Bavin Balakrishnan
Department of Obstetrics Gynecology, Baby Memorial Hospital, Kozhikode, Kerala

Corresponding Author: Dr. Bavin Balakrishnan, MD, DNB; Diploma in Endoscopy (C/CE, France) Consultant Gynecologist, Division of Reproductive Medicine and Minimal Access Surgery, Department of Obstetrics Gynecology, Baby Memorial Hospital, Kozhikode, Kerala. E-mail: bavinb@gmail.com

ABSTRACT

Background: One in five  women bleed so heavily  during  their periods that they have to put their normal lives on hold just to deal with the heavy blood flow! Heavy menstrual  bleeding  (HMB)  has an adverse effect on the quality of life of many  women. Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding in the absence of organic disease.

Introduction

One in five  women bleed so heavily  during  their periods that they have to put their normal lives on hold just to deal with the heavy blood flow! Heavy menstrual  bleeding  (HMB)  has an adverse effect on the quality of life of many  women. It is not a problem associated with significant mortality.  In order for women to be treated successfully, it is essential that the underlying problem be understood by both the patient and the healthcare professional.  Till last decade, hysterectomy was offered as the first line treatment; however matters  have changed with alternative effective  treatments.

  • Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding in the absence of organic disease. (Pitkin J. 2007 May)
  • The diagnosis of DUB can only be made once all other causes for abnormal, or heavy, uterine bleeding have been excluded. The pathophysiology is largely unknown.
  • It usually presents as heavy menstrual bleeding (HMB). HMB  is defined  as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination  with other symptoms.

As Clinicians, we  may see  DUB  commoner  in adolescents, and women in late 40’s. DUB affects more  than  30% of women  and account for a significant reason for gynecological referral.  It was estimated that in 5 years of referral; more than 60% of women will have undergone hysterectomy making it the commonest major gynecological operation. In fact. British Medical Journal  May 2007 writes that ‘’one in 20 of women aged 30- 49 consults her GP each year with menorrhagia”. Menorrhagia is derived from Greek and literally means to burst forth monthly (mene, the moon and rhegnymi, to burst Forth).  Concerns about the invasiveness of  hysterectomy  have led to development  of minimal access approaches  including endometrial  resection and ablation. With the development of minimal access techniques it is possible to destroy the endometruim in situ; in short a day care operation. Literature mentions at least 1 in 5 women who undergo these procedures  will require  further  surgery  at a later stage. Effective medical therapies still stands a place in the management of DUB.

Cause

The precise cause of DUB is thought to lie at the level of the endometruim itself. Homeostasis during menstruation is achieved by vasoconstriction, until the  bleeding is finally checked  by repair  of  the endometrial vessels in the first 7 days of the cycle. A number of factors are thought to be involved in the local control of menstrual blood loss and abnormalities in the prostaglandin and fibrinolytic systems in the endometruim have led to rational medical approach to the treatment of heavy bleeding in these women.

Framework for analysis

Of the several frameworks for  analyzing  the consultation, two methods are known; ‘biological model’ where physical processes are measured and compared with a ‘normal’ reference. Another approach is a psychosocial model where the woman’s psychological disturbance and social impairment are the focus. In reality, most clinicians use a combination of the two models.

The history should aim at defining the nature of bleeding, potential pathology, and identifying patient’s ideas,  concerns,  issues,  expectations, and needs.

Questions about medical history should include the following:

  • Signs and symptoms of hypovolemia,
  • Diabetes mellitus,
  • Hypertension,
  • Hypothyroidism,
  • Hyperthyroidism,
  • Liver disease,
  • Medication usage, including exogenous hormones, anticoagulants, aspirin, anticonvulsants and antibiotics,
  • Alternative and complementary medicine modalities, such as herbs and supplements.

Research guidelines do not recommend measurement of menstrual blood loss by any method, rather by woman herself.

