Fetal protection against masculinization with hyperreactio luteinalis and virilization.

Abstract

In a unique patient with secondary amenorrhea and hirsutism prior to pregnancy, lutein cysts with hyperreactio luteinalis enlarged the ovaries to a diameter of 25 cm during pregnancy. The purpose of the study was to explore the possibility that placental aromatization of androgens may be a metabolic barrier that offers protection against masculinization of a female fetus. Maternal serum, umbilical cord serum and lutein cyst fluid were analyzed for testosterone, progesterone and estradiol content. The cardinal clinical findings were marked maternal virilization but no fetal masculinization. At the time of delivery, massive ovarian production of testosterone and a large maternal-fetal testosterone gradient were found. The maternal arm vein testosterone level, 15,000 ng/dl, was about 100 times normal level, the material ovarian vein level was 51,800 ng/dl, while the cord blood level was only 465 ng/dl. At the same time there was an increase in fetal cord blood estradiol to 33 ng/ml, a 7-fold increase compared to normal cord levels. A protective mechanism for the fetus may exist when maternal androgens are markedly elevated due to a maternal endocrinopathy concurrent with pregnancy. Our data are compatible with the concept that placental aromatization of androgens may function as a metabolic barrier, thus offering protection to the fetus from excessive maternal androgens. Another facet of the protective mechanism may be increased fetal exposure to potent estrogens, which may buffer the influence of androgens reaching the fetus.