ABNORMAL VAGINAL BLEEDING IN REPRODUCTIVE YEARS

FROM MENARCHE TO MENOPAUSE.

Generally we discuss the causes of vaginal bleeding, including the local vaginal, cervical and even urethral bleeding including bleeding from the uterus. I have decided to divide this in two sections. In the first section I will discuss the causes of local bleeding, that is bleeding from the vagina, cervix and rarely from the urethra. These disease processes like anywhere else can be divided, into, infections, trauma, foreign body and pre-cancer and cancer. These have been briefly discussed in the post on vaginal bleeding in adolescence. These never cause profuse vaginal bleeding. It is usually a blood stained often smelly discharge. Candidiasis a very common infection in women almost never causes significant bleeding. Trauma after sexual interference or otherwise can cause moderate bleeding. I always remember a young bride brought to our hospital from the railway station having had sex in the train on her honeymoon journey, which bled so profusely that she required a blood transfusion. Similarly trauma can cause moderate to profuse bleeding. I have witnessed these after severe motor car accidents. Foreign bodies also usually cause blood stained smelly discharge, a left over tampon is a common example, and I have removed 100’s of these in my working life. Vaginal and vulval carcinomas are usually a disease of older post menopausal women. Cervical cancer and precancerous lesions of the cervix are common in this age group often precancerous lesions of the cervix are silent.

In the past fifty years a lot of attention was paid by doing cervical smears. Since we have vaccines for the human papilloma virus, which is the causative virus for cervical cancer, things have improved.  Cervical cancer is still very prevalent in developing countries as most of them have no access to the vaccine and even no facility for cervical cytology. In India some gynaecologists have started to do a simple vinegar test which is giving good results to detect pre-cancer of the cervix. Cervical cancer always causes vaginal bleeding, again often it is a blood stained smelly discharge. It is often very distressing to tell a woman that you have advanced cancer when she only has a blood stained discharge. Besides these, vaginal bleeding can also come from the bladder opening, the urethra or bladder infection or from the rectum, it may just be due to haemorrhoids or even rectal cancer. When you experience vaginal bleeding never forget to ask about bladder infections or rectal bleeding.

Let me now discuss the real causes of abnormal uterine bleeding. (AUB) I have briefly explained the menstrual cycle in my previous posts.  Some woman often have moderate to severe bleeding with their periods along with some pain. Until very recently there was no clear understanding of these problems. One woman can have more than one, two or even three   problems. These lead to chronic ill health and infertility, loss of work and income. Until recently there was no universal nomenclature or classification system for the gynaecological problems.  It made life difficult for the clinicians, patients and research scientist. Luckily in 2010-2011, AUB had been classified by a great Acronym,Palm-coein (prounounced  pahm_koin) which has been approved by the International Federation of Gynaecology and Obstetrics(FIGO).This was published in 2011 by Elsevier Ireland Ltd. I read this in the international journal of Gynaecology and Obstetrics (Volume 113, 2011). I was so elated by finding this classification and all the explanations.

POLYP (P)

In this classification P stands for polyp. They can be of many types, cervical, Endocervical (arising in the cervical canal) endometrial and rarely placental (left over placental tissue after a delivery). They arise from the thickening of the local lining; have some vessels, fibrous and muscular tissue. These polyps often produce no symptoms but generally cause intermittent blood stained discharge. They also have some pain as the uterus contracts trying to get rid of them. The diagnosis is made by good quality ultrasound or by a procedure called saline sonography in which we take an ultrasound after putting some saline in the uterine cavity.

They should be surgically removed and tested by pathology they are almost always benign and harmless but a minority may have a malignant potential.

 ADINOMYOSIS (A)

The word a stands for a condition called Adenomyosis. I wonder why Endometriosis is not included in this group, as this is often a cause of abnormal uterine bleeding which is often painful. Adenomyosis, in a way is endometriosis of the uterus. Endometriosis means that the uterine lining is present outside the uterine cavity affecting the ovaries, tubes, and surrounding area. In Adenomyosis this lining is present within the muscles of the uterus causing abnormal painful bleeding. This diagnosis can be made by ultrasound and an MRI. It is included in AUB classification, but there are several different pathology descriptions from the uterus. Until then the authors of PALM-COEIN agree that Adenomyosis should be included in the classification of AUB, if the diagnosis is confirmed at least by ultrasound, until further classification is done for Adenomyosis.

LEIOMYOMA (L)

The word L in this classification stands for leiomyoma, commonly called Fibroids. This is the most common cause of AUB. Almost 60 to 70 %women in the world get these in their life time. They are not always symptomatic.  They can vary in size from an apple to a very large watermelon. I have removed two fibroids size of watermelon. The symptoms depend where they are located. One of these women did not have any problems except for a large mass.

They are further classified depending where they are located. Intramural means within the uterine muscles, subserous means outside the muscles, and submucous involving the endometrial cavity. These are the most significant as they cause AUB, infertility, post coital bleeding and miscarriages.

A woman can have many fibroids; once upon a time I have removed as many as 25 fibroids from one woman.

She was young and keen to have a baby .She did succeed in having a baby.

ENDOMETRIAL HYPERPLASIAAND MALIGNANCY (AUB-M)

The other cause of AUB is abnormal endometrial proliferation called atypical hyperplasia and endometrial malignancy.  Although uncommon it cannot be ignored. It does happen in reproductive age groups, and is most common in 50 and 60 year olds. It is sub classified, using WHO previous FIGO system. This often happens if the hormone system is imbalanced and oestrogen is predominant as it can happen when menstrual cycles are anovulatory(meaning that they are not making an egg)as happens in polycystic ovarian syndrome, premenopausal years when the ovarian activity goes abnormal, hormones as treatment  with oestrogens only as some times in HRT. This can also happen if women are obese with a body mass index more then 35.  Many reactions in our body happen due to obesity, such as diabetes high blood pressure, enzymes from the fatty tissues, hormone binding and insulin binding chemicals (Called globulins) result in free floating hormones with a predominance of oestrogen activity resulting in endometrial hyperplasia. This in the end is the main cause of endometrial cancer; most recently WHO has classified Endometrial Hyperplasia, in two groups; one with no atypical cells; the other with atypical cells. This has made life very simple. Ones with no atypical cells hardly ever develop endometrial cancer (may be 1-3%) where ones with atypical cells have a risk of almost 50 percent and need urgent and major treatment. I will discuss this in the next post

COAGULOPATHIES (AUB-C)

Coagulopathies includes disorders of blood coagulations. These are inherited or caused by infections or drugs. Most bleeding disorders most often present in adolescence, they also have tell tale signs such as bleeding from the nose, and easy bruising. The most common inherited, bleeding disorder in women is vonWillebrands disease, (they are deficient in 2 clotting factors) about 1% women suffer from this in the general population but all of them do not get heavy AUB. Deficiency of other clotting factors is very rare. The most common acquired bleeding disorders are platelet (these are the most essential part of blood coagulation) disorder, and leukaemia. The most common problems are decreased levels of platelets. Along with others, I am of the opinion that if bleeding disorders are suspected, it is worthwhile to have an input from a haematologist. Severe liver disease can also cause bleeding problems due to clotting factor deficiency.