Physical examination of the woman by observation, abdominal palpation, visualization of the cervix and bimanual (internal) examination has the purpose of detecting underlying pathology to inform treatment and the need for investigations. The examination should look for the following:

  • Trauma to the vaginal walls or cervix
  • Retained foreign body
  • Cervical or vaginal laceration
  • Bleeding from the cervical os.

Approximately 90%  of DUB results from anovulation, and 10% occur with ovulatory cycles.

Description  for  bleeding  pattern

Dysfunctional bleeding from the uterus can be described as follows:

  1. Menorrhagia – Prolonged (>7 d) or excessive (>80 mL daily) uterine bleeding occurring at  regular intervals.
  2. Metrorrhagia – Uterine  bleeding  occurring  at irregular and more frequent than normal intervals.
  3. Menometrorrhagia – Prolonged or excessive uterine bleeding occurring at irregular and more frequent than normal intervals.
  4. Intermenstmal bleeding (spotting) – Uterine bleeding of variable amounts occurring between  regular menstrual periods.
  5. Polymenorrhea – Uterine  bleeding  occurring  at regular intervals of less than 21 days.
  6. Oligomenorrhea – Uterine  bleeding occurring  at intervals of 35 days to 6 months.
  7. Amenorrhea – No uterine bleeding for 6 months or longer.

The major categories of DUB include the following:

  • Estrogen breakthrough bleeding
  • Estrogen withdrawal bleeding
  • Progestin breakthrough bleeding.

Workup for  DUB calls for several studies to ensure hemodynamic stability.

  1. A full blood count test should be carried out on all women with HMB. This should be done in parallel with any HMB treatment offered.
  2. Testing for coagulation disorders (for example, von Willebrand disease) should be considered in women who  have  had  HMB  since   menarche  and  have personal or family history suggesting a coagulation disorder.
  3. Thyroid   function  tests  are   not   routinely recommended, but worth considering  in selected cases.
  4. Our next modality of investigation for identification of structural  abnormality is Ultrasound. This imaging modality is of immense value if done  by TVS, endovaginally. The information to be sought are cavity echo of the uterus, myometrial echoes, if suspicion of adenomyosis  I endometrial  thickness I adnexal pathology assessment.
  5. Saline infusion sonography may be used as second line for establishing cavity assessment.
  6. Hysteroscopy  should be used as a diagnostic  tool only when ultrasound results are inconclusive, for example. to determine the exact location of a fibroid or the exact nature of the abnormality.
  7. If appropriate, a biopsy should be taken to exclude endometrial cancer or atypical hyperplasia. Indications for a biopsy include, for  example, persistent intermenstrual  bleeding, and in women aged 45 and over treatment failure or ineffective  treatment.
  8. Dilatation and curettage alone should not be used as a diagnostic toot.

The guidelines  place a high value on the need for education and information provision for women with HMB. A woman with HMB should  be given the opportunity to review and agree any treatment decision. She should have adequate time and support from healthcare professionals in the decision- making process.

Treatment

Objectives

  • To control bleeding
  • Prevent  recurrence
  • Preserve the opportunity for future child bearing if patient desires

Pharmaceutical treatment should be considered where no structural or histological abnormality is present, or for fibroids less than 3 cm in diameter which are causing  no distortion of the uterine cavity. The   healthcare professional should determine whether hormonal contraception is acceptable to the woman before recommending treatment (for example, she may wish to conceive). The scientific basis for the hormonal treatment is on the anovulatory status of  the  woman. The  bleeding  arises from abnom1alities of the hypothalanlic-pituitary-ovarian­ endometrial axis. This results in  anovulatory (generally) irregular cycles, which  are  particularly common at  the  time of  menarche and  around  the perimenopause. The  failure of  the  ovulation  and progesterone induced  luteal phase transformation of the endometruim results in bleeding that is often heavy, less clearly defined  and irregular.

