flashes or night sweats
forever
Prevalence of Hot Flashes
Menopause
Years Before
Years After
3
2
1
1
2
Kronenberg F. Ann N Y Acad Sci. 1990;592:52-86.
3
Clinical Issues of Menopause:
Sleep Disturbances
• Trouble getting and staying asleep
• Triggers may be joint pain, flashes, stress
• Usually cause fatigue, poor focus, and
irritability
• Often associated with underlying sleep
disorder
• Melatonin, Trazodone, non-BZD’s, BZD’s,
sleep hygiene, meditation
• Progesterone may help
Clinical Issues of Menopause:
Cognition (“Menopause Fog”)
• Forgetfulness, “cloudy” thinking
• Due to variations in estrogen
– Exacerbated by multi-tasking, depression, anxiety
• Treatment includes daily physical exercise and
adequate sleep
• Refer for neurocognitive testing for dementia
or ADHD if severe
– Alzheimer’s Dementia is more common in older
women
Clinical Issues of Menopause:
Psychological Symptoms
• Menopause does not cause depression
– Depression is more likely to resurface if present
prior to menopause
• Anxiety is frequent
– Stressors: children leaving, ill parents, job
changes, financial, marriage, physical changes
• Counseling, cognitive behavioral therapy,
antidepressants, BZD’s, exercise, estrogen
Clinical Issues of Menopause:
Urinary Health
• Ureteral thickening
recurrent cystitis,
frequency
• pH rises
alters vaginal flora balance
• Loss of pelvic organ support
cystocele,
rectocele
• Loss of pelvic floor tone
incontinence,
muscle spasms
• Overactive Bladder (wet or dry)
Clinical Issues of Menopause:
Sexual Function
• Majority of women state their
sexual relationships did not change
during menopause
• Most common complaints: low
libido, vaginal dryness
• Barrier methods of prevention
should be encouraged for sexually
active women with a new partner
Clinical Issues of Menopause:
Hair Changes
• Female pattern hair loss
(FPHL): thinning on the crown
– Hypoestrogenemic and relative
hyperandrogenic state
• Estrogen prolongs anagen phase
• Testosterone shortens anagen
phase with progressive
miniaturization of susceptible
hair follicles
– Off-label treatment may include
antiandrogens (spironolactone)
or topical minoxidil, biotin,
finasteride
Clinical Issues of Menopause:
Dental Health
• Hormone receptors exist in
the basal and spinous layers
of the epithelium and
connective tissue
• Fluctuations of sex
hormones around
menopause have been
implicated in inflammatory
changes in gingiva
– Atrophy of bony tooth sockets
leading to gum retraction,
periodontal pocket
development, bacterial
invasion, and periodontitis
• Rate of systemic bone
loss is a predictor of
tooth loss
– For each 1%/year
decrease in BMD, the
risk for tooth loss more
than quadruples
Clinical Issues of Menopause:
Bone Loss
Clinical Issues of Menopause:
Bone Loss
• First 5 years after menopause is time of more
accelerated bone loss
• DXA indicated for patients with risk factors,
and for those whom treatment would be
initiated
– http://www.shef.ac.uk/FRAX/tool
– NOF Clinician’s Guidelines
Clinical Issues of Menopause:
Body Composition Change
• Average weight gain = 5 lbs.
