ANDROSTENEDIONE INCREASES ESTRADIOL LEVELS BUT NOT PRETERM LABOR

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It has been reported that intravenous administration of androstenedione ( 4A) leads to labor and delivery by increasing the concentration of estradiol (E2) in the maternal circulation and stimulating increased nocturnal uterine activity (Nat Med 2:443, 1996). Initial experiments in our laboratory demonstrated that E2-benzoate did not precipitate preterm delivery in non-instrumented animals (AJOG 145:920, 1983). We therefore studied the effect of 4A given SQ in instrumented and non-instrumented rhesus monkeys. Androstenedione was administered (6-30 mg, BID, SQ) to 5 rhesus monkeys beginning on day 132-142 of pregnancy. Two animals were instrumented with maternal and fetal vascular and amniotic fluid catheters on day 122. Three animals were not instrumented and blood was drawn by venipuncture. One instrumented animal delivered preterm (day 145) 60 hours after the beginning of treatment; all other animals delivered spontaneously at term (day 160-172) after 21-40 days of treatment. The animal that delivered early had nocturnal episodes of uterine activity (UA) prior to 4A administration whereas the other animal did not show nocturnal UA until delivery. None of the uninstrumented animals delivered before term. Maternal plasma hormone levels are shown below (Pre = pre-treatment; post = post-partum; 0 = day of delivery; mean + SEM; * = different from pre, P>0.05 ANOVA) Days Pre- E2 E1 4A T DHT P4 DHEAS Cortisol partum (pg/ml) (pg/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) (ng/ml) Pre 451q39 117q17 1.4q0.2 0.2q0.04 0.2q0.03 3.7q1.0 269q55 310q57 16-25 1960q129* 1073q158* 25.8q3.8* 4.4q0.3* 2.5q0.4* 3.5q0.5 154q16 334q33 6-15 1971q105* 1161q101* 52.2q17.6* 5.3q0.7* 3.01q0.5* 4.0q0.5 143q15 323q28 1-5 1553q173* 1178q317* 30.5q9.8* 4.1q0.9* 2.0q0.6* 3.6q0.5 187q33 321q39 0 1717q224* 1069q283 66.9q19.4* 6.5q1.4* 2.6q0.9* 5.9q2.6 174q18 356q75 Post 77q28 35q16 10.7q5.9 1.6q0.7 1.1q0.5 1.4q0.2 107q35 262q37 These data suggest that high levels of estradiol after androstenedione administration do not necessarily lead to preterm delivery. The inability of the uterus of some animals to achieve quiescence after surgical instrumentation may facilitate preterm delivery associated with androstenedione administration.