SECONDARY AMENORRHEA-HYPERPROLACTINEMIA

One of the other common problems with periods is the rise in the hormones called prolactin. Prolactin is secreted by the pituitary gland which has a vital role in the reproductive function.
It is an essential factor for secretion of breast milk after child birth, it has a negative effect on the pituitary function, such as production of LH and FSH this we have discussed in the menstrual cycle.
An excess of prolactin is called Hyperprolactinemia , can be caused from some medications such as the drug used for underactive thyroid and the drug used for pituitary itself. Drugs used for mental disorders can also cause an increase in prolactin.

Increased levels of prolactin can be found in ten percent of the population. The women usually present with small periods , absent periods, infertility and galactorrhea (milk secretion from the breast).
Men can also get this problem with low gonadal function.
There is a complex physiological control of the pituitary prolactin secretion.
This includes many drugs and thyroid function.
One of the most important causes of increased prolactin is a pituitary tumour called Prolactinoma, they are usually benign. The thyroid underactivity also causes the increases in prolactin levels, there are several mechanisms which are involved however these are dealt with by an endocrinologist.
As gynaecologists we mainly deal with period problems and infertility.

To start with we should try and find out the cause of the increased prolactin level, asses their other medical history, drugs they are on and thyroid function.

The pituitary gland is located in the brain at the cross junction of the two optic nerves called optic chiasma.
When the pituitary gland is enlarged it puts pressure on the optic nerves and cause headaches, nausea, and disturbance in the visual field.
So this should be investigated by a CT or MRI if it is available. It is often a good idea to have the eyes checked by a good ophthalmologist.
If a prolactin level is not high and there is a macroadenoma (enlarged pituitary tumour) then it is often treated by an endocrinologist.
The drugs we commonly use for alleviated prolactin levels are Bromocriptin 50 to 100mgs used twice daily, this usually brings their periods back and helps them to get pregnant.
The other drug that is used, is called Dopamine Agonist and it is used once a week. It is often used when patients do not respond to Bromocriptin.
The surgery is only carried out if the prolactin level does not respond to drugs or pituitary macroadenoma is present or if their are any other tumours present in the surrounding area and this decision is taken by neurosurgeons.

This is a very simplified version of a condition called Hyperprolactinemia.
This mainly causes secondary amenorrhea and infertility in women, however it is easy to diagnose and treat, so do not despair, have yourself checked out if you have infrequent periods , no periods, infertility and milk secretion from the breast.
   

POLYCYSTIC OVARIAN SYNDROME

PCOS is one of the most complex disorders of modern society, about five to ten percent of the female population suffers from PCOS. In America there are five million women suffering from it.
In Madame Tussauds Wax museum in London in 1964 I saw a pair of wax figures of an elderly man and a women with long beards , somewhat obese and a child of about five years old standing in between them. This tells the major story of PCOS, obesity, hairiness(hirsutism) and infertility.

PCOS was first described in 1935 by two physicians Stein and Leventhal and therefore in days gone by it was often called Stein-Leventhal Syndrome.

In those days it was very rare and in my five years at medical school I saw about five cases. Now in my retirement fifty years later, I was seeing almost ten cases a week.
There is actually no international agreement as to what it should be called, but for the time being we have agreed to call it Polycystic Ovarian Syndrome all this is mainly due to failure of ovulation.  This confusion is because there are many complex signs and symptoms of the disease and it is difficult to justify them by one explanation.

The main symptoms are irregular periods, obesity, hirsutism, hormone disturbances and polycystic ovaries. These women also suffer from infertility. If a women has no polycystic ovaries on ultrasound she could still be suffering from PCOS. The National Health Service in the United Kingdom estimates that one in five women has polycystic ovary on ultrasound but has no symptoms.
They are just labelled as Polycystic Ovaries.