OVULATORY DYSFUNCTION DISORDERS (AUB-O)

Until recently when abnormal uterine bleeding occurred, In absence of any detectable uterine pathology it was called dysfunctional uterine bleeding(DUB), which the FIGO are now trying to discard in preference to their new classification of AUB. Ovulatory disorders encompass a wide range of disorders ranging from no periods, to scanty periods, irregular bleeding, and unscheduled bleeding, to very heavy profuse bleeding requiring urgent medical or surgical treatment. This happens due to failure of ovulation, there is no progesterone, for a normal menstrual cycle. This often happens in adolescence, and at the time of menopause transition, or abnormal endocrine activity such as PCOS, Hypothyroidism, increased Prolactin levels. Besides these, mental stress, eating disorders, anorexia, excessive exercise (these usually cause no periods), and obesity.
ENDOMERTIAL (AUB-E)

Under normal menstrual cycle menstruation is a very regulated process .under the hormonal control of the menstrual cycle, the bleeding starts when the progesterone

is withdrawn The bleeding process starts, with, this the platelets gather and a plug  is formed , soon after fibrin deposition happens his closes the bleeding blood vessel. Along with this fibrinolysis occurs to keep the blood fluid. Complex reactions take place within the  endometrium with the help of substances called prostaglandins E  and F alpha. Many other hormone and chemicals interact with each other to keep the bleeding under control.  They are vasoconstrictors, and

Coagulants, some are vasodilators and anticoagulants. Tissue factors within the endometrium and coagulation factors keep the endometrial bleeding under control, imbalance between these is probably often the cause of HMB. Recent research has led to a thinking that haemostatic agents such as Tranexamic acid and Desmopressin(Synthetic drug) can help with HMB even in situations of Coagulation disorders. In spite of this knowledge we do not have any tests to measure endometrial dysfunction. This diagnosis is made by exclusion of other local pathologies.

There is no direct relationship between Pelvic inflammatory disease and AUB. It is suspected that 1 in 4 women with Pelvic inflammatory disease may get intermenstrual bleeding or prolonged bleeding. This may also occur if there is deficiency

In endometrial healing .This relationship is often suspected when an endometrial picture showing inflammatory cells particularly a silent infection with Chlamydia (A common sexually transmitted infection). Sometimes abnormal bleeding is also seen in early cases of pelvic tuberculosis. The bleeding (HMB) due to endometrial problems should be classified by exclusion of other causes such as ovulation.

This in the opinion of researchers, needs further evaluation

IATROGENIC (AUB-I)

By iatrogenic causes of AUB we mean drugs, and treatments that cause AUB. These are mainly hormone Drugs we use to regulate the menstrual cycle or for contraception if forgotten or lost due to gastrointestinal causes. This can cause what we call break through bleeding (BTB). Smoking also causes BTB because of enhanced hepatic function .Other causes of reduced oestrogens and progesterone are drugs such as antiepileptic, antibiotics and drugs used for mental disorders. Progesterone only contraceptives such as depo-provera

And implanon( the rod we put in the arm) also causes AUB more so in the smokers. The uterine loop, the intrauterine systems used for contraception (Mirena containing levonorgestrel) also causes AUB, particularly in the first 6 months after insertion. Other very important cause for AUB is women on anticoagulants for medical treatment.  There is very simple explanation that they fail to make adequate clotting.

One recent cause for iatrogenic AUB is called uterine isthmocele secondary to caesarean section. Dehiscence of the uterine scar creates a pouch like reservoir where the blood collects during menstruation, these women present with previous caesarean sections followed by post menstrual AUB and pain.  This is repaired by hysteroscopy or laparoscopy. The other important cause of iatrogenic AUB is the drug, used for breast cancer Tamoxifan. They cause endometrial polyps and proliferation and even cancer thus causing AUB.

ENTITIES NOT YET IDENTIFIED (AUB-N)

These include condition such as endometritis, arteriovenous malformations, hypertrophy of myometrium and the role of endometrium in haemostasis. These need to be further worked, biochemically or biologically before they can be classified.

In my next post I will discuss the management and treatment of Abnormal Uterine Bleeding

ABNORMAL VAGINAL BLEEDING IN REPRODUCTIVE YEARS

FROM MENARCHE TO MENOPAUSE.

Generally we discuss the causes of vaginal bleeding, including the local vaginal, cervical and even urethral bleeding including bleeding from the uterus. I have decided to divide this in two sections. In the first section I will discuss the causes of local bleeding, that is bleeding from the vagina, cervix and rarely from the urethra. These disease processes like anywhere else can be divided, into, infections, trauma, foreign body and pre-cancer and cancer. These have been briefly discussed in the post on vaginal bleeding in adolescence. These never cause profuse vaginal bleeding. It is usually a blood stained often smelly discharge. Candidasis a very common infection in women almost never causes significant bleeding. Trauma after sexual interference or otherwise can cause moderate bleeding. I always remember a young bride brought to our hospital from the railway station having had sex in the train on her honeymoon journey, which bled so profusely that she required a blood transfusion. Similarly trauma can cause moderate to profuse bleeding. I have witnessed these after severe motor car accidents. Foreign bodies also usually cause blood stained smelly discharge, a left over tampon is a common example, and I have removed 100’s of these in my working life. Vaginal and vulval carcinomas are usually a disease of older post menopausal women. Cervical cancer and precancerous lesions of the cervix are common in this age group often precancerous lesions of the cervix are silent.

