Dysfunctional uterine bleeding (DUB) is abnormal uterine bleeding occurring in the absence of any obvious pathology.

Management strategies are discussed below:

Acute episode of  DUB in the perimenopausal period:

In the perimenopausal period the patient is most likely to be suffering from anovulatory bleeding.However it is mandatory  to rule out pregnancy and pelvic infection as possible causes of bleeding. Hypothyroidism is common in this age group, and should be ruled out by history and clinical examination.It is not necessary to do endocrinological tests for hypothyroidism in all patients with abnormal uterine bleeding(27). A careful medical history should be taken to rule out diseases of the liver,adrenals.She should be questioned regarding the use of anticonvulsants.  When all functional causes of abnormal bleeding are ruled out a diagnosis of DUB is made.  In this age group it is mandatory to do an endometrial sampling to rule out carcinoma(26).

Scenario Abroad:In some countries,endometrial sampling is done using 3mm plastic suction cannulas, the names of some of them being ,Pipelle, Explora,vabra aspirator, Z-Sampler,&Endosampler(2). Studies have found office endometrial sampling superior to D & C(28). An alternative is to do a transvaginal ultrasonography on day 4,5,or 6(17). An endometrial thickness of <5mm rules out endometrial hyperplasia. In cases where it is more than 5mm or when the image is not clear, a procedure called saline infusion sonohysterography could be performed. In this procedure, the uterine cavity is slightly distended with saline and then,TVS done. This delineates the endometrium better, and allows for better diagnosis of endometrial polyps and small submucous myomas sonographically.  Dilatation and curettage is done only when medical treatment fails .Whenever curettage is done it is best done hysteroscopically as a blind D& C has proved to miss out lesions quite often(28).

Indian scene: In our country, endometrial sampling devices are not common. Thus in cases as the one mentioned above,wherever vaginal sonograpy is available it could be done and if the endometrial lining is <5mm on day 4,5 or 6 of the period,one could reasonably rule out hyperplasia and go in for medical treatment.  In centres where vaginal sonography is not possible, and in cases where the endometrium is >5mm on day 4,5 or 6,a dilatation and curettage is mandatory to rule out malignancy. A hysteroscopic biopsy as a primary diagnostic modality for DUB may not be practical in our setup.  In cases where a vaginal sonogram picks up an endometrial polyp, in well informed and willing patients, a hysteroscopic polypectomy would be ideal. After a D&C, quite often, the bleeding abates, but it is better to put the patient on maintenance medical therapy to avoid recurrence.

 Medical management : In most of the literature,I-V estrogens or high dose OC-pills are cited as the first line of treatment^.(25,26,28).From a  survey conducted in India, we find that progestogens, and in particular, norethisterone is the most popular drug used in India.  Norethisterone or Medroxyprogesterone could be used to arrest an acute episode of bleeding. Majority of doctors in the survey were using Norethisterone in the dose of 15mg /day to stop acute bleeding.  But if a dose of 15mg of Norethisterone/Norethindrone does not stop bleeding, one should step up the dose before calling it a failure of therapy.  Norethisterone could be given in doses of upto 30mg/day. 16% of doctors in the survey were found to be  using    Norethisterone in this dose.Once the bleeding has stopped, the dose could be tapered to 15mg daily and this dose continued for 21 days.

 Medroxy progesterone  could be given in a dose of 60-120mg on the first day and 20 mg daily in the subsequent days.

Monophasic OC pills could also be used to control acute uterine bleeding.  To stop an acute episode of bleeding, OC-pills should be given in the dose of 1 tablet four times a day ^(25,26,28).Even if the bleeding stops, the treatment should be continued for 7 days. In such a high dose, the patient may experience severe nausea or vomiting and antiemetics should be given simultaneously.  After 7 days, the dose should be reduced to one/day and continued for 21 days^.(28) .Another regimen is to give Regular oral contraceptives containing  35mug of ethinylestradiol in a regimen of 4 tablets for the first day, 3 for the second day, 2 for the third day, and then 1 per day until the pill pack is finished^.(12)

