MEANING OF MENOPAUSE AND MERIT AND DEMERIT
MENOPAUSE
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Menopause
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Classification
and external resources
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Menopause is the permanent cessation of the primary functions of the
human ovaries[1]:
the ripening and release of ova and the release of hormones that
cause both the creation of the uterine lining
and the subsequent shedding of the uterine lining (a.k.a. the menses or the period). Menopause typically (but not always) occurs
in women in midlife, during their late 40s or early 50s, and signals the end of
the fertile phase of
a woman's life.[2]
The transition from reproductive
to non-reproductive is the result of a reduction in female hormonal
production by the ovaries. This transition is normally not sudden or abrupt,
tends to occur over a period of years, and is a natural consequence of aging.
However, for some women, the accompanying signs and effects that can occur
during the menopause transition years can significantly disrupt their daily
activities and sense of well-being. In addition, women who have some sort of
functional disorder affecting the reproductive system (e.g., endometriosis,
polycystic
ovary syndrome, cancer of the reproductive organs)
can go into menopause at a younger age than the normal timeframe. The
functional disorders often significantly speed up the menopausal process and
create more significant health problems, both physical and emotional, for the
affected woman.
The word "menopause"
literally means the "end of monthly cycles" from the Greek word pausis
(cessation) and the root men- (month), because the word
"menopause" was created to describe this change in human females, where the end of fertility is traditionally
indicated by the permanent stopping of monthly menstruation
or menses. However, menopause also exists in some other animals, many of which
do not have monthly menstruation;[3]
in this case, the term means a natural end to fertility that occurs before the
end of the natural lifespan.
The date of menopause in human
females is formally medically defined as the time of the last menstrual period
(or menstrual flow of any amount, however small), in those women who have not
had a hysterectomy. Women who have their uterus removed but retain their ovaries do not
immediately go into menopause, even though their periods cease. Adult women who
have their ovaries removed however, go immediately into surgical menopause, no
matter how young they are.
Menopause is an unavoidable change
that every woman will experience, assuming she reaches middle age
and beyond. It is helpful if women are able to learn what to expect and what
options are available to assist the transition, if that becomes necessary.
Menopause has a wide starting range, but can usually be expected in the age
range of 42–58.[4]
An early menopause can be related to cigarette smoking, higher body mass index,
racial and ethnic factors, illnesses, chemotherapy, radiation and the surgical
removal of the ovaries, with or without the removal of the uterus.[4]
Menopause can be officially declared
(in an adult woman who is not pregnant, is not lactating,
and who has an intact uterus) when there has been amenorrhea
(absence of any menstruation) for one complete year. However, there are many
signs and effects that lead up to this point, many of which may extend well
beyond the "official" declaration date of menopause. These include:
irregular menses, vasomotor instability (hot flashes
and night sweats), atrophy of genitourinary tissue, increased stress, breast tenderness, vaginal
dryness, forgetfulness, mood changes, and in certain cases osteoporosis
and/or heart disease.[5]
These effects are related to the hormonal changes a woman’s body is going through,
and they affect each woman to a different extent. The only sign or effect that
all women universally have in common is that by the end of the menopause
transition every woman will have a complete cessation of menses.
Age
In the Western world,
the most typical age range for menopause (last period from natural causes) is
between the ages of 40 and 61[6]
and the average age for last period is 51 years.[7]
The average age of natural menopause (in Australia) is 51.7 years,[8]
although this varies considerably from one individual to another. In India and the Philippines,
the median age of natural menopause is considerably earlier, at 44 years.[9]
Girl
before menarche
Woman of
reproductive age, see menstrual cycle
Older
woman in post-menopause
Additional
factors
On average, women who smoke cigarettes
experience menopause significantly earlier than non-smokers.[10]
Women who have undergone hysterectomy with ovary conservation go through
menopause on average 3.7 years earlier than the expected age.
Premature
menopause
In rare cases, a woman's ovaries
stop working at a very early age, ranging anywhere from the age of puberty to age
40, and this is known as premature
ovarian failure (POF). Spontaneous premature
ovarian failure affects 1% of women by age 40, and 0.1% of women by age 30. POF
is not considered to be due to the normal effects of aging. Known causes of
premature ovarian failure include autoimmune disorders, thyroid disease, diabetes mellitus,
chemotherapy,
being a carrier of the fragile X syndrome gene, and radiotherapy.
However, in the majority of spontaneous cases of premature ovarian failure, the
cause is unknown, i.e. it is generally idiopathic.[11]
POF is diagnosed or confirmed by
high blood levels of follicle
stimulating hormone (FSH) and luteinizing hormone (LH) on at least 3 occasions at least 4 weeks apart.[11]
Rates of premature menopause have been found to be significantly higher in
fraternal and identical twins; approximately 5% of twins reach menopause before the age
of 40. The reasons for this are not completely understood. Transplants of
ovarian tissue between identical twins have been successful in restoring
fertility.
