Author : Richard J. Santen Endocrinologist University of Virginia, Charlottesville, VA
2008-06-10
2008-06-10
Menopause -What Is It? : How can one manage the problems related to it?
* The underlined words are defined in the glossary at the end of the article
Click on figures to enlarge and read.
Pre-menopause
In order to understand menopause*, it is first necessary to define what occurs before this change, and why. After the onset of puberty at approximately age 11-13, a girl’s ovaries produce two hormones, estradiol, and progesterone in a cyclic fashion (Figure 1). At the same time, the ovaries release one egg per month, which is then available for fertilization by a male sperm. At the onset of puberty, there are approximately 500,000 eggs in the ovary, but a gradual reduction in the number of eggs occurs each year as a woman ages, until all are gone at menopause. Estradiol is responsible for breast development during puberty but after puberty this hormone stimulates the lining of the uterus (womb). During the monthly menstrual cycles, the levels of estradiol go up and then down, but follow a standard pattern. Beginning on day one of the menstrual cycle (the day when bleeding stops), the levels of estradiol gradually increase and rise to their highest levels at midcycle (about day 14). It is at this time that the ovary passes an egg and the time of maximal fertility occurs.
During the last 10 days of the cycle (approximately days 15-25), estradiol levels are somewhat lower but together with progesterone stimulate the lining of the uterus to allow acceptance of fertilized eggs, a process necessary for a woman to become pregnant. Just before menstruation occurs, the levels of both estradiol and progesterone drop rapidly, and the lining of the uterus is shed, a process which results in menstrual bleeding on approximately days 26-30.
This finely tuned process is regulated by the master gland in the body called the pituitary,
which secretes two hormones into the blood: follicle stimulating
hormone (FSH) and luteinizing hormone (LH). The production of estrogen
is stimulated by FSH and progesterone, by LH. Together, these hormones work together to cause regular monthly menstrual cycles.
This normal reproductive time in a woman's life is called the pre-menopause.
Cyclic menstrual periods continue until menopause when the monthly
menstrual periods permanently stop. In smokers this occurs, on average,
at age 49 and at age 51 in non-smokers. However, some women experience
menopause up to 5 years earlier or later than this.
Peri-menopausal transition
Approximately 2-5 years before a woman stops having menstrual periods completely, there is a transitional period which is called the peri-menopausal transition. Several things happen during this time in a woman's life. The menstrual periods become less regular. Rather than having menstrual bleeding every 30 days, this may occur at intervals as short as every two weeks or as long as every three to four months. The amount of estrogen made does not change substantially and, in fact, increases slightly. FSH, the hormone made by the pituitary, goes up to some extent. However, there are often times during the peri-menopausal transition when the ovary stops making female hormones temporarily. When the hormone levels, and particularly estradiol, drop sufficiently, a variety of symptoms may occur including hot flashes, increased irritability, increased anxiety, and lack of stable mood (1).
The
diagnosis of the peri-menopausal transition is difficult since it does
not depend upon measurement of female hormones in the blood or in the
urine. Because these hormones can fluctuate substantially
during the peri-menopausal transition, single measurements or even
multiple measurements will not predict whether a woman will resume
having normal cycles several months later. Only if a women
stops menstruating for more than one year can one conclude that the
peri-menopausal transition is over and that menopause starts. The
peri-menopausal transition is often not treated since the symptoms may
be temporary and only occur when the estradiol levels are very low.
However, in some cases, the symptoms are quite troubling and it is
necessary to administer estrogen and a progestin, usually in the form of
a birth control pill, to control these symptoms.
Menopause
Menopause is defined as the complete
cessation (stopping) of menstrual periods for 1 year or longer.
Menopause results because the ovaries stop working and lose their
ability to make estrogens and progesterone. Consequently, the levels of
these two hormones in the blood drop dramatically at the onset of
menopause and remain low permanently. The pituitary gland senses this and increases the hormones, FSH and LH, normally used to regulate the ovaries during menstrual cycles. Also at menopause, the ovary no longer contains eggs or in rare cases, just a few. The time after the onset of menopause is called the post-menopausal period.
Estradiol circulates in the blood of pre-menopausal women at levels ranging from 50 pg per milliliter of blood (one milliliter is approximately 1/5th of a teaspoon; pg is a unit of weight) on the first day of the cycle to as high as 600 pg/ml at midcycle (Figure 1). At menopause, the levels drop to less then 10 pg/ml. Health
care providers often confirm the diagnosis of menopause by measuring
FSH and LH (which are elevated) and estradiol (which is low or
undetectable).
Some
women may have had their uterus removed surgically, a procedure called a
hysterectomy, but the decision was made to leave the ovaries in. These women have no menstrual periods but may not as yet have undergone menopause since their ovaries are still working. Menopause
is not present unless the ovaries stop making estrogen and
progesterone. Hot flashes and other symptoms of menopause may occur
abruptly in women without a uterus but often they don’t suspect that the
symptoms are caused by menopause. The reason is that they lack the
obvious sign that the menstrual periods have stopped as a clue that they
have undergone menopause. In these women, menopause can only be diagnosed by measuring FSH, LH, and estradiol.
Menopausal symptoms
Once menopause has been diagnosed, symptoms or problems involving several organs may occur in some women. The five most common include those related to (1) vasomotor instability, (2) urogenital atrophy, (3) accelerated bone loss, (4) increased frequency of heart disease, and (5) mood changes/depression (2).
Vasomotor instability: With
the fall in estrogen at the time of menopause, the blood vessels become
unstable with respect to the amount of blood that they carry to the
skin. This problem, called vasomotor instability, causes hot flashes which can cause frequent awakening when they occur at night.
Urogenital atrophy: The urogenital tract, which includes the bladder, uterus and vagina, loses tissue in a process called urogenital atrophy. This causes symptoms of burning or pain when
urinating or frequent urinary tract infections. There can also be a
loss of urine, either spontaneously or during stress, which is called incontinence. Drying and itching of the vagina and pain during intercourse (intimacy) may also develop.
Accelerated bone loss: The bones begin to break down more rapidly and lose calcium. This leads to loss of bone, a condition called osteopenia and later to a more severe loss called osteoporosis. With osteoporosis, women lose height as bones in the spine shrink in height. Also their backs may begin to curve more and what is called a “Widows Hump” or “Dowagers hump” develops. Finally, bone fractures may occur when an older woman falls. Hip fractures are a major cause of both hospitalization and death in elderly women.
Increased frequency of heart disease: Lack of estrogen speeds up the development of heart disease. Women begin to catch up to men in their risk of having a heart attack after the onset of menopause.
Mood changes/depression:
The brain often responds to a lack of estrogen by functioning
differently and causing depression, sadness, mood swings, memory loss,
irritability, or a lack of well-being. The link between menopause and depression appears to be physical, and not simply of psychological origin. The first link between depression and estrogen was noticed in studies of post-partum depression, a condition that can occur just after childbirth when estrogen levels are very low.
Other symptoms: Several other conditions are thought to occur more commonly after menopause in women who do not take estrogen. Alzheimer's disease, memory loss, colon cancer, degenerative arthritis, and macular degeneration
are some of these conditions (2). However, a cause and effect
relationship between estrogen and these problems has been controversial.
Thinning of the skin is more clearly linked to a reduction in estrogen
levels.
Duration of symptoms: Menopause is a process involving several organs of the body and some symptoms and problems go away while others continue. For
example, menopause causes symptoms such as hot flashes, which usually
go away after a few months to a few years after the start of menopause. Others such as urogenital atrophy remain until some treatment is given. Other
aspects of menopause do not cause symptoms but make a woman more likely
to have other conditions like heart disease or osteoporosis, which may
not resolve or be prevented without treatment.
