Adrenal dynamic responses to physiologic and pharmacologic adrenocorticotropic hormone stimulation before and after ovarian steroid modulation in women with polycystic ovary syndrome

Objective: To test the hypothesis that in women with polycystic ovary syndrome (PCOS), adrenal cytochrome P450c 17α activity is different after physiologic vs. pharmacologic ACTH stimulation and that ovarian activity promotes adrenal hyperactivity that is different after physiologic vs. pharmacologi...

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Bibliographic Details
Published in:Fertility and sterility 1999-03, Vol.71 (3), p.439-444
Main Authors: Gonzalez, Frank, Chang, Lillie, Horab, Theresa, Stanczyk, Frank Z, Crickard, Kent, Lobo, Rogerio A
Format: Article
Language:English
Subjects:
20-lyase hyperactivity
adrenal androgen sensitivity
adrenal dynamic testing
Adrenocorticotropic Hormone - blood
Adult
Biological and medical sciences
Cosyntropin - therapeutic use
Female
Female genital diseases
GnRH agonist
Gonadotropin-Releasing Hormone - agonists
Gynecology. Andrology. Obstetrics
Hormones - blood
Humans
Hyperandrogenism - complications
Leuprolide - therapeutic use
Medical sciences
Ovary - physiology
Pilot Projects
Polycystic ovary syndrome
Polycystic Ovary Syndrome - blood
Polycystic Ovary Syndrome - complications
Polycystic Ovary Syndrome - drug therapy
Polycystic Ovary Syndrome - enzymology
Steroid 17-alpha-Hydroxylase - metabolism
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Summary:Objective: To test the hypothesis that in women with polycystic ovary syndrome (PCOS), adrenal cytochrome P450c 17α activity is different after physiologic vs. pharmacologic ACTH stimulation and that ovarian activity promotes adrenal hyperactivity that is different after physiologic vs. pharmacologic ACTH stimulation. Design: Prospective controlled pilot study. Setting: Reproductive endocrinology unit of an academic medical center. Patient(s): Six women with PCOS who had adrenal hyperandrogenism were compared with four women with normal ovulation. Intervention(s): Adrenal dynamic blood sampling was performed before and after 6 months of GnRH agonist administration. Main Outcome Measure(s): Comparison of physiologic and pharmacologic ACTH-stimulated levels of progesterone, 17-hydroxyprogesterone, and androgens before and after ovarian steroid modulation. Result(s): In women with PCOS, exaggerated responses of androstenedione and 11β-hydroxyandrostenedione as well as elevated ratios of 17-hydroxyprogesterone to progesterone and of androstenedione to 17-hydroxyprogesterone after physiologic ACTH stimulation did not persist after GnRH-agonist administration. Three of the six women with PCOS had an increased response of androstenedione and a ratio of androstenedione to 17-hydroxyprogesterone that were >2 SD above the mean of those in the women with normal ovulation after pharmacologic ACTH stimulation; this finding persisted after GnRH-agonist administration. Conclusion(s): In women with PCOS, increases in adrenal androgen sensitivity after physiologic ACTH stimulation reflected in both arms of cytochrome P450c 17α activity may be influenced by ovarian activity. However, 17,20-lyase hyperactivity in a subset after pharmacologic ACTH stimulation may be an intrinsic adrenal disorder.
ISSN:0015-0282
1556-5653
DOI:10.1016/S0015-0282(98)00469-5