SYMPTOMS OF MENOPAUSE

Menopause, the biological milestone in our lives, typically announces its impending arrival by menstrual irregularity, fatigue, hot flashes and night sweats. There are also subtle physical and psychological symptoms that we experience, culminating in the end of the familiar monthly menstrual cycle. If you are experiencing any of these symptoms or are approaching 40 to 45 years, it is wise to discuss these issues with your doctor.

            Strictly defined, the very last day of menstruation is called menopause after it has stopped for a period of twelve months. This end of menstrual cycling usually occurs between the ages of 40 and 60 years, with the average age being 51. Menopause can be a welcome relief from the fear of pregnancy and painful or irregular bleeding often accompanied by menstrual migraine and premenstrual tension. Women are unique beings who, unlike females of other species, continue to live long after the end of their fertility. In the 21^st century a woman can look forward to another 30 to 40 years or longer after her menopause, because of the advances in medical science and better socioeconomic conditions.

            This end of the reproductive years is known by various names — the change, the climacteric and, most popularly, menopause. The word menopause is derived from two words - the Greek meno meaning month and pause meaning cessation. Although menopause technically refers to that one day in a woman’s life when her periods stop, the effects of that loss of reproductive (ovarian) function extend over years, both before and after, that one day. The word climacteric is used to define these years of physical and emotional changes.

Since the duration of these midlife changes now called menopause transition is about 10 years in the context of chronic illness, endocrine disorders, menstrual problems, fertility problems. In 2001 it was decided to study the changes of the reproductive aging. The scientists of five different countries and multiple disciplines sat to classify them into different stages. This was called STRAW-Stages of Reproductive Ageing Workshop.  After ten years a more comprehensive basis for assessing reproductive maturity is described. (And this is STRAW+10) The first stages of this reproductive function have regular menstrual cycles, later the cycles are often irregular, the fertility decreases and the main pituitary hormone for the maturation of the egg (FSH) can increase. At this stage a woman can have some symptoms such as hot flashes at random  times of day and night and in the premenstrual stage, they have premenstrual tension. In the following stages now called menopause transition when the menstrual cycle varies the fertility decreases. The hormone studies are often done especially in women who are anxious to have a baby late in life. The FSH is variable. The two other hormones which we now study are called Antimullarian and Inhibin B  are low. The number of maturing follicles in the ovary is low. The women start having hot flashes. In this part of this menopause transition the FSH is variable. (Should be done on the second day of the cycle) and later on in menopause transition it becomes higher, the symptoms become pronounced. This is also expressed as peri menopause.

In the final stage the menstrual cycle stops and when it has stopped for one year it is called menopause when, the FSH is usually high, and Antimullarian Hormone and Inhibin B is very low. The chances of pregnancy are considered very low or negligible. Personally I have seen two women having a baby at 54 and 56 years of age without any treatment, and a great surprise to them. As time goes on menopausal women start getting symptoms related to external genitalia. These are painful dry vagina, painful sex and urinary symptoms, such as poor control and repeated urinary infections. Recently this has been studied and is given a new name Genitourinary Syndrome of Menopause. These late symptoms get worse and never improve. Depending on your menstrual cycle, symptomatology and supportive criteria you can assess when your menopause is coming irrespective of your age and nationality. It can often take up to 7 years from the start of symptoms to the end of periods. That’s why it was named Climactric after a Greek world meaning 7.

Surgical menopause

            The surgical removal of both ovaries (called bilateral oophorectomy) is sometimes necessary in the treatment of breast cancer or other conditions. Such removal of the ovaries results, of course, in the sudden loss of a woman’s ovarian hormones, and produces a surgical menopause. The symptoms that result from a surgical menopause can be very distressing. This is due to sudden withdrawal of hormones, and often more severe than, a normal menopause.

Hysterectomy (the surgical removal of the uterus) does not induce a true menopause, because, although the periods stop, the ovaries continue to manufacture the female hormones in the normal cyclical way.

            Menopause sometimes occurs about five years earlier in women who have had a hysterectomy and in women who smoke. For these women, menopausal symptoms, rather than the cessation of periods, herald the start of menopause. For some women, a blood test may be needed to confirm menopause.

