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.