Approaches to management of menopause
General concepts:
Many women consider that menopause is a normal process and not a
disease condition in and of itself. This point of view favors management
with relatively simple measures. Many of the symptoms associated with
menopause can be alleviated by lifestyle changes and other maneuvers
that do not require medication. Other symptoms may be sufficiently severe to require either hormonal medication or non-hormonal agents to treat specific aspects of menopause. It
is necessary for each individual to handle menopause differently, based
on the severity of problems balanced against the risks of therapy.
Tailored to you: Hormonal and other medications are associated with substantial benefits but also with a wide variety of risks. For
that reason, a general approach to management of menopause is to form a
partnership with your health care provider. Together you can assess
the risks of various complications of menopause and the severity of
your symptoms. With this risk/benefit information, you can choose how to
handle menopause, with only lifestyle changes on the one hand, or
various treatments on the other. This has been called an “individually
tailored” approach to management of menopause.
Recent information about hormonal therapy
Background: The
majority of symptoms related to menopause occur because of a drop in
female hormone levels. For this reason, hormonal therapy is the most
effective means of managing menopausal symptoms. This section will
outline the risks and benefits of hormone therapy as determined by
recent observational as well as randomized clinical
trials. The following section summarizes information from ongoing
research studies that you have read about in the newspapers or seen on
television. Because this information has generally been very confusing
to the non-expert, the following section will attempt to put these
studies into perspective. A better
understanding about hormone therapy has now been gained from multiple
studies and expert discussion of the large amount of information
accumulated over the past few years.
From
a historical point of view, it is important to point out why large
randomized clinical trials of hormone therapy were necessary. From
the mid-1970s until the beginning of the 1990s, hormone therapy for
menopause was thought to represent replacement of a missing hormone and
was called “Hormone Replacement Therapy” or HRT. Health
care providers felt that the hormones lost at menopause needed to be
replaced. It was standard practice for physicians to give thyroid
hormone when the thyroid gland stopped working. They
reasoned that when the ovary stopped working, female hormones should
similarly be replaced. This concept regarding estrogen and loss of
ovarian function was generally accepted by the medical community. For
this reason, an increasing number of women were being treated with
hormonal therapy for the menopause over the period from the 1970s to the
late 1990s.
Prior to the late 1990s, all of the information on HRT was obtained from observations in patients taking these hormones. This means that groups of women taking hormones or not taking them were compared as to development of various diseases. These observational studies indicated a substantial benefit for prevention of heart disease, osteoporosis, bone fractures, and relief of hot flashes. However,
none of these studies took into account possible biases that might
provide alternative explanations for the benefits of hormone therapy.
A
wise group of physicians, and in particular, Elizabeth Barrett-Conner,
raised the possibility that there might be substantial biases in the
evaluation of the data available. For example, women
taking hormonal therapy are generally healthier, of a higher
socio-economic class, more frequent visitors to their physicians,
exercise to a greater extent, and have a lower underlying risk of
developing breast cancer or heart disease than women choosing not to
take hormonal therapy. Barrett-Conner reasoned that the decrease in
heart disease observed in women taking hormone therapy could be due to
the fact that the hormone users were healthier to begin with.
Randomized clinical trials: Because
of these potential biases in observational studies, experts decided
that randomized clinical trials were necessary. In this type of trial, a
woman is assigned by a coin toss or by a computer to take either a placebo (“sugar pill”)
or a pill containing the hormones. Neither the women in the study, nor
the researchers decide or know which pill the women are taking. The
women are followed over a long period of time to see what benefits or
harm might occur. One advantage of a randomized clinical trial is that
the group of women receiving the placebo and the group receiving hormone
therapy are balanced as to each possible risk factor such as smoking
history, degree of blood pressure elevation, history of breast cancer in
the family, and other factors. Randomized clinical trials
are thought to be the most accurate way of determining benefits and
risks of various medications and the least susceptible to bias.
Specific trials: The first randomized study was called the HERS trial, which examined the effect of estrogen plus a progestin on the development of heart disease (3). Since
the prevailing thought in the mid-1990s was that everyone should be
treated with HRT, the HERS trial, as well as later studies, enrolled
women ranging from 50 to 80 years of age. When the study was published after completion, it reported that estrogen plus progestin was associated with an increased risk of heart disease. This
was a major shock to the medical community because the observational
studies had previously shown a decrease in heart disease with hormone
therapy. Not long after this, the Women's Health Initiative (WHI) study of estrogen plus progestin also reported an increased risk of heart disease in women receiving hormone replacement therapy(4). The WHI study was very influential because it involved nearly 16,000 women who were followed for 7 years.
The
WHI then conducted another study in women taking estrogen alone (5). It
is standard practice that menopausal women who have had a hysterectomy
are only given estrogen. The progestin component is not needed since
this is used to prevent uterine cancer which will not develop in women
with no uterus. For this reason the WHI study group
designed a trial-comparing placebo with estrogen alone in women whose
uterus had been surgically removed. This study also reported no improvement in heart disease in women receiving estrogen.
Based
on these three studies (HERS, WHI estrogen /progestin and WHI estrogen
alone), it is no longer recommended that women take hormone therapy primarily
as a means to prevent heart disease (3-5). Also based on these studies,
the word used to describe hormone therapy for menopause was changed. The word HRT (hormone replacement therapy) is no longer used and the term MHT (menopausal hormone therapy) is generally substituted.
The HERS and the two WHI studies also showed an increased risk of thrombo-embolic events (blood clots in the legs or lungs; otherwise called veno-thrombotic events or VTEs) in women taking menopausal hormone therapy. Stroke was increased as well. The risk of breast cancer was increased in the women taking estrogen plus progestin in the WHI study. Surprisingly, those
on estrogen alone did not have an increased risk but paradoxically,
there was a suggestion of a reduction in breast cancer risk (3-5).
Less
emphasis was given by the communications media to that fact that the
WHI studies also demonstrated major benefits from menopausal hormone
therapy. Most important was a 40% reduction in broken bones (fractures).
In the estrogen plus progestin trial, colon cancer was also reduced by
40%, but this was not seen in the estrogen alone part of the study. In
the women taking estrogen alone, there was a 30% reduction in death
over the time of the study. Interestingly, this fact was largely ignored
by the television and newspaper media.
Another
large study was reported at about the same time. This was called the
Million Women Study (6) because of the number of women included in the
findings. Conducted in the United Kingdom, this study only observed
women who were taking or not taking hormones, and did not randomize them
(i.e., coin toss selection) to one treatment or another. Because of its
large size, this study has been very influential even though only an
observational study. This study largely confirmed the findings of the
WHI and HERS studies.
These four studies (the HERS study,
the two WHI studies and the Million Women’s study) all alerted the
medical community and women to the risks associated with taking
menopause hormone therapy. In the United States and in
Western European countries, the number of women taking menopause hormone
therapy declined by 80% shortly after these reports came out in
newspapers and on television.
Concerns raised about the WHI studies: When the results of the WHI studies
were completed and reported, a number of informed experts began to
point out some major flaws in these randomized controlled trials (7). The
first flaw was that the average age of women in these trials was 63 and
some women were up to 79 years of age. Most women starting menopausal
hormone therapy are much younger. The possibility was raised that use of
hormone therapy shortly after the start of menopause in younger women
might be beneficial with respect to heart disease. They suggested that
the harm from hormonal therapy might only occur in older women. The
other flaw was that the symptoms of menopause such as hot flashes, mood
changes, irritability, and depression were not considered at all. This
was because the studies were designed mainly to see if MHT prevented
heart disease.
Effect of age on results:
These concerns led to a later re-analysis of the WHI studies to take
age into account. Women were divided into three groups: those age 50 to
59; age 60 to 69, and age 70 and older (8). In another analysis, the WHI
subjects were divided into those experiencing menopause less than 10
years previously, 10 to 20 years previously, and greater than 20 years
previously. These studies, taken together, were reassuring
with respect to the risk of menopausal hormone therapy during early
menopause. They indicated that MHT does not increase the risk of heart
disease and may reduce it by as much as 25-50% in women during the first
10 years after menopause or in women aged 50-59. It is important to
know, however, that this new analysis showed that the increased risk of
stroke was seen in both the younger and older women. Experts concluded
from this that the causes of heart disease and stroke are different, as
are the effects of MHT on these two conditions.
