Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women
RB Barnes, RL Rosenfield, DA Ehrmann, JF Cara, L Cuttler, LL Levitsky and IM Rosenthal
Department of Obstetrics/Gynecology, University of Chicago, Pritzker School of Medicine, Illinois 60637.
Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
often have a polycystic ovary-like syndrome, consisting of
hyperandrogynism, infertility, menstrual irregularities, and elevated LH
levels. This is generally considered secondary to poor control of the
congenital adrenal hyperplasia. However, our experience led us to suspect
that ovarian hyperandrogenism occurs even when congenital adrenal
hyperplasia is well controlled on glucocorticoid therapy. Therefore, we
tested the hypothesis that congenital adrenal virilizing disorders result
in ovarian hyperandrogenism. We studied eight women with congenital adrenal
virilizing disorders, seven with well controlled classic 21-hydroxylase
deficiency and one with congenital virilizing adrenal carcinoma removed at
1.7 yr of age. We also studied six women with late-onset 21-hydroxylase
deficiency, without signs of congenital virilization. An ovarian source of
androgens was assessed after suppressing adrenal function with
dexamethasone and then testing pituitary-ovarian function by a GnRH agonist
(nafarelin) test. Five women with congenital adrenal virilizing disorders
(four with classic 21-hydroxylase deficiency and one with congenital
virilizing adrenal carcinoma) and one women with late-onset 21-hydroxylase
deficiency had ovarian hyperandrogenism as determined by subnormal
suppression of free testosterone after dexamethasone and/or by increased
17- hydroxyprogesterone response to nafarelin while on dexamethasone. All
women with congenital adrenal virilization and ovarian hyperandrogenism had
elevated LH levels after dexamethasone or elevated early LH response to
nafarelin, which suggests that LH excess is the cause of their ovarian
hyperandrogenism. This was not the case for the late- onset
21-hydroxylase-deficient woman. Our data are compatible with the hypothesis
that congenital adrenal virilization programs the hypothalamic-pituitary
axis for hypersecretion of LH at puberty. This is postulated to frequently
cause ovarian hyperandrogenism even when adrenal androgen excess is
subsequently controlled by glucocorticoid therapy.
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