Premature menopause

            If menopause happens before 40 years of age it is called premature menopause. If it happens very early, for example, in the 20s, it is called ovarian failure or premature ovarian insufficiency rather than premature menopause. For younger women who have no periods for any length of time and are having symptoms, premature menopause is a possible explanation. Of course, pregnancy is also a possibility and it is therefore essential to exclude pregnancy before attributing the absence of periods to premature menopause. This can also happen after receiving chemotherapy or radiotherapy for cancer.  

Personal story

Premature menopause causing psychological stress

            Gina, a 22-year-old law student and keen sportswoman of Italian descent, was a classic case of premature ovarian failure. She had not had a period for five months and she had occasional hot flushes. Her general practitioner who believed that her strenuous sports activity had caused her periods to cease referred her to a gynaecologist. Absence of periods often happens with excessive physical activity which affects young women can also cause infrequent or absent periods. However, various hormone blood level tests showed that she was suffering from premature ovarian sufficiency. Gina took consolation from the rapid strides being made by the IVF fertility program which may eventually provide a solution to her problem. Immediately though, the answer was for her to go on HRT, Gina had psychological counseling to cope with the devastating consequences of possibly never being able to have a child. However in 2018 there are drugs called kisspeptins which could have helped her. However these drugs are not yet available for clinical use.

            Women reaching middle age may experience several other problems unrelated to menopause or oestrogen deficiency. Problems of ageing such as arthritis and diseases such as diabetes and high blood pressure often start at this time. Many social and psychological barriers also arise. A lack of career fulfillment, ageing parents to care for, marital disharmony and difficulties with growing children all create additional stress. The problems at middle age are therefore often a combination of biological (ageing and menopause), psychological and social upheavals.

Oestrogen deficiency score chart

Menopause Evaluation Sheet

Name:

This evaluation of symptoms can help your doctor decide if you have low levels of the hormone oestrogen and whether treatment might help you.

You or your doctor can do the scoring.

Score:

0 if no problem           1 if mild

2 if moderate   3 if severe

Oestrogen deficiency symptoms Score
Hot flashes (Flushes)
Light_headed feeling/dizziness Headaches
Crawling under the skin
Sleeplessness/altered sleep pattern
Irritability
Depression
Unloved feelings/unappreciated
Anxiety
Mood changes
Backache
Joint pains Muscle pains
New facial hair
Dry skin
Unusual tiredness
Less sexual feelings
Dry vagina
Uncomfortable intercourse
Urinary frequency
TOTAL SCORE

Assessment

A score over 15 usually indicates oestrogen deficiency.

20-40 is common in untreated women.

(Modified from: Jones MM, Marshall DH, Nordin BEC. Curr Med Res Opin 1977; 4 (suppl.13): pages12—20.)

Specific menopausal symptoms

Menopausal problems can be short-term or long-term. Hot flashes are the most obvious distressing symptom which brings a woman to a doctor. Other symptoms are general sweating, night sweats, muscle aches and pains, joint pains and a peculiar sensation of ants crawling on the skin called formication. A second group of symptoms include urogenital changes, manifested by dryness of the vagina, bladder problems such as the frequent desire to empty the bladder, and the loss of bladder control. (As mentioned earlier as genitourinary syndrome of menopause) These symptoms are due to atrophy (thinning) of the vagina and the urethra resulting from oestrogen deficiency. A third group of symptoms embrace psychosomatic ailments of confusion, loss of self—image, loss of memory, agitation, irritability, headaches not previously experienced and depression.

Long-term, postmenopausal women suffer an increased incidence of heart disease, a thinning of their bones (osteoporosis) and atrophy of the genital organs. It has been shown in studies that only 3% to 4% of women seek medical advice about these issues at this time.

For treatment to be effective, it is important to distinguish between oestrogen deficiency symptoms and those caused by other problems.

Hot Flashes

            A hot flush is a sudden transient feeling of heat over the head, neck and chest, starting from the chest. It causes flushing of the skin which is obvious to other people. What causes a hot flush is not clearly understood, but it is likely to have something to do with the hypothalamus, a key nerve centre in the brain. The reduced oestrogen levels irritate the neuroreceptors in the hypothalamus and these in turn signal the blood vessels in the skin to dilate. The increased blood flow through the dilated vessels heats up the skin, and causes the flush, while the skin temperature is rising during the several minutes of the flush, the body temperature drops by a few degrees. The cooling effect is accentuated because a chill feeling follows the evaporation of the newly formed perspiration from the skin. As a result of cooling, our body’s defense mechanism takes over and the adrenal gland releases a hormone called adrenaline. This stress response causes constriction of the blood vessels, and the hot flush ends.