A follow-up to the WHI heart studies then showed that use of estrogen alone in the 50-59-year-old age group reduces the amount of calcification in the arteries of the heart (coronary
arteries) in women taking estrogen alone for the first 8 years after
menopause (9). Calcification in the arteries of the heart is a sign used
as a means to predict who will develop heart disease later in life
(i.e., the more the calcium, the higher the risk of developing heart
disease later).
New conclusions:
Based upon these studies, most experts now believe that the harmful
effects of estrogen or estrogen plus progesterone on heart disease are
likely to be age-related. Women recently menopausal
probably experience benefit with a reduction in heart disease risk,
while those menopausal for more than 10 years experience harm. Critical
analysis of this information, however, suggests that new randomized
trials are needed to confirm this possibility. Such clinical trials are
currently underway.
Breast cancer risk: Another major issue regarding hormone therapy in menopause is whether or not this causes an increased risk of breast cancer. The WHI study of estrogen plus progestin clearly showed a 26% increased relative risk of breast cancer when taken over a 5-10 year period (4). The United Kingdom’s Million Women Study also
reported an increased risk of breast cancer with estrogen plus
progestin(6). From all of the data available, it appears that use of
estrogen plus a progestin does increase breast cancer risk. Estrogen alone probably does not if taken for 5 years or less but more information about this is needed (10;11).
Risk and benefits to an individual woman:
As the results of these trials have been discussed widely, many health
care experts have tried to put them in perspective as to the magnitude
of the risks and benefits to an individual woman. It is a
particularly important issue to consider how many women would be harmed
by taking MHT, estrogen plus a progestin or estrogen alone. The
reports of the studies in the lay press and on television emphasize the
relative risks from taking menopausal hormone therapy. For example, it was widely publicized that estrogen plus a progestin causes a 26% increase in risk of breast cancer. It
is actually more appropriate to consider the actual number of women who
would be benefited or harmed rather than the relative percentages.
To
do this, one must know the chances of getting these conditions without
taking hormones and then the excess chances of getting these conditions
caused by taking hormones. Because of this, the New York
Times, and other media as well as medical investigators, have begun to
express risks as the excess number of women per 1000 who would benefit
from or be harmed by taking menopausal hormone therapy for 5 years or
more. With this analysis (Tables I and II), the use of
estrogen plus progestin is associated with several benefits when taken
for five years. These include a reduction of colorectal
cancer in 3 out of 1000 women taking estrogen/progestin and hip fracture
in 2.5 out of 1000. Risks include excess stroke in 4 out of 1000,
breast cancer in 4 out of 1000, heart attacks in 3.5 out of 1000, and
blood clots in the legs or lungs (VTE) in 9 out of 1000. In the Tables,
the percentage risk or benefit from each of these is also listed for
comparison.
These
same estimates have been determined for use of estrogen alone. Hip
fractures are prevented in 2.5 out of 1000 women with no change (or a
reduction) in heart attacks or breast cancer. Risk of blood clots in leg
or lungs (VTE) is 9 out of 1000, and stroke is 6 out of 1000. These
estimates include all of the patients in the trial and will certainly be
somewhat different when one considers younger versus older women.
There are other beneficial effects of taking hormonal therapy during menopause. Data
suggest that these reduce the onset of diabetes by about 30% over a
5-year period, but it is not known whether these effects continue over a
longer period of time (4). In addition, estrogen increases the quality
of skin by reducing its gradual thinning, usually seen at the time of
menopause.
Role of risk versus benefit for you: Careful
thought about these studies indicates that you should know your own
underlying risk of certain conditions before you make a decision to take
hormones. This involves a tailored approach to making a
decision. If you have a high risk of developing heart disease, use of
menopausal hormone therapy would not be a good idea. On
the other hand, MHT for the short term might be very helpful for you if
you have severe symptoms of menopause such as hot flashes, and a low risk of breast cancer or heart disease. In
general, the recent studies show that the younger you are and the
shorter the duration of menopause, the more benefit you will gain and the less harm will result from MHT.
To
make an informed decision, you need to consider what chances you would
have of being benefited or harmed by MHT. As shown in Table I, if you
take estrogen and a progestin for 5 years, there is a 4 chances in 1000
risk that you will get breast cancer that you would not otherwise have had,
had you not taken MHT. This is what the term “excess risk” means. On
the other hand, you have 3 chances out of 1000 that a colon cancer will
be prevented. You will appreciate that the odds of risk and benefit seem
smaller if you consider “excess risk” or benefit as opposed to
percentage risk.
What have the recent studies taught us?
The recent, randomized controlled trials of hormone therapy and menopause have caused much controversy among health care providers and confusion for women. A common comment is that the medical profession is continually changing its mind about hormone therapy. This is certainly true but this has happened because the information now is so much better. It should be recognized that as a result of these randomized clinical trials, much more is known about hormone therapy during menopause. These
studies have allowed a rational approach to selecting who should go on
hormone therapy and who should use other treatments for menopause. Decisions
can now be based on objective calculations of risk and benefit tailored
to the individual patient. As a result of these trials, women are much
better informed about how to manage menopause.
Management of menopause
In
the remainder of this discussion, attention will be directed to each of
the five major problems associated with menopause (Tables IV and V). The
specific characteristics of these problems will be identified, the
potential approaches to managing them will be outlined, and the risks
and benefits of hormonal versus non-hormonal approaches will be
discussed.
Vasomotor instability.
This term refers to the fact that the blood vessels in the body can change rapidly in women with low estrogen levels. This results in an increased delivery of blood to the skin, particularly of the face, head, and upper chest. This increased delivery of blood causes a sensation of increased warmth, which is called a hot flash or hot flush. Characteristically, hot flashes come on suddenly and last approximately 5 to 10 minutes before they subside. After the cessation of a hot flash, a woman will feel cold and clammy because of the increased perspiration on the skin. Hot flashes can awaken women from sleep at nighttime and can be associated with fatigue during the day due to sleep deprivation. Hot flashes are usually less troublesome during the daytime but can be severe in some women.
Recent studies by medical investigators have shown that hot flashes result from an abnormality in temperature regulation (12). Normally, one does not feel overly warm or cold if the body temperature either goes up or goes down by as much as 1 or 2°F. During
menopause, the temperature need only change by a 1/2 degree Fahrenheit
either up or down to trigger either a feeling of warmth or a feeling of
being too cold. In technical terms, the amount that the temperature can change without symptoms is called the “thermo-regulatory neutral zone.” This zone narrows when the estrogen levels fall during the menopause.
This new understanding of menopause allows rational use of certain lifestyle changes. For
example, if one is in a warm room that could cause hot flashes to
occur, the most effective approach is to take off a sweater or to remove
certain layers of clothing. After the hot flash, when one becomes cold or clammy, one can then re-add the layers of clothing. Since
stress or anxiety can increase the frequency of hot flushes, relaxation
tools can be helpful. In this regard, a technique called paced respirations can be helpful. This is a method of timing the rate of breathing which in effect is a means of relaxation.
How many women actually develop hot flashes? A very large study across the United States called the Swan Study examined nearly 70,000 women (13). Information
from this study would indicate that as many as 10 or 15% of
pre-menopausal women develop hot flashes and 60- 80% at the onset of
menopause. In the majority of women, hot flashes gradually diminish over 2-3 years after the onset of menopause. However, in as many as 10- 20% of women, hot flashes continue for as long as 10- 15 years. The WHI studies provided important information on the frequency of hot flashes. From ages 50-59 , 27% of women had moderate or severe hot flashes which diminished to 14% at ages 60-69, and 8.6% at ages 70-79 (8). Those less than 10 years from onset of menopause had a 21% prevalence of moderate or severe hot flashes compared with 14% with menopause 10-19 years earlier and 12% with menopause greater than 20 years before. While not commonly appreciated, acute illness or stress can cause hot flashes to return temporarily. When
a woman has not experienced them for a period of 5-10 years, certain
illnesses, such as overactive thyroid, infection, weight loss, or
trauma, can bring back the hot flashes for a temporary period of time.