Antifibrinolytic  agents, such  as tranexamic acid, provide  a rational  and effective treatment reducing the MBL by 50%. It is also effective for intra-uterine contraceptive induced dysfunctional uterine bleeding. The  incidence of  adverse effects is related  to  the dose  of  drug  prescribed. A  third of women experience gastrointestinal  side  effects following treatment with  a dose  of 3 – 6 g daily. The dose related side effects may be minimized after the first 3 days  of  menses  ceased, or  limiting  to  the same period of medication. There is no evidence to prove thromboembolic diseases or rise in the incidence of embolic phenomenon. Thus it remains as safe early first line therapy for reducing the bleeding.

Anti prostaglandins: NSAJDS remain popular choice for  the treatment of HMB.  Their  main  mechanism of  action  is to decrease endometrial PG (prostaglandin) concentrations. The  NSAJD  most often used is mefenamic acid; reducing blood loss upto 56%. The beneficial effect also includes relief from dysmenorrhoea, headache, nausea, that persists for months. Systemic progestogens such as Norethidrone, and Medroxyprogesterone acetate offer  a logical approach to the treatment  of anovulatory DUB.

Intra uterine progestogens: MIRENA, the  device delivers 20mcg of levonorgestrel to the endometruim every  24 hour in a sustained release formulation that can  last  up to 5 – 7 years.  The  main  side effect  is irregular  breakthrough  bleeding a n d  spotting particularly within the first few months after insertion of the system.  These  events  must be discussed with patient prior to insertion  of the system. Combined Pill reduces MBL by  endometrial suppression (50%). Nevertheless, the pill is limited by the risks of thrombosis in elderly aged women. At a dose of 3 -4 pills daily in divided doses,  it may be used in acute bleeding  DUB.

Guidelines

  1. NSAJDS are used in management of reduction of MBL, mefenamic acid 500 mg every 6 hours and continued  till bleeding ceases or even justified  in the first 3 days  of the  menstrual  cycle. The  NSAIDS can be m onotherapy or combination with other pills. It is most effective in ovulatory  DUB.
  2. lnhibitors of fibrinolysis have a procoagulant activity, indicated  in ovulatory DUB. Epsiolon-aminocaproic acid (EACA), tranexamic acid and para­ aminomethylbenzoic acid are used. It is preferred to combine these  with pills or progestogens for better efficacy.
  3. Ergot derivatives,  as  methyergometrine should  not  be advocated for  lack of efficacy and limited  by serious side effects.
  4. Progestogens or synthetic progestins are of significant value in anovulatory DUB in reduction of MBL. The regime  of oral  norethidrone 5 mg twice daily/ oral  Medroxyprogesterone acetate 30 mg in divided doses/oral or vaginal micronised progesterone in doses of 300  mg daily  are used. The  protocol is either last ten days of the menstrual cycle or day 5 to day 26 of the menstrual cycle.
  5. A seven year intrauterine device,  MIRENA which releases levonorgestrel reduced MBL by 83% in 3 months  and by 97%  in 12 months. The latest guidelines of the NICE, UK recommends this system as first  of  the order  for  hormonal   management of DUB.
  6. Danazol at doses  of 400  mg daily did  reduce  the MBL; however the serious androgenic side  effects limited  its use in DUB.
  7. Gonadotrophin  releasing agonists by  creating medical  menopause  is  of  value  as  last  resort especially  in those preferring to choose child bearing later.
  8. Oral  synthetic progestin ‘s  is  of  significance  in reduction  in acute bleeding DUB
  9. Ongoing use of NSAIDS and or tranexamic acid is recommended for as long they are found  to be beneficial by the woman.
  10. Use  of  NSAIDs and/or  tranexamic acid  should be stopped if it does not improve symptoms within three  menstrual cycles.
  11. When a first pharmaceutical treatment has proved ineffective, a second  pharmaceutical treatment can be  considered rather than  immediate referral  to surgery.

