Rationalising Hormonal treatment for DUB (Dysfunctional Uterine Bleeding)

Use of Streroid Hormones for treatment of DUB is declining, and often it's treated with non-hormonal medication, and the patient ends up in a hysterectomy. It's quite sad to see a heatlhy uterus being removed, for a problem that 's somewhere else. Let me try to go into physiological background of DUB and try to make the use of steroid hormone more effective.

HPO axis - a digital system : HPO axis is an independent functional unit, that's anatomically distributed at distant sites in the body. It has an amazing behaviour that's either it's normal, when it's ovulatory, secretes estrogen and progesterone in a regular oscillatory pattern. Or, it's abnormal, when it's anovulatory, and hormonal secretion is almost continous and in constant quantities (only estrogen, no progestrone). This is so, because it's the natures check against impregnation at unwanted times. Nature takes care that, the organism doesnt become pregnant, at unoptimal time, during it's physical and enviornmental crisis, and endanger it's pregnancy and itself. Nature does this by checking the ovulation. so, it's interesting that, all the system in the body, the psyche, hormones, physical status, nutrion etc effect HPO, though it is not effected by the end organ -uterus itself. Thus HPO is aware of the health status of the body itself, but unaware of the bleeding problems in the uterus. Probably, in the wild, it needn't know because, a woman had hardly any time for menstruation. The ovulation acts as a check valve. If the condition are suboptimal, the nautre aborts the sytem, before ovulation, and prevents a pregnancy.

In a Normal Ovulatory cycle, after the endometrium is shed, it's healed by the estrogen coming in in the following cycle. Estrogen proliferates the endometrium rapidly and heals it. Thus, if we take the lesson from nature, estrogen is the best to stop a bleeding. Progestrone in the secretary phase makes the endometrium compact, and also, at it's withdrawal causes, sever vasospasm, which causes global shedding of the endometrium, and also, limits the bleeding. Thus, the bleeding mechanism, has a natural builtin mechanism to prevent excess bleeing too. This, when the system is ovulatory.

In anovulatory state (not cycle, as HPO has stopped oscillating) the HPO gives out continous estrogen, which proliferates the endometrium beyond the capacity of it's stroma, endometrium is shed from places, thus last longer, and because there's no vasospasm due to absence of progestrone, bleeding is heavy.

Thus in treating DUB, our aim will be to:

• 1. make sure, the uterus is sequentioally stimulated by estrogen and progestrone
• 2. to convert anovulator HPO into ovulatory (if possible)

In an anovulatory woman, we can acheive our first goal, by supplementing progestrone. She gets estrogen which comes at a steady state from the HPO, so, we have to leave about 2 weeks after the menstruation, then give her progestrone tablets for about 10 days.

If the patient presents with bleeding, we have to arrest bleeding. The patient cant accept to wait till bleeding stops naturally. We have to give her estrogen to acheive this, then continue estrogen for about 2 weeks, followed by progestrone. An anovulatory woman will have slightly reduced estrogen, than the end-follicular phase of a ovulatory woman. (if the estrogen increases to normal level, she'll have LH surge and ovulation. Thus ovulation acts as a check against hyper-estrogenemia) Common practice is to give such women progestrone at higher dose, but usually she bleeds irregularly on such treatment. Estrogen acheives hemostases effortlessly.

To make the HPO ovulatory, it's better to suppress it completely, for sometime, and then, when it starts functioning again, probably, it'll be ovulatory. OC pills (estrogen+progesterone) is best to acheive this. HPO is complex system, with many interacting hormones. We cant convert it to ovulatory, by trying to make small changes. The tendency to anovulation varies among women, thus, some women have strong tendency to anovulation, owing to their enzyme variations, fat levels,other hormone levels etc. Once a woman becomes anovulatory, the HPO remains in that state, unless it's put back into track by some luck. So, if a woman bleeds irregulary 3 times in 8 months, she didnt have 3 anovulatory cycles, rather, she was anovulatary for 8 months, since, the HPO became deranged in the first instance.

Evidence in Obstetric Practice (for obstetricians)

Scientific Medicine has its traces in allopathy, which was not strictly any system of medicine. Samuel Hahneman, founder of homeopathy, called other doctors as allopaths, which means 'other than disease', to denote, they dont deal with or cure any disease. It's a shame that, allopaths owned up this abuse, and accepted the term.

Allopathy turned into Scientific Medicine gradually, when it adapted scientific methods into it's practice. Science is an enterprise to find out the objective truth. It explores new avenues in thoughts and knowledge, and meticulously examines them, before imbibing them.


