How Does Progestogen Cause Endometrial Bleeding?

Bleeding of the endometrium, when induced by progestogen, is known as breakthrough bleeding. This kind of bleeding is not menstruation. Indeed, it differs from normal menstruation in several ways.

Menstruation takes place when the endometrium in its secretory phase is subjected to falling levels of ovarian steroids. Most of the menstrual blood loss occurs through the spiral arterioles, together with the collapse and shedding of most of the functionalis. Progestogen-induced breakthrough bleeding, on the other hand, usually occurs from the smaller capillaries and veins. Breakthrough bleeding starts and stops irregularly and unpredictably, coming from an endometrium that shows none of the cyclical changes of the normal endometrium.

Of course, different women respond differently to the use of progestogen-only contraceptive methods. Changes may also vary according to the type of progestogen and the dose. With Norplant use, prolonged and irregular breakthrough bleeding is usually at its worst during the first 12 months of use, becoming more regular thereafter. With DMPA, users also start by experiencing prolonged and irregular bleeding, but later on this pattern is replaced by increasing periods of amenorrhoea. However, it is currently unclear just what causes this to happen.

In women using Norplant, the endometrium may be only 2–20% of the thickness of mid-secretory endometrium. At the same time, in contrast to the reduction in the volume of the endometrium, there is often an increase in vascular density with, sometimes, reduced arteriole development and the appearance of large thin-walled venules. Other typical endometrial changes induced by the use of progestogen-only contraceptives include: elevated progesterone receptor and reduced estrogen receptor levels, elevated levels of vascular endothelial growth factor (VEGF), reduced endothelin and increased neutral endometrium that is exposed to progestogen exhibits changes in comparison with a normal endometrium, it is unclear whether breakthrough bleeding is due to increased susceptibility, increased breakdown and damage, or reduced repair and clotting. Whatever the reason, experience shows the importance of good counselling. If a woman is informed of the side-effects and understands them before she starts to use a progestogen-only contraceptive, this will increase her acceptance of subsequent breakthrough bleeding.

Source: Rogers AW. Mechanisms of progestogen-induced endometrial bleeding. Gynaecology forum, 1999, 4(3):17–21.

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