PCOS is often referred to as a "Silent Killer" because the diagnosis is difficult and if left undiagnosed in women they develop massive obesity, insulin resistance, Type2 Diabetes, high cholesterol, heart disease, sleep apnoea, metabolic syndrome, gestational diabetes, increased risk of uterine and breast cancer.
PCOS the ovarian function is very disturbed because they do not produce hormones to trigger ovulation. The growth of the growing egg(The Follicle)stops in the middle and little cysts remain in the ovary filled with fluid and as a result they produce an excess of male hormones called androgens(Testosterone).There is an excess of oestrogens as well.
The ovary grows in size causing pain and failure to ovulate as a result the menstrual cycle stops.
Increase in testosterone causes hirsutism and also can result in a male type of baldness.
The diagnosis is usually made by symptoms of irregular periods, hairiness, acne, obesity and infertility. The investigations that are relevant are polycystic appearance of the ovary, and altered hormone studies.
Most experts around the world are not sure what causes PCOS however most feel that altered hormone levels probably play a key role along with Insulin Resistance and Obesity.
With insulin resistance they produce to much testosterone  and this stops the development of the egg and with insulin resistance they become obese which makes PCOS worse.
In my personal experience I have found PCOS common in young girls who were obese and their parents had diabetes.

Diagnosing Polycystic Ovarian Syndrome includes:
1- Hormone Levels
2- Ultrasound Size of the Ovary and the number of follicles on the ovary
3-Test to exclude Diabetes
4-High Cholesterol levels
5-Thyroid Function
6-Prolactin is rarely raised causing irregular period
7-Rule out other causes such as pituitary and adrenal diseases

Management of PCOS
There is no definitive cure for PCOS, we only treat the symptoms.
This depends on the patients age and the main problems. It is best to have a multi specialist consultation including gynaecologist, endocrinologist, dietician, physiotherapist, psychologist, infertility expert and a dermatologist.

Treatment Options of PCOS
1-Multispeciality Consultation
2-Life style factors must be altered, this helps not only PCOS but also insulin resistance, metabolic syndrome and risk factors such as Type2 Diabetes, high cholesterol and so on.
3-Weight Loss, Weight Loss, Weight Loss cannot be over emphasised.
4-Exercise within your tolerance and capabilities. Ideally 150 minutes a week.
5-Contraceptive pills in younger women are useful, many of these newer pills contain anti-androgen hormones which helps with the acne and hairiness. Please discuss these with your doctor as some of these have a slightly increased risk of deep vein thrombosis.
6-There are anti-hormone medications that you can buy individually that act against testosterone. These take a few months to show the benefits.
7-Metformin(Glucophage) has a beneficial affect on your general health caused by insulin resistance. There are many other drugs in this group they are called Glitazone, but in Australia Metformin is commonly used. A combination of these drugs is also thought to be helpful.
8-Patient suffering from infertility in addition to lifestyle and weight loss need other drugs such as Clomiphene which is often used in conjunction with Metformin.
9-If Clomiphene fails to produce ovulation then we use special drugs called Gonadotrophins. These drugs increase risk of  multiple pregnancies. Recent researchers have shown that a new drug called Letrozole works better, it has less side effects and the risk of multiple pregnancies is less.
10-Surgical treatment this consists of diathermy of the ovary and this helps with ovulation. If the Clomiphene has failed it works after the drilling of the ovary.
11-You require a curettage if you are having unexplained bleeding from the uterus this will tell us the cause of bleeding and what to do next.
12-Bariatric surgery of various types(Surgery to lose weight) is very useful, this should not be taken lightly as it has many complications and is very expensive. The simplest of this is gastric banding.

In conclusion PCOS is a manageable problem do not neglect it, if you look after yourself you will be happy and healthy. A long time ago when laparoscopy, ultrasounds and drilling of the ovaries was not available the surgeons performed what was called a wedge resection of the ovaries, this helped in a few cases of infertility. It suggests to me that the removal of the thick stromal tissue decreased excessive secretion of the hormone called luteinizing hormone and this helps ovulation.

As there is no definitive treatment for PCOS some of the researchers are trying to see if we can prevent it. Towards this a group of young girls aged between 8  and 12 suggesting signs of PCOS were given Metformin, they were restudied at 18 years of age, in the treated group there were only 5 percent who developed PCOS, whereas, in the untreated group 50 percent developed PCOS.
Hopefully after further study this may provide prevention of PCOS in some girls.

Follow the lifestyle factors, of losing weight, exercise, correct diet and see if you can live without the PCOS and the whole mess of endocrine problems that you have. It is just not the ovaries.  We have not yet succeeded in untangling the whole complex web of these problems.

SECONDARY AMENORRHOEA (SECONAMEN)

As we have seen in our previous posts, the female sex organ ovary responds to hormone messages from hypothalamus and pituitary glands, this cyclic function is called hypothalamic pituitary ovarian axis. This produces regular menstrual cycles, we have seen that sometimes these menstrual cycles never commence and this situation is called Primary Amenorrhoea, however when a woman has commenced her regular menstrual cycle and then she stops the cycle it is called Secondary Amenorrhea(seconamen).