At the heart of science is an essential tension between two seemingly contradicting attitudes, an openness to new ideas, no matter how bizarre or counterintuitive they may be and the most ruthless skeptical scrutiny of all ideas, old and new.
- Carl Sagan

Scientif method in Medicine is Evidence based Medicine. Evidence is collected based on existing practice using Randomised Controlled Studies, using blinding, to validate the usefullness of a diagnostic or treatment modality. Because there are many variables involved in any particular case, many a times, evidence may be contrary to logic or experience.

So, in EBM we should continouly evaluate our practice, and adopt to the evidence. We evaluate some of the evidences in Obstetric practice.

Folate supplementation till 3m [Ia]
Normal exercise encouraged [II]
Sexual intercourse not associated with increased risk of preterm delivery [Ia]

there's strong evidence to encourage folate prescription, which is indeed the practice. The advice on physical activity varies among practitioners, evidence says that normal activity can be carried out, and sexual activity is not a problem too.

Weight : obesity assessment (BMI) at booking. No indication for repeated weighing.

At least in India, the main component of an antenatal check up is blood pressure measurement, weighing the lady, and assessing her fundal height. Interestingly, in none of the international antenatal check up protocols (RCOG, ACOG), repeated weighing of the patient is included. Though a nomal pregnant lady increases her weight, in a regular manner, throught the pregnancy, the association of any deviation from this normal patter with abnormal pregnancy is lacking. Similarly, a normal weight gain at times is associated with abnormal pregnancy outcome too. Usual justification for weight measurements are, that they predict preeclampsia, IUGR, macrosomia etc. In actual studies, weight measurements failed to show any advantage in prediction or follow up of these cases compared to no weight measurement.

Fundal height
Routine growth assessment by USG or doppler not recommended [Ia]

Regular meausrement of fundal height is included in all antenatal protocols, and is indeed the practice. Routine use of USG or doppler in all cases in growth assessment has not been found to be any benifit (high level of evidence)

Movement charts dont reduce late pregnancy still births.

Routine daily counting by women followed by appropriate action when movements are reduced seemed to offer no advantage over informal inquiry about movements during standard antenatal care and selective use of formal counting in high risk cases. [II]

Movement charts of different types - to count fetal movements for one hour, 3 hour, different times of days, count to ten etc - were deviced, to help the patient (any doctor) assess fetal well being herself. But in actual practice, such elaborate methods have no advantage to a casual about the movement: "is your movements alright?"

Effect of FMC in high risk pregnancy is not known. It would seem prudent to advice women deemed at high risk of fetal compromise to pay careful attention to their fetal movements. The women who report an alteration in the movements, some form of assessment should be offered. [IV]

While the use of elaborate fetal movement charts in low risk pregnancy is definitely nill, even in high risk pregnancy, there's no evidence of their use. expert opinion is that, a woman may just be adviced to 'listen' to her movements carefully, and report if there's any deviation from normal.


NST – analysis of 13 trials of NST failed to demonstrate any significant effect on perinatal outcome.

In a systemic review of 4 RCTs, NST was associated with a trend towards increased perinatal mortality.

NST should not be relied upon as the sole means of establishing fetal well being [Ia]

CTG, once highly hailed, has repeatedly failed in RCTs to show any benifit. This may be due to it's -routine use, in large number of uncomplicated cases, and misinterpretation of normal fetal inactivitiy period as fetal compromise.


Systemic review of 4 RCT s failed to demonstrate any significant benefit of BPP compared with NST. The review concluded that the current evidence is insufficient to reach any definite conclusions about the benefit or otherwise of the BPP [Ia]

BPP (usually by manning score) also fail to show any advantage in assessing a compromised fetus.

I am personally, a bigger fan of BPP than just NST. BPP evaluates fetal movements and breathing, which stop earlier, due to effect of hypoxia in the periphery of fetal brain, than changes in reactivity and variability in NST, which are due to hypoxia in the central autonomous regions in the brain, which is a later event, due to better perfusion in central brain.

I feel, as further evidence accumalates, BPP will be shown to be a useful tool, and NST, if used selectively, and with better knowledge of fetal physiology, will be useful too.


Routine scanning after 24 weeks not useful [Ia]

Serial growth measurements may be undertaken in high risk women [IV]

Liquor volume to be considered.

again, the vaule of routine scanning is null.


