Extremely high levels of estradiol and testosterone in a case of polycystic ovarian syndrome. Hormone and clinical similarities with the phenotype ofthe alpha estrogen receptor null mice

A 19-year-old nulliparous hirsute woman was evaluated for the very high ser um levels of testosterone (T) and estradiol (E-2) measured in an outside la boratory. Menarche had occurred at 11 years and was followed by regular men ses. We confirmed the high levels of T (9-16 ng/ml, nv 0.2-0.8) and E-2 (>1 000 pg/ml, nv 30-120). LH and FSH were consistently high (73-118 mU/l and 1 829 mU/l, respectively; LH/FSH ratio=4.1-4.7) and responsive to iv GnRH (LH baseline=118 mU/l, 30 min=290; FSH baseline=25 mU/l, 30 min=46). The unsti mulated values contrasted with those (LH=12, FSH=8 mU/l) measured in the ou tside laboratory, suggesting antigenically anomalous gonadotropins. 17-OH-p rogesterone was normal (0.5 ng/ml). After 1 mg dexamethasone, serum cortiso l was normally suppressed (24-->0.4 mu g/dl), T declined minimally (9-->8.6 ng/ml) and E-2 remained high (>1000 pg/ml). An exploratory laparotomy was performed, and two enlarged ovaries with multiple cysts as in a typical pol ycystic ovarian syndrome (PCOS) were seen. Before the wedge re-section of t he ovaries, hormones were assayed in the ovary veins (right ovary: T=30 ng/ ml, Pg=17 ng/ml, E-2=>5000 pg/ml; left: T=14 ng/ml, Pg=14 ng/ml, E-2=>5000 pg/ml). Histologically, the follicle cysts showed luteinization of the thec a interna; there was no evidence for ovary tumor in either ovary. After 21 days of 35 mu g ethynyl-E-2+2 mg cyproterone acetate (CA), E-2=3,000 pg/ml, T=1.4 ng/ml, LH=10.5 mU/I and FSH=4.1 mU/l. After three cycles of the said therapy (but with 50 mg CA in the first 10 days of each cycle), E-2 was 16 00 pg/ml, T 1.7 ng/ml, LH 7.1 and FSH 4.6 mU/l. Based on similarities with the phenotype of the ct estrogen receptor knockout female mice (alpha ERKO) , one possible explanation for the puzzling clinical and biochemical pictur e of our patient is resistance of alpha ER to estrogens. This is the first case of PCOS with extremely high E-2 and T. Thus, the differential diagnosi s of high levels of E-2+/-T should include PCOS. (C) 2000, Editrice Kurtis.