Background
The menopause transition, and
postmenopause itself, is a natural life change, not a disease state or a
disorder. The transition itself has a variable degree of effects: it can be a
difficult time of life.
Menopause is perhaps most easily
understood as the opposite process to menarche, the
start of the monthly periods. However, menopause in women cannot satisfactorily
be defined simply as the permanent "stopping of the monthly periods",
because in reality what is happening to the uterus is quite secondary to the process; it is what is happening
to the ovaries that is
the crucial factor.
As an illustration of the central
role that the ovaries play, it is worth pointing out that when for medical
reasons the uterus has to be surgically removed (hysterectomy)
in a younger woman, her periods will of course cease permanently, and the woman
will be incapable of pregnancy, but as long as at least one of her ovaries
is still functioning, the woman will not have reached menopause. Even
without the presence of the uterus, ovulation
and the release of the sequence of reproductive hormones will continue to cycle
on, until menopause is reached. In contrast to this, in circumstances where a
woman's ovaries are
removed (oophorectomy), even if the uterus were to be left
intact, the woman will immediately be in "surgical menopause".
Surgical menopause is a menopause which is induced both suddenly and totally,
by removal of both ovaries prior to the age of natural menopause.
On average, assuming there has been
no surgical intervention, the first evidence of the onset of the menopause
transition time is slight variations in the length of the menstrual cycle.
These variations become more pronounced over time, and eventually lead to
cycles that can be considerably longer or considerably shorter than usual, flow
that can be significantly lighter or heavier than usual, skipped ovulations,
skipped periods, and spans of time of many months with no flow at all, after
which menstruation may resume. The transition is considered to be over once a
woman has experienced 12 months without any menstrual bleeding at all, even
though perimenopause effects may extend well beyond this point in time. The
term "perimenopause", which literally means "around the
menopause", refers to the menopause transition years, a span of time both
before and after the date of the final episode of flow.
The
hormonal context
The stages of the menopause
transition have been classified according to a woman’s reported bleeding
pattern, supported by changes in the pituitary follicle-stimulating
hormone (FSH) levels.[12]
In younger women, during a normal menstrual cycle
the ovaries produce estradiol, testosterone and progesterone
in a cyclical pattern under the control of FSH and luteinising hormone (LH) which are both produced by the pituitary gland.
Blood estradiol
levels remain relatively unchanged, or may increase approaching the menopause,
but are usually well preserved until the late perimenopause. This is presumed
to be in response to elevated FSH levels.[13]
However, the menopause transition is characterized by marked, and often
dramatic, variations in FSH and estradiol levels, and because of this,
measurements of these hormones are not considered to be reliable guides
to a woman's exact menopausal status.[14]
Menopause is based on the natural or
surgical cessation of estradiol and progesterone production by the ovaries,
which are a part of the body's endocrine system
of hormone
production, in this case the hormones which make reproduction possible and
influence sexual behavior. After menopause, estrogen continues to be produced
in other tissues, notably the ovaries, but also in bone, blood vessels and even
in the brain.[15]
However the dramatic fall in circulating estradiol levels at menopause impacts
many tissues, from brain to skin.
In contrast to the sudden fall in
estradiol during menopause, the levels of total and free testosterone,
as well as dehydroepiandrosterone
sulfate (DHEAS) and androstenedione
appear to decline more or less steadily with age. An effect of natural
menopause on circulating androgen levels has not been observed.[16]
Thus specific tissue effects of natural menopause cannot be attributed to loss
of androgenic hormone production. However, women who have had their ovaries
surgically removed, who have had their ovaries damaged by chemotherapy or
radiotherapy, or who have ovarian gonadotropin suppression, do have loss of
ovarian androgen production as a result.
Menopause can be surgically induced
by bilateral oophorectomy (removal of ovaries), which is often, but not always, done
in conjunction with removal of the Fallopian tubes (salpingo-oophorectomy) and uterus (hysterectomy).
Cessation of menses as a result of removal of the ovaries is called
"surgical menopause". The sudden and complete drop in hormone levels
usually produces extreme withdrawal symptoms such as hot flashes, etc. Removal
of the uterus without removal of the ovaries, a hysterectomy, does not cause
menopause, although pelvic surgery can often precipitate a somewhat earlier
menopause, perhaps because of a compromised blood supply to the ovaries.
Terminology
There is some overlap in the meaning
of the various terms used to refer to menopause and the menopause transition
years. In addition some of the terms are used differently in common parlance
than they are by medical professionals.
Menopause
Clinically speaking, menopause is
tied to a specific date. Assuming the woman still has a uterus, menopause is
defined as the day after her final episode of menstrual flow finishes. This
date is fixed retrospectively, once 12 months have gone by with no menstrual
flow at all. At this point a woman is considered to be a year into
postmenopause, is considered to be infertile, and no longer needs to take into
consideration the possibility of pregnancy.
In common parlance, however, the
word "menopause" usually refers not to one day, but to the whole of
the menopause transition years. This span of time is also commonly called the change
of life, the change, or the climacteric and more recently is
known as "perimenopause", (literally meaning "around
menopause").