Many remedies have been suggested for treatment of hot flashes in the medical and lay literature. However, extensive studies have not been able to show that soy products, herbal remedies, multivitamins, or herbal plant extracts actually reduce the frequency of hot flashes(14;15). When
medical scientists study hot flashes, it is routinely observed that 30%
of women will respond to a placebo with a reduction of hot flashes. In
general, this placebo effect is what happens when one takes herbal
products or soy products and women experience about a 30% improvement. The
one herbal product that shows some promise is called Black Cohosh , and
it has been shown in some but not all studies to reduce the frequency
and severity of hot flashes when compared to a placebo (16). Vitamin E
may also reduce hot flashes by 10% when compared to a placebo (2).
Who should be treated for hot flashes? It
has been the experience of many physicians that hot flashes during the
daytime can often be tolerated by adopting lifestyle changes. However, it is now known that hot flushes disturb sleep and may diminish cognitive function if sufficiently frequent during the night (12). The first step in deciding about treatment is to determine how bothersome hot flashes are to you initially. If
they disturb your sleep, result in decreased cognitive function or in
fatigue during the daytime, you should then consider treatment for this
condition. Intolerable hot flashes during the daytime are another reason
to take some type of treatment. There are both hormonal and non-hormonal treatments for hot flashes.
Unless
there are clear reasons not to take hormonal therapy (see Table III),
female hormones including estrogens and progestins (or progesterone) are
generally used as the most effective treatment for hot flashes. These cause a 70- 80% reduction in the frequency and severity of hot flashes. In the past, the most common hormonal treatment was Premarin which is a natural extract of pregnant mare urine. Premarin contains various female hormones and/or estrogen like compounds. Since Premarin has been used over the last 40 or more years, health care providers are familiar with its risks and benefits. Because
of the emphasis in recent years regarding the adverse effects and risks
of estrogens, health care providers are now recommending the lowest
doses of hormone which work. These lower doses would
include 0.3 or 0.45 mg of Premarin daily rather than the previously
prescribed doses of 0.625 and 1.25 g daily. Many other
estrogen preparations are also available which can be given by patch, in
a gel applied to the skin, by a high dose vaginal ring, and by a nasal
spray. In a woman who still has her uterus, a progestin must be given in
addition to estrogen in order to prevent the development of endometrial
cancer. There are very many synthetic forms of progestin which can be used or one can use progesterone itself.
It
is currently recommended by the US Food and Drug Administration, the
FDA, that hormone therapy be used in the lowest possible dose to relieve
symptoms and for the shortest duration possible. Since
hot flashes are most severe during the first 5 years following
menopause, it is generally recommended that hormone therapy be used for a
period of up to 5 years after the menopause.
If hormones are contraindicated, a number of other ways of treating hot flashes have been developed. One option is to use a class of drugs called selective serotonin uptake inhibitors, or SSRIs, which are usually used to treat depression but work for hot flashes as well. Several
of these are available and the most active are thought to be
venlafaxine (Effexor) and paroxetine (Paxil) (14). These reduce hot
flashes less effectively than estrogens, but cause an approximately 60%
reduction in the number and severity of hot flashes. Recent studies have shown that gabapentin (Neurontin) is also effective in treatment of hot flashes and, in high doses, may be as effective as estrogens (14). This agent is particularly useful for treating hot flashes that awaken one from sleep at night. Drowsiness, a major side effect of Neurontin, can actually be a benefit as a means to get to sleep more easily.
Gabapentin also reduces both night time and day time hot flashes. The
blood pressure drug clonidine can be effective and seems to benefit
some women substantially while others may not be helped at all. A progestin called Megace (megestrol acetate) has also been shown to be effective for hot flashes. How safe megestrol acetate is when used for a long time is not known.
Urogenital atrophy
This term means a loss of the tissue that lines the vagina or the bladder, the sac in which the urine is stored. Urogenital atrophy involves symptoms related to both the urinary and the genital systems. Genital atrophy causes dryness or itching in the vagina, pain during sexual intercourse, and swelling of the tissues around the entrance of the vagina. Symptoms relating to atrophy of the urinary system include frequent urinary tract infections, pain during urination, the need to urinate urgently or often, and involuntary loss of urine (incontinence).
For treatment of urogenital atrophy, you can take estrogens in many forms. The
major question is whether a woman can safely use estrogen as topical
therapy in her vagina without it being absorbed into her body. It
was previously known that vaginal creams produce estrogen levels in the
blood stream that are one fourth that of the same amount of estrogen
taken in pill form by mouth. This suggested that all
vaginal estrogens have effects on parts of the body other than the
vagina. However, it is now known that the locally inserted estrogens are
four times more active in the vagina than when given by pill.
Knowing
this information, physicians now have found that vaginal estrogen can
be given relatively safely. However, this requires a very low dose given
vaginally. In this way, your vaginal tissues improve with very little estrogen being absorbed into the body. The
vaginal doses used now are about 1/10 of the estrogen doses that were
prescribed by physicians 2 decades ago. Estrogen is put into cream
containing either Premarin or estradiol (the form of estrogen made naturally by the ovary). Estradiol can also be given by a tablet put into the vagina (Vagifem) (17). At the start of this therapy, the cream or tablet is put into the vagina daily. After a month you can then decrease to twice a week or even less. Women like the fact that they can adjust the dose to their own needs for relief of symptoms.
The
vaginal estrogen ring device called “Estring” also releases a small
amount of estradiol into the vagina. The ring stays in the vagina for
three months without changing and it continues to release estrogen. The amount delivered is also very low and you will experience almost complete relief of symptoms (18).
Who should consider using vaginal estrogens? Most women benefit from the use of estrogens taken as a pill or by patch. However, many women are concerned about the harmful effects of estrogen on the body such as breast cancer or blood clots. If severe symptoms of urogenital atrophy are present, these women can consider the use of low-dose vaginal estrogen. The amount absorbed into the body is very small and should help to greatly reduce the risks associated with oral estrogens.
Can a woman use anything other than estrogen to relieve symptoms? Non-hormonal moisturizers such as Replens are available (19). You
need to put this into the vagina three times a week to improve dryness.
It should be recognized that Replens does not increase the thickness of
the vaginal lining, an effect that estrogen has. Many women find Replens to be very helpful. One approach is for you to use the vaginal moisturizers as the first step to relieve symptoms. If this is not effective, the next step is for you to use vaginal estrogen creams or estrogen tablets locally.
Accelerated Bone loss:
Keeping the bones healthy: From age 30 onward, women gradually lose bone and this accelerates for the first 5 years after menopause (20). The best way to keep your bones healthy and to minimize bone loss is to establish a healthy pattern of living. This sounds a little vague, like motherhood and apple pie, but there are specific things you can do. First avoid anything that is known to cause bone loss. Smoking, drinking too much alcohol, not having enough exercise, taking cortisone-like medications, and lack of sunlight; all of these can speed up bone loss. You must also build up bone. Exercise, walking a minimum of 20 minutes 3 times per week, is beneficial in building new bone. Exercise really works. Astronauts in space lost about 30% of their bone calcium after 2 weeks in space. Now they exercise on special equipment while in space to prevent bone loss.