In the past fifty years a lot of attention was paid by doing cervical smears. Since we have vaccines for the human papilloma virus, which is the causative virus for cervical cancer, things have improved.  Cervical cancer is still very prevalent in developing countries as most of them have no access to the vaccine and even no facility for cervical cytology. In India some gynaecologists have started to do a simple vinegar test which is giving good results to detect pre-cancer  of the cervix. Cervical cancer always causes vaginal bleeding, again often it is a blood stained smelly discharge. It is often very distressing to tell a woman that you have advanced cancer when she only has a blood stained discharge. Besides these, vaginal bleeding can also come from the bladder opening, the urethra or bladder infection or from the rectum, it may just be due to haemorrhoids or even rectal cancer. When you experience vaginal bleeding never forget to ask about bladder infections or rectal bleeding.

Let me now discuss the real causes of abnormal uterine bleeding.(AUB) I have briefly explained the menstrual cycle in my previous posts.  Some woman often have moderate to severe bleeding with their periods along with some pain. Until very recently there was no clear understanding of these problems. One woman can have more than one, two or even three   problems. These lead to chronic ill health and infertility, loss of work and income. Until recently there was no universal nomenclature or classification system for the gynaecological problems.  It made life difficult for the clinicians, patients and research scientist. Luckily in 2010-2011, AUB had been classified by a great Acronym,Palm-coein (prounounced  pahm_koin) which has been approved by the International Federation of Gynaecology and Obstetrics(FIGO).This was published in 2011 by Elsevier Ireland Ltd. I read this in the international journal of Gynaecology and Obstetrics (Volume 113, 2011). I was so elated by finding this classification and all the explanations.

POLYP (P)

In this classification P stands for polyp. They can be of many types, cervical, Endocervical (arising in the cervical canal) endometrial and rarely placental (left over placental tissue after a delivery). They arise from the thickening of the local lining; have some vessels, fibrous and muscular tissue. These polyps often produce no symptoms but generally cause intermittent blood stained discharge. They also have some pain as the uterus contracts trying to get rid of them. The diagnosis is made by good quality ultrasound or by a procedure called saline sonography in which we take an ultrasound after putting some saline in the uterine cavity.

  

They should be surgically removed and tested by pathology they are almost always benign and harmless but a minority may have a malignant potential. 

 ADINOMYOSIS (A)

The word a stands for a condition called Adenomyosis. I wonder why Endometriosis is not included in this group, as this is often a cause of abnormal uterine bleeding which is often painful. Adenomyosis, in a way is endometriosis of the uterus. Endometriosis means that the uterine lining is present outside the uterine cavity affecting the ovaries, tubes, and surrounding area. In Adenomyosis this lining is present within the muscles of the uterus causing abnormal painful bleeding. This diagnosis can be made by ultrasound and an MRI. It is included in AUB classification, but there are several different pathology descriptions from the uterus. Until then the authors of PALM-COEIN agree that Adenomyosis should be included in the classification of AUB, if the diagnosis is confirmed at least by ultrasound, until further classification is done for Adenomyosis.

LEIOMYOMA (L)

The word L in this classification stands for leiomyoma, commonly called Fibroids. This is the most common cause of AUB. Almost 60 to 70 %women in the world get these. They are not always symptomatic.  They can vary in size from an apple to a very large watermelon. I have removed two fibroids size of watermelon. The symptoms depend where they are located. One of these women did not have any problems except for a large mass.

They are further classified depending where they are located. Intramural means within the uterine muscles, subserous means outside the muscles, and submucous involving the endometrial cavity. These are the most significant as they cause AUB, infertility, post coital bleeding and miscarriages.

A woman can have many fibroids; once upon a time I have removed as many as 25 fibroids from one woman.

She was young and keen to have a baby .She did succeed in having a baby.

ENDOMETRIAL HYPERPLASIAAND MALIGNANCY (AUB-M)

The other cause of AUB is abnormal endometrial proliferation called atypical hyperplasia and endometrial malignancy.  Although uncommon it cannot be ignored. It does happen in reproductive age groups, and is most common in 50 and 60 year olds. It is sub classified, using WHO previous FIGO system. This often happens if the hormone system is imbalanced and oestrogen is predominant as it can happen when menstrual cycles are anovulatory(meaning that they are not making an egg)as happens in polycystic ovarian syndrome, premenopausal years when the ovarian activity goes abnormal, hormones as treatment  with oestrogens only as some times in HRT. This can also happen if women are obese with a body mass index more then 35.  Many reactions in our body happen due to obesity, such as diabetes high blood pressure enzymes from the fatty tissues, hormone binding and insulin binding chemicals (Called globulins) result in free floating hormones with a predominance of oestrogen activity resulting in endometrial hyperplasia. This in the end is the main cause of endometrial cancer; most recently WHO has classified Endometrial Hyperplasia, in two groups; one with no atypical cells; the other with atypical cells. This has made life very simple. Ones with no atypical cells hardly ever develop endometrial cancer (may be 1-3%) where ones with atypical cells have a risk of almost 50 percent and need urgent and major treatment. I will discuss this in the next post

COAGULOPATHIES (AUB-C)

Coagulopathies includes disorders of blood coagulations. These are inherited or caused by infections or drugs. Most bleeding disorders most often present in adolescence, they also have tell tale signs such as bleeding from the nose, and easy bruising. The most common inherited, bleeding disorder in women is vonWillebrands disease, (they are deficient in 2 clotting factors) about 1% women suffer from this in the general population but all of them do not get heavy AUB. Deficiency of other clotting factors is very rare. The most common acquired bleeding disorders are platelet (these are the most essential part of blood coagulation) disorder, and leukaemia. The most common problems are decreased levels of platelets. Along with others, I am of the opinion that if bleeding disorders are suspected, it is worthwhile to have an input from a haematologist. Severe liver disease can also cause bleeding problems due to clotting factor deficiency.

OVULATORY DYSFUNCTION DISORDERS (AUB-O)

Until recently when abnormal uterine bleeding occurred, In absence of any detectable uterine pathology it was called dysfunctional uterine bleeding(DUB), which the FIGO are now trying to discard in preference to their new classification of AUB. Ovulatory disorders encompass a wide range of disorders ranging from no periods, to scanty periods, irregular bleeding, and unscheduled bleeding, to very heavy profuse bleeding requiring urgent medical or surgical treatment. This happens due to failure of ovulation, there is no progesterone for a normal menstrual cycle. This often happens in adolescence, and at the time of menopause transition, or abnormal endocrine activity such as PCOS, Hypothyroidism, increased Prolactin levels. Besides these, mental stress, eating disorders, anorexia, excessive exercise (these usually cause no periods), and obesity.