Maintenance therapy: Progestins are commonly used in North America and the UK. ⁽²⁸⁾This is also true in India. Oral medroxyprogesterone acetate 10 mg a day from days 16 through 25 each cycle may be given. Alternatively, Norethindrone/Norethisterone 5 to 10 mg one to three times a day may also be used to manage recurrent anovulatory dysfunctional uterine bleeding. Progestins are generally administered for 7 days (minimum duration for the prevention of hyperplasia) to 12days of each cycle^.(26)  For anovulatory patients who are difficult to treat, the course of progestin therapy can be extended for 14 to 21 days each month. Prolonged use of high-dose progestins is associated with side effects, which include fatigue, mood changes, weight gain, and atherogenic changes in the lipid profile^.(13)Dydrogesterone,a progesterone that has a structure very similar to progesterone and micronised progesterone, which is natural progesterone in the micronised form has also been studied for the treatment of DUB. Both agents  are costly (Dydrogesterone-Around Rs.10 for a 5mg tablet&micronised progesterone Rs 18 for a 100mg tablet).Dydrogesterone may be given in the dose of  10mg b.i.d (together with estrogen) for 5-7 days to arrest bleeding & in the dose of 10mg b.i.d (together with estrogen) from 11th- 25th day of the cycle to prevent bleeding. In a study comparing the effects of micronized progesterone (300 mg per day) and the progestin norethisterone (15 mg per day) in premenopausal women, menstrual cycles were well controlled with either agent, but cessation of dysfunctional uterine bleeding was achieved more frequently in the women who took micronised progesterone⁽²⁶⁾ Another alternative is to use Combined oral contraceptive pills which  have been shown to effectively reduce menstrual bleeding by up to 60% in normal uteri.  OC pills given for 2-3 months result in a stable, atrophic endometrium.  The most common side effects include weight gain, abdominal discomfort, and midcycle breakthrough bleeding. 

DUB in the reproductive age group:

In women in the reproductive age group, pelvic infection and pregnancy should be ruled out by pelvic examination, urine pregnancy test, and if necessary vaginal ultrasonography. Any abnormality detected should be treated accordingly. A routine haemogram should be done.  If there are no abnormalities detected, a diagnosis of dysfunctional uterine bleeding should be made.  Dysfunctional uterine bleeding in this age group could be ovulatory in nature,although typically the history of regular menstruation on a monthly basis indicates ovulatory cycles.  In practice, a specific diagnosis often is not sought if the patient is not immediately desirous of pregnancy.  Instead empirical medical therapy is begun^.(30) 

Women with ovulatory dysfunctional bleeding are usually not lacking in  progestin, but have underlying imbalances in prostanglandins.  Nonsteroidal antiinflammatory drugs like Mefenamic acid 500mg , Ibuprofen 400mg three times a day,Diclofenac sodium could correct the prostaglandin imbalance^.(13)  NSAID’s are known to reduce flow by 20%.  NSAIDs need not be used through out the cycle.Tranexamic acid in the dose of 2g/day could be  used as an antifibrinolytic agent.  Ethamsylate was used as a plasminogen activator inhibitor, but controlled studies show conflicting results about it’s efficacy.. It is used extensively in India. 20% of doctors in our survey have mentioned the use of drugs like Ethamsylate,NSAIDs,etc for the control of bleeding in the reproductive age group .Preparations containing vitaminK,,Vitamin C ,and flavonoids (e.g:GynaeCVP,Styptovit,Styptomet) have been found useful for the treatment of menorrhagia, though the last study on the use of Vitamin K (Menadione)  was done 57 years ago. If the above measures do not reduce bleeding, hormonal therapy with progestogens or oestrogen could be tried.The long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage and a combination of one or more of the agents mentioned above may be required along with  hormonal treatment.

Heavy DUB in the very young girl in the menarchal age group:

At the outset, any pelvic abnormality should be ruled out.  A pelvic examination may be embarassing for the patient and may not yield much information in an unwilling patient.  An abdominal ultrasound examination can rule out most of the pelvic pathologies. Once uterine or ovarian pathologies are excluded, a bleeding diathesis should be ruled out.  Recent studies have shown that as much as 20% of patients with menorrhagia may have a bleeding diathesis(29).History of easy bruisability, bleeding from minor trauma should be taken.A detailed physical examination must be done to look  for pallor, bleeding spots and hepatosplenomegaly.  A total count, haemoglobin value, bleeding time, clotting time, prothrombin time and Activated partial thromboplastin time should be done.  A correct diagnosis of coagulopathy made at this time will have important implications for the management of future pregnancies, as APH and PPH can be anticipated and treated(28). 