After menopause, you should take 1500 mg of calcium daily; this is the same as drinking six glasses of milk each day. Because that may be difficult, you may instead want to take 1000 mg of calcium in tablets such as Os-Cal or calcium citrate or extra strength Tums or a chocolate (and other flavors) candy containing calcium called Viactiv. An
additional 500 mg of calcium usually is present in the normal diet from
dairy products including milk. If you add this up, the 1000 mg from
tablets and 500 mg in the diet makes the 1500 mg needed. In women over age 70, vitamin D supplements also are usually given and should be considered for younger women as well. Your
health care provider can determine your need for vitamin D by measuring
blood levels of this vitamin. These steps will be enough for many women
to prevent bone loss so that they will have a lower risk of bone
fractures.
Who should be treated with medication? It is not always necessary to take female hormones or another drug to prevent osteoporosis. However, the key is to know how much bone you have already lost and whether you are at high risk for fractures (20). Usually it is necessary to have a bone density scan, otherwise call a DEXA (dual X-ray absorptiometry scan). This enables you to find out whether you need to take a medication to maintain healthy bones. If the bone scan shows a reduction of bone (osteopenia), but not yet osteoporosis,
then other risk factors are taken into account before determining the
need for medication. With osteoporosis, medication is nearly always
needed.
Where to start in managing bone loss? An
analysis of your risk and a bone scan (DEXA) can guide you and your
health care provider to the best decision. Risk factors for fracture include smoking, a family history of fracture or osteoporosis, excessive alcohol intake, a
body weight of less than 129 pounds, unsteadiness on one's feet, poor
vision, and decreased muscle strength in the lower body. A group of
experts have recently published a risk evaluation method which includes many of the above listed factors (20).
For
women with a lower risk of developing fractures, lifestyle changes to
increase exercise and calcium intake are the most appropriate way to
prevent later fractures, as described above. For others, bone loss may be moderate or severe and the risk of fracture
high. Other women who are initially at low risk can continue to
experience bone loss even with good lifestyle changes. These women will
need to consider medications for treatment.
Therapies available:
Hormone therapy:
In women ages 50-59 or less than 10 years postmenopausal, hormone
therapy is usually considered unless contraindicated (Table III).
Estrogens work by blocking bone breakdown. Low doses are
effective in preventing further bone loss and the considerations for its
use are similar to those for hot flashes.
Treatment with bisphosphonates: These are non-hormonal drugs, which work by blocking the normal breakdown of bone. At any given time, the body is both making new bone and breaking down old bone (Figure 2). This process is called remodeling, just as if you were remodeling your house, throwing out the old and installing the new. The bisphosphonates work by blocking the breakdown of old bone. Using the analogy of remodeling, the bisphosphonates keep you from throwing out the old bone.
There are currently several oral drugs which have been approved by the food and drug administration, which are in the bisphosphonate
class (2). These include alendronate, (Fosamax), risedronate (Actonel)
and ibandronate (Boniva). Alendronate and ibandronate must be taken once
each week but only ibandronate can be taken as infrequently as once
each month. Women can have difficulties when they take bisphosphonate
drugs orally. These drugs are not absorbed well when they are swallowed. Patients must take them on an empty stomach, remain sitting or standing, and have nothing else but a glass of water for the next 30 minutes. Two bisphosphonates are now available as intravenous medications that can eliminate the need to take the bisphosphonate orally. One
of these, zoledronic acid (Recast), needs only be given only once per
year while the other, ibandronate (Boniva), needs to be given once every
3 months. Use of these medications is considered to be cost effective
if the risk of fracture is high enough (21).
Estrogens and the bisphosphonates work about equally with respect to their
effects on bone (2). Success can be measured by finding out how much
new bone is formed over a 2-year period and by calculating how many
broken bones are prevented. With the bisphosphonates and
estrogen, spinal bone mineral density increases by about 4% during the
first year and 5-7% in the second year. Up to 50% of new fractures
(broken bones) are prevented by either bisphosphonates or estrogen.
In
women who receive the bisphosphonates for 5 or more years, a drug
holiday – going off the drug for a period of time -- is often
recommended. Loss of bone after stopping these drugs is
slowed down even though the drug is no longer taken. This is because the
bisphosphonates stay in the body for up to 7-10 years after these drugs
are stopped. Some women develop bone or joint pain on the
bisphosphonates and must either lower the dose or stop the medication to
relieve these symptoms.
Forteo: For
women with severe osteoporosis, a drug that acts like another hormone
in the body, parathyroid hormone, can be given by needle injection once
each day. This drug, called Forteo, works by increasing the amount of
new bone formed. Forteo is taken for a 2-year period and is the most effective way of increasing the amount of bone. After 2 years of Forteo, the average amount of bone increases by approximately 15%.
SERMs: Another way to treat or prevent osteoporosis is to use a type of drug called a selective estrogen receptor modulator (SERM). An
ideal drug of this type would do the right things in the parts of the
body that need the healthful effects of estrogen and prevent harmful
estrogen effects on other organs. The ideal drug should
prevent hot flashes, act as an estrogen in the brain to prevent mood
change, prevent breast cancer, maintain the bones, and reduce the risk
of cancer in the uterus. No such drug currently exists. However,
raloxifene (Evista) is a designer estrogen that can do many of the things just mentioned. This drug has been approved for preventing or treating osteoporosis. Researchers have found that raloxifene acts as
an anti-estrogen on the uterus and does not increase the risk of
uterine cancer when given without a progestin. It also acts similarly to
estrogen to block bone breakdown. For this reason, it is approved for the treatment of osteoporosis or for its prevention. Most importantly, raloxifene blocks the effect of estrogen on breast tissue. Recent studies have shown that it causes nearly a 50% reduction in new breast cancer cases. A
drawback of raloxifene is that it can cause hot flashes. Other SERMs
are now being developed which may eliminate the hot flash effect.
Calcitonin: A
nasal spray to deliver a hormone called calcitonin has been used in the
past to prevent fractures but is not nearly as effective as the
bisphosphonates or the use of parathyroid hormone.
Acceleration of Heart Disease
Acceleration of the development of heart disease is a common component of menopause. Prior to the HERS and WHI studies, it was thought that estrogen would be the best way to prevent the acceleration of heart disease. However, the HERS and both WHI studies showed an overall worsening of heart disease When the effect of age was later studied, however, the worsening only occurred in older women and younger women appeared to have a reduced chance of developing heart disease (8). Further studies will be required before recommending hormonal therapy to younger women to prevent heart disease. In the meantime, the approach to this problem is to determine the risk that an individual woman will have a heart attack. This can be determined using a new risk evaluation tool, specifically designed for women, called the Reynolds risk model (22). This can be found on the Internet. http://www.reynoldsriskscore.org/.
If
you have a low risk of developing heart disease, lifestyle
modifications such as low-fat diet, weight reduction diet, increasing
exercise, and cessation of smoking are recommended. If you
have a moderate to high risk of developing heart disease (10% risk or
greater over 10 years), intervention with medication is usually
appropriate. Drugs called “statins” are very effective in lowering bad cholesterol levels and have been shown to reduce the risk of heart disease. Another
agent called Zetia blocks cholesterol absorption from the intestines
and also lowers cholesterol levels but its use was recently called into
question (New York Times, 1-15-08). The omega-3-fatty acids can also be
used to lower blood fat levels. Since high blood pressure is a risk
factor for heart disease and is more common in postmenopausal women,
blood pressure lowering medications are prescribed for menopausal women
with hypertension (high blood pressure).
Depression/mood changes
In some women, the drop in estrogen at menopause may cause mood changes or depression and hormone therapy can benefit these women. However, for women who cannot take estrogens or are concerned about potential risks, a number of medications can be used as alternatives. The SSRIs (selective serotonin reuptake inhibitors) are drugs that are very effective for moderate or severe depression. This class of drugs works by increasing the amount of a chemical called serotonin, a substance thought to be related to depression. The newer generation of SSRI antidepressants is associated with fewer side effects than older drugs such as Elavil. Depression appears to respond to the SSRIs whether or not the problem is caused by a lack of estrogen.