There is also another word mixed with seconamen called oligomenorrhoea, this means that the periods are somewhat irregular and infrequent.


The two physiological causes of seconamen are pregnancy and menopause.


Doesn't matter how old or young a women is between the ages of twelve and fifty always make sure she is not pregnant. Many people consider seconamen only if they have missed two or three months, but I do not agree with that , I feel one should do a pregnancy test or see a clinician after six weeks especially if this is an unplanned pregnancy.
In my practising lifetime I have seen three females aged twelve, thirteen and fifty-one with unexpected pregnancy. The two young girls in fact had never had a period.
The twelve year old was a school girl who went for a picnic and perhaps became pregnant with her very first period, she had a very complicated pregnancy and she and her mother looked after the baby well.
The other person I saw was a thirteen year old girl who had no idea about menstruation or realities of life. She was left alone with her sixteen year old cousin and they had sex and when we saw her she was full term pregnant and in labour.
We delivered the baby and with the consent of the mother and other parties the baby was adopted.
The third person I saw was a fifty-one year old women who was in menopause transition.
It is important to continue contraception if you do not want to get pregnant in later years of your life for twelve to eighteen months when you have stopped having periods.


The other common causes of seconamen are
1- Obesity
2- Too Much Exercise
3-Losing too much weight as in sports women*
4-Anorexia
5-Anxiety and Stress (such as exams, new job, domestic problems and so on)
6-Drugs used to treat psychological disorders
7-Under Active and Over Active thyroid
8-Failing Hypothalmic Pituatary and Ovarian Axis 
9-Pituitary Tumour - Prolactinoma
10-Polycystic Ovarian Syndrome


Generally the symptoms of seconamen are not very conspicuous despite the fact that you have not had a period. You may have some change in your moods, diet habits, nausea and vomiting if you are pregnant.
If that's the case you can do a home pregnancy test or go and see your GP.


Look into your weight, stress, anxiety, abnormal thyroid function, polycystic ovary syndrome as they can all affect your weight gain or loss.
*Losing too much weight by exercising has been documented to being a risk factor for seconamen , infertility and osteoporosis.


The three most important reasons for Secondary Amenorrhea  to be discussed further are failing ovarian function, pituitary and hypothalamic function and polycystic ovarian syndrome.
I am sure you all know about PCOS which is the most discussed women's problem in modern society.
I will discuss these in my next post.

PRIMARY AMENORRHOEA CONTINUED

TURNER SYNDROME

One of the other causes of Primary Amenorrhoea is Turner Syndrome where one of the female sex chromosomes is missing.
They are usually of shorter stature, they usually appear in teenage years due to lack of developmental disorder.
Some of these features are seen in this picture. They do have a uterus and maybe very small ovaries and the ovarian failure leads to Amenorrhoea. Diagnosis is made by clinical features, chromosomal analysis and ultrasound.
The current medical research in IVF can help some of these women to achieve a pregnancy with donor eggs.
I had two such patients that I looked after, they require hormone replacement to keep them healthy until the normal age of menopause.
The other common cause of primary amenorrhoea can be what we call Congenital Hyperplasia. This is due to a deficiency of a particular enzyme.
As a result of this the female baby becomes masculinised, it can happen in male foetuses as well, these babies are born with ambiguous genitalia but their chromosomes are normal.
These children have multiple problems with adrenal function. they need to be treated with paediatric endocrinologists.
Many other causes of primary amenorrhoea are tumours of the pituitary, failure of the female organs to develop and the failure of the organs to function.
Primary Amenorrhoea is a difficult complex disorder of infancy, child hood adolescence it needs to be treated by a group of experts including paediatricians and gynaecologists.
However don't forget the simple diagnosis of pregnancy should not be forgotten as a young girl with normal secondary sexual characters maybe pregnant although she has not had a period. The very first ovulation she can conceive. I have seen two such cases in my time. One of these girls was only twelve years of age and was brought to hospital at full term in labour.
This is just a very brief summary of Primary Amenorrhoea just to point out  some important points;
1- When a baby is born with ambiguous sex it should be seen urgently by a paediatrician.
2- Babies suffering from Congenital Adrenal Hyperplasia (CAH) can be both male or female and their external sex is confusing, they also suffer from salt losing problems. They are life threatening and should be seen by a paediatrician.
3- The most common causes of Primary Amenorrhoea are Chromosomal Abnormalities - 50%
4- Hypothalamic Hypogonadism including Hypothalmic Amenorrhoea - 20%
5- Malformation of pelvic organs for example absence of the uterus, vaginal septum and imperforate hymen -20%
6- Pituitary disease , like tumours and infections -5%
7- Excessive weight loss like Anorexia Nervosa , obesity, psychiatric disorders and malnutrition -5%

