For a
good understanding of menopause, it is important to know something of the
workings of the human female body.
Essential female organs
Anatomically
the female internal genitalia lie in the pelvic cavity on the pelvic floor. The
pelvic floor is the lower part of the female body surrounded by a group of
bones, one on either side, called the pelvic bones. These bones are covered by
muscles, fascia and skin, like a thick curtain separating the inside organs
from the outside world. These tissues make up the pelvic floor. The main organ
the uterus (which carries the pregnancy) lies on the pelvic floor. In front of
the uterus lies the urinary bladder. The bladder tube, called the urethra,
opens in front of the vagina. Behind the uterus lies the last part of the bowel
called the rectum. Its outside opening, the anus, lies behind the vaginal
opening. The uterus is kept in place by many rope like tissues called ligaments
which are attached to the pelvic bones like ropes securing a tent to its pegs.
Childbirth weakens the pelvic floor and contributes to prolapse (falling down)
of the pelvic organs: the bladder, uterus and rectum. (More pictures)
The Ovaries and the
Fallopian tubes
The
ovaries are the two female sex glands lying on either side of the uterus
attached to it by ligaments and fallopian tubes.
The
ovaries are grayish yellow in colour and solid, generally the size of a
hazelnut but with variation depending on their dynamic state, due to various
stages of maturing follicles. The two fallopian tubes are a connecting link
between the uterus and the ovary. The free end of the fallopian tube is like a
octopus tentacles shielding the ovary, so that as soon as an egg is released from
the ovary it is directed into the tube where it meets its mate the sperm. The fertilization
takes place and the fertilized egg is deposited into the uterus which is
prepared to receive it.
Externally,
the genital organs are the opening of the vagina and the surrounding folds of
skin. The vagina is protected by a perforated membrane called the hymen. The
vaginal opening is surrounded by two little folds of skin called the labia
minora. Where these folds join is a small cylindrical projection called the
clitoris. Richly supplied with blood vessels and nerves, the clitoris is
subject to arousal. The labia minora are surrounded by two further folds of
skin on either side called the labia majora. Like the labia minora, they become
thin (atrophic) with age and because of the declining oestrogen supply.
The
Bartholins glands, one on each side of the opening of the vagina, secrete
fluids during sexual activity which further helps to lubricate the vaginal
area.
Endocrine glands and
hormones
Most
bodily functions are controlled by natural chemicals — hundreds of them. One
group of chemicals, called hormones, is secreted by specialised glands, the
endocrines. These hormones are carried to distant organs via the blood stream
where they exert their influence.
They
influence activities such as the regulation of body temperature, metabolism,
repair, growth and reproduction. A proper balance of hormones is important in
maintaining our mental and physical wellbeing. Significant or prolonged
disturbances in this finely tuned hormone balance may result in endocrine
disorders such as menstrual irregularities, infertility, diabetes or the
swelling of the thyroid gland. Many medical experts feel that menopause is also
an endocrine disorder, since the oestrogen deficiency that occurs after
menopause differs so markedly from the premenopausal state. Others argue that
the loss of oestrogen production after menopause is a natural part of the
ageing process.
In the human body there are seven
main endocrine glands and many hormones. Located deep in the brain is the
region called the hypothalamus which influences functions such as body temperature
control, the wake and sleep cycle, blood pressure, water balance, sweat
secretion and sexual behavior. It also produces hormones which control the
activity of another endocrine gland called the pituitary gland situated nearby.
The pituitary in turn influences the activities of other endocrine glands
including the thyroid, adrenals and the ovaries. For this reason the pituitary
is often called the master gland.
The
thyroid gland is located in the neck. It is responsible for maintaining many
aspects of the body’s metabolism or chemistry; it is the energy control mechanism.
This gland can become over or under active causing women to be over active or
slow and tired. These disorders often occur at the time of menopause.
Embedded
in the thyroid gland are four parathyroid glands which help to maintain proper
blood levels of calcium, and therefore play a role in the maintenance of bone
calcium and bone density. The cells responsible for secretion of insulin which
controls blood sugar levels are located in the pancreas and are called the
Islets of Langerhans.
Lack of
insulin causes diabetes. Menopause is sometimes said to be analogous to
diabetes, since the lack of oestrogen and lack of insulin both adversely affect,
many parts of our body.
There are
two adrenal glands, one located on the top of each kidney. They secrete several
hormones which influence salt and fluid balance, blood pressure, skin
pigmentation and the body’s response to stress. Small amounts of male sex
hormones, androgens, are also produced in the adrenals of men and women. These
can be converted to oestrogens in the body fat of women, and represent the main
source of oestrogens in women after menopause.