UADW analysis improves outcome in high risk women [Ia]

UADW holds no advantage in low risk pregnancies [Ia]

Umbilical artery Doppler is useful only in high risk cases.


Although bed rest oftern is recommended, no evidence shows that bed results in improved outcome or increased fetal birthweight for fetuses with suspected IUGR. the increased uterine blood flow that occurs when the patient is in the lateral recumbent position theoretically may result in some benefit for fetuses with asymmetric IUGR. However, a paucity of data supports this theory.

Lot of women are confined to lie on their sides by their obstetricians, and then complain of pain and uneasiness in their sides, and joints. We should restrain from this practice till solid evidence is obtained about its usefullness. I now, dont advice any woman to lie on side.


Low dose aspirin of no benefit [Ib]

Maternal nutritional supplement may increase adverse outcome

while a few studies have shown benifit of aspirin in very early onset IUGR, systemic reviews of RCTs show no benifit.


Social support failed to improve outcome [Ib]

Hospitalisation for bedrest led to increase in preterm births [Ib]

So, here's the eveidence for TLC, tender loving care. it was used, when you dont know what to do! It was supposed to cure repeated aboritons, previous bad obstetric history etc. But evidence is, it's uselss.


Ritodrine has no significant benefit, although it reduces the number of women delivering within 48 hours [Ia]

Atosiban not more effective than beta-agonist [Ib]

No use of antibiotics in uncomplicated preterm labor [Ia]

That's the evidence in treating pre term labor. Beta mimetics were used not only in preterm labor but even as prophylactics. they are of no significant benifit!


Asymptomatic women with short cervix – risk of PTL rises only 4% at 11-20mm

Circlage led to improvement only after 3 or more previous very early deliveries [Ib]

Even assessment of Cervix is questionable, in asymptomatic women, and Circlage is nearly useless.


Universal Screening [IV]

Monitor post prandial values [Ib] preferrably 2 hour values [IV]

?Antepartum fetal monitoring

It's surprising that, for a common disease like diabetes, and for which every lady is screened, there's no solid evidence yet, about universal screening. There has been certain trends towards using fasting blood sugar values, evidence says, post prandial values are more useful in monitoring the treatment.
there's no use of regualar antepartum fetal monitoring, which are geared for baby who's undergoing slowly developing placental insuffiency, which is not the case in diabetes.


Insulin therapy: FBS [IV], PPBS [III], AC [II]

Oral Hypoglycemics [IV]

Delivery at 38-40 weeks [Ib]

In initiating insulin therapy, abdominal circumference is more of value than PPBS, which is more reliable than FBS. slightly early deliver is recommended (with good evidence)


There is currently no evidence to suggest that MAS would be prevented by elective delivery by cesarean section of infants with meconium-stained liquor. Perhaps this is not surprising, as neither the conditions for nor the timing of aspiration can be predicted.

So, there's no use looking for meconium, and then rushing the patient to operation theater. Mostly, you get a good baby out, and in case, baby is depressed, you dont alter the outcome, as it's already depressed. Rather rely on other indicators of fetal well being.

Pelvimetry performed either clinically or radiologically does not provide any useful information. [Ia]

So, stop the habbit of writing 'pelvis adequate', in every PV examination.

given that the reduction in length of labor (60-120 min [Ia] )is not large and that there is a potential for increase in the need for urgent delivery for suspected fetal compromise, it has been suggested that amniotomy should be reserved fro women with abnormal labor progress.

ARM to detect meconium need not be done, as detecting meconium doesnt alter the management. Routine amniotomy to speed up the labor is depracated.

Formulated by O'Driscoll et al.

Strict diagnosis of labor, early amniotomy, oxytocin infusion, one to one care

Achieved low cesarean rates, which meta-analysis failed to show

Professional support, exclude partner from labor room [Ib]

There was a trend towards 'The active management of labor' which was a deivation from traditional 'wait and watch' policy. but recent evidence doesnt support any advantage of putting all laboring women into a race against each other. the reduction of cesarean section, which was the original motive was acheieved only by O'Driscoll, the original proponent of ACM, and it could not be achieved in later studies. Interestingly, allowing patient's near and dear to Labor room, has not been advantageous.

Delivery:

Pelvic support: hands on or hands poised study : no advantage of one method over the other [Ib]

Episiotomy : continous non-locking repair less painful than standard interrupted repair

the pelvic support, routinely practiced, is useless in preventing perieal tears.
Episiotomy can be sutured in different ways than traditional ways, and I use continous (from apex of mucosa to the last skin, and i finish up the ends in vagina than on skin)