40 million menopausal women in
the U. S. presently
Spontaneous or Natural Menopause – 12 months of
amenorrhea with no obvious pathological cause. Age
range of onset is 40-58 years with the average age of
Induced Menopause– due to surgery, chemotherapy or
radiation therapy which can happen at any age.
Premature Menopause or Ovarian Failure –defined as
less than age 40.
Transient – due to eating disorders or stress.
Permanent – due to autoimmune disorders or genetic
abnormalities (may be confirmed by karyotyping), usually 2/3 of
the causes are idiopathic.
A woman’s medical and menstrual hx and symptoms are
sufficient to confirm the diagnosis of menopause.
Serum FSH can potentially allow an earlier diagnosis of
menopause but must be consistently elevated > 30
Hormonal contraceptives may lower FSH levels making
it difficult to diagnose menopause – measuring FSH on
the 7th pill free day was not a sensitive test. You may
need to measure FSH:LH ratio looking for > than 1 or
estradiol < than 20 pg/ml on the 7th pill free day.
Always remember thyroid disease can mimic
menopause, a TSH measurement may be necessary.
Vasomotor Symptoms – Hot
flashes and night sweats. In the
U.S., about 75% of women
experience vasomotor symptoms
during the transition from
postmenopause which last a
median of 3.8 yrs. 25% of
women have symptoms that
continue for longer than 5 yrs.
90% of women experience
vasomotor symptoms with
surgical menopause and their
symptomatology may be worse
than for women experiencing
Vulvar and Vaginal Atrophy with vaginal
dryness and painful intercourse. Lack of
estrogen also causes the urethra to
become thinner and less efficient with
detrusor pressure at the urethral opening
decreasing, both during and after voiding.
These changes increase a women’s risk of
vaginal and urinary tract infections, and
also urinary incontinence.
Sexual Dysfunction - ? Related to all of the
changes of the genitourinary tract can result in
dyspareunia, leading to a decreased interest in
sexual intercourse. Fatigue and depression
brought on by the vasomotor symptoms and
sleep disturbances of menopause can
exacerbate this lack of interest in coitus.
Also possible decrease levels of endogenous
testosterone especially in women who have
undergone sugical menopause may cause
Do You Treat with Hormonal
The Women’s Health Initiative Study was
terminated in 1998 due to harmful
outcomes associated with hormonal
replacement therapy such as an increase
in invasive breast cancer, coronary heart
disease, pulmonary embolism and stroke.
Although it was the largest and best
controlled, blinded study it had several
Women’s Health Initiative Study
Average age of women in the trail was 63.2. This mean does not
reflect the customary hormonal therapy user who is 10 to 30 years
Only one regime of hormonal replacement, 0.625mg of estrogen
with 2.5mg of progesterone was used.
The women used in the study had an overall higher risk for heart
disease than the general population.
Breast Cancer was associated with those women who had been
previous on hormonal replacement therapy suggesting that
exposure to hormones required at least 5 years before an effect was
noted and also those women diagnosed in the first year of the trial
suggest that the cancer was preexisting. The increase risk is small
in the WHI study, being 4 to 6 additional invasive cancers per
10,000 women who use it for 5 or more years.
The WHIMS, a supplementary study to the WHI, found an increase
in Alzheimer. The findings of increase dementia was for those
women over the age of 65. These findings have little relevance to
hormonal replacement therapy given to women during the
menopausal transition who are 10 to 15 years younger.
The HERS study (mean age of
66.7 years and established
CHD) showed a increase in
cardiovascular events in the first
year and a decrease over time,
suggesting that an at-risk group
of women were affected
particularly in the first year. The
WHI study also observed an
increase in heart attacks during
the early stages of treatment.