IATROGENIC (AUB-I)

By iatrogenic causes of AUB we mean drugs, and treatments that cause AUB. These are mainly hormone Drugs we use to regulate the menstrual cycle or for contraception if forgotten or lost due to gastrointestinal causes. This can cause what we call break through bleeding (BTB). Smoking also causes BTB because of enhanced hepatic function .Other causes of reduced oestrogens and progesterone are drugs such as antiepileptic, antibiotics and drugs used for mental disorders. Progesterone only contraceptives such as depo-provera

and implanon( the rod we put in the arm) also causes AUB more so in the smokers. The intrauterine systems used for contraception (Mirena containing levonorgestrel) also causes AUB, particularly in the first 6 months after insertion. Other very important cause for AUB is women on anticoagulants for medical treatment.  There is very simple explanation that they fail to make adequate clotting.

One recent cause for iatrogenic AUB is called uterine isthmocele secondary to caesarean section. Dehisence of the uterine scar creates a pouch like reservoir where the blood collects during menstruation, these women present with previous caesarean sections followed by post menstrual AUB.  This is repaired by hysteroscopy or laparoscopy. The other important cause of iatrogenis AUB is the drugs used for breast cancer Tamoxifan. They cause endometrial polyps and proliferation and even cancer thus causing AUB.

The above image is of Uterine Isthmocele being corrected.

ENTITIES NOT YET IDENTIFIED (AUB-N)

These include condition such as endometritis, arteriovenous malformations, hypertrophy of myometrium and the role of endometrium in haemostasis. These need to be further worked by biochemically or by biologically before they can be classified.

In my next post I will discuss the management and treatment of Abnormal Uterine Bleeding.

PUBERTY MENORRHAGIA

As I have already mentioned in different paragraphs earlier, puberty signifies sexual maturity. It takes place in stages from about 10 to 15years of age; the culmination of puberty is Menarche, the start of menstrual cycle. It is now ,that a young girl becomes a woman and can reproduce. They develop breasts pubic and axillary hair and gain height. It takes some time for their menstrual cycles to mature and become regular. At this stage it also does not produce an egg every month; these cycles are called anovulatory cycles. There are many other reasons why these cycles are anovulatory. As mentioned in previous posts on menstrual cycle. The menstruation works by ,well controlled activation between three main endocrine glands Hypothalamus and Pituitary in the brain and the Ovary, this is called Hypothalamus Pituitary and Ovarian axis (HPOAXIS).Maturation of the HPOAXIS is characterised by the frequency and amplitude of secretion of GnRH(Gonadotrophin releasing ) hormone from the hypothalamus which regulates the production of FSH and LH from the pituitary. The basal FSH and LH are enough to help with the maturation of the follicle but inadequate to cause ovulation, thus resulting in anovulatoy cycles. This upsets the complex mechanism of normal menstrual cycle

This takes time to mature after menarche. This is the main physiological reason for irregular heavy periods. When this happens from menarche to 19 years of age it is called puberty menorrhagia.

HOW MENSTRUAL BLEEDING OCCURS AND STOPS

When the Oestrogen and Progesterone are withdrawn during the menstrual cycle the growing superficial layers of the endometrium start shedding, it is auto digested by a complex mechanism. The basal layer of the endometrium starts regrowing for a new cycle .With many other complex changes the blood vessels retract and the bleeding stops. There are 2 hormones secreted by the endometrium when it is disintegrating, prostaglandin PGF2 (vasoconstrictor and platelet aggregator) and PGE2 (vasodilator and week platelet aggregator) under the influence of Oestrogens and Progesterone. In normal menstruation the ratio of PGF2and PGE2 is 2:1. Together they balance the menstrual bleeding.    If there is no ovulation in absence of progesterone PGF2 decreases, PGE2 increases resulting in more vasodilatation and more bleeding hence menorrhagia.

POLYCYSTIC OVARIAN SYNDROME

The other reason for puberty menorrhagia is a condition called, Polycystic Ovarian syndrome (PCOS) This is a complex endocrine disorder of reproductive years and can occur at any age. It is estimated that at present there are about 6-10 % of women who suffer from this problem. In addition to excessive bleeding they generally have no periods, hair on the face and body, acne, pigmentation of the neck, obesity, and infertility and may have diabetes or tendency to be diabetic.

I have described this problem under a special post on PCOS early last year.

COAGULOPATHIES (BLEEDING DISORDERS)

In our bodies there are mechanisms built in, so that they come into play when we are bleeding. This is done by coagulants and cells in the blood called platelets. When this coagulation system is disturbed, people suffer from bleeding disorders.  These can be inherited or can happen by viral infections, drugs and radiation therapy. Platelet deficiency and platelet function disorders; cause menorrhagia from the start of periods.  This is often severe and often requires blood transfusion and even platelet transfusion. The other problem caused by bleeding disorders is called vonwillebrands disease. This is an inherited disease caused by a defect in vonwillebrands factor; this prevents both platelet adhesion and clotting which are both important to stop bleeding. Besides these, there are many other problems which can cause excessive bleeding, these can be pelvic infections, early stages of pelvic tuberculosis (Rare in developed countries however seen mainly in developing countries), drugs, and some intrauterine contraceptive devices, then local uterine polyps and uterine fibroids; although rare in this age group

can cause heavy bleeding .Pregnancy related complications are often a cause of excessive bleeding. In a woman who is bleeding always do a pregnancy test and make sure she is not bleeding due to some complication of pregnancy  One very important and a fairly common problem at puberty is a condition called Endometriosis. In this condition the lining of the uterus is scattered outside the uterus. This can happen in very young teenagers. This causes heavy periods, irregular bleeding and pain. In spite of years and years of research we cannot yet explain why this happens. Besides these thyroid dysfunctions a particularly underactive thyroid can also cause menorrhagia.

WHAT IS MEMORRHAGIA?

Normally it takes 4-5 days for menstruation to stop and the average blood loss is 80 mls. If it lasts for 7 days or more, a teenager soaks a tampon or a pad in less than an hour and has

to change pads during the night, passes blood clots with her menstrual bleeding and feels very tired, has anaemia then she is surely bleeding; too much.

When she presents to her doctor, she should take a proper medical and family history.  Examine her for pallor (Anaemia) any lymph nodes, abdominal examination for spleen, liver any abdominal masses e.g. a fibroid. Examine the skin for bruising (this happens with bleeding disorders), hairiness on the face and body, as can happen in PCOS.

The main tests required are blood tests for anaemia, bleeding disorders, thyroid function tests, pregnancy test endocrine tests (POCS) and pelvic ultrasound. Some special tests such as vonwillebrand factor are also required.

