Around 1970s, I treated many cases of severe preeclampsia, using various antihypertensive drugs and monitor P-LAP activities in maternal sera. In every case I had encountered intra-uterine fetal death, regardless of increased or controlled maternal blood pressure, I was a bit confused. And I was deeply nervous about my attempted treatments without using antihypertensive drugs.


I then searched for historical treatment records of preeclampsia. Finally I found an article published by Smith and Smith (1). This original article was basically suggesting alleviation of symptoms in severe preeclampsia by administration of two kind of sex steroid hormones for up to 7 days or slightly shorter.


In 1969, I attempted with my first patient of severe preeclampsia at my father’s private clinic, a treatment essentially based on two sex steroids. Daily administration with the dose essentially similar to the protocol which we have proposed (2) and strictly monitored by the daily measurement of P-LAP activities, under the consent of the patients and her husband.


Her pregnancy carried over approximately three weeks more in improved hypertensive conditions. Then I decided the termination of pregnancy due to a tendency of decreasing P-LAP activities observed along with increasing blood pressure irrespective sex steroid treatment.


“Sex steroid treatment with dose increasing manner by gestational week (sex steroid treatment)” for severe preeclampsia and preterm labor has limitation in its clinical effect. It is preliminary a stage of the clinical application of P-LAP or APA itself, i.e., administration of recombinant form of these peptidases. Nevertheless, it might be a clinically meaningful tool; that monitoring pathological changes through P-LAP and APA activities in patients with preeclampsia and preterm labor.


Daily injections of two steroid hormones may not be practical. Presently in my clinic, I use depot type administered in every 3 or 4 days interval essentially similar doses to the protocol which we have proposed (2) per gestational week   in accordance with the measurements of maternal serum P-LAP activities.


1.     Smith GV, Smith OW , J Clin Endocrinol 1941;1:477-484]

2.     Mizutani S, Mizutani E, Exp Clin Endocrinol Diabetes 2015;123:159-164