– Increased central fat
distribution
• Weight gain assd with
–
–
–
–
Metabolic Syndrome
Hot flashes
Sleep deprivation
Sedentary lifestyle
• Decrease in muscle mass
– Resistance training most
beneficial
Hypertension:
Gender and Age Effects
Age
Men (%)
Women (%)
20-34
11.1
6.8
35-44
25.1
19.0
45-54
37.1
35.2
55-64
54.0
53.3
65-74
64.0
69.3
75 and older
66.7
78.5
All
34.1
32.7
% of level at -6 months before menopause
LDL Cholesterol Levels After Menopause
Menopause
110
100
90
-24
-18
-6
-12
0
Months
Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31
6
HDL Cholesterol Levels After Menopause
% of level at -6 months before menopause
110
100
Menopause
90
-24
-18
-6
-12
0
Months
Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31
6
Endothelial Cell Layers in Healthy Postmenopausal and
Premenopausal Women
•
Postmenopausal cells show
evidence of endothelial cell
death, denudation, and RBC,
platelet, and protein
attachment, as well as fractured
basal membranes, and loss of
intercellular junctions
•
Premenopausal cells show tight
connections, a continuous layer
of endothelial cells, and thick
plasma membranes
Compounded
“Bioidentical” Hormones
• Dosing schedule mimics premenopausal state in
postmenopausal women
• Plant derived hormones modified to be identical
to human molecules
• Not regulated for purity of modification process
• Saliva levels do not accurately measure tissue
levels
• Progestogen skin cream has not been proven
effective to prevent endometrial cancer
Hormone Therapy (HT)
• Estrogen (E)
treats:
– Hot flashes
– Night sweats
– Mood
– Vaginal dryness
– Cognitive slowing
• Progesterone (P)
treats:
– Endometrial
proliferation from
estrogen
stimulation
HT Regimen Choices: Cyclic: daily E with
cycles of P vs. Continuous Combined
Cyclic
Advantages
• Predictable withdrawal
bleeding every month
Disadvantages
• 2-pill dosing may
discourage compliance
• Withdrawal bleeding
persists indefinitely
Continuous Combined
Advantages
• Most women will achieve
amenorrhea in time
• Convenient 1-pill dosing
enhances compliance
and ensures appropriate
progestin treatment
• Lower risk of endometrial
hyperplasia compared with
cyclic regimen
Disadvantages
• Unpredictable spotting
• Daily progesterone exposure
and side effects
The Women’s Health Initiative in
Women With Uteri
The Women’s Health Initiative in
Women Without Uteri
Estrogen and Progestin Risks
• Venous thromboembolism (DVT, PE) risk is
increased with both E and P use
– Risk appears reduced in transdermal estrogen vs
oral
– Risk appears reduced in first and second
generation progestins vs newer
• Arterial clot risk is higher in smokers, and
women with HTN, DM, and high cholesterol
• Risks of both types increase with age
“The Timing Hypothesis”
(Early exposure to HT might be good!)
• Sex steroid hormones alter the biology of
vessel wall cells and the inflammatory cells
that accumulate differently according to the
stage of the disease
– It is likely that early physiological sex hormone
replacement can improve or reverse early
endothelial dysfunction
– HT given in advanced atherosclerotic lesions likely
predisposes the lesion to inflammatory and
hemostatic abnormalities
Assess Your Patient’s Risk Before
Starting HT
High Blood
Pressure
Diabetes
Smoking
Time Since
Menopause
Heart Attack
Stroke
Breast Cancer
Blood Clot
Safety of
Hormone
Treatment
Next Studies to Evaluate Type and
Exposure Age
• Elite: Early Versus Late Intervention Trial With
Estradiol
– Oral E2 vs. placebo
– Measuring Carotid intimal medial thickness
• KEEPS: Kronos Early Estrogen Prevention Study
– CEE vs transdermal E2 with micronized
progesterone
– Measuring carotid IMT
Non-Estrogen Symptom Therapies
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•
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•
•
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•
Selective Serotonin Reuptake Inhibitors
Serotonin Norepinephrine Reuptake Inhibitors
Gabapentin
Clonidine
OTC Vaginal moisturizers and lubes
Vitamin E, coconut oil, olive oil
Phytoestrogens (soy, black cohosh, flax)
Variable Stimulation of the Estrogen
Receptor Results in Tissue Specific
Responses
Creating the Perfect Estrogen
Replacement
Newest Menopause Therapies
• Duavee (CEE + bazedoxifene)
– FDA-approved for vasomotor symptoms and
prevention of postmenopausal osteoporosis
• Osphena (Ospemiphene)
– FDA-approved for painful intercourse due to
vulvovaginal atrophy
Menopause Summary
• The sex hormone deficiency of menopause
affects nearly every cell of the body
• Vascular disease, osteoporosis, genitourinary,
dental, and skin changes increase in prevalence
after menopause
• Estrogen and non-estrogen treatments are
available for symptom management
• Hormone therapy given near the age of
menopause has many benefits, but the safety
data is inconclusive
Thank You!
Questions?
Arrange for a 4th-year rotation in Women’s Health in my clinic!