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

Abstract

A 19-year-old nulliparous hirsute woman was evaluated for the very high serum levels of testosterone (T) and estradiol (E2) measured in an outside laboratory. Menarche had occurred at 11 years and was followed by regular menses. We confirmed the high levels of T (9-16 ng/ml, nv 0.2-0.8) and E2 (>1,000 pg/ml, nv 30-120). LH and FSH were consistently high (73-118 mU/l and 18-29 mU/l, respectively; LH/FSH ratio=4.1-4.7) and responsive to iv GnRH (LH baseline=118 mU/I, 30 min=290; FSH baseline=25 mU/l, 30 min=46). The unstimulated values contrasted with those (LH=12, FSH=8 mU/I) measured in the outside laboratory, suggesting antigenically anomalous gonadotropins. 17-OH-progesterone was normal (0.5 ng/ml). After 1 mg dexamethasone, serum cortisol was normally suppressed (24-->0.4 microg/dl), T declined minimally (9-->8.6 ng/ml) and E2 remained high (>1,000 pg/ml). An exploratory laparotomy was performed, and two enlarged ovaries with multiple cysts as in a typical polycystic ovarian syndrome (PCOS) were seen. Before the wedge resection of the ovaries, hormones were assayed in the ovary veins (right ovary: T=30 ng/ml, Pg=17 ng/ml, E2=>5,000 pg/ml; left: T=14 ng/ml, Pg=14 ng/ml, E2=>5,000 pg/ml). Histologically, the follicle cysts showed luteinization of the theca interna; there was no evidence for ovary tumor in either ovary. After 21 days of 35 microg ethynyl-E2+2 mg cyproterone acetate (CA), E2=3,000 pg/ml, T=1.4 ng/ml, LH=10.5 mU/l and FSH=4.1 mU/I. After three cycles of the said therapy (but with 50 mg CA in the first 10 days of each cycle), E2 was 1,600 pg/ml, T 1.7 ng/ml, LH 7.1 and FSH 4.6 mU/I. Based on similarities with the phenotype of the alpha estrogen receptor knockout female mice (alphaERKO), one possible explanation for the puzzling clinical and biochemical picture of our patient is resistance of (alphaER to estrogens. This is the first case of PCOS with extremely high E2 and T. Thus, the differential diagnosis of high levels of E2 +/- T should include PCOS.

Hormonal Imbalance in Polycystic Ovarian Syndrome (Pcos) in Teaching Hospitals in Ekiti State, Nigeria

“…There was significant increase (p < 0.05) in the testosterone concentration of PCOS group when compared with Non-PCOS control group (Table 1). This study is in agreement with the work of Bartolone et al (2000) who reported an extremely high level of Testosterone in PCOS [19]. This emphasizes the importance of testosterone in diagnosing of PCOS.…”

“…The concentration of Estradiol in PCOS subjects in this study increased significantly in comparison with the control subject (Table 1). This correlates with the research work of Bartolone et al who reported an extremely high level of Estradiol in PCOS, and suggested that the differential diagnosis of high levels of E2 +/− Testosterone should include PCOS [19].…”

Hormone Imbalance in Women with Infertility Caused by Polycystic Ovary Syndrome: Is There a Connection with Body Mass Index?

“…Anovulation is associated with low estradiol secretion, mainly due to peripheral extraglandular conversion and minimal progesterone production [48]. Hashemi et al found decreased estradiol levels in PCOS, while studies point out to exceedingly high estradiol levels [49], [50]. The increase in the level of bioavailable estradiol in PCOS can be attributed to reduced sex hormone-related globulin levels [51], which are also associated with obesity and testosterone levels [38].…”

Are There Any Sensitive and Specific Sex Steroid Markers for Polycystic Ovary Syndrome?

“…Serum concentrations of E1 and estradiol (E2) are higher in women with PCOS than controls, but the ranges overlap widely (15,16). It has also been suggested that impaired FSH release by chronic acyclic estrogen production derived from nonglandular aromatization of circulating androgens could be responsible for anovulation in PCOS (14).…”