            The number of hot flashes women experience is variable. There may be several in a day, several a night or they may be continuous, one after another. Night sweats are the same phenomenon as hot flashes except that they occur during the night. Because they occur during sleep, the hot flash is not felt as much as the consequent cold sweat.

While hot flashes usually occur spontaneously, they may also be initiated by external factors such as sudden unexpected noise or a fright. A stressful work or home environment can greatly increase the frequency and severity of hot flashes. They do not have any serious long-term effects, although some of the insomnia and fatigue that occurs at menopause may be caused by the night sweats.

            These symptoms are the commonest of menopausal problems. About seven out of every ten menopausal women experience hot flashes and more than 60% experience hot flushes for 12 months and up to 5 years after menstruation stops. Hot flashes often continue for several years after menopause. For many women, they start a few years before their periods actually stop; that is, during the time when they are experiencing menstrual irregularities.

            Hot flashes can be a very distressing condition. A general consensus is that hot flashes undermine a woman’s self-confidence making her self- conscious of her body in a negative way. They are a contributing factor to the psychological symptoms accompanying menopause.

Fatigue

            Fatigue is a very common problem during menopause. There are several general causes for tiredness which should be excluded before associating it with menopause. For example, menstrual irregularities and heavy periods causing anaemia (lack of haemoglobin in the blood) can cause tiredness. An often overlooked cause of fatigue is poor diet and the stress of the daily demands of being a mother, running a home and a job at the same time. Thyroid disorders and diabetes are also very common at this age and should be excluded.

            It is important to evaluate your working hours and conditions before attributing fatigue entirely to menopause. It is also important to exclude any other disease or biological changes which may be responsible.

Urogenital Syndrome or Genitourinary Syndrome of Menopause

This terminology: was replaced by a term called Genitourinary Syndrome of Menopause (GSM) at a meeting of International Society of Women’s Sexual Health and at the North American Society of Menopause in 2014.This was much better as this included all the organs which are affected by the decrease in the level of oestrogen such as vulva, vagina and bladder. These symptoms mostly occur three to eight years after menopause. They mainly affect female urinary activity and genital function. Lack of oestrogen is the main reason for changes in the urinary and genital tract. After menopause, there is a progressive deterioration in these organs and their functions, ultimately causing a dry, shrinking vagina which leads to increasing dryness diminished capacity and elasticity. Sexual stimulation is also diminished and it takes longer to reach if at all an orgasm. Vaginal atrophy and dryness varies from woman to woman. Larger women are less seriously affected because their body fats continue to produce and store an oestrogen called oestrone. Lack of oestrogen seriously affects urinary performance because the urinary bladder is believed to be oestrogen dependent.

Initially, there may be repeated infections (cystitis), frequency and urgency and some stress incontinence (spilling of urine under stress such as coughing, sneezing, laughing or dancing). As the years go by, these symptoms can become more serious and incontinence can become a great handicap. In caring for the geriatric population, incontinence is a major determining factor in finding accommodation in nursing homes. The most common urological complaint a gynaecologist deals with is incontinence. For younger women, it is generally stress incontinence and, for older women, it is generally due to overflow. Difficulty in emptying the bladder completely is another problem experienced by elderly women.

The important role played by oestrogen in the proper functioning of the urinary system is not completely clear. The lack of oestrogen, together with a generalised loss of muscle tone, are the major factors in compromised urinary function after menopause. However, while oestrogen replacement helps many women with such difficulties, it does not help all. Thus, other causes of this particular symptom should be considered and treated accordingly. There are many vulval diseases which also cause vulval pain; they are usually auto immune or atrophic. They should be looked for as they can also cause vulval cancer. The treatment of GSM is discussed along with other treatments for menopause.

Irregular or absent menstrual cycles

            By definition, menopause is the end of the menstrual cycle. However, before menopause arrives, irregularity of cycles is common. Irregularity can be frequent periods, infrequent periods, too much bleeding or too little bleeding. The reason is that the failing ovaries are not ovulating; there is no progesterone produced to ripen the lining of the uterus (the endometrium) and regulate the menstrual cycle. This is perhaps the earliest symptom of menopause and is often not recognized as such. In the past, many women in their late 30s and early 40s who consulted their doctor about irregular periods were described as suffering from dysfunctional bleeding. This term means abnormal uterine bleeding in the absence of any uterine fibroids or other medical reason. The bleeding is generally due to a hormonal imbalance.