The word menopause is also often
used in popular parlance to mean all the years of postmenopause.
Perimenopause
Perimenopause is the term used to
describe the menopause transition years. In women who have a uterus,
perimenopause describes the years before and after the final period (although
it is only possible to determine in retrospect which episode of flow was indeed
the final period). As a medical convenience, perimenopause is technically
defined as the time from which menses start to become irregular and FSH levels
have increased, until the time when it is known that periods have ceased
completely. However, the hormonal changes are gradual, both in onset and in
termination, and therefore the various possible perimenopause effects often
start before and continue after this neatly defined time slot.
During perimenopause, the ovarian
production of the estrogens and progesterone
becomes more irregular, often with wide and unpredictable fluctuations in
levels. During this period, fertility diminishes, but is not considered to
reach zero until the official date of menopause. The official date is
determined retroactively, once 12 months have passed after the last appearance
of menstrual blood.
Signs and effects of the menopause
transition can begin as early as age 35, although most women become aware of
the transition in their mid to late 40s, often many years after the actual
beginning of the perimenopausal window. The duration of perimenopause with
noticeable bodily effects can be as brief as a few years, but it is not unusual
for the duration to last ten or more years. The actual duration and severity of
perimenopause effects for any individual woman currently cannot be predicted in
advance. Even during the process, the course of an individual woman's
perimenopause can be difficult if not impossible to predict.
During the perimenopause years, many
women undergo noticeable and clinically observable physical changes resulting
from hormonal fluctuations. The most well-known of these is the "hot
flash" or "hot flush", a sudden temporary increase in body
temperature. The "flash" sensation in a "hot flash" occurs
as the body temperature soars upward, reaching a peak very rapidly. The
"hot" sensation in a "hot flash" is not the initial temperature
rise; instead, it is a reaction to the slowness of the body's return to a more
normal temperature range.
Hot flashes can be so strong that
they raise the body temperature multiple degrees in a very short period of
time; this extreme temperature differential can cause the sufferer to feel weak
and break out in heavy sweating. Despite the discomfort to the woman, hot
flashes are not considered harmful by physicians. In most cases, flashes can be
treated to ease extreme discomfort, using prescription medications such as hormone
replacement therapy (HRT) or SSRI medications, or by using over-the-counter plant estrogens
and herbal remedies. Many women manage hot flashes by dressing in ways that
dissipate heat quickly (natural fibers, loose clothing, easily removable layers
of lightweight garments) as well as mechanical means which help the body to
remove excess heat, such as fans, drinking ice water, and staying in cool
rooms.
Other common effects encountered
during the perimenopausal period include mood changes, insomnia, fatigue, and memory problems.
Menopause may, in some women, bring
about a sense of loss related to the end of fertility. In addition this change
often occurs at a time of life when other stressors may be present in the life
of a woman:
- Having to deal with caring for, and/or the death of, elderly parents
- The so-called "empty-nest syndrome" when children leave home
- The birth of grandchildren, which places people of "middle age" into a new category of "older people" (especially in those cultures where being older is a state that is not venerated but looked down on)
Recent research shows that melatonin
supplementation in perimenopausal women can produce a significant improvement
in thyroid function and gonadotropin levels, as well as restoring fertility and
menstruation and preventing the depression associated with the menopause.[17]
Premenopause
Premenopause is a word used to
describe the years leading up to the last period, when the levels of
reproductive hormones are already becoming lower and more erratic, and the
effects of hormone withdrawal may be present.
Postmenopause
The term postmenopause is
applied to women who have not experienced a menstrual bleed for a minimum of 12
months, assuming that they do still have a uterus, and are not pregnant or lactating.
In women without a uterus, menopause or postmenopause is identified by a very
high FSH level. Thus postmenopause is all of the time in a woman's life that
take place after her last period, or more accurately, all of the time that
follows the point when her ovaries become inactive.
A woman who still has her uterus
(and who is neither pregnant nor lactating) can be declared to be in
postmenopause once she has gone 12 full months with no flow at all, not even
any spotting. When she reaches that point, she is one year into postmenopause.
The reason for this delay in
declaring a woman postmenopausal is because periods are usually extremely
erratic at this time of life, and therefore a reasonably long stretch of time
is necessary to be sure that the cycling has actually ceased completely.
At this point a woman is considered
infertile, and no longer needs to factor in the possibility of becoming
pregnant. However the possibility of becoming pregnant has usually been very
low (but not zero) for a number of years before this point is reached.
In women who have no uterus, and
therefore have no periods, post-menopause can be determined by a blood test
which can reveal the very high levels of Follicle
Stimulating Hormone (FSH) that are typical of
post-menopausal women.
A woman's reproductive hormone
levels continue to drop and fluctuate for some time into post-menopause, so any
hormone withdrawal symptoms that a woman may be experiencing do not necessarily
stop right away, but may take quite some time, even several years, to disappear
completely.
Any period-like flow that might
occur during postmenopause, even just spotting, must be reported to a doctor. The
cause may in fact be minor, but the possibility of endometrial cancer must be checked for and eliminated.
