Saturday, February 20, 2010

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.