The main
hormones involved in menopause are called sex hormones, and are secreted by
specialised endocrines called sex glands: ovaries in women and testes in men.
The ovaries
Women have two ovaries. If one is
not working, the other can carry out the complete function of both. This
amazing organ lies dormant until puberty at which time it becomes constantly
active creating regular monthly cycles extending over thirty to forty years.
This activity finally comes to an end at menopause.
The
ovaries’ function is to facilitate and maintain pregnancy, and they do so by
secreting oestrogens and progesterone. This function is realised through the
complex menstrual cycle which is also influenced by hormones from the
hypothalamus and the pituitary gland. Ovaries also secrete small amounts of the
male hormones, androgens.
Each
ovary consists of two layers, the outer cortex and the inner medulla. The
outer-most layer of the cortex forms a covering which has a supporting mesh
called the stroma. In the stroma, along with blood vessels and nerves, are
scattered immature eggs called primordial follicles. In the developing foetus,
the first sign of ovarian formation appears around six to eight weeks after
conception. At this time, millions of primordial follicles are stored in the
fetal ovary. By twenty weeks of foetal life there are seven to ten million
primordial follicles which are rapidly reduced to two million at birth and then
slowly reduced to three to four hundred thousand at puberty. Some forty years
later only a few hundred follicles are left, and these are incapable of maturation
or hormone secretion.
Menopause
means no more egg maturation and therefore very little oestrogen. This
oestrogen often comes from the conversion of testostrone secreted by the adrenal
glands into oestrogens by the body fat. This is why some obese women suffer
less from menopausal symptoms.
Age
20 weeks of foetal age 20million
primordial follicles (egg buds)
At birth 2
million primordial follicles
At puberty 500
thousand primordial follicles
Menopause Few
or no primordial follicles
Despite decades of medical research
some aspects of ovarian function still remain a mystery. We are unable to say
what triggers ovarian activity at puberty. It is also uncertain what starts the
menarche (the first menstruation) and what causes the abrupt end of egg
maturation and menstrual cycling. It is believed that until puberty there is a
suppression of the hypothalamic hormone called gonadotropin-releasing hormone
(GnRH). GnRH stimulates the pituitary to produce its hormones; follicle
stimulating hormone (FSH) and luteinizing hormone (LH). These hormones
ultimately cause the egg maturation and ovulation (the release of the mature
egg from the ovarian follicle)
As the prepubertal suppression of
GnRH production is eased, FSH and LH are produced, leading to the first
menstrual cycle. Slowly the functioning of the hypothalamus, pituitary and ovaries
become more integrated and regular menstrual cycles result. This theory has
changed in the last decade. The latest research in Philadelphia discovered new
hormones in 1996 called Kisspeptin secreted in the hypothalamus with several
other hormones. They enter the receptors in the pituitory which is supposed to
control or start the puberty and menstrual cycle. A lot of work is being done
in this area. Other substances paracrine polypeptids called NeuroKinnin B, Dinorphin (together called KNDY) have stimulatory
and or inhibitory effect on GnHR release. This can be used to stimulate Hypothalamus,
Pitutory, and Gonadal function. This is also useful for management of
infertility, Delayed puberty, Hypothalamic Hypogonadism, absence of periods (Amenorrhea)
and hypogonadism with diabetes. The other group where KNDY can be used when it
is over active such as; precocious puberty and polycystic ovarian syndrome.
Originally these hormones were being used to suppress gonadal function in
Breast Cancer, Prostate Cancer, Endometriosis, and Uterine Fibroids. In fact
these were called Metastatin. These recently discovered hypothalmic
polypeptides; Kisspeptin, Neurokinnin and Dynorphin, offer a great therapeutic
benefit so far for difficult conditions
to treat . However to date, they are not
yet available for clinical use.
The menstrual cycle
Menstruation typically starts
between the ages of ten and fifteen. Impulses in the form of hormones (GnRH)
from the hypothalamus stimulate the pituitary gland to produce FSH. Under the
influence of FSH, several primordial follicles start maturing but only one
becomes the dominant follicle or egg for that cycle. The oestrogen produced by
the egg stimulates a surge in the production luteinizing hormone by the
pituitary gland and this causes ovulation. The surge of LH causes ovulation in
the middle of the cycle about fourteen days after the follicle starts growing.
After the egg is released the remaining cells of the empty follicle form called
corpus luteum. (Latin for yellow bodied) which then produces the second female
hormone, progesterone in the menstrual cycle. In the first two weeks of the
menstrual cycle leading up to ovulation estrogens help the growth of the lining
of the uterus (The Endometrium).
In the
first two weeks of the menstrual cycle, leading up to ovulation, the oestrogens
help the growth of the lining of the womb (the endometrium). In the second two
weeks, the progesterone matures or ripens this lining.