TREATMENTS

One has to be very sensitive and careful in treating these teens particular in some countries such as Pakistan, Egypt and other countries because of their cultural differences.  Initially non hormonal therapy is used during menstruation. Some drugs called prostaglandin synthetase inhibitors are initially used. The most common drug is called Mefaminic acid, 500 mgs followed by 250 mgms 6hrly or less for 2-3 days during bleeding time. These drugs can cause stomach upset and thrombosis problems, however they   also help with period pain. The other drugs are very effective and commonly used and are called Tranexmic acid. It is given 1-2gms per day it is a very effective. It can also be given intravenously. It is also being used for bleeding due to trauma; in fact they are using it for post partum bleeding. Anaemia also requires correction either by blood transfusion, iron transfusion or simple oral iron if it is not too bad. Hormonal treatment with progesterone is useful when the cycles are anovulatory.  This can be followed by cyclical progesterone. The simple and very easy treatment is combined oral contraceptive pill, if the woman and her family agree. In women with very profuse bleeding, when their blood volume is disturbed, they were treated by blood transfusion and intravenous equine oestrogens. 25mgms every 4 hours for 24 hours and the bleeding generally settles in 24 hours. Then Oral oestrogens can be used.  For women with vonwillebrands disease; Tranexamic acid can be used. They also respond to oral progesterone .Tranexamic acid is a relatively cheap drug and is available all round the world under different names. WHO recommends this drug as an essential medication for all emergencies round the world? Besides these treatments an intrauterine device with a hormone impregnated called levonorgestral( MIRENA)is , very useful. Once fitted inside the uterus it lasts for 5 years. A special preparation called desmopressin acetate is also very useful for vonwillebrands  disease .This is not always easily available, long term we try to manage with combined oral contraceptive pill and  tranexmic acid during period . This protects the fibrin hence helping with coagulation. If the woman has any local disease such as uterine polyp or a fibroid it is surgically treated. For POCS we give combined oral contraceptive pills. 

PRECOCIOUS OR PREMATURE PUBERTY

When an individual matures both emotionally and physically and becomes an adult capable of reproduction through the natural development of the reproductive organs, it is expressed as puberty. It happens in stages, both in boys and girls. The age when it happens depends on race, nutrition and

genetics . The normal age of maturation in a girl is about 10 -11 years, in boys it is 9 to 12 years. The girls have their first period about the age of 11. This is called menarche.

To start with if your child is 6 years of age or younger and shows development of breast buds, growth spurt, axillary hair, problems at school and if she has a period; you have to be worried, this is surely precocious puberty.  Please tell your child honestly what is going on. Tell her this is normal as you grow older but for some reason your body has started developing earlier.

The good news is that these children can be treated. To understand what causes premature maturation let us revise what starts maturation in the first place. In the brain (The Hypothalamus) starts the process, how we do not know. The brain secrets a hormone called Gonadotropin- releasing hormone (GnRH). This acts on our main endocrine gland which is the pituitary gland located in the brain, which in turn realeases two more hormones, follicle – stimulating hormone (FSH) and luteinizing hormone (LH). These act on the ovaries in the female, producing oestrogens and small amounts of testosterone. In boys they act on the testicles producing testosterone. The oestrogens and testosterone cause puberty changes in boys and girls. In girls testosterones helps with the growth of axillary and pubic hair. The hormone called LH is involved with ovulation.

When this maturation occurs at a very young age it is called Precocious Puberty. Puberty can also be delayed causing anxiety again. We will discuss this in another blog.

These early developmental changes when they arise in the brain, are called central precocious puberty. This can also happen due to brain tumours, infections of the brain, too much fluid in the brain (Hydrocephalous), radiation to the brainThere are peripheral problems (outside the brain) which can cause precocious puberty. . Congenital problems and congenital adrenal hyperplasia. McCunes – Albright syndrome, is also a congenital disorder which causes hormone problems and finally an under active thyroid gland can also cause precocious puberty

These can be due to tumours of the adrenal glands, ovarian cysts and ovarian tumours.

  

WHAT ARE THE RISK FACTORS

Girls of African American origin, obese girls and exposure to hormones which can be used for treatment of other medical conditions and radiation for tumours or leukemia.

COMPLICATIONS

Initially they grow taller than their age, then they stop once they achieve puberty; because their bones stop growing earlier than usual. Treatment started early will help them to grow taller. The girls whose bodies are changing become very self conscious withdrawn and depressed.

DIAGNOSIS

You must take your child to a Paediatrician or a Paediatric endocrinologist.  They will study your family medical history, the child’s history and do a general examination. They will also do blood tests, mainly hormones, including Thyroid, ultrasound of the Ovaries. X-ray of bones to assess the bone age and magnetic resonance of the brain to see if there are any brain conditions. These tests will help them to know if the precious puberty is of peripheral or central origin.

TREATMENT

The child if of an understanding age, should be explained what is going on. Reassured and praised where possible, such as any achievement in sport, school which will help to build self confidence. Generally no treatment is offered if the child is about 8 years of age. For precocity of central origin GnRH   analogue therapy is offered, named LEUOPROLIDE as an injection once a month until the age of puberty. It suppresses the GnRH activity. 16 months after the treatment is stopped maturation starts again.

Any other peripheral diseases are treated as well, such as an under active thyroid or any tumours, which are removed. This   analysis does not cover precocious puberty in boys.

SUMMERY

Precocious Puberty is when a child’s body develops like an adult at a very young age. It is a very rare condition and occurs once in 5000 children, but once it happens it is frightening. Do not panic.  It is easily diagnosed and treated.

Puberty includes rapid growth of bones muscles and genitals, body shape and size changes and it can reproduce. The cause of this precocious development is often not understood. Sometimes infections, injuries, tumours, brain abnormalities and radiation cause these problems. The treatment includes stopping   any further maturation.

ABNORMAL BLEEDING IN WOMEN IRREGULAR AND HEAVY

Adolescent Girls and Children

In this post I will discuss the causes of abnormal bleeding in women. This can happen in any age group. I will divide this into a number of posts. In the first post I will talk about the causes in children and adolescence. There are 4 reasons for this abnormal bleeding.

1) Vaginal Infections: vulvovaginitis, this is a common infection of the external part of the young girls vulva and vagina.

