Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

OBJECTIVE

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea.

DESIGN

Controlled clinical study.

SETTING

Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy.

PATIENT(S): Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group.

INTERVENTION(S): Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv).

MAIN OUTCOME MEASURE(S): Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A).

RESULT(S): Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls.

CONCLUSIONS

Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.