If you have only mild depression or mood changes, you may benefit from relatively simple measures such as discussion of stressful life situations with a health care professional. In some women, the mood changes are severe and medication may help. Many
women consider using other approaches such as herbal medicines like St.
John's wort, exercise, counseling, support groups, or lifestyle
changes. Help is available from many health care providers, so ask for help if you think you need it. Remember that mood changes or depression can result from the hormonal changes at menopause. Don't feel that you should be able to conquer the problem yourself. Oftentimes, you will benefit from a better understanding of the effects of hormonal changes and ways to deal with them.
Controversies
Whether or not estrogen can prevent Alzheimer's disease or loss of cognitive (intellectual) function is controversial. Observational studies originally suggested that this was the case. However, the WHI study showed that, if anything, estrogens increased the rate of cognitive dysfunction in older women. For this reason hormone therapy is not recommended to prevent Alzheimer's or changes in cognitive function.
It also controversial whether or not herbal remedies are effective. Experts caution that one should be careful about information
obtained from health food stores that offer herbal remedies. While
herbs may offer relief, they have not been scientifically studied as
carefully as FDA-approved medications. Since 1994 it has been legal to
sell plant products in the United States as herbs or diet supplements as
long as no medical claims are made and the products have not been
proven unsafe. The manufacturing quality of herbal products often is a
problem. Information about safety and effectiveness do not have to be
reported to any state or federal agency. These issues have made the use
of herbal substances controversial. An important principle is to be sure
your health care provider knows about your choices of non-prescription
substances.
| Symptom: Hot Flashes | ||
| Treatment | Dose | Pros and Cons of Treatment |
| Systemic Estrogen* (Menopausal Hormone Therapy) | Lowest dose possible (see Table IV) | Pros: Very effective at relieving hot flashes; also helps prevent vaginal thinning; prevents bone loss Cons: Increased risk of breast cancer when combined with a progestin; increased risk of uterine cancer if estrogen is taken without progesterone; increased risk of blood clots |
| SSRI drugs Paroxetine Venlafaxine Fluoxetine |
10-20 mg daily, orally
37.5 – 75 mg daily, orally
20 mg daily, orally
| Pros: Shown to be effective for hot flashes and also for depression Cons: Causes mood changes; can affect sex drive; paroxetine can have adverse interactions with tamoxifen |
| Neurontin | 300-1000 mg at bedtime; or 300 mg 3 times daily (max 2700 mg daily), orally | Pros: Effective for relieving hot flashes, particularly at night; aids in getting to sleep Cons: Dizziness and lethargy if used during daytime |
| Clonidine patch | TTS #1,2, or 3;or 0.1 mg daily orally | Pros: Controls blood pressure as well as hot flashes Cons: Only a small percent of patients respond with a reduction of hot flashes |
| Megestrol acetate | 20 mg twice daily, orally | Pros: Effective progestin treatment for hot flashes Cons: Weight gain; not studied well in women who have had breast cancer |
| Vitamin E | 800 IU daily, orally | Pros: May reduce number and severity of hot flashes in some women Cons: No toxicity of vitamin E; some people get headaches ; scientific support for its effectiveness is very weak |
| Black Cohosh | 40 mg daily, orally | Pros: Natural product Cons: Proof of efficacy weak |
| Medroxyprogesterone acetate | 400 mg intramuscular injection every 3 months | Pros: Very effective for relieving hot flashes; as effective as estrogen Cons: Weight gain; requires injection, safety in breast cancer patients not fully proven |
| Symptom: Urogenital Atrophy | ||
| Systemic Estrogen* (Menopausal Hormone Therapy) | (See Table IV) | Pros: Helps keep vaginal tissue from thinning; also helps prevent bone loss; very effective against hot flashes Cons: Increased risk of breast cancer when combined with a progestin ; increased risk of uterine cancer if estrogen is taken without progesterone; increased risk of blood clots |
| Vagifem estradiol tablets | 25 mcg twice each week vaginally | Pros: Ease of insertion; not messy Cons: Some absorption into body |
| Estradiol cream (Estrace) | 1/8 of an applicator twice each week vaginally | Pros: Effective Cons: Messy |
| Conjugated estrogen cream | 1/8 of applicator twice each week vaginally | Pros: Effective Cons: Messy |
| Vaginal moisturizers | Apply vaginally 3 times weekly | Pros: Effective moisturizer; over-the-counter product Cons: Some women don't like these products, because of consistency or smell; does not thicken the vaginal lining; not as effective as estrogens |
| Water-soluble lubricants | Apply vaginally just before intercourse | Pros: Effective lubricant; over-the-counter product (Note: There is difference between lubricant and moisturizer) Cons: Some women don't like these products because of their consistency or smell; does not thicken the vaginal lining |
| Low dose vaginal estrogen ring Estring |
Insert every 3 months into vagina.
7.5 mcg delivered daily into vagina
| Pros: Helps keep vaginal tissue from thinning; small increased risks compared with higher doses of estrogen when using Estring Cons: Some absorption of estrogen into the body occurs but this is small with Estring. Confusion arises regarding the high dose estrogen vaginal ring (Femring) which can cause substantial estrogen absorption into the body |
| High dose vaginal estrogen ring Femring | Insert every 3 months into vagina. 50-100 mcg delivered daily into vagina | Pros: Helps keep vaginal tissue from thinning; delivers enough estrogen into the body to reduce bone loss and to decrease hot flashes Cons: Greater risk from estrogen than low dose ring because of greater absorption into the body; confusion with Estring which delivers lower amount of estrogen daily. |
| Accelerated Bone Loss | ||
| Systemic Estrogen* (Menopausal Hormone Therapy) | (See Table IV) | Pros: Very effective at relieving hot flashes; also helps prevent vaginal thinning; prevents bone loss Cons: Increased risk of breast cancer when combined with a progestin; increased risk of uterine cancer if estrogen is taken without progesterone; increased risk of blood clots |
| Calcium | 1500 mg (two 500 tablets + dietary calcium), orally | Pros: Not actually a medication Cons: Causes constipation |
| Vitamin D | 800 IU daily, orally | Pros: Helps body absorb calcium Cons: Large amounts of vitamin D can cause build-up of calcium in blood which could lead to heart and lung problems and kidney stones |
| Nasal Calcitonin | 200 units intranasally once daily | Pros: Slows bone breakdown Cons: Headaches, dizziness, diarrhea, lack of desire for eating, nose bleeds (with nasal form); much less effective than bisphosphonates |
| Bisphosphonates Alendronate Risedronate Ibandronate Zolendronic acid |
35 mg orally once weekly for osteopenia; 70 mg orally once weekly for osteoporosis
35 mg orally once weekly
150 mg orally once per month; 3 mg intravenously once every 3 months4 mg intravenously once yearly | Pros: Very effective against bone loss Cons: Common to have gastrointestinal problems when taking these drugs orally; can cause injury to esophagus unless taken with lots of water while sitting upright or standing;rarely causes jaw necrosis (death of cells in the jaw) |
| Tamoxifen | 20 mg daily, orally | Pros: Lowers risk of breast cancer; reduces risk of fractures Cons: Increases risk of uterine cancer, blood clots; increases hot flashes; irregular vaginal bleeding |
| Raloxifene | 60 mg daily, orally | Pros: May lower risk of breast cancer; prevents fractures Cons: Increases risk of blood clots; hot flashes; leg cramps |
| Teriparatide (Forteo) | 20 mcg subcutaneously daily for 2 years | Pros: More effective than other agents Cons: Expensive; requires daily injection |
| Depression/Mood Changes | ||
| Counseling | Interaction with psychiatrist, psychologist, social worker, primary care physician, or other health care provider | Pros:
Can be empowering to understand your physical and mental challenges at
this time of life and discuss them with a mental health expert Cons: Can be expensive; may not work as well as medications |
| SSRI drugs Citalopram Fluoxetine Paroxtene Sertraline Duloxetine venlafaxine | As recommended by physician | Pros: Shown to be effective for depression; some reduce hot flashes Cons: May cause mood changes; can affect sex drive; some types such as paxil or Zoloft may interfere with effect of tamoxifen |
| Other classes of antidepressants Bupropion Trazodone tryptophan | As recommended by physician | Pros and cons will be discussed with physician. |
| Systemic Estrogen* (Menopausal Hormone Therapy) | See Table IV | Pros: Very effective at relieving hot flashes; also helps prevent vaginal thinning; prevents bone loss Cons: Increased risk of breast cancer when combined with a progestin; increased risk of uterine cancer if estrogen is taken without progesterone; increased risk of blood clots |
| Acceleration of Heart Disease | ||
| Statins Lovostatin Atorvastatin Fluvastatin Pravastatin Rosuvastatin simvastatin | As recommended by physician | Pros: Only a few side effects; effective Cons: Must be taken long term |
| Ezetimibe (Zetia) | 10 mg orally daily | Pros: Well tolerated Cons: Recent study suggests that it might not prevent heart disease |
*Short-term
goals of estrogen treatment are different from the long-term goals.
