Download The Menopausal Patient - DMC Huron Valley

The Menopausal Transition
Dr. J. Mladic
Ob/Gyn Associate Physicians
Jan 28, 2010
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Menopause is the time
when permanent
cessation of
menstruation has
occurred for 12 months
following the final
menses.
The decrease in the
amount of ovarian
follicular estrogen
synthesis occurs
gradually over several
years.
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Unlike the age of menarche, which is affected by
nutritional status and general health, the age of menopause
occurs secondary to a genetically programmed loss of
ovarian follicles.
The age of menopause is reduced by about two years in
women who smoke.
There is also a tendency for women who have never had
children and for those with more regular cycles to have an
earlier age of menopause.
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Other factors that may be important in
determining the age of menopause include:
 A family history of early menopause
 A history of type 1 diabetes mellitus
 galactose consumption
 The presence of a variant of form galactose1-phosphate uridyl transferase
 Shorter cycle length during adolescence
Clinical Manifestations
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Abnormal Bleeding
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Chronic anovulation and progesterone deficiency in
this transition period may lead to long periods of
unopposed estrogen exposure and therefore
anovulatory bleeding and endometrial hyperplasia.
Oligomenorrhea for six or more months, or an
episode of heavy dysfunctional bleeding is an
indication for endometrial surveillance.
Endometrial biopsy is the standard to rule out the
occurrence of endometrial hyperplasia, but many
clinicians are comfortable screening with transvaginal
ultrasound.
Irregular or heavy bleeding during the menopausal
transition may be treated with low-dose oral
contraceptives or intermittent progestin therapy.
Endometrial Ablation
Endometrial ablation techniques
are FDA approved to treat some
causes of abnormal uterine
bleeding. Endometrial ablation
provides a minimally invasive,
outpatient treatment option for
patients who require surgical
intervention.
Clinical Manifestations
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Hot Flashes
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Hot flashes occur in about 75 percent of menopausal women in the
United States.

The flashes most often begin in the perimenopausal period when
relative estrogen deficiency occurs together with cycle irregularity
secondary to anovulation, although in some women they do not
begin until after menopause.

Hot flashes are almost always due to the onset of menopause; other
possible causes are rare.
Clinical Manifestations
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Hot flashes typically begin as a sudden sensation of heat
centered on the face and upper chest that rapidly becomes
generalized. The sensation of heat lasts between two and
four minutes, is often associated with profuse perspiration
and occasionally palpitations, and is often followed by
chills and shivering.
Hot flashes usually occur several times per day, although
the range may be from only one or two each day to as
many as one per hour during the day and night.
Hot flashes can cause arousal from sleep, leading to sleep
disturbances. In addition, many women have profuse
perspiration which can be embarrassing in social
situations.
Prevalence
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A systematic review of menopausal symptoms
estimated that vasomotor symptoms occur in 14 to
51 percent of women before the perimenopausal
transition, 35 to 50 percent in perimenopause, and
30 to 80 percent after menopause.
It is generally believed that hot flashes do not
occur in premenopausal women because serum
estrogen concentrations are never very low, even
during the menstrual period. However, a large
observational Swan study found that 20 percent of
premenopausal women reported hot flashes.
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More than 80 percent of women who have hot
flashes will continue to have them for more than
one year.
Untreated, hot flashes stop spontaneously within
a few years of onset in most women.
However, it is estimated that nine percent of
women continue to experience hot flashes
beyond the age of 70 years.
Genitourinary Symptoms
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Vaginal dryness
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The mucosal lining of the vagina and
urethra are very sensitive to estrogen, and
estrogen deficiency leads to thinning of the
vaginal epithelium. This results in vaginal
atrophy, causing symptoms of vaginal
dryness, itching and often, dyspareunia.
The prevalence of vaginal dryness in one
longitudinal study was 3, 4, 21, and 47
percent of women in the reproductive,
early
menopausal
transition,
late
menopausal transition, and three years
postmenopausal stages, respectively.
In a large prospective cohort study of
women ages 40 to 55 years, the overall
prevalence of vaginal dryness was 13.1
percent, but the prevalence was lower in
the early menopausal transition, and
increased across the transition.
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On exam, the vagina typically appears pale, with
lack of the normal rugae and often has visible
blood vessels or petechial hemorrhages.