Indications
and signs
During the menopause transition
years, as the body responds to the rapidly fluctuating and dropping levels of
natural hormones, a number
of effects may appear. Not every woman experiences bothersome levels of these
effects; the range of effects and the degree to which they appear is very
variable from person to person.
Effects that are due to low estrogen
levels (for example vaginal atrophy and skin drying) will continue after the
menopause transition years are over; however, many effects that are caused by
the extreme fluctuations in hormone levels (for example hot flashes and mood
changes) usually disappear or improve significantly once the perimenopause
transition is completely over. All the various possible perimenopause effects
are caused by an overall drop, as well as dramatic but erratic fluctuations, in
the absolute levels and relative levels of estrogens and progesterone. Effects
such as formication (crawling, itching, or tingling skin sensations), may be
associated directly with hormone withdrawal.
Both users and non-users of hormone
replacement therapy identify lack of energy as the most
frequent and distressing effect.[18]
Other effects can include vasomotor
symptoms such as hot flashes and palpitations,
psychological effects such as depression, anxiety, irritability, mood swings,
memory problems and lack of concentration, and atrophic effects such as vaginal
dryness and urgency of urination.
The average woman also has
increasingly erratic menstrual periods, due to skipped ovulations. Typically,
the timing of the flow becomes unpredictable. In addition the duration of the
flow may be considerably shorter or longer than normal, and the flow itself may
be significantly heavier or lighter than was previously the case, including
sometimes long episodes of spotting. Early in the process it is not uncommon to
have some 2-week cycles. Further into the process it is common to skip periods
for months at a time, and these skipped periods may be followed by a heavier
period. The number of skipped periods in a row often increases as the time of
last period approaches. At the point when a woman of menopausal age has had no
periods or spotting for 12 months, she is considered to be one year into
post-menopause.
One way of assessing the impact on
women of some of these menopause effects is the Greene Climacteric Scale questionnaire.
Vascular instability
- Hot flashes or hot flushes, including night sweats and, in a few people, cold flashes
- Possible but contentious increased risk of atherosclerosis[19]
- Migraine
- Rapid heartbeat
Urogenital atrophy, also known as vaginal atrophy
Main article: Atrophic vaginitis
- Thinning of the membranes of the vulva, the vagina, the cervix, and also the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas.
- Itching
- Dryness
- Bleeding
- Watery discharge
- Urinary frequency
- Urinary incontinence
- Urinary urgency
- Increased susceptibility to inflammation and infection, for example vaginal candidiasis, and urinary tract infections
Skeletal
- Back pain
- Joint pain, Muscle pain
- Osteopenia and the risk of osteoporosis gradually developing over time
Skin, soft tissue
- Breast atrophy
- breast tenderness +/- swelling
- Decreased elasticity of the skin
- Formication (itching, tingling, burning, pins and needles, or sensation of ants crawling on or under the skin)
- Skin thinning and becoming drier
Psychological
- Depression and/or anxiety
- Fatigue
- Irritability
- Memory loss, and problems with concentration
- Mood disturbance
- Sleep disturbances, poor quality sleep, light sleep, insomnia and sleepiness[20][21]
Sexual
- Dyspareunia or painful intercourse
- Decreased libido
- Problems reaching orgasm
- Vaginal dryness and vaginal atrophy
Cohort studies have reached mixed conclusions about medical conditions
associated with the menopause. For example, a 2007 study found that menopause
was associated with hot flashes; joint pain and muscle pain;
and depressed mood.[22]
In the same study, it appeared that menopause was not associated with poor
sleep, decreased libido, and vaginal dryness.[22]
However, in contrast to this, a 2008 study did find an association with poor
sleep quality.[23]
Cause
The causes of menopause can be
considered from complementary proximate (mechanistic) perspectives (how it happens) or from
ultimate (adaptive evolutionary) perspectives (why it happens). The latter
group are hypotheses only.
Proximate
perspective
Natural or physiological menopause
occurs as a part of a woman's normal aging process. It is the result of the
eventual depletion of almost all of the oocytes and ovarian follicles[24]
in the ovaries. This causes an increase in circulating follicle
stimulating hormone (FSH) and luteinizing hormone (LH) levels because there are a decreased number of oocytes and follicles responding to these hormones and producing
estrogen. This decrease in the production of estrogen leads to the
perimenopausal symptoms of hot flashes, insomnia and mood changes. Long term
effects may include osteoporosis and vaginal atrophy.