Medical therapy:

        Any anaemia should be treated with haematinics or blood transfusion according to severity.  Acute 

        bleeding can be controlled with hormone therapy even in the patient with coagulation disorders. Thus

        while the results of the blood tests are awaited, hormone therapy could be started.

a)       Oral contraceptive pills with 35micrograms of estrogen and a progestin 6-8hourly could be tried along with antiemetics if necessary for 24-48 hours(26).  If the bleeding continues the dose should be increased by using pills containing 50micrograms of oestrogen every 6 hours.  When the bleeding stops, the dose should be tapered over a week to 1 pill daily. When the initial packet is empty, she should immediately begin a new 28 day packet of 35microgram pills.  The menstrual period immediately following the treatment may be heavy due to the estrogenic content of OC –pills.

b)       Progestins: Norethisterone/Norethindrone could be tried in the dose of 30 mg/day in divided doses for 3 days . The dose could be tapered to 15mg /day once the bleeding abates and continued for a total of 21 days. 

Medroxy progesterone acetate in the dose of  60-120 mg during the first day of admission and 20 mg/day for the following 10 days  was found effective in one study(16). 

Maintenance therapy could be given with either Norethisterone(5-10mg one to three times/day) or Medroxyprogesterone 10mg a day on days 16 through 25 each cycle(13) .  For anovulatory patients who are difficult to treat, the course of progestin therapy can beextended for 14 to 21 days each month.  Cyclic administration of combination oral contraceptives is effective in reducing the risk of recurrent bleeding episodes. 

Minimal but irregular bleeding in the adolescent:

If the adolescent girl can tolerate the bleeding emotionally and physically, she can be followed without hormonal intervention. NSAIDs could decrease the flow and a multivitamin with iron could be given prophylactically. Although convincing studies are not there, Ethamsylate, preparations like Gynae CVP,Styptovit, etc could also be tried.  But if the girl is anemic (History of being too tired to study is often given), or is bothered that the bleeding affects her day to day life, a combined oral contraceptive containing 30-35 microgram of estrogen can be prescribed along with iron.  All patients taking oral contraceptives should be seen at 1,3,and 6 months.  If the adolescent has done well and does not wish to continue the oral contraceptive, it may be stopped at that time. 

Minimal irregular bleeding  in the perimenopausal woman:

A cervical polyp should be ruled out. A transvaginal sonogram should be done to rule out endometrial polyps.  If no obvious cause is found, the intermittent vaginal spotting is probably associated with minimal(low) estrogen stimulation(estrogen breakthrough bleeding). (3) In this circumstance, where minimal endometrium exists, the beneficial effect of progestin treatment is not achieved, because there is insufficient tissue on which the progestin can exert action. 1.25mg Conjugated   estrogen or 2mg estradiol daily can be prescribed for 7-10 days.  All estrogen therapy should be followed by progestin withdrawal or continued OCP.

Post-menopausal bleeding :

The golden dictum was that a woman with postmenopausal bleeding should be diagnosed to have endometrial carcinoma unless  proved otherwise.  But in the changed scenario of today a lot of other factors have to be taken into consideration.  Awareness of hormone replacement therapy having increased, a lot of general practitioners have also started using hormone replacement therapy.  Patient should be directly questioned on the use of hormone replacement therapy.  If she is on estrogens, the dose should be adjusted or alternate therapy advocated. Other wise the management is the same as for the perimenopausal woman.

Failure of medical treatment:

When medical treatment fails the following interventional procedures could be resorted to:

1.        Endometrial ablation: The endometrium could be ablated using hysteroscopic resection with electricity or laser.It can be done only for the woman who has completed her family.

Thermal ablation: The endometrium could be ablated using hot solutions . This could be done using company made thermal ablators or using the foley’s catheter.The author has been doing thermal ablation using foley’s catheter for the past  7 years with 80% success rate.

2.        Levenorgestrel releasing intra-uterine contraceptive devices: These are progesterone releasing devices placed in the uterus.

 There may be troublesome spotting in the initial months, but ultimately there is amenorrhoea or oligomenorrhoea. It is ideal for the woman who has not completed her family.

3.Hysterectomy.

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