Vaginal pH, which is usually <4.5 in the
reproductive years, increases to the 6.0 to 7.5
range in postmenopausal women not taking
estrogen.
The increase in pH and vaginal atrophy may lead
to impaired protection against vaginal and
urinary tract infection.
Sexual dysfunction
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Estrogen deficiency leads to a decrease in blood
flow to the vagina and vulva. This decrease is a
major cause of decreased vaginal lubrication and
sexual dysfunction in menopausal women.
Vaginal dryness and dyspareunia may also
contribute to reduced sexual function.
Symptoms related to genitourinary atrophy are
quickly responsive to estrogen therapy, in
particular, vaginal estrogen therapy.
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Breast pain — Breast pain and tenderness are
common in the early menopausal transition, but
begin to diminish in the late menopausal
transition.
Menstrual migraines — Menstrual migraines are
migraine headaches that cluster around the onset
of each menstrual period. In many women, these
headaches worsen in frequency and intensity
during the menopausal transition.
Skin changes — The collagen content of the skin
and bones is reduced by estrogen deficiency.
Decreased cutaneous collagen may lead to
increased aging and wrinkling of the skin.
Pharmacologic Treatment for
Menopausal Symptoms
Estrogen therapy — Postmenopausal hormone
therapy is currently recommended short-term for
the management of moderate-to-severe vasomotor
flushes.
 Long-term use for prevention of disease is no
longer recommended.
 Women with mild hot flashes do not usually require
any pharmacologic intervention.
 For women with moderate-to-severe hot flashes, the
most effective therapy is estrogen.
In women who have not had a hysterectomy, estrogen should
always be given in combination with a progestin, to prevent the
occurrence of endometrial hyperplasia.
Estrogen therapy is recommended for as short a duration possible
for relief of moderate-to-severe hot flashes.
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Short-term therapy is considered
to be two to three years, and
generally not more than five
years.
Other factors to consider include
the patient's age, sleep, sexual
function, medical history and
quality of life.
Estrogen Products
Oral Estrogens*
Estradiol
Estrace (Warner Chillcott)
0.5, 1, 2 mg
Gynodiol (Novavax)
0.5, 1, 1.5, 2 mg
Esterified estrogens
Menest (Monarch)
0.3, 0.625, 1.25, 2.5 mg
Estropipate
Ogen (Pharmacia)
0.75, 1.5, 3 mg
Ortho-est (Women First Healthcare)
0.78, 1.5 mg
Conjugated equine estrogens (CEE)
Premarin (Wyeth-Ayerst)
0.3, 0.45, 0.625, 0.9, 1.25 mg
Conjugated synthetic estrogens
Cenestin (Elan)
0.3, 0.45, 0.625, 0.9, 1.25 mg
Enjuvia (Elan)
0.625, 1.25 mg
Estrogen-progestin combinations
Prempro (Wyeth-Ayerst)
0.3 mg CEE/1.5 mgmedroxyprogesterone, 0.45/1.5 mg,
0.625/2.5 mg, 0.625/5 mg
Ortho-Pretest (Monarch)
1 mg estradiol/0.9 mg norgestimate
Activella (Pharmacia)
1 mg estradiol/0.5 mg norethindrone acetate
FemHRT (Warner Chilcott)
5 mcg ethinyl estradiol/1 mg norethindrone acetate
Angeliq (Berlex)
1 mg estradiol/0.5 mg drosperinone
Transdermal estrogens*
Estradiol patches
Alora (Watson)
0.025, 0.05, 0.075, 0.1 mg/d
Climara (Beriax)
0.025, 0.05, 0.06, 0.075, 0.1 mg/d
Esclim (Women First)
0.025, 0.0375, 0.05, 0.075, 0.1 mg/d
Estraderm (Novartis)
0.05, 0.1 mg/d
Vivelle (Novartis)
0.025, 0.0375, 0.05, 0.075, 0.1 mg/d
Estrogen-progestin patches
Combi-Patch (Novartis)
0.05 mg estradiol/0.14 mg norethindrone, 0.05 mg/0.25 mg
Climara Pro (Berlex)
0.045 mg estradiol/0.015 mg levonorgestrel
Gel
EstroGel (Solvay)
1.25 g (0.75 mg estradiol)
Emulsion
Estrasorb (Novavox)
0.025 mg estradiol/pouch
Intravaginal rings*
Femring (Warner-Chilcott)
0.05 mg estradiol/day over 3 months
Alternative treatments for the
Treatment Menopausal Symptoms
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Black cohosh: Phytoestrogens of black cohosh
rhizome have mild estrogenic binding effects.