Adaptive
hypotheses
The
mother hypothesis
The mother hypothesis suggests that
menopause was selected for in humans because of the extended development period
of human offspring and high costs of reproduction so that mothers gain an
advantage in reproductive fitness by redirecting their effort from new
offspring with a low survival chance to existing children with a higher
survival chance.[31]
The
grandmother hypothesis
The Grandmother hypothesis suggests that menopause was selected for in humans because
it promotes the survival of grandchildren. According to this hypothesis, post reproductive
women feed and care for children, adult nursing daughters, and grandchildren
whose mothers have weaned them. Human babies require large and steady supplies
of glucose to feed the growing brain. In infants in the first year of life, the
brain consumes 60% of all calories, so both babies and their mothers require a
dependable food supply. Some evidence suggests that hunters contribute less
than half the total food budget of most hunter-gatherer societies, and often
much less than half, so that foraging grandmothers can contribute substantially
to the survival of grandchildren at times when mothers and fathers are unable
to gather enough food for all of their children. In general, selection operates
most powerfully during times of famine or other privation. So although
grandmothers might not be necessary during good times, many grandchildren
cannot survive without them during times of famine. Arguably, however, there is
no firm consensus on the supposed evolutionary advantages (or simply neutrality)
of menopause to the survival of the species in the evolutionary past.
Indeed, analysis of historical data
found that the length of a female’s post-reproductive lifespan was reflected in
the reproductive success of her offspring and the survival of her grandchildren.[32]
Interestingly, another study found comparative effects but only in the maternal
grandmother – paternal grandmothers had a detrimental effect on infant
mortality (probably due to paternity uncertainty).[33]
Differing assistance strategies for maternal and paternal grandmothers have
also been demonstrated. Maternal grandmothers concentrate on offspring
survival, whereas paternal grandmothers increase birth rates.[34]
A problem concerning the grandmother
hypothesis is that it requires a history of female philopatry
and yet present day evidence shows that the majority of hunter-gatherer
societies are patriarchal.[35]
In addition, all variations on the mother, or grandmother effect fail to
explain longevity with continued spermatogenesis in males (oldest verified
paternity is 94 years, 35 years beyond the oldest documented birth attributed
to females).[36]
It also fails to explain the detrimental effects of losing ovarian follicular
activity, such as osteoporosis, osteoarthritis,
Alzheimer’s disease and coronary artery disease.[37]
Management
Perimenopause is a natural stage of
life. It is not a disease or a disorder, and therefore it does not
automatically require any kind of medical treatment at all. However, in those
cases where the physical, mental, and emotional effects of perimenopause are
strong enough that they significantly disrupt the everyday life of the woman
experiencing them, palliative medical therapy may sometimes be appropriate.
Hormone
replacement therapy
In the context of menopause Hormone
replacement therapy or HRT, known in Britain as
Hormone Therapy or HT, refers to the use of estrogen plus progestin
for a woman who has an intact uterus, or estrogen alone for a woman who has had
a hysterectomy.[38]
Traditionally such therapy was provided as tablets but now is available in a
range of formulations including skin patches, gels, skin sprays, subcutaneous
implants and so forth. A popular alternative to conventional HRT is a synthetic
hormone (derived from the Mexican yam) called tibolone. Of the
non hormonal therapies for hot flushes, some of the SSRIs appear to provide some pharmaceutical relief.[39]
Adverse effects of HRT appear to vary according to formulation and dose. See
the section below on "Adverse effects of conjugated equine
estrogens".
In addition to relief from hot
flashes, hormone therapy can alleviate vaginal dryness, improve sleep quality
and joint pain. It is also extremely effective for preventing bone loss and osteoporotic
fracture.[40]
A woman and her doctor should
carefully review her situation, her complaints and her relative risk before
determining whether the benefits of HT/HRT or other therapies outweigh the
risks. Until more becomes understood about the possible risks, women who elect
to use hormone replacement therapy are generally well advised to take the
lowest effective dose of hormones for the shortest period possible, and to
question their doctors as to whether certain forms might pose fewer dangers of
clots or cancer than others.
Until recently the most widely used
estrogen preparation worldwide in postmenopausal women was oral conjugated equine estrogens. Other oral oestrogen preparations include synthetically
derived piperazine estrone sulphate, estriol, micronised estradiol and
estradiol valerate. Estradiol may also be used transdermally as a patch or gel,
as a slow release percutaneous implant, and more recently as a metered dose
skin spray. Intravaginal estrogens include topical estradiol in the form of a
ring or pessary, estriol in pessary or cream form, dienoestrol and conjugated
oestrogens in the form of creams. Oral micronised estradiol and other oral
estrogen preparations may result in up to 10 fold higher levels of circulating estrone
sulphate than transdermally administered
estradiol at comparable or even higher doses.[41]
This is of concern in that estrogen sensitive tissues such as breast and endometrium
have high capacity to metabolise estrone sulphate through to estradiol. Orally
administered estrogen therapy also increases sex
hormone binding globulin (SHBG) to
a greater extent than non orally administered estrogens. SHBG binds estrogen
and testosterone in the blood and this may result in a clinically significant
reduction in the bioavailability of these hormones. Thus it would seem that the
prescription of oral estrogen therapy should be at the lowest available dose to
minimise effects on circulating estrone sulphate and SHBG.