Other causes of abnormal bleeding and absent periods should be excluded before labeling this as menopausal. These problems can be due to a range of causes varying in severity from simple fibroids to uterine cancer or even pregnancy

Muscle and joint aches and pains

            After the ovaries begin to fail, the ligaments and tissues which connect various parts of the skeletal system become lax resulting in decreased muscle strength. The looseness gives rise to a variety of aches and pains. Laxity of the muscles is accompanied by loss of elasticity of the ligaments and the cumulative effect is more aches and pains in the shoulders, elbows and back.

            With age, we can also expect some degree of osteoporosis and consequent pain. Osteoporosis can cause fractures of the vertebrae and then curvature of the spine. When the curvature is very marked, it is known as dowager’s hump and results in loss of height.

            With an adequate amount of physical activity, these symptoms are prevented as exercise enhances the wellbeing of the muscles, ligaments and the bones. Oestrogens are also believed to have some benefits like, as an anti-inflammatory agent thus preventing pain as well as preventing osteoporosis.

            A combination of lack of oestrogens, poor physical activity and menopausal changes exacerbate muscle aches and pains. Many women are treated as if they suffer from osteoarthritis and are often given aspirin and other non—steroidal anti-inflammatory drugs which can cause side—effects such as stomach ulcers.

Other symptoms

            As the ovaries fail, there is a relative proportional increase of the male hormones, androgens, mainly testosterone and androstenedione. These hormones can lead to the appearance of pimples and facial hair, and the thinning and loss of scalp hair. HRT can improve these distressing conditions. Sometimes, a drug, Aldactone, can be used to neutralise androgens and decrease facial hair.

Skin and hair

            The skin constantly changes with age due to deterioration from excessive exposure to sun. The ageing of the skin starts at about 30 years. These changes are accentuated by the hormonal changes at menopause. At this time, the elastin and collagen in the skin decreases although it is not yet understood why. The loss of collagen, in the initial years of menopause is far more than in subsequent years. The deficiency of elastin and collagen causes wrinkles and dryness. Women who have been on prolonged corticosteroid therapy, or who suffer from adrenal disease, have diminished collagen tissue. Corticosteroids, commonly used for asthma, have an adverse effect on skin and bones.

            HRT can be beneficial. Oestrogen and testosterone help the skin by protecting the loss of collagen and elastin, increasing the skin’s water content (called “hydration”) and improving blood circulation. Recent research has shown that skin changes often almost disappear within six months of starting HRT, after which there is no further significant improvement as there is an optimum collagen content that women achieve.

            Acne at menopause can be treated by general cleansing of the skin, by nutritional creams and by HRT which restores the hormonal balance in favour of oestrogen. Some doctors use aldactone to neutralise the testosterones. This may result in side—effects such as depression, diminished sex drive and a tendency to a husky voice. These drugs have a place when acne is very severe.

            At menopause, new facial hair can commonly appear. HRT can lessen facial hair. In severe cases, medication is prescribed for a few months at a time. Simple depilatory creams may be used. Baldness is rarely seen in menopausal women; if it does occur, it is important for your doctor to exclude other causes of hair loss.

            Care of our skin is important at any age. Australia has the world’s highest incidence of skin cancer. Avoid unnecessary exposure to the sun by using a broad-brimmed hat, wearing a long-sleeved top and using a SPF-15-plus protective sun cream every day

            Other simple measures for skin care include correct diet and lifestyle factors such as reducing your intake of fat and salt, eating plenty of raw fruits and vegetables, drinking plenty of water, quitting smoking and cutting your alcohol consumption. Other positive aids to the good health and wellbeing of your skin are regular washing, gently massaging your skin with one of the many specialised skin brushes and using moisturising creams.

Personal story

Distressing male pattern hair distribution and hair loss

            Claire, 49, a shop assistant, cried as she took off her hairpiece concealing a large bald patch. She described how she had been embarrassed and dismayed by her creeping hair loss over two years from menopause and chronic emotional stress. She was reassured that HRT could prevent the condition worsening and might even improve it. She was prescribed a hormonal combination of oestrogen and progestogen to combat the testosterone, the biological culprit. After eight months of HRT, her hair loss stabilised.