Surgical Options

The  surgical  options  include dilation, curettage/endometrial  ablation/ hysterectomy.  The  surgical management is reserved for those patients who are unresponsive, hemodynamically un stable,  and excessive bleeding must be stopped within short span of  time. Curettage  will reduce the acute blood loss and may resume at the next cycle  unless medical therapy is initiated. Endometrial ablation is reserved for those women desiring for preserving the uterus, failed  medical  therapy, no future fertility,  normal cervical cytology and endometrial  histology or even other pelvic  disease. The technique  involves  destruction   of  endometruim by  laser, /  roller electrocautery, /  ball end electrode.

Thermal balloon technique

Thermal balloon ablation of the endometruim involves inserting a balloon tipped catheter  in to the uterine cavity inflating the balloon so it conforms to the shape of the cavity and then beating the fluid within it to 85 C. There are currently two devices  available, The thermachoice  and cavaterm system.

The other systems are

  1. Endometrial laser intra uterine thermotherapy
  2. Intra uteri ne surgery using co axial electrode
  3. Hydrothennal ablation of the endometrium
  4. Cryo ablation of the endometrium
  5. Photodynamic endometrial ablation
  6. Radio  frequency induced  thermal endometrial ablation
  7. Microwave endometrial ablation

Rates of success  defined  as amenorrhea  or lesser flow cycles or normal menstrual flow varies between 80% to 95%. Hysterectomy is a definite surgery and treatment too, and has rates of patient satisfaction. It is appropriate for associated pelvic pathology, say myoma or prolapse. Women offered  hysterectomy should be informed about the increased risk of serious complications (such as intraoperative  haemorrhage or damage to other abdominal organs) associated with hysterectomy  when  uterine fibroids are  present. Women should be informed about the risk of possible loss of ovarian function and its consequences, even if their ovaries are retained  during hysterectomy. Individual assessment is essential when deciding the route of hysterectomy. The following  factors need to be taken into account:

  • presence of other gynaecological conditions or disease
  • uterine size / presence and size of ute1ine fibroids
  • mobility and descent of the uterus
  • history of previous surgery

Key points

  • Management of DUB should be individualized and a plan of management to be developed for the control of excessive uterine bleeding in the specific patient.
  • Mefenarnic acid and tranexamic acid combination have been shown  to reduce  the bleeding by 50%, with fewer side effects; forming the first line agents for the treatment of DUB.
  • The pill reduces bleeding by 50%, provides good cycle control and effective contraception.
  • The Levonorgestrel  intrauterine system  reduces menstrual blood loss by over 80% and may offer acceptable alternative to other medical treatment and surgery.
  • Thermachoice balloon device is most studied,  and reported.
  • Most of the techniques use disposable probes, increasing the costs which need research.
  • Women can choose the therapy medical or surgery.
  • Hysterectomy should be considered only when other options  have failed, are  contraindicated, or  are declined by the woman.
  • Women offered  hysterectomy  should  have a full discussion of the implication of the surgery before a decision  is  made. The discussion  should include: sexual feelings, fertility impact, bladder function, need for further treatment, treatment complications,  the woman’s expectations, alternative surgery   and psychological impact.

End Note

Author Information

Dr. Bavin Balakrishnan, Consultant Gynecologist,
Division of Reproductive Medicine and Minimal Access Surgery, Department of Obstetrics Gynecology, Baby Memorial Hospital, Kozhikode,  Kerala

Conflict of Interest: None declared

References

  1. Heavy  menstrual bleeding. National  Collaborating Centre for Women and Children’s Health; Commissioned by  the  National  Institute  for  Health and  Clinical Excellence. January 2007. Published by the RCOG Press at the Royal College of Obstetricians and Gynaecologists, 27 Sussex Place, Regent’s Park, London NW14RG. [Source]
  2. Pitkin J. Dysfunctional uterine bleeding. BMJ. 2007 May 26;334(7603):1110–1. [Pubmed] | [Crossref]
  3. Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2000;(2):CD001016. [Pubmed] | [Crossref]
  4. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivelä A, et al. Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet. 2001 Jan 27;357(9252):273–7. [Pubmed] | [Crossref]
  5. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev. 2006;(2):CD003855. [Pubmed] | [Crossref]