If
conception occurs, nutrition and support is provided by this lining for the
growing embryo. Progesterone levels remain elevated, ensuring the stability of
the womb lining, and enabling the pregnancy to continue. However, if fertilization
does not occur, an abrupt fall in oestrogen and progesterone levels takes place
about 10—12 days after ovulation.
This drop
in hormone levels destabilizes the lining of the womb, which is then shed as
menstrual flow indicating the end of the ovarian cycle. Regular menstruation is
a reassuring visual sign that the ovarian function is normal. A new cycle of
egg maturation begins.
At the
time of menstruation other specific chemicals called prostaglandins are
produced in the endometrium which may be responsible for period cramps,
headaches, nausea and dizziness accompany a menstrual period
Regular
menstrual cycles continue for thirty to forty years, the reproductive years of
a woman’s life. During these years, a woman can menstruate 400—500 times. The
only time when the lack of a period is normal is during pregnancy and
lactation. Otherwise the absence of a period may indicate disturbances of the
ovarian function.
By the
age of 40 to 45 years, most of the primordial follicles are used up. There is
erratic maturation of the remaining follicles and often irregular menstruation.
This irregularity is usually accompanied by an overall decrease of oestrogen
levels. When the oestrogen level is low the pituitary gland receives an impulse
to secrete increasing quantities of FSH. This is an attempt to stimulate the
remaining follicles, which are usually less responsive and fails to mature, and
hence fails to produce oestrogen or progesterone.
Occasionally, ovulation can occur
during these years of irregular menstrual cycles prior to menopause. However,
when all the follicles are exhausted, or any that remain do not mature despite
increasing amounts of FSH from the pituitary, the ovarian cycle and
menstruation cease. The complete cessation of the menstrual cycle announces the
onset of menopause.
Menopause is therefore correctly
dated only in retrospect by the absence of any further period. The age when it
usually happens is around 50 years although there are racial, genetic and
socioeconomic variations to this mean age. During the period of irregular
menstrual cycles prior to menopause the blood FSH level may be high but the LH
level can be normal. Women are still at risk of conceiving, although the risk
is small. It is only after blood levels of FSH are shown to be consistently
high that pregnancy cannot take place (except by some freaky ovulation) and
true menopausal status is confirmed. This phase of a woman’s menstrual function
is called menopause transition or perimenopause. This happens several years
before menopause. It is often called climactric (meaning seven in Greek). As
all ready mentioned during this time symptoms of menopause such as, hot flushes,
dry vagina and mood swings start to happen.
Oestrogens
There are three main types of
oestrogens; oestradiol, oestrone and oestriol.
Oestradiol is the most potent of the oestrogens. Oestrogens are mainly
produced by the maturing egg follicles. In the prepubertal years, small
quantities of oestrogens are produced from the ovaries before regular
menstruation is established. Some of the oestrogens are derived from the
conversion of androgens (secreted by the ovaries and adrenals) to oestrogens.
This conversion takes place in body fat.
Besides
their role in reproduction, oestrogens perform several other important
functions. During puberty, they help the growth of the sexual organs: the
breasts, uterus, fallopian tubes, vagina and vulva. The child’s figure changes
to a female figure with increased fat deposition and bone mass. Oestrogens are
responsible for the distinctive female body shape because they regulate the
specific distribution of the body’s fat in the hips, abdomen and upper arms.
The development of under-arm and pubic hair is due to an increase in androgens
from the adrenals and the ovaries. Subsequently ovulation starts and women
begin their reproductive life. During a normal menstrual cycle, the oestrogen
level varies from being very low just before and on the first day of
menstruation, after which it starts to increase as the new follicle matures
Oestrogens
help the development and maintenance of bone mass and the body’s other structural
tissues such as collagen. The wellbeing of the cardiovascular system appears to
be enhanced by an adequate supply of oestrogen which helps to protect women
from coronary artery disease.
Progesterone
Progesterone is produced by the corpus
luteum of the ovary in the second half of the menstrual cycle. It plays an
important role in reproduction, and is essential for the maintenance of a
pregnancy. Its main functions include the maturation of the lining of the
uterus, the thickening of the cervical secretions, maturation of the cells of
the vaginal lining and the relaxation of the body muscles in general. It helps
the glandular development in the breasts. It can cause a slight rise in body
temperature, fluid retention, acne and mood swings. These signs indicate that
ovulation has taken place.
Recent
evidence also suggests that progesterone helps in the maintenance of bone mass
and in the prevention of osteoporosis.