Short-term therapy is designed to relieve symptoms; long-term therapy
helps to prevent bone loss. If you take hormones for less than three to
five years, the risks are relatively low. If you are concerned about
bone loss and are thinking about taking hormone therapy for more than
five years, consult with your doctor to see whether hormone therapy or
an alternative treatment is best for you.
Some estrogen products
Reproduced with permission from: Treatment of Menopausal Vasomotor Symptoms. Med Lett Drugs Ther 2007; 49:15 and 71. Copyright © 2007 The Medical Letter, Inc. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Getting information: Sources of information that you may find helpful include:
General information:
North American Menopause Society (NAMS) http://www.menopause.org/Consumers/.
Guidelines from professional societies
Guidelines
regarding treatment of the menopause have been published by the North
American Menopause Society, The World Menopause Society, the American Society of Reproductive Medicine, and Up-To-Date.
Guidelines of the North American Menopause Society
"The
role of local vaginal estrogen for treatment of vaginal atrophy in
postmenopausal women: 2007 position statement of The North American
Menopause Society" -- Menopause 2007.
“Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of
–“Menopause”
Patient information of women’s health issues
Up to Date
American Society of Reproductive Medicine
Glossary
Alzheimer's disease
A
disease in which the brain gradually deteriorates and one progressively
loses memory, the ability to speak, and the ability to feed oneself. In the end stages, this disease results in death.
Anti-estrogen
A drug that blocks the harmful effects of estrogen on certain tissues like the breast.
Atrophy
A
condition in which a given tissue is no longer stimulated by a hormone.
This results in changes that interfere with the function of that organ. For
example, the lining of the vagina undergoes atrophy after menopause and
for this reason infection and painful sexual intercourse can occur.
Bad cholesterol
A type of cholesterol that increases the risk of heart disease. It is also called low density lipoprotein (LDL) cholesterol.
Bladder
A sac in which your urine is stored until urination.
Blood clots
Blood
cells can form a thickened area, which is called a clot that moves
through the blood and can cause damage by blocking blood vessels.
Bone formation
A process in which new bone is made to replace old bone, which is removed. This
occurs during the process of bone remodeling, just like the remodeling
of a house, where old things are removed and new things are put in.
Bone mineral density
This is a term used to describe the amount of calcium present in bone. When
the bone mineral density is low, there is a reduced amount of bone and
either osteopenia, which is a moderate loss of bone or osteoporosis,
which is severe loss of bone occurs. This is determined by an X-ray
technique called DEXA (see below)
Bone resorption
A process in which bone is removed to make way for new bone that forms. This occurs during the process of bone remodeling.
Calcitonin
A
hormone made by the thyroid gland which causes blockade of the
breakdown of bone. This can be used by nasal spray to prevent or treat
osteoporosis. Calcitonin is much less effective than the
bisphosphonates, estrogen, or Forteo and is not used commonly at the
present time.
Clinical trial
When
physicians want to learn how a medication works, they design a clinical
trial in which patients are treated according to a specific protocol. They closely examine what happens in groups of patients studied and followed over time. Usually one group is given one drug and a second group another drug. Sometimes a drug is compared with a placebo.
Cognitive function
Intellectual
capacity such as memory, ability to make decisions, to use numbers, to
exercise judgment, or to understand difficult concepts is defined as
cognitive function.
Contraindication
Medical reasons not to take a medication.
Coronary
This
word refers to the main arteries supplying blood to the heart. When the
coronary arteries are clogged, heart problems can develop.
Designer estrogens
These are drugs which have been developed to act as estrogens on some tissues and as estrogen blockers on others. An
example is called raloxifene which blocks the effects of estrogen on
the breast and uterus and acts as an estrogen on the bone.
DEXA scan
Dual x-ray absorptiometry scan. This
is an x-ray technique used to measure the amount of bone present. With
this measurement, one can determine if there is bone loss, either
osteopenia or osteoporosis.
Estradiol
This is the major female hormone, which is made primarily in the ovaries.
Estrogen
This
is a general term for female hormone. There are three specific female
hormones, which are called estradiol, estrone, and estriol. These
female hormones cause breast development of young girls and regulation
of the monthly menstrual cycle. In the absence of estrogens, several of
the symptoms of menopause occur.
FSH
Follicle
stimulating hormone. This hormone is made by the pituitary gland and
stimulates the ovary to make estrogen. When estradiol levels in the
blood become low in the pre-menopausal time of life, the pituitary
responds by increasing the levels of FSH. This serves to regulate the
menstrual cycle. At menopause, when the estrogen levels are very low
permanently, FSH rises to very high levels.
Gallbladder
This is a sac which stores bile. Bile is a substance that helps digest the food you have eaten.
Genital
A
term used to describe the external reproductive areas of a woman’s body
such as the outer and inner labia (lips) and the vagina.
Good cholesterol
A type of cholesterol that protects against heart disease. It is also called HDL cholesterol.
Hormone
A substance formed in a type of organ in the body called a gland. The hormone is then carried through the blood to another organ where it acts on that tissue in a specific manner.
Hormone replacement therapy
This treatment includes the use of estrogen plus a progestin. It can also refer to estrogen replacement alone in women who have had a hysterectomy.
HRT
The abbreviation for hormone replacement therapy
Hot flash or hot flush
When
there is a sudden flow of blood to the skin which causes a feeling of
warmth and the sensation of a hot flash. This is caused by a lack of
female hormone.
Incontinence
Loss
of urine, which occurs spontaneously and is not under voluntary
control. This can occur with increased frequency during stress, may
result in continuous leaking of small amounts of urine, or can be
intermittent and not associated with any particular situation.
Ischemic heart disease
Type of heart disease that causes heart attacks. The word ischemic refers to the lack of blood flowing to the critical areas of the heart.
LDL cholesterol
A type of cholesterol that increases the risk of heart disease. It is commonly called bad cholesterol
LH
Luteinizing
hormone. This hormone is made by the pituitary gland and stimulates the
ovary to make progesterone. When estradiol levels in the blood become
low in the pre-menopausal time of life, the pituitary responds by
increasing the levels of LH. This serves to regulate the menstrual
cycle. At menopause, when the estrogen levels are very low permanently,
LH rises to very high levels
Libido
The interest in and the urge to have sex (intimacy/sexual intercourse).
Macular degeneration
A
condition in which the portion of the back of the eye called the retina
undergoes degeneration or loss of functioning tissue. This occurs
specifically in the part of the retina, called the macula, which
controls fine vision. The first symptom of macular degeneration may be
loss of the ability to read, even with reading glasses.
MHT (menopausal hormone therapy)
This
term replaces the term, HRT or hormone replacement therapy. Menopausal
hormone therapy (MHT) is considered to be more appropriate because it is
not necessary to replace ovarian hormones in all women. In the women
who choose to take hormone therapy at menopause, MHT better describes
what they are taking.
