INVITATION ARTICLES - Rationalizing Hormonal treatment for DUB - By Pravin Gopinath


Use of Steroid 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 healthy uterus being removed, for a problem that is 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 behavior that's either it is 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 continuous and in constant quantities (only estrogen, no progesterone). This is so, because it is nature’s check against impregnation at unwanted times. Nature takes care that; the organism doesn’t become pregnant, at an un-optimal time, during its physical and environmental crisis, and endanger its 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, nutrition 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 conditions are suboptimal, the nature aborts the system, before ovulation, and prevents a pregnancy.


In a Normal Ovulatory cycle, after the endometrium is shed, it's healed by the estrogen coming in the following cycle. Estrogen proliferate the endometrium rapidly and heals it. Thus, if we take the lesson from nature, estrogen is the best to stop a bleeding. Progesterone in the secretary phase makes the endometrium compact, and also, at its withdrawal causes, sever vasospasm, which causes global shedding of the endometrium, and also, limits the bleeding. Thus, the bleeding mechanism has a natural built in mechanism to prevent excess bleeding too. This occurs when the system is ovulatory.
In anovulatory state (not cycle, as HPO has stopped oscillating) the HPO gives out continuous estrogen, which proliferates the endometrium beyond the capacity of its stroma, endometrium is shed from places, thus last longer, and because there's no vasospasm due to absence of progesterone, bleeding is heavy.

Thus in treating DUB, our aim will be to:

1. Make sure, the uterus is sequentially stimulated by estrogen and progesterone
2. To convert anovulatory HPO into ovulatory (if possible)

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


If the patient presents with bleeding, we have to arrest bleeding. The patient can’t accept to wait till bleeding stops naturally. We have to give her estrogen to achieve this, and then continue estrogen for about 2 weeks, followed by progesterone. An anovulatory woman will have slightly reduced estrogen, than the end-follicular phase of an 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 progesterone at higher dose, but usually she bleeds irregularly on such treatment. Estrogen achieves hemostasis 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) are the best to achieve this. HPO is complex system, with many interacting hormones. We can’t 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 irregularly 3 times in 8 months, she didn’t have 3 anovulatory cycles, rather, she was anovulatory for 8 months, since, the HPO became deranged in the first instance.



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