In those women who have no uterus
(usually due to a previous hysterectomy), estrogen alone is a suitable hormone
therapy and is in fact preferable to continuing to use progesterone when its
function as a moderating influence on growth of the endometrium
(uterine lining) is no longer required. Women who still have a uterus need to
take progesterone in addition to estrogen to protect against the
development of endometrial hyperplasia and endometrial carcinoma.
Oral administration of progesterone
is convenient, however the oral micronised form is rapidly metabolized and
inactivated in the liver, therefore high doses must be administered to achieve
adequate circulating blood levels. Synthetic progestins
have been developed and are prescribed to overcome this problem. Synthetic
progestins are more resistant to liver metabolism, therefore lower doses can be
used to achieve the desired endometrial effect. It is not uncommon for women to
experience side effects with progesterone or progestin therapy. Progesterone
may cause sedation so is best taken at bedtime.[42]
Synthetic progestins may cause irritability and mood changes in some women.[43]
Conjugated
equine estrogens
See also: Types
of Hormone Replacement Therapy
Conjugated equine estrogens contain
estrogen molecules conjugated to hydrophilic
side groups (e.g. sulfate) and are produced from the urine of pregnant Equidae
(horses) mares. Premarin is the prime example of this, either alone or in
Prempro, where it is combined with a synthetic progestin, medroxyprogesterone
acetate.
Women had been advised for many
years by numerous doctors and drug company marketing efforts (at least in the
USA) that hormone therapy with conjugated equine estrogens after menopause
might reduce their risk of heart disease
and prevent various aspects of aging. However, a large, randomized, controlled
trial (the Women's
Health Initiative) found that women undergoing HT or
HRT with conjugated equine estrogens (Premarin), in
combination with a synthetic progestin (medroxy pogesterone acetate (Premarin
plus Provera, known as Prempro)), had an increased risk of breast cancer
and heart disease.[44]
An increase in breast cancer risk was not seen in the Women's Health Initiative
study of conjugate estrogen alone (Premarin) versus placebo, however this study
was stopped prematurely as an increased risk of stroke was observed in women
treated with Premarin.[45]
Although this increase in risk was small overall, it passed the thresholds that
had been established by the researchers in advance as sufficient to ethically
require stopping the study.
When these results were first
reported in 2002, the popular media sensationalized the story and exaggerated
the risk, while the manufacturer continued to attempt to minimize the degree of
risk. However most news stories failed to mention that the average age of the
women in WHI was 62 years old, significantly older than the time when most
women start HRT, and in fact many years into postmenopause. To enroll in the
study, patients had to be asymptomatic
of hot flashes, so they would not know whether they received the placebo. For
these reasons, WHI was not representative of generally accepted clinical
practice.
The 2002 and 2003 announcements of
the Women's Health Initiative of the American National Institute of Health and The Million Women Study of the UK
Cancer Research and National Health Service collaboration respectively, that HRT treatment coincides
with an increased incidence of breast cancer, heart attacks and strokes, lead
to a sharp decline in HRT prescription throughout the world,[46][47][48]
which was followed by a decrease in breast cancer incidence.[49][50]
On hearing the news about the WHI
study, many women discontinued equine estrogens altogether, with or without
their doctor's knowledge. The number of prescriptions written for Premarin and
PremPro in the United States dropped within a year almost to half of their
previous level. This sharp drop in usage was followed by large and successively
larger drops in new breast cancer diagnoses, at six months, one year, and 18
months after the drop in Premarin and Prempro prescriptions, for a cumulative
15% drop by the end of 2003. However, the apparent meaning of this correlation
is called into question by the fact that prescriptions of Prempro and Premarin
fell dramatically in Canada as well, but no similarly dramatic drop in Canada's
breast cancer rates was observed during the same time period. Studies
designed to track the further progression of this trend after 2003 are under
way, as well as studies designed to quantify how much of the drop was related
to the reduced use of HT/HRT.[45]
The WHI study results have created a
new scenario for postmenopausal women.[51]
Researchers at The University of
North Carolina at Chapel Hill are currently undergoing a study to determine if
estrogen replacement therapy can improve cardiovascular health and prevent
depression in perimenopausal women between the ages of 45 and 55.[52]
Dr. David Rubinow, UNC's chair of Psychiatry, and one of two principal
investigators on the NIH-funded 5-year study, notes there is a very important
difference between the UNC study and the WHI estrogen study. Dr. Rubinow states
that “the Women’s Health Initiative study led to the mistaken belief that
estrogen replacement therapy is bad for all women. And as a result, it has
served to deprive some women of a treatment that might greatly and favorably
impact their lives. Much of the negative impact of estrogen that they found was
related to the fact that most of the women in the Women’s Health Initiative
study were far past the menopause and up to 79 years old.” Dr. Rubinow
continues by explaining that “there are now a large number of studies that
demonstrate what has been called the timing hypothesis. That is, giving
estrogen within a year or two of menopause has beneficial effects, but giving
estrogen in women more than five years beyond the menopause can actually be
harmful. When the women who were close to menopause were looked at separately,
the adverse effects on the heart were not seen and in fact some suggestion of
beneficial effects was seen. Perimenopausal women in the Women’s Health
Initiative who received estrogen had significantly lower coronary artery
calcification compared to the women who didn’t take estrogen.” As Dr. Rubinow
states, “given the mortality and morbidity associated with depression and heart
disease, and the tremendous increase in risk of these disorders during the
perimenopause, it is critical that we identify those women who will be helped
by estradiol.”[53]
Antidepressants
Antidepressants such as paroxetine
(Paxil), Fluoxetine
hydrochloride (Prozac), and Venlafaxine
hydrochloride (Effexor) have
been used with some success in the treatment of hot flashes, improving sleep,
mood, and quality of life. Paroxetine and venlafaxine may cause nausea and
insomnia. In addition, venlafaxine may cause dry mouth, constipation and
decreased appetite whereas paroxetine may cause headaches. There is a
theoretical reason why SSRI antidepressants might help with memory problems: they
increase circulating levels of the neurotransmitter serotonin
in the brain and restore hippocampal function.[62]
Fluoxetine
hydrochloride (Sarafem) is also prescribed for premenstrual
dysphoric disorder (PMDD), a mood disorder often
exacerbated during perimenopause. PMDD has been found by PET scans to be
associated with dysregulation of serotonin pathways in the brain[63] and
to respond quickly and powerfully to SSRIs[citation
needed].