The two studies did reinforce
that older women with CVD who
have not taken hormonal
replacement therapy should not
So what about lower doses of
The HOPE study examined the use of lower doses in
healthy women age 40-65 and found that similar benefits
were achieved regarding reduction in hot flashes, and
prevention of bone loss. The Nurses Health Study has
suggested that lower doses may protect against stroke,
with the study demonstrating absolute risk of stroke
almost tripled for women on at least 0.625mg of estrogen
as compared with those taking a 0.3 mg dose. With
respect to breast CA, studies, though controversial,
contend that there is direct evidence to suggest that
lover doses are correlated with a lower risk of breast
Today the general indications for hormonal
therapy are the treatment of moderate to severe
menopausal related vasomotor symptoms and
the prevention and possible treatment of
osteoporosis. Women at high risk for serious
medical outcomes with the use of estrogen
include those with a history of breast cancer,
those with an elevated risk for both ovarian and
breast CA due to genetic factors, family hx or
both; and those at high risk for CVD. Other risk
factors include hx of PE, DVT, CVA or liver
Using Hormonal Preparations
When the benefit outweighs
the risk consider using
hormonal therapy in lower
doses for shorter periods of
If lower doses not effective
than consider standard dose
therapy or twice daily
therapy with half doses or
even consider transdermal
administration (bypasses the
liver so no increase in TG or
HDL.) which delivers more
consistent blood levels of
estrogen. Remember if the
woman has a uterus, you
must also treat with both
estrogen & progesterone.
Oral Estrogen Products
Conjugated Equine Estrogen – Premarin,
doses are 1.25, 0.9,0.625, 0.45, 0.3mg/d
Synthetic Conjugated Estrogen –
Cenestin, 0.3, 0.45, 0.625, 0.9, 1.25
Estradiol – Estrace, 0.5,1.0, 2.0 –
transdermal patches are made of this.
Very few head to head trials comparing
Preparations for Postmenopausal
has decrease rate of
breakthrough – Prempro
bleeding and fewer Continuous Cyclic –
endometrial bx than Premphase
cyclic regimen. Intermittent Combined
and still having
menses, consider low
can be used to tx
vasomotor S/S but
like estrogen has
been linked to
increase risk of breast
When Hormone Therapy isn't an
Neurontin 300mg Qd-
BID – consider
SSRI’s being the
Soy foods or isoflavone
supplements - ? use in women
with hx of breast cancer because
of their estrogen effect. The most
popular OTC tx presently.
Black Cohosh – Clinical evidence
mixed but trials ongoing. At this
time the suggestive use of
Remifemin 20mg – 2 tabs
Vitamin E – clinical evidence show
mixed results. 800 IU/day
OTC topical progesterone cream –
not recommended due to content
and concentrations differ widely in
a variety of preparations and ?
Also not recommended at this
time is dong quai, evening
primrose oil, ginseng, licorice,
chinese herb mixtures,
acupuncture or magnet therapy
Vulvovaginal Changes with
Vaginal Dryness/Atrophic Vagnitis – Systemic hormonal therapy not
recommended unless treating also moderate to severe vasomotor S/S or for
First line treatment is vaginal lubricants that are water soluble and advise if
possible regular sexual stimulation.
Vaginal Estrogen Rings – Estring & Femring are available with concerns
with Femring for systemic effects. It is possilbe to use Femring for both
vaginal therapy and systemic therapy. Ring last 90 days.
Vaginal Estrogen Tablets –Vagifem, usual dose is 1x/day x 2 wks then
Vaginal Estrogen creams – (Estrace or Premarin) 1x/day x 2 wks than 1-
If using unopposed estrogen locally for long periods of time, yearly vaginal
Ultrasound may be needed to assess the endometrium.
Urinary Symptoms During
Estrogen Therapy is not recommended with
Stress or Urge incontinence. Clinical trials have
shown no benefit.
Assess for UTI, diabetes, drug interaction or
cognition related phenomena if urinary
Frequent UTIs can be due to lack of estrogen –
only vaginal estrogen preparations have been
proven to work with decreasing the frequency of
UTIs in menopausal women.
The HERS study showed no benefit with using
systemic estrogens to treat reoccurring UTIs.