Androgens
Androgens (androstenedione and testosterone) are derived from the
adrenal glands and ovaries. They are mainly responsible for muscular
development, growth of body hair, sense of wellbeing and play a part in sexual
desire. At menopause, androgens are converted to oestrogens in body fat. This
conversion supplies some oestrogen to women after menopause although in a much
decreased amount. Nonetheless, the presence of oestrogen from this source
prevents many postmenopausal women from experiencing effects of menopause such
as hot flashes, emotional disturbances and atrophy of the genital organs
including the breasts. Obese women are less likely to suffer some effects of
menopause as their larger supply of body fat can help in maintaining reasonable
levels of oestrogens by this conversion. Of course, obesity brings with it
other problems, including irregular bleeding, endometrial thickening and
increased risk of cancer of the uterus.
Because of a relative excess of androgens, which are male hormones,
facial hair may appear for the first time after menopause. As years go by, the
acute symptoms of oestrogen-deflciency such as hot flashes abate, but the
long-term effects of oestrogen deprivation such as osteoporosis, thinning and
shrinking of the genital organs and adverse effects on the cardiovascular
system become more significant. According to the National Heart Foundation,
heart disease is the leading cause of death for Australian women, representing
24.6% of all deaths. Fifty per cent of all postmenopausal women die of heart
disease.
Eventually, the ovary is exhausted and does not produce even enough
androgens to be converted to oestrogens. The contribution made by the adrenal
gland proves inadequate; consequently the effects of oestrogen deficiency
become more and more severe.
Changes to expect around and
after menopause
The ovary at menopause shrinks to
the size of an almond. Opinions differ about the number of remaining follicles
at this stage: from a few hundred to none. The follicles do not respond to
increasing quantities of FSH. Small amounts of oestradiol may still be produced,
but this is about one tenth of the amount produced during the menstrual cycle.
The ovarian stroma increases its secretion of androgens due to the stimulation
from increased FSH levels. Some of these androgens are converted to oestrogens
in menopausal women. These oestrogens (predominantly oestrone) are not as
potent as the oestradiol secreted by the maturing follicles.
The pituitary produces increasing
amounts of FSH and LH — up to five times more than during the reproductive
years. After a certain point, there is no further increase. Androgen levels may
be relatively high compared with oestrogen levels. The total cholesterol level
in the blood is increased and the ratio of low—density (‘bad’) cholesterol to
high—density (‘good’) cholesterol increases, raising the risk of heart disease.
There is also new evidence that the absence of oestrogen adversely affects the
tone of the arterial walls.
Calcium balance is also adversely
affected, causing thinning of the bones and osteoporosis. Consequently the risk
of fractures increases. The breasts may change in size. In some women, the size
increases from fat deposition. Such fat deposition takes places in other parts
of the body particularly the abdomen, hips and arms which then causes a change
in body shape and weight distribution. Meanwhile, the uterus decreases in size
and the lining thins out. The cervical secretion decreases. The vagina becomes
thinner and smaller. It loses its elasticity, lubrication and acidity. During
the reproductive years, the acidity of vaginal secretions helps prevent vaginal
infections.
The
external genitalia (the vulva) undergoes thinning. However the pad of fat on
top of the pubic bone called the mons pubis often gets thicker from fat
deposition.
Pubic
hair becomes sparse. Sexual desire in some women increases due to high androgen
levels, while in others, it decreases as a result of pain during sexual
intercourse, caused by a dry vagina.
Key points
1.
The ovary, the female sex
gland, is the main organ concerned with menstruation, reproduction, production
of the female hormones oestrogen and progesterone, and menopause.
2.
The ovary lies dormant from
birth to puberty and becomes dormant again at menopause, after four decades of
reproductive activity.
3.
It is now being researched, what
biological catalysts activate, and then end, ovarian activity. Further to this
key point, in 1990 a neuron called kisspeptin was discovered in Hershey (Pennsylvania)
it is named after the Hershey’s Kisses (Chocolate Bars), so that everybody will
know where it was discovered. In the last ten years lots of research has been
done on Kisspeptin and it has been concluded that Kisspeptin neurons joined to
GPR54 are singularly essential to initiate gonardotrophrin secretion at
puberty. They are essential at the start of puberty but they do not control
when the puberty starts. Originally this gene was responsible for the suppression
of the spread of melanoma and breast cancer. It may become a very useful tool
in the in the near future for the, management of infertility IVF. Hypogonadism,
premature puberty and polycystic ovarian syndrome as these hormones can both
stimulate and inhibit the activity of GnRH and luteinizing hormones.
4.
Oestrogens play the key role in
maintaining a woman’s health during the reproductive years. The lack of
oestrogens may cause complex physical and emotional problems often associated
with the menopausal years.
Chapter 2
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