Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test
BACKGROUND
Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A).
METHODS
Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4–7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all.
RESULTS
Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671–0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, P< 0.01). Glucose intolerance was absent in PCOS-A, but present in 30% of PCOS-T (P < 0.001). Most of the PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese.
CONCLUSIONS
Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.
Supplementary Material
Abstract
BACKGROUND
Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A).
METHODS
Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4–7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all.
RESULTS
Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671–0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, P< 0.01). Glucose intolerance was absent in PCOS-A, but present in 30% of PCOS-T (P < 0.001). Most of the PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese.
CONCLUSIONS
Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.
SHBG, sex hormone-binding globulin testosterone-binding capacity.
Conversion multipliers to SI units: Total testosterone 0.0347 (nmol/l), free testosterone 3.47 (pmol/l), androstenedione 0.0349 (nmol/l), 17OHP 0.0303 (nmol/l), DHEAS 0.0271 (µmol/l).
P values versus PCOS-T: <0.01.
P values versus PCOS-T: <0.001.
*P values versus controls: <0.05.
**P values versus controls: <0.01.
***P values versus controls: <0.001.
Values are expressed as number (% of total).
Functional ovarian hyperandrogenism in PCOS is indicated by either the presence of PCOS-T (17OHP hyper-response to GnRHa test) or a positive SDAST.
Functional adrenal hyperandrogenism in PCOS is indicated by a positive ACTH test.
Conversion to SI units: Progesterone × 0.0318 = nmol/l, 11-deoxycortisol × 0.0289 = nmol/l, 17-hydroxypregenolone × 0.0316 = nmol/l, dehydroepiandrosterone × 0.0347 = nmol/l.
PCOS patients divided into those with (FAH-positive) or without (FAH-negative) elevated dehydroepiandrosterone peak in response to ACTH.
*P values versus controls: <0.05.
**P values versus controls: <0.01.
***P values versus controls: <0.001.
P values versus FAH-positive: <0.05.
P values versus FAH-positive: <0.01.
P values versus FAH-positive: <0.001.
WC, waist circumference; T, testosterone; A'dione, androstenedione; HOMA, homeostatic model assessment index; ISI, insulin sensitivity index.
Hirsutism score according to Ferriman–Gallwey.
*P = 0.05.
**P < 0.01.
***P < 0.001 versus group I. (PCOS-A with abnormal SDAST).
Click here to view.Acknowledgements
The referrals of gynecology clinic patients by Dr Anthony Caruso is appreciated. Our special thanks to Neal Scherberg, Ph.D. and Kiang-Teck J. Yeo, Ph.D. of the University of Chicago Hospital Laboratories for providing the assay comparison data.