This is a Comfortable Position for a Child to be Examined

This happens because the young girls have less resistance to infections which may be due to lack of oestrogens (oestrogens only happen in our body when periods start).This is not difficult to treat you can take a swab from outside the vulva and vagina to see what the infection is. Always tell the children and young girls to keep their vulva and vagina clean. Wash it with water if possible. Always use loose cotton under wears as this helps with the soreness and healing.  Applying a bit of Vaseline is a very simple trick. Do not wear very tight undergarments or share them. Do not wear panties to bed. Do not put any antiseptic such as Dettol in the water. Avoid baths if you can have a shower.

You can bath your bottom in a basin. Have a very clean basin on the toilet seat, fill it up with about 15 litres of cooled boiled water, add 2 tablespoons of salt, and sit in the water for 10 to 15 minutes.

It is very soothing. The swabs that where originally taken will show the infection and your GP, will prescribe the appropriate treatment. If the swab shows an infection called tricomonas or gonorrohea, beware. These are sexually transmitted infections. You as a mother will have to explore it further. Constiption should be avoided, as most of these vaginal infections come from the anus.  Threadworms are very common in young girls. When the children scratch the minute eggs of threadworms get transmitted to the vagina and irritate the child, but there no discharge. Please get the stool examined. It is easy to get rid of the threadworms. Always teach your child to wipe their bottom from front to back. Candidiasis is not such a common infection in children unless she has taken antibiotic or she is diabetic a taken bath with her mother who carries an infection.

I started the discussion about vaginal bleeding but got side tracked by vaginal discharge. One of the rare causes of blood stained discharge in children is a foreign body. In my time I have removed a few of these, such as, a safety pin, mother’s hairpin, and a lolly. If the discharge is bloody always try to look inside the vagina. A nasal speculum is a very good tool with a light. These may need to be removed under anaesthesia. I was able to remove a safety pin with a sterilized pair of tweezers.

One of the rare skin conditions that can affect very young girls is called Lichen sclerosis. This occurs at either end of a female’s life. We do not know what causes it, may be immunological. The girls present with intractable pain, itching and difficulty or pain on passing urine. Often there is some bleeding. On looking at it the skin appears dry shiny stretched and pigmented. It is a chronic condition and can last a long time. It has malignant potential.

The Above Picture is of a Normal Vagina

The Vulval Changes in Lichen Sclerosis

               

On looking the skin looks white and shine, pigmented and crinkly. In these cases we should try and exclude any sexual abuse. The diagnosis is confirmed by skin biopsy. The treatment should be started early. In asymptomatic or very mild cases soft emollient is enough. Local Corticosteroids are required in more well defined cases; in more severe cases stronger corticosteroids are used. Rarely immunological suppressants are used in combination with local high potency corticosteroids. Recently cell therapy is being tried by some plastic surgeons. The good news is, in most girls it resolves by puberty. Recurrences can happen; these cases should be followed up after 6 months and then yearly.

Other causes of vaginal bleeding can be due to injury; this can happen in school play grounds, bicycle riding or foreign bodies just being there or when they are sharp and big and sexual interference. If the injury is blunt not bleeding and the vulva is swollen it need reassurance, pain relief and cold compress. If bleeding it needs repair under anaesthesia. Sexual interference can be very traumatic. You have to work out who the offender is, look for sexually transmitted infections, and be very sympathetic to the family. I can never forget a case which I had to deal with of a 6 year old girl in 1968 when I was a very new gynaecologist with no experience in children. This girl was brought in with profuse bleeding on Sunday at midnight after being   assaulted by a big man by sexual intercourse. She was sleeping outside on the street with mum and dad in terrible heat. I called the theatre staff an anaesthetist, blood transfusion services, and the police, I got the terrible man arrested I took the child to the theatre tried to stop the bleeding. The whole area was so damaged could not make out what was what, however 3 hours I was able to stop the pouring of blood, it was still dribbling. I was unable to find a paediatric surgeon. We also gave her 2 units of o negative blood (o negative blood is a universal donor) as that was all I could get. I needed help from other specialists such as a internist or interventionist but these were just fancy words in those days. She ultimately died 2 days later. That was a very sad day in my very new profession. I can still remember her face.

The cause of bleeding can be paediatric malignancies and premature puberty.

Paediatric malignancies of the genital tract are extremely rare say about 5%of the total malignancies in children they are usually referred to tertiary centres where they have a paediatric gynaecologist. They happen both in girls and boys; they often arise in the left over remnants of embryonic tissue, use of diethylstilboestrol during pregnancy to prevent the miscarriage (this used to be practiced long time ago).

The discussion on paediatric malignancy and premature puberty is outside the scope of this blog. I will discuss premature puberty in the next 

PREMENSTRUAL SYNDROME

Premenstrual Syndrome (previously and even now called premenstrual tension) is one of the most common problems woman suffer soon after the menstrual cycle starts. Almost 50 to 95 % of women suffer from this condition in some form (may be very mild) some time in their life during their menstrual cycles. It is worst between the ages of 20 to 40, around peri menopausal time, and often in post natal time.

This does not happen during pregnancy as women have no periods during pregnancy. This is a series of symptoms that women suffer in the last week of their menstrual cycle (luteal phase). It lasts for about 7 -10days settling down soon after the menstruation (bleeding) starts. It has been cited resulting in poor studies, work performance, domestic life, criminal acts, life threatening, even suicide and murders.  When the problem becomes very severe, it is called premenstrual dysphoric disorder (PMDD). This happens in 3 -8% of those women who suffer premenstrual syndrome (PMS). Even in my own working life, I have witnessed many serious crimes, suicides and murders.

For a very long time medical specialists did not believe in this, they thought it was all in the women’s mind. Luckily for those who suffer from this terrible disability, it is now well recognised as a problem of women’s reproductive life.

  WHAT CAUSES IT?