The investigations are mainly;
1- Chromosomes, 2- Imaging, 3- Hormone Studies

Treatment depends on the cause mainly;
1- Lifestyle Factors, 2- Hormones, 3- Surgical Corrections

Finally don't forget pregnancy and take your child for medical advise as soon as possible.
       

PRIMARY AMENORRHOEA

In this post today we will talk about Amenorrhoea(AMENO), this can be Primary or Secondary.
Primary Amenorrhoea a women has never had a period, but in secondary Amenorrhoea a period did start and then stopped.
(The word AMENORRHOEA is derived from the Greek A meaning NO and Men means month and Rhoea means flow.)

Today we will only discuss about Primary Amenorrhoea as the two topics together make a very long post.
To have normal periods you need a normal brain hypothalamus pituitary function as described in the menstrual cycle, and in addition to this you need a normal functioning ovary and a normal uterus, cervix and vagina. In addition to this there hormones should be co-ordinated and beside the ovary some other hormones also participate , such as the thyroid and general health also plays a role.
The abnormalities often start during foetal development due to chromosome and genetic defects.
The management of this problem should start at birth especially if the sex of the new born is ambiguous. These problems can be classified in various groups but I will just talk about random abnormalities. The domain of the treatment of these complicated abnormalities is in the hands of paediatric endocrinologists.

One of the interesting and not so rare conditions is called Androgen Insensitivity Syndrome is when a foetus who is genetically male(who has one X and Y chromosome) is resistant to male hormones(called Androgens). As a result the foetus develops the features of a female baby, and when this child grows up it looks like a very attractive female. She is tall, slim, attractive with normal breast development, flawless skin, however the female organs are not there except for a small depressed area for the vagina. These are called complete Androgen Insensitivity. Some of these may be incomplete and then they have features of both sexes. The testes often lie in the lower abdominal area , if that is the case they should be removed as they are prone to cancer. This individual always grows as a female and the diagnosis is made when they have no period(Primary Amenorrhoea). The diagnosis is confirmed by blood tests, and genetic testing which will be XY and ultrasound which will show no female organs. these women are treated by hormone replacement therapy , psychological counselling and removing of small testicles as already mentioned.

Most of these individuals suffering from AIS live as women and become involved in sports, modelling and working in the hospitality industry. In fact some of these women in these trades became very famous, and in fact until very recently if there was any doubt about there femineity there chromosomes were tested and if found to be XY they were removed from these sports, but since then it has been worked out that these androgens in these women do not work like normal androgens hence the name AIS, so this rule of ruling out AIS women with XY chromosomes from the sports has been removed.
In this day and age where we have the access and knowledge to all these tests that can be done, we should test a child when it is born should the genitalia be inconclusive.

One of the other situations that you may come across is a young girl who is between 14 and 16 years of age, has normal secondary sexual features but has not had a period, she should be investigated, they can often have pre menstrual symptoms, regular menstrual period pain but no period.
They often have an obstructive abnormality of the genital tract, meaning thereby their cervix, vagina and the hymen. They have a period but the blood cannot flow. If not released it gathers within the vagina, the uterus and the tubes whereby destroying them. The hymen abnormality is easily fixed by a cross incision on the area. If there is a vaginal septum it can be removed, the cervical stenosis is difficult to correct. If the uterus is absent and the ovaries are present the women do suffer pre menstrual symptoms but generally they do not have any complications, these days these women can have a surrogate pregnancy by using their egg and their partners sperm. If there were any problems with the vagina causing difficulty during sex it can be constructed.

We will continue this conversation in the next post.

