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Menopause and Hormone

Replacement Therapy
Sandra E. Brooks, MD, FACS, FACOG
Associate Professor
Director, Div GYN Oncology
Dept. Obstetrics and Gynecology
University of Maryland School of Medicine

What is Menopause?

During the perimenopausal period (up to 10 years before


menopause), the ovaries decrease production of the "female
hormones" estrogen and progesterone, the hormones which
allow a woman to become pregnant and to menstruate.
Hormones also affect many other functions in a womans
body such as the circulatory system, urogenitary system,
nervous system, skeletal system, memory, sexuality, skin,
vision, and teeth.
The average age for menopause in American women is 51
Because most women will live a third of their life after
menopause, it is important to be aware of the symptoms,
systemic effects, and available treatment options associated
with estrogen loss.

Acute Effects of Menopause

Reproductive Tract:
Symptoms: cessation of menses, hot flashes,
decreased vaginal lubrication
Signs: vaginal epithelial atrophy, decreased
size of uterus, cervix, or ovaries
Urinary Tract:
Symptoms: urgency, frequency, nocturia
Signs: urothelial atrophy, hypertonic unstable
bladder
Breasts:
Symptoms: decreased tenderness
Signs: decreased size, fewer benign cysts

Late Effects of Menopause

Osteoporosis
decreased trabecular bone density due to increased
osteoclastic activity
Cardiovascular Disease
the most common cause of death in women
rate of CVD increases steadily reaching parity with
men by age 70
lipid profile changes:

increased LDL
decreased HDL

Risks and Benefits of Estrogen Plus


Progestin in Healthy Postmenopausal
Women (WHI)1- 1993-1998
Objective:

To assess the major health benefits and risks of


HRT in the U.S. based on a randomized controlled
primary prevention trial

WHI Study
16,080 Women age 50-79
No prior hysterectomy
8506
Premarin 0.625 mg/d
Provera 2.5mg/d

7574
Control
Placebo

WHI Study
HRT increased Risk of Heart Disease

Coronary

Heart Disease 29%

non-fatal MIs within 1 yr.

Stroke

41% I

increase in stroke began within 2


years

DVT

207%
PE 213%

Conclusions of Womens Health Initiative


Study

HRT should not be initiated or


continued for primary prevention of
Heart Disease
The risks of cardiovascular disease
and breast cancer must be weighed
against the benefits of fracture
reduction and postmenopausal
symptom relief.

Estrogen in the Prevention of


Atherosclerosis Trial2- 2001

Objective:

To examine the effects of unopposed 17- estradiol on


atherosclerosis progression via a randomized, double-blind,
placebo-controlled trial

Methods:

Study Population:
222 women aged 45 years and older
Experimental Group
unopposed 17- estradiol (1 mg/d)
Control Group
placebo

Conclusions of HERS
No overall benefit of hormone
treatment
Unexpected pattern of increased risk
during the first year of follow-up
7 other randomized clinical trials
conclude:
HRT does not reduce risk of adverse
event in women with heart disease

Response to WHI
Important
Women

to note:

with severe hot flashes were not


enrolled in large numbers
WHI only applies to w omen 50-79 who are
taking premarin/provera
Premarin only arm continues

Contraindications to HRT

Pregnancy or Breastfeeding.
Liver disease
Undiagnosed vaginal bleeding.
History of certain cancers.
History of deep vein thromboses
or other blood clotting disorders.

HRT relieves Hot Flashes, Vaginal Dryness


and Insomnia but may have Side Effects

Return of periods
Irregular vaginal bleeding/spotting
Headache
Nausea
Breast tenderness
Bloating (progesterone)
Weight gain (progesterone): generally only 2-3 pounds can be
blamed on the hormones: the rest is decreased metabolism
associated with menopause, increased caloric intake and/or
decreased exercise.
May exacerbate depression (progesterone)
Enlargement of uterine fibroids
Exacerbation of endometriosis
Fluid retention (may exacerbate asthma, epilepsy, migraine, heart
disease, kidney disease)
Spotty darkening of the skin

Who should take HRT?


Role of HRT for any indication other than
symptomatic relief of severe hot flashes
Premature menopause
Alternatives

Selective serotonin re uptake inhibitors for hot


flashes
SERMs or bisphosphonates for prevention of
osteoporosis
Statins for cholesterol
Vaginal estrogen or rings, lubricants for vaginal
dryness

Alternatives to HRT
PHYTOESTROGENS

There are 3 main groups: isoflavones, lignans, and


coumestans.
Isoflavones are considered weak estrogen receptor
modulators; they mimic the role of estrogen. However, they
can mimic the good actions and the not so good- they can
also function to block the action of estrogen at some sites
It is still unclear whether these herbs are safe for women at
risk for breast cancer or its recurrence.
Recommended dose of 6.5 g of soy per serving for a total of
25 g per day. Medical facts about soy:
Soy contains 3 isoflavones: Daidzin, genistin, and glysitin.
In addition to its preventive benefits in cardiovascular
disease, soy has been shown to reduce the frequency of
hot flashes and to reduce the incidence of osteoporosis.
Six studies have shown that soy isoflavones can reduce
the frequency of hot flashes.
To mimic the typical Japanese diet, women should get 60-90
mg of soy isoflavones per day. 1 cup of tofu = 75 mg= the
same half cup of soybeans = 3 cups of soy milk.

Herbal Preparations

Black cohosh: This is currently touted as the herbal


preparation most likely to prevent hot flashes. Clinical studies
have been done to show a reduction in the frequency and
intensity of hot flashes, improvement in global menopausal
symptoms, and in vaginal lubrication. It is probably the most
well studied of the phytoestrogenic herbal preparations. Most of
these studies were not nearly as well designed as most
physicians would like,

Red Clover: This herb contains four isoflavones,


including genistein, the most active component of soy.
The most popular dietary supplement derived from red
clover is Promensil .

Clinical trials with Promensil did survey women to test


their level of satisfaction; 93% of users said they wanted
to continue taking it. A 500 mg Promensil tablet contains
40 mg of plant estrogens. This is the equivalent of one
cup of soy milk and four cups of chickpeas.

Herbal Preparations

Ginkgo biloba:
This herb is commonly used as a mood elevator or to
improve memory and other cognitive functions. It has also
been documented to cause bleeding problems in several
individuals, with or without other medicines. Speak with
your physician if you plan to take this herb, especially if
you are taking medicines for bleeding or clotting problems
or for arthritis.
Wild yam:
This has been touted as a natural source of natural
progesterone. It contains diosgenin, which is not
converted to active hormones in the body however, and it
has been shown to have NO effects on estrogen or
progesterone receptors.
Vaginal Lubricants: There are numerous non-prescription
vaginal lubricants on the market such as K-Y Jelly and
Vagisil . Never use a water insoluble preparation in the
vagina, e.g. Vaseline .

References and Links


1)

2)
3)

4)

5)
6)
7)

Writing Group for the WHI Investigators 2002.


Journal of American Medical Association July 17,
2002 288: 321-333
Menopausal Medicine Vol 11, 2003/
Kuller, Lewis H. 2002. Arteriosclerosis, Thrombosis
and Vascular Biology January 1, 2003; 23(1): 1116
Herrington, David, MD, MHS 2003. Hormone
Replacement Therapy and Heart Disease:
Replacing Dogma with Data. Circulation Jan 7,
2003; 107(1) :2-4.
ACOG.org
Cancer.org
WCN.org