We don’t exactly understand what causes it. It is probably the result of irregular hormone changes during the ovarian cycle (menstrual cycle). Withdrawal of oestrogens and progesterone in the second half of menstrual cycle, sensitivity to progesterone may also be the cause. The second major problem is thought to be cyclical ovarian activity and the effect of oestradiol and progesterone on the neurotransmitters in the brain. These  neurotransmitters, are called Serotonin, Gamma-aminobutricacid (GABA)are other important key factors .Vitamin B6  magnesium deficiency and hormones such as serotonin, endorphins, and prostaglandins also play an important role. It is possible that this is an exaggerated response of some organs in the body, such as the breasts, brain and joints to these various hormone changes their withdrawal or deficiency or excess. One of the reasons why researchers were not able to give it a diagnosis, as it has too many symptoms; some authors have enumerated as many as 150 different symptoms. How is the diagnosis made?  The most important is the history. The clinician should ask his/her patient about when it happens, and what happens. This should be documented in writing in relation to the menstrual cycles for at least 2-3 cycles. That will give the diagnosis. No tests are required unless there are any associated problems. Sometimes a haemoglobin and thyroid function and prolactin (other hormone) tests are also done .Rarely it may be required to exclude Bipolar disorders (PSYCHIATRIC DISORDER). If the symptoms are in peri menopausal years a FSH is done to exclude menopause

The problems of PMS, Postnatal depression and increased peri menopausal depression occur in the same individuals so it was thought that there may be a genetic predisposition. A gene on oestrogen receptor alpha is being implicated. A lot more research is required to substantiate this.

Symptoms of PMS

These are divided into two groups

1) Psychological and Behavioural

These are mainly mood swings irritability, lazy and tired, inadequate sleep, feeling anger for no reason, anxiety and loss of control. These symptoms can make life very difficult if you are a professional woman doing a ward round or a court case. Your cognitive ability can also suffer. Food cravings are also very real.

2) Besides these there many physical symptoms, of these very severe headache is the worst. You can have very tender breasts, back ache, skin rash, pimples or acne and fluid retention. This adds to the weight gain. 

How to manage PMS or its severe form PMDD

In milder cases or in fact in all the cases we should pay attention to life style factors. Regular exercise walks meditation, Pilates, good sleep, avoid stress, alcohol, caffeine, tobacco and eat a well balanced and proper diet; rich in green leafy vegetables, fruits, lentils and some modern super foods such as quinoa, flax seeds and chia seeds. Most of these and others are very rich in Omega 3 and 6 fatty acids and linolenic acid.  Premenstrual syndrome is a complex cluster of symptoms difficult to explain, it is possible that these dietary supplements rich in these acids alter the fatty metabolism and alters the tissue sensitivity to another hormone called Prolactin. Prolactin is not directly related to PMS, but when prolactin is high, symptoms of PMS are more intense in women with Bipolar disorders. Symptoms of bipolar disorder become intense in the premenstrual phase. A lot of research is being done on management of women with both PMS and Bipolar.

With a correct life style you can help your PMS as it reduces fluid retention, mood swings, and breast tenderness. Nibbling with healthy foods, e.g.: carrots celery and nuts, occasional dark chocolate, instead of commercial fried food and biscuits.

Complementary Treatments (CAMS) for PMS.

These CAMS are as ancient and as multiple as PMS symptoms.

Many of these are not licensed and proven to be of value, yet women swear by them. Celery seeds were very popular at one stage, as they cause diuresis which helped with bloated feeling, weight gain and to some extent breast tenderness. I never prescribed it, and never come across it being used in recent times.

Evening Primrose oil was used by many clinicians as well as other health professionals who recommended it. 1-2g of evening primrose oil was prescribed daily, either in the last two weeks of the menstrual cycle or continuously. It is still used today. It is generally useful particularly for very severe breast tenderness. It contains a chemical, gammalinolenic acid, which is required for production of prostaglandins in our body which in turn are necessary for many biological functions.

It comes as 1000 mg capsules, up to 2 capsules three times a day are recommended .Most recent research suggests that this is not used, unless breast problems are very severe.

Vitex Angus castus is another herbal remedy which is very popular. It is called by many different names. The tree is called a Chaste tree. Its extract (from fruits and leaves) is useful in the management of PMS, as it contains many chemicals such as flavinoids and iridoidglycosides.

It helps to regulate the bleeding and the menstrual cycle, tension, breast tenderness, and fluid retention. The dose is 1 tablet of 350 micrograms three times a day. The only problem with vitex is that it is difficult to find a standardised dose. 

The other herbal remedy often used is called St John’s Wort. It is useful for depression, cognitive and emotional problems. It is not to be used if you are already taking traditional medical drugs as it reacts with them. There are many other herbs recommended for PMS, such as lemon balm, turmeric and saffron. Please do not use them as their use is controversial and there are conflicting reports on them.

MEDICAL TREATMENTS OF PMS

Vitamin B6 this has been used for a long time for management of PMS. A dose of 50 mgms is given daily or in the second half of the menstrual cycle. Some clinicians use 100mgms but recent research suggest it is useless to use 100 mgms. There is very little evidence to show that it has more than marginal benefits.

Magnesium may have some benefit if used in dosage of 250 mgm per day. It can be tried for 2-3 months.

Calcium and Vitamin D

High doses of calcium have some benefit.  Try about 400mgms of calcium daily with 700 INU of vitamin D .When I was a child my mother was given an IV calcium injection with the start of PMS symptoms. This was very long time ago. From memory I think it helped her.

Spironolactone, these are potassium sparing diuretic that prevents your body from absorbing too much salt and prevents your potassium levels getting low, these help with bloating and breast tenderness. They have a limited use in PMS but are very useful in many other problems. It should not be used if you have kidney disease or high potassium. It is produced in our body by the Adrenal glands.

Danazol is a synthetic drug, its main use is for a condition called Endometriosis; I am sure most of you have heard this name as it is a very common female painful condition. This is not recommended for PMS, although it decreases GnRH hormone levels and theoretically may help. But it has two draw backs as it can cause masculization in women using it for long or if by any chance she gets pregnant it can cause masculization of the female foetus.

Women using all these remedies must remember about contraception.    

These were all marginal treatments. Let us talk about the definitive treatment of PMS and PMDD.

The real treatment is by suppressing the ovarian hormones. All oral contraceptive pills can be used, but the one which are most recommended are what we call third and fourth generation pills. This means that their quality has improved after every new type that has been invented. These are called  Yasmin or Yaz . These contain 20  micrograms  oestradiol and progesterone called drosperinone(30 mgm) for 24 days , instead of normal 21 days, thus the duration of PMS is reduced or it is hardly there; in spite of this it is recommended that this can be used as a continuous pill for 4 months, thus minimising the duration of PMS.  The main risk factor that remains is the risk of DVT. Be guided by previous history or family history before prescribing this pill or any pill. You have to make sure that a woman does not smoke, is under 35 years of age, and does not have any other risk factors such as blood pressure. Most of the pills are now very safe as regards DVT. As they contain newer, safer oestrogens and very safe progesterones and risk of DVT is negligible.