.[ Blood pressure medicines
Blood pressure medicines including clonidine
(Catapres) are about as effective as antidepressants for hot flashes, but do
not have the other mind and mood benefits of antidepressants. However they may
merit special consideration by women suffering both from high blood pressure
and hot flashes.[65]
Alternative
medicine
It is important to examine the claim
that herbal remedies help relieve menopausal symptoms.[66]
Some botanical sources, referred to as phytoestrogens,
do not simply mimic the effects of human steroidal estrogen but exhibit both
similar and divergent actions. The ultimate actions of these compounds in
specific cells is determined by many factors including the relative levels of
the estrogen receptors ER alpha and beta and the diverse mix of coactivators
and corepressors present in any given cell type. Thus they have been described
to act somewhat like selective
estrogen receptor modulators
(SERMs). Effects vary according to the phytoestrogen studied, cell line,
tissue, species and response being evaluated.[67]
Systematic reviews of intervention
studies question the validity of the proposed benefits of phytoestrogen
supplementation, with little data in postmenopausal women to support a role for
phytoestrogens as an alternative for conventional HT.[68]
Femarelle
is a mixture of DT56a soy derivative and ground flaxseed at a ratio of 3:1, for
oral administration. Each capsule contains 344 mg soy and 108 mg
flaxseed – altogether 430 mg powder. It is being promoted for the treatment
of menopause and prevention of bone loss and has
also been described as having SERM qualities,[69]
thereby reducing the safety risks involved in estrogenic-like treatments[citation
needed]. In 2008 the European Food Safety Authority concluded that
"a cause and effect relationship has not been established between the
consumption of Femarelle and increased BMD, increased bone formation, or
decreased risk of osteoporosis or other bone disorders in post-menopausal
women.".[70]
In the area of complementary and alternative
therapies, acupuncture and acupressure treatments are promising. Numerous studies
indicate positive effects, especially on hot flashes[71][72]
[73]
but also others[74]
showing no positive effects of acupuncture regarding menopause.
There are regular claims that soy
isoflavones are beneficial concerning some symptoms of menopause. Isoflavones
are naturally occurring compounds, and daidzein and genistein are the main
isoflavones found in soy.[75]
After consuming soy containing daidzein some, but not all, humans produce S-equol
(7-hydroxy-3-(49-hydroxyphenyl)-chroman),[76]
which may have some health benefits, particularly the reduction of some
menopausal symptoms.
The ability to transform daidzein
into S-equol is based on the presence of certain intestinal bacteria. In
fact, several studies indicate that only 25 to 30 percent of the adult
population of Western countries produces S-equol after eating soy foods
containing isoflavones,[77][78][79][80]
significantly lower than the reported 50 to 60 percent frequency of
equol-producers in adults from Japan, Korea or China.[81][82][83][84]
S-equol is not of plant origin. Kenneth D. R. Setchell, Ph.D., et al.,
proposed in 2002 that S-equol had potential for disease prevention and
treatment. The scientists stated "There is good rationale for expecting
greater efficacy in equol-producers because equol binds with greater affinity
to estrogen receptor than daidzein."[85]
Recent human clinical studies showed
that S-equol provided as a standardized soygerm-based dietary supplement
helped reduce menopausal symptoms, bone loss and crow’s feet skin wrinkles in
menopausal women. Studies of Japanese postmenopausal women documented that
those who can produce S-equol after soy consumption had milder menopause
symptoms than those who were equol nonproducers.[86][87]
Key basic animal and human studies, in both women in Japan and the United
States, have documented the efficacy and safety of the soygerm-based supplement
containing S-equol to modify menopause symptoms, particularly the
reduction of the severity and frequency of hot flashes and neck and shoulder
stiffness.[88][89][90][91]
However, one study[92]
indicated that soy isoflavones did not improve or appreciably affect cognitive
functioning in postmenopausal women.
