The case for less-than-monthly progestogen in women on HT: is transvaginal ultrasound the key?

Unopposed estrogen (previously called ERT, now referred to as ET) increases a patient's risk of endometrial cancer. The addition of a progestogen to estrogen (previously called HRT, now referred to as HT) will decrease that additional risk of endometrial cancer although it will not eliminate it. Initially this was always done in a sequential fashion. More recently, continuous-combined HT, utilizing daily progestogen, has been popularized. Increasingly, published data points to progestogen and estrogen together causing an increase in the risk of breast cancer two to three times above that of estrogen alone. In the past, less-than-monthly progestogen has been attempted. It results in less bleeding, as well as some simple hyperplasia. Transvaginal ultrasound has a very poor positive predictive value (4% for serious endometrial disease and 9% for any endometrial disease) but a very high negative predictive value (99%) when the echo is distinct, and thin (<5 mm). Thus, patients with an initial thin distinct endometrial echo can begin with unopposed estrogen. At 3 months, they get a progestogen withdrawal of 12 days and the endometrial echo is measured again. If thin and distinct (<5 mm), the interval between progestogen withdrawals can be further increased and in some women potentially eliminated. If the echo is not sufficiently thin, although this does not necessarily indicate anything more than proliferative endometrium, those patients may require either monthly progestogen or continuous-combined HT. The advantage for the successful patient is less progestogen exposure, as little as 24 days per year in most patients, and less bleeding (although because the majority will bleed, the patient has to be willing to accept a withdrawal bleed that she has planned and can control the timing of by when she chooses to take the progestogen). The patient should have an easily visible thin endometrial echo before initiation. Some women will not lend themselves to a reliable assessment of the endometrial echo (at least not without saline infusion enhancement). Examples of such patients are those with an axial uterus, coexisting fibroids, marked obesity, and previous endometrial ablation. Such an approach will allow a large number of patients whose initial endometrial echo is easily visualized to minimize their progestogen dose.