Oestrogen patches are very useful for treatment of PMS. In milder cases women are given oestrogen patches for 5-7 days when the symptoms generally start in varying strengths (25, 50, 75, 100mirograms) depending on the severity of symptoms. I have very good experience with these, they work well.

Oestradiol patches have also been studied. 100 micrograms of oestradiol was used twice weekly with cyclical progesterone. It was found to be useful. Progesterone is required for the protection of the lining of the uterus called the endometrium; if it is exposed to oestrogens for any length of time it thickens (Hypertrophy) and can cause bleeding and endometrial cancer. Progesterone should be used in the lowest possible dosage required. Your care giver will make sure if you have any reason why you should not be given oestrogens, such as history of breast cancer, DVT and blood pressure. Progesterone can be used as oral and intravaginal. This regime does not totally suppress ovulation so some other contraception will be required. I have a thought that an intrauterine Mirena can be used, and then progesterone will not be required. There is one problem with Mirena in itself, can cause low PMS like symptoms. The researchers have not done studies on the safety of this method (oestradiol patches with progesterone) as regards its effect on breast and endometrium. However in 20 years of their use of this method they did not find any adverse effects.  Come to think about it they were just trying to manipulate the normal menstrual cycle in the reproductive age group. Micronized progesterone orally or vaginally is very well tolerated. 100 to 200 mgms micronized progesterone is used for twelve days in each cycle. It can be used either orally or vaginally

Progesterone only drugs for PMS

These have been in use for a while mainly for contraception. These are depoprovera (250mgm) given every 12 wks by injection, etonorgestrel(implanon Nxt68mg) implanted in the arm under the skin lasts for 3 years, and progesterone only pills , the ones commonly used were called mini pills. Cerazette(Desogestrel) contains75 micrograms.they are given as one tablet daily These progesterone only contraceptives do suppress ovaries, but these tend to replace cyclical symptoms to continuous low grade PMS like symptoms. They also tend to cause irregular bleeding. 

GnRH or Gonadotrophic hormones recommended for treatment of PMS at present. They have been used for many years. They should be used in very severe cases or when the woman does not respond to other simpler treatments.  This is very expensive treatment and causes menopause like symptoms if used for, it can also causes the loss of bone density. The drugs used are called 1)Goserelin injection 3.6 mg four weekly. The other drug used is2) leuprolide acetate (lupron).As GnRH cause severe menopausal symptoms the women need HRT. The commonly used is called Tibilone (Livial) which is a synthetic steroid with oestradiol, progesterone and testosterone function. In case we use oestrogen progesterone women can have PMS like symptoms again. In cases on GnRH for more than I one year bone density should also be measured to exclude osteoporosis. These should be used only for short duration say 6 months, because of serious side effects. GnRH is also used for endometriosis, and shrinking the size of fibroids when they are large before surgical removal.

SELECTIVE SEOTONIN REPUPTAKE INHIBITORS (SSRI)

There is increasingly proven evidence that the chemical called serotonin is important in the causation of PMS and PMDD

Serotonin is a chemical messenger. It helps in many parts of our body particularly mood stabilizer, (HAPPY HORMONE), eating digestion healthy sleeping and the brain. In the brain it acts as a transmitter of messages in the nerve fibres and cells of the brain. “The neurotransmitters”. Serotonin deficiency causes depression and most of the symptoms of PMS and PMDD

It is found in the gut, brain and blood platelets. Many foods, such as eggs, cheese, milk, pineapple, tofu, salmon and kiwi fruit are rich in serotonin.  Exercise, sunshine and positive thoughts also help. SSRI are a class of drugs used for depression. We do not know how exactly they work but while transmitting messages they increase the level of serotonin where the message is to be transferred. It is used in cases of severe depression and PMS and PMDD. Women are happy to take it, as the regime of giving it for Pms or PMDD is different than given for severe depression. Drugs Escitalopram (LEXAPRO), Fluoxtine(PROZAC),and  Setraline(ZOLOFT) are commomly used. It is recommended that dose of 20mgms per day is given from 15 -28 days of the cycle. The benefit is immediate.  If the treatment is used only in the luteal phase of the menstrual cycle the dependence  to these drugs is unlikely. It is good to involve a psychiatrist in this treatment if a woman agrees

COGNATIVE BEHAVIOR THERAPY

This is a short psychotherapy which is oriented to change the perception, thinking feelings and behaviour of a woman which may be related to her personal problems.  This has been found useful, especially when used with SSRI’s.

SURGERY FOR SEVERE PMS AND PMDD

Surgery which is required or commonly done is a total hysterectomy and removal of both tubes and ovaries.

The removal of the ovaries is most important as they are the offending organ. It is best to do this after a trail of GnRH drugs and HRT so that you know that the woman can cope with this final treatment.  After this they only require Oestrogens, no progesterone is required as they 

have no uterus. HRT becomes very simple and free of most side effects as ESTRADIOL patches can be used. The strength of the patch can be guided by the intensity of a woman’s

symptoms.

SUMMARY

Although PMS and PMDD are known for more than 100 years, we do not clearly understand it.  In 1800 it was referred to as hysteria, like many other female disorders which the doctor did not understand.  It was Robert Frank who first described it as a hormone dependent disorder, but he was on the wrong track as he pointed out that it was due to excess of oestrogens. It took a female doctor to prove what it was. She (K Dalton) fought a murder case in 1953 and proved it to be due to PMS. Then she wrote an article in BMJ She said that such a large number of women do not have to suffer from  such a large number of physical and emotional symptoms each month for so many years of their lives . Modern medicine should help their misery.Thankfully it is being tackled now.  I think in one, sentence we can say it is a hormone dependent Depressive disorder, which creates a lot of misery for women. Alternatives’ to traditional help of diet, exercise, no alcohol, tobacco and good diet is showing some promise.

But a lot more work is required to prove that they are useful.  Some of these remedies are ANGUSCastes . Red clover (PROMENSIL) St John’s Wort.  Drugs used often such as diuretics. neurofen( NASIDS) progestogens should be replaced by newer generation of pills( YAZ ,YASMIN ). They are very effective and can be used continuously up to 4 months. The only problem is the minuscule risks of DVT. Please do not give it to a woman if there are any risk factors. SSRI are extremely useful and can be used for long time if only used in the second half of the menstrual cycle. GnRH is also excellent treatment, but it is expensive and HRT required for this is also expensive .Unfortunately it has long term serious side effects –osteoporosis. Hystrectomy and bilateral salpingo-oophrectomy is the last tool we have. It can be used in very severe cases with HRT.