Standardized extracts have been demonstrated to
improve
menopausal
and
premenopausal
symptoms in clinical studies.
Contraindicated in individuals with a history of
estrogen-dependent tumors or endometrial cancer.
Black cohosh may cause nausea, vomiting,
headache, and hypotension at higher dosages.
Osteoporosis
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Osteoporosis or osteopenia occurs in about 44
million American men and women, accounting for
55 percent of the population age 50 and over.
Osteoporosis is defined as "a skeletal disease
characterized by compromised bone strength
predisposing a person to an increased risk of
fracture".
Diagnosis of Osteoporosis
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Bone strength primarily reflects the integration of bone
density and "quality". In the absence of a fragility fracture,
bone mineral density by dual-energy X-ray absorptiometry
is the clinical tool used to diagnose osteoporosis according
to the classification of the World Health Organization.
BMD that is 2.5 standard deviations or more below the
mean BMD of a young-adult reference population, which
is a T-score of -2.5 or less, qualifies for a diagnosis of
osteoporosis, provided that other causes of low BMD have
been ruled out.
As BMD decreases, fracture risk increases as a continuum,
with no "fracture threshold." In one analysis, for every one
SD decrease in BMD at the hip, there is a 2.6-fold increase
in the risk of hip fracture.
Maximizing Peak Bone Mass
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PBM is the maximum bone mass achieved in life. The
time of PBM is not known with certainty, but probably
occurs in the third decade of life in most individuals, with
variability according to ethnicity, sex, skeletal site, and
method of BMD measurement.
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Nutrition — Good nutrition from infancy through adolescence,
with particular attention to adequate daily intake of calcium and
vitamin D, is a key component in the attainment of maximum
PBM.
Physical activity — Observational, retrospective, and
prospective randomized trails have demonstrated beneficial
effects of exercise on bone accumulation during growth, with
particular benefit from high impact exercise.
Minimizing Bone Loss
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Bone loss may begin soon after PBM is attained:
 A longitudinal study of 620 men and women
age 20 to 89 showed a small bone loss (<0.4
percent per year) at the hip and spine in
premenopausal women, with a tripling of the
bone loss rate in the early postmenopausal
years.
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Stabilizing BMD or reducing the rate of bone
loss is the primary objective in the prevention of
osteoporosis once PBM has been attained.
A typical rate of bone loss in early
postmenopausal estrogen deficient women is
probably about 1.0 to 1.5 percent per year, with a
small percentage of women being "rapid bone
losers" who may lose as much as 3 to 5 percent
of bone mass per year.
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Adequate calcium and vitamin D intake can
result in positive calcium balance and a reduction
in the rate of loss of bone.
In postmenopausal women with osteoporosis,
intake of at least 1200 to 1500 mg of elemental
calcium (total diet plus supplement) and 800 IU
of vitamin D daily is suggested.
Calcium supplementation in excess of 500
mg/day should be given in divided doses.
Pharmacological therapy
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Bisphosphonates — Medications in this class of
potent antiresorptive agents have been shown to
increase BMD and reduce fracture risk.
Those currently available for the prevention of
postmenopausal osteoporosis are:
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alendronate (5 mg/day or 35 mg/week),
risedronate (5 mg/day or 35 mg/day), and
ibandronate (150 mg/month).
Discontinuation of Estrogen
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Many women have no trouble stopping estrogen, and are able to
stop without assistance.
In women whose vasomotor symptoms at the start of therapy
were only mild-to-moderate, we suggest having the patient
attempt abrupt discontinuation. This may be followed by a
second attempt using a taper if the patient experiences
bothersome symptoms.
In patients with a history of severe vasomotor symptoms at
baseline, a very gradual taper (typically over six months to one
year) is suggested.
The North American Menopause Society suggests that after a
failed attempt at stopping therapy, extended use of hormone
therapy may be reasonable in women who feel that the benefits
of symptom relief outweigh risks. In this setting, additional
attempts should be made at a later date to stop the hormone
therapy.
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Droegemeuller Comprehensive Gynecology: Menopause 1127-1258
Precis Reproductive Endocrinology ACOG
Up to Date Menopause: Clinical Manifestations