   

PUBERTY

In this post we will talk about puberty. Puberty is the time when young girls undergo changes to their body, which matures them into being a woman, and from then on, they can carry on the most important human function of reproduction.
When I was a young girl there was no sex education in those days, and we never understood what puberty was. I remember one fine morning at the school that I had some vaginal bleeding and my best friend who was in my class who was slightly older than me and I went to her saying that I have got Tuberculosis down below. In those days the only cause of any bleeding we had known was Tuberculosis of the lung. She told me that it was menstruation and we discussed this in detail as she had started having her periods one year earlier. So you can see that the time of puberty varies in individuals depending on their general health, nutrition and lifestyle.
Therefore my sex education was derived from my classmate.
The boys also undergo maturation slightly later than girls, but in this post we will focus on girls only.
The word Puberty is derived from the Latin called PUBERATUM MATURATION.

As discuss in my previous post on menstruation we have certain glands in our body called endocrine
glands which produce chemicals that produce hormones. These hormones are linked to the site of the action via the blood stream. The main glands concerned in our maturation are Hypothalamus, Pituitary and Ovaries(Sex Glands in Females and Testes in the Male).

 What happens at puberty under the direction of these hormones from the brain and the gonads, the breasts start to grow like little buds and then the second area of change is the appearance of pubic hair and axillary hair. In addition to the breasts and the hair their bodies start to change shape as years go by, they also have a special body odour. It is not uncommon for them to get changes in their skin and develop pimples.
In the genital area the mucosa of the vagina thickens and the labia minora changes. The vagina thickens and its PH changes. The eggs start to undergo maturation.  The uterus enlarges and it achieves adult size and finally menstruation starts. Recently the hormone called Kisspeptin has been identified from the hypothalamus and this is supposed to kick start the menstrual cycle.

There can be some developmental abnormalities at puberty which we will discuss in future posts.

In summary the main hormones involved are from the hypothalamus,( Kisspeptin, GnRH,) Pituitary,(LH , FSH), Ovaries(Estradiol and Progesterone).
They have a self regulating control.
A small amount of testosterone comes from the ovary and another gland called Adrenal.
Adrenal is useful for the development of hair follicles.
We have also described these in the menstrual function.

MENSTRUAL CYCLE AND MENSTRUATION

All living beings great and small have the main function of reproduction including humans.
The menstrual cycle is an integral part of this reproductive function. It is called menses and it is derived from the Latin word meaning monthly.
The main organs involved in this monthly cycle are Hypothalamus and Pituitary and they are located in the brain. The main female sex gland is called the ovary and it is located in the abdomen close to the uterus and the two tubes. The uterus is connected to the outside world by the cervix and the vagina. The chemicals produced by the hypothalamus and pituitary glands are called hormones which in turn act on the ovary which produces its own hormones. They help in the maturation of the egg and preparation of the uterus to receive the egg if fertilised.
If the pregnancy does not occur the prepared lining of the uterus is shed causing bleeding and this is called menstruation.Usually the menstruation starts around the ages of ten to fourteen years, and lasts for forty years in a women's life. The menstrual bleeding lasts three to seven days and blood loss is about 30 - 50 mls. The cycle usually varies between twenty-one to thirty five days.

It is only recently that we have started to understand what triggers the menstrual cycle.
They have found a new chemical called Kisspeptin which is supposed to trigger the hypothalamus to produce a hormone called GnRH.
GIIRH stimulates the pituitary to produces 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.

Under the influence of FSH, several primordial follicles start maturing but only one becomes the dominant follicle for the cycle.  The growing egg produces oestrogens, The oestrogens produced by the egg stimulate a surge in the production of another hormone LH by the pituitary gland. This surge in 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 turn into what is called the corpus luteum (Latin for ‘yellow body’) which then produces the second of the female hormones, progesterone, in the second half of the menstrual cycle. 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 fertilisation does not occur, an abrupt fall in oestrogen and progesterone levels takes place about 10—12 days after ovulation. This drop in hormone levels destabilises the lining of the womb, which is then shed as menstrual flow indicating the end of the ovarian cycle.

Menstruation is a reassuring 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 which can accompany a menstrual period.

 

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.

      4.   Oestrogens play the key role in maintaining a woman’s health during the reproductive years.

      5.   There are many issues about menstruation that need to be discussed, such as;

A-Puberty, B-Amenorrhoea,(No Periods), C-Premenstrual tension(PMT),D-Painful Periods,

E-Heavy and Irregular Bleeding, F-Polycystic Ovaries, G-Contraception.

All these problems will be discussed in future posts.