Formication

Formication is the sensation of crawling under the skim. The feeling is caused by vascular changes in the skin at the time of menopause. The condition usually improves or completely disappears soon after starting HRT.

Some more unusual symptoms include tingling in the ears, dizziness, painful leg cramps and a bloated feeling.

Emotional disturbances

Psychological disturbances which many menopausal women commonly complain of are depression, insomnia, panic attacks, mood swings, irritability and lack of self-confidence. These feelings often appear before the symptoms of hot flushes. Short-term memory loss is also complained about but this may be more age related because it also affects men.

Although HRT relieves these symptoms for many women, there is no conclusive proof that these symptoms are the direct result of oestrogen withdrawal. Many women seek to blame oestrogen withdrawal when their real problems may be stress related at home or work. At this time of life, women are prone to fretting about their changing body shape, weight gain, sagging breasts, wrinkles around the eyes, career unfulfillment, problem children and a disappointing marriage. Emotional symptoms from the time of menopause are very difficult to classic and may be unrelated to lack of oestrogen.

With our present state of knowledge, we are unable to explain how and why HRT can give many of these women relief from their emotional symptoms. Some of this improvement may be the result of the tranquility they achieve from HRT’s correction of their hot flushes. However, there are an equal number of women who pass through menopause without any emotional trauma.

Premenstrual syndrome (PMT) is a group of symptoms which affects women in their third and fourth decade, ultimately merging with perimenopausal symptoms. It is a stressful combination of physical and psychological symptoms which occurs regularly before the start of menstruation. Symptoms can include headaches, irritability, depression, mood swings, menstrual migraine and suicidal tendencies. There can also be poor performance, clumsiness, and changes in weight, tender breasts and fluid retention. The exact cause of PMT is not known.

Personal story

Persistent headaches which, in reality, were hot flushes

            Joan, a hotel chef, who had a hysterectomy and removal of both ovaries at 36 because of severe infection from the Dalkon Shield complained to her doctor of headaches. Six months after her operation she began to suffer persistent headaches which were actually hot flushes. Various doctors considered the condition to be persistent headaches which were not relieved by pain killers. She was referred to a dentist who believed the malalignment of her jaw was causing the persistent pain.

Finally, she started taking HRT and within two weeks felt better.

Personal story - Hot flushes, insomnia and lack of concentration

            Janet, 51, an architect, was worried about her mood swings, difficulty in concentrating, lack of sleep and unpredictable hot flushes. Her menstrual cycle, for the past 18 months, had become irregular and her last menstrual period was four months ago. Her past medical history was unremarkable except that she had had varicose veins surgically removed from both legs.

            She had not taken any medication in the past. Her father died of coronary heart disease at the age of 56 after several years of suffering from angina which had also afflicted her mother. Her menopausal status was suspected from her irregular menstrual cycle and symptoms and was confirmed with an elevated FSH level by her blood test. HRT was recommended to control her symptoms and to prevent her from developing heart disease because of her family history which put her in a high risk category

Key points

1.     After menopause the oestrogen levels progressively decline, causing several permanent changes. Menopause is not a transitory phase, but a permanent one in your life because the oestrogen deficiency is permanent.

2.     Symptoms of menopause are many and varied, extending from psychological to physical manifestations. The commonest are hot flushes, irregular bleeding, vaginal dryness and mood swings. Menopausal symptoms are not a universal experience for women. Many women suffer from urinary and genital problems as already mentioned called Genital Urinary Syndrome which is a very uncomfortable progressive  problem affecting the quality of life

3.     Symptoms can start many years before and continue many years after your last menstrual period. If you are experiencing any of these symptoms, it is wise to discuss them with your doctor, particularly one with a special interest in menopause

4.     There’s no conclusive evidence to suggest that menopause causes any psychological problems. Many women claim that HRT helps their mood changes, energy levels and memory

5.     The health of a woman’s skin is linked with her overall oestrogen supply, in a similar way to that of her bones.

6.     These symptoms can occur for many other reasons. All possible causes should be looked for, and excluded, before HRT is started.

7.     HRT is the focus of the effective treatment of menopause. However, about 15% of women do not require therapy because they are still capable of making some oestrogen. On the other end 15% require HRT all their lives.

KNOWING YOUR BODY AND HOW IT WORKS

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