Menopause
Time of life when the ovaries stop making estrogen and the monthly menstrual periods stop. Change of life is another way to describe menopause.
Menstrual
Refers to the process of menstruation (see below)
Menstruation
When female hormone levels fall during the monthly cycle, the lining of the uterus is shed and bleeding occurs through the vagina. Some call this a “monthly” or a monthly period.
Observational study
In
this type of study, groups of patients who are already receiving
certain therapies are carefully observed to analyze the safety and
effectiveness of one therapy compared to another. Because
there's no random selection procedure, bias may influence the results
and sometimes this type of study sometimes gives results that are
incorrect. Randomized trials are much more accurate means of testing the safety and efficacy of drugs.
Oophorectomy
Removal of the ovaries by surgery.
Osteopenia
Represents
a condition where there is a moderate loss of bone. A woman with
osteopenia has a risk of broken bones that is higher than normal but not
as high as with the more severe condition called osteoporosis. Osteopenia is detected by an X-Ray method called a DEXA scan (see above).
Osteoporosis.
This is a condition of very low amounts of bone. With this problem, there is a high frequency of broken bones, especially in the spine and hip. As
osteoporosis progresses, a woman becomes shorter in overall height
because the vertebrae in the spine collapse. The spine also becomes
curved resulting in a what is called a Widow’s Hump. Osteoporosis is detected with a radiologic method called a DEXA scan.
Ovary
One of a pair of female glands that produce eggs and the female hormones, estrogen, and progesterone. The ovary also produces male-type hormones called androgens.
Peri-menopausal Transition
Describes the approximately 2-5 years of life just before menstrual periods stop completely because of menopause. During this time, symptoms of menopause may occur but then later disappear, only to recur again.
Pituitary
The
gland that sits in the lower part of the skull just above the sinuses
in the nose. It is often called the master gland because the pituitary
controls growth via growth hormone, milk production via prolactin, the
thyroid, adrenals, and reproductive glands, including the ovaries in
women and testicles in men.
Placebo
During
a clinical trial, one group of patients is often given a “dummy pill”
which looks similar to the hormone pill used in the trial. The common
word for “placebo” which was used formerly was “sugar pill.”
Post-menopausal
Describes
the time after menopause when the monthly menstrual periods stop and
the ovaries no longer make estrogen. This condition usually continues
for the remainder of a woman’s life. In rare instances, a few menstrual
cycles return, even after they have stopped for more than one year. This
is the reason that some women are said to have “menopausal babies.”
Post-partum depression
Women
may become severely depressed starting shortly after childbirth. This
is related to the marked drop in estrogen levels after pregnancy.
Pg/milliliter
Hormone
levels in blood are usually stated to be the concentrations found in
one milliliter (ml) of blood. One milliliter is approximately 1/5 of a
teaspoon of blood. The term pg is a unit of weight using the metric system. One pg is actually 1000
billion fold lower than a gram. To indicate how small a number this is,
one kilogram is 1000 grams and one kilogram weighs 2.2 pounds.
Pre-menopausal
Describes a time of life when a woman gets monthly periods and her reproductive function is normal.
Progesterone
A
female hormone that acts on the uterus to prepare for receiving an egg
following fertilization by a sperm from a male partner. The drop in
progesterone levels each month causes the bleeding associated with
menstrual period.
Progestin
This is a synthetic form of progesterone. This
class of drugs was originally developed for use in birth control pills.
These hormones work very similarly to natural progesterone on the body.
Randomized trial
A
type of clinical trial in which 2 or more types of treatment or 1
treatment and a placebo are compared. The purpose of a randomized trial
is to eliminate bias and to learn how the treatments affect groups of
patients. A randomization process is used to assign patients to the
therapy they will receive. That decision is not made by the researchers
running the study. Randomization is a method that
determines the therapy for a participant of the study by a coin toss or
similar computer technique. The advantage of a randomized
trial is that the groups being treated usually have similar ages, ethnic
backgrounds, and risk factors. The outcomes being studied (for example
the number of heart attacks) are primarily determined by the treatments
themselves and not other factors. The randomized clinical trial is
thought to be the most accurate way of finding out information about
hormone or other therapy and is the least susceptible to potential bias.
SERM
This is a “nick name” for selective estrogen receptor modulator. Others call this class of drugs “designer estrogens.” These
agents act like estrogens on some organs such as bone but as
anti-estrogens on other organs, such as the breasts. With the right
combination of actions, these drugs could potentially increase the
benefit of estrogens without increasing their harmful effects or side
effects. At the present time, SERMs such as raloxifene are available and
others are in development. No SERM can yet do exactly all of the things
that are necessary to eliminate their side effects but in time, such
agents might become available.
Thermo-regulatory neutral zone
The
body temperature that can change without symptoms. An analogy to help
understand the concept of the thermoregulatory zone is to consider what
happens with the furnace in your house. Normally when the temperature drops by about 2°F, the furnace comes on and warms the room. When the room is sufficiently warm, the furnace goes off. The
furnace is set so that the temperature in the room must drop by about
2°F before it comes on and rise by the same amount for the furnace to
stop. If the temperature does not drop by 2 degrees, the furnace does
not go on. This two degree difference would be called the
thermo-regulatory neutral zone. As an analogy to the
menopause, the temperature in the room would only have to change by one
half degree Fahrenheit for the furnace to go on or off. The reason for
hot flashes during the menopause is that the thermo-regulatory neutral
zone is narrowed. Now only small changes in body temperature, as little
as ½ degree, will trigger hot flashes.
Thrombo-embolic
A
thrombus is a blood clot that forms in the body, usually in the deep
veins of the leg. These clots block the vein and can cause severe pain
due to the inflammation at the block, a condition called deep venous
thrombosis or DVT. When the blood clot breaks off and travels to the
lung, this is called an embolism. Together, DVT and lung embolism, are
called by the word, thrombo-embolism.
Triglyceride
A type of fat, like cholesterol, that circulates in the blood and increases the risk of heart disease.
Urogenital atrophy
This refers to two separate problems. One is genital atrophy and the other is atrophy of the urinary system. Genital atrophy means that the tissues of the vagina become thinner because of the lack of estrogen. This results in itching, pain during sexual intercourse, and a greater frequency of vaginal infection. Atrophy of the urinary system causes changes in the system that controls urination. The tissues of the urinary bladder and urethra (the tube that leads out of the bladder) become thinner. This results in more frequent release of urine, incontinence and frequent urinary symptoms or urinary system infections.
Uterus.
The organ in which a baby grows inside of a woman. The
uterus is also called the womb. The tissue that lines the uterus is
called the endometrium. During menstrual bleeding, the endometrium is
being shed.
Vagina.
The canal through which babies are born. It leads from the woman's outer sex organs into the uterus.
Vascular system.
The system of blood vessels including the arteries, veins, and capillaries that are found throughout the body.
Vasomotor instability.
A condition that causes hot flashes. The
blood vessels become unstable, a condition called vasomotor
instability, and suddenly open up to allow a large amount of blood to
flow through the skin. This results in redness of the face, a sensation of a hot flash, and the sudden sensation of warmth. These
symptoms last for 1-5 minutes followed by coldness and clamminess
because of the cooling effect of perspiration. Opening up of the blood
vessels to allow increased blood flow to the skin is a way that the body
uses to cool itself down. When the ambient temperature rises, the blood
vessels open up to allow heat to be transferred out of the body from
the skin. At the same time, sweating occurs so that evaporation causes
cooling. In menopausal women, this cooling mechanism occurs with just a
small rise in temperature rather than with the large rise necessary in
pre-menopausal women.
VTE
Veno-thrombotic
event. This refers to a problem in the veins whereby blood clots form
and cause 2 types of events; deep venous thrombosis ( blood clots in the
veins of the leg which are deep down below the skin) or blood clots
that break off and travel to the lungs (pulmonary emboli).
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