Other remedies which work in some
studies, but in other studies[citation
needed] appear to be no better than a placebo,[93][94]
include red clover isoflavone extracts and black cohosh.
Black cohosh (Cimicifuga racemosa, also known as Actaea racemosa)
is a North American native plant. It has common usage internationally for the
treatment of hot flushes and sweats experienced by postmenopausal women.
However, study results do not support a benefit of black cohosh for the
treatment of menopausal symptoms.[94]
Black cohosh has been associated with reports of acute liver toxicity[95] and a
concern has been raised regarding the stimulation of pre-existing breast cancer
based on an animal study.[96]
One study found, black cohosh and red clover, when compared to a placebo, did
not reduce the number of vasomotor symptoms, although safety monitoring
indicated that chemically and biologically standardized extracts of black
cohosh and red clover were safe during daily administration for 12 months.[97]
Another study reported that black cohosh used in isolation, or as part of a
multibotanical regimen, had little potential to relieve vasomotor symptoms.[98]
More promising data from an emerging
treatment comprising a multibotanical compound MF-101 (trade name Menerba) can
be located here Menerba
Education
Many women arrive at their menopause
transition years without knowing anything about what they might expect, or when
or how the process might happen, and how long it might take. Very often a woman
has not been informed in any way about this stage of life; at least in the US,
it may often be the case that she has received no information from her
physician, or from her older female family members, or from her social group.
In the US, there appears to be a lingering taboo which hangs over this subject. As a result, a woman who
happens to undergo a strong perimenopause with a large number of different
effects, may become confused and anxious, fearing that something abnormal is
happening to her. There is a strong need for more information and more
education on this subject.[18]
Other
therapies
- Lack of lubrication is a common problem during and after perimenopause. Vaginal moisturizers can help women with overall dryness, and lubricants can help with lubrication difficulties that may be present during intercourse. It is worth pointing out that moisturizers and lubricants are different products for different issues: some women feel unpleasantly dry all of the time apart from during sex, and they may do better with moisturizers all of the time. Those who need only lubricants are fine just using the lubrication products during intercourse.
- Low-dose prescription vaginal estrogen products such as estrogen creams are generally a safe way to use estrogen topically, to help vaginal thinning and dryness problems (see vaginal atrophy) while only minimally increasing the levels of estrogen in the bloodstream.
- In terms of managing hot flashes, lifestyle measures, such as drinking cold liquids, staying in cool rooms, using fans, removing excess clothing layers when a hot flash strikes, and avoiding hot flash triggers such as hot drinks, spicy foods, etc., may partially supplement (or even obviate) the use of medications for some women.
- Individual counseling or support groups can sometimes be helpful to handle sad, depressed, anxious or confused feelings women may be having as they pass through what can be for some a very challenging transition time.
- Osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise. The bisphosphate drug alendronate can help prevent loss of bone mass, reducing the risk of fractures, according to a Cochrane review of studies. This applies both to women that have suffered bone loss but have not yet suffered fractures, and women that have suffered both bone loss and fractures.[99]
- The risk of acute myocardial infarction and other cardiovascular diseases rises sharply after menopause, but the risk can be reduced by managing risk factors, such as tobacco smoking, hypertension, increased blood lipids and body weight.[100][101]
Society
and culture
The cultural context within which a
woman lives can have a significant impact on the way she experiences the
menopausal transition. Within the United States, social location affects the
way women perceive menopause and its related biological effects. Research
indicates that whether a woman views menopause as a medical issue or an
expected life change is correlated with her socio-economic status.[102]
The paradigm within which a woman considers menopause also influences the way
she views it: women who understand menopause as a medical condition rate it
significantly more negatively than those who view it as a life transition or a
symbol of aging.[103]
Ethnicity and geographical location
also play a role in the experience of menopause. U.S. women of different
ethnicities report significantly different types of menopausal effects. One
major study found Caucasian women most likely to report what are sometimes
described as psychosomatic symptoms, while African-American women were more
likely to report vasomotor symptoms.[104]
Additionally, while most women in the United States have a negative view of
menopause as a time of deterioration or decline, some studies seem to indicate
that Asian women have an understanding of menopause that focuses on a sense of
liberation, and celebrates the freedom from the risk of pregnancy.[105]
Diverging from these conclusions however, one study appeared to show that many
U.S. women "experience this time as one of liberation and
self-actualization."[106]
Postmenopausal Indian women can enter Hindu temples and participate in rituals,
marking it as a celebration for reaching an age of wisdom and experience.
Generally speaking, women raised in
the Western world live long enough so that a third of their life is spent in
post-menopause. For some women, the menopausal transition represents a major
life change, similar to menarche in the magnitude of its social and psychological
significance. Although the significance of the changes that surround menarche
is fairly well recognized, in countries such as the USA, the social and
psychological ramifications of the menopause transition are frequently ignored
or underestimated.[citation
needed]
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