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17-hydroxyprogesterone responses to gonadotropin-releasing hormone disclose distinct phenotypes of functional ovarian hyperandrogenism and polycystic ovary syndrome.
J Clin Endocrinol Metab. 2007 Nov; 92(11):4208-17.JC

Abstract

CONTEXT

The exaggerated 17-hydroxyprogesterone response to GnRH agonists, which reflects functional ovarian hyperandrogenism (FOH), is believed to be the prominent abnormality in women with polycystic ovary syndrome (PCOS).

OBJECTIVE

Our objectives were to quantify the prevalence of PCOS with FOH and to evaluate whether the presence of FOH may distinguish different clinical and biochemical phenotypes.

DESIGN, SETTING, AND PARTICIPANTS

We conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women.

MAIN OUTCOME MEASURES

A hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression.

RESULTS

Based on the data obtained in the control subjects, the PCOS patients were divided into two groups, one with a normal (NR-PCOS, n = 78) and one with a high 17-hydroxyprogesterone response (HR-PCOS, n = 70) to buserelin. The two groups of PCOS subjects had similar anthropometric parameters and clinical signs of hyperandrogenism. Age and body weight at menarche were significantly lower and higher, respectively, in the HR-PCOS group than the NR-PCOS group. Moreover, the HR-PCOS group had higher basal testosterone (P < 0.001), free androgen index (P < 0.01), 17-hydroxyprogesterone (P < 0.05), estrogens (P < 0.05), area under the curve for insulin (insulin(AUC)) (P < 0.05), and C-peptide(AUC) (P < 0.01) and lower insulin sensitivity (as composite insulin sensitivity index) (P < 0.05) than the NR-PCOS group. The response of 17-hydroxyprogesterone to (1-24)ACTH (as percent variation) was lower in the HR-PCOS group with respect to the NR-PCOS group (P < 0.05), whereas the response of cortisol, androstenedione, and dehydroepiandrosterone was similar. Finally, the HR-PCOS group had lower percent suppression of androstenedione (P < 0.001) and 17-hydoxyprogesterone (P < 0.05) to dexamethasone. In a multiple regression model applied in all PCOS women, insulin(AUC) but not androgens or markers of insulin resistance predicted the 17-hydroxyprogesterone response to buserelin to a highly significant extent (t = 3.269; P < 0.01).

CONCLUSIONS

This study indicates that the paradigm that FOH is a specific feature of the PCOS status can no longer be sustained. We have shown that women with an exaggerated 17-hydroxyprogesterone response to a GnRH agonist, buserelin, are characterized by more severe hyperandrogenemia, glucose-stimulated beta-cell insulin secretion, and worse insulin resistance than those without evidence of FOH. Our data may be consistent with the hypothesis that excess insulin may represent a candidate factor responsible for FOH in these women, through the overactivation of the cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) enzyme pathway.

Authors+Show Affiliations

Division of Endocrinology, Department of Internal Medicine, Sant'Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy. renato.pasquali@unibo.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17785360

Citation

Pasquali, Renato, et al. "17-hydroxyprogesterone Responses to Gonadotropin-releasing Hormone Disclose Distinct Phenotypes of Functional Ovarian Hyperandrogenism and Polycystic Ovary Syndrome." The Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 11, 2007, pp. 4208-17.
Pasquali R, Patton L, Pocognoli P, et al. 17-hydroxyprogesterone responses to gonadotropin-releasing hormone disclose distinct phenotypes of functional ovarian hyperandrogenism and polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(11):4208-17.
Pasquali, R., Patton, L., Pocognoli, P., Cognigni, G. E., & Gambineri, A. (2007). 17-hydroxyprogesterone responses to gonadotropin-releasing hormone disclose distinct phenotypes of functional ovarian hyperandrogenism and polycystic ovary syndrome. The Journal of Clinical Endocrinology and Metabolism, 92(11), 4208-17.
Pasquali R, et al. 17-hydroxyprogesterone Responses to Gonadotropin-releasing Hormone Disclose Distinct Phenotypes of Functional Ovarian Hyperandrogenism and Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2007;92(11):4208-17. PubMed PMID: 17785360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 17-hydroxyprogesterone responses to gonadotropin-releasing hormone disclose distinct phenotypes of functional ovarian hyperandrogenism and polycystic ovary syndrome. AU - Pasquali,Renato, AU - Patton,Laura, AU - Pocognoli,Patrizia, AU - Cognigni,Graciela Estela, AU - Gambineri,Alessandra, Y1 - 2007/09/04/ PY - 2007/9/6/pubmed PY - 2008/1/3/medline PY - 2007/9/6/entrez SP - 4208 EP - 17 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 92 IS - 11 N2 - CONTEXT: The exaggerated 17-hydroxyprogesterone response to GnRH agonists, which reflects functional ovarian hyperandrogenism (FOH), is believed to be the prominent abnormality in women with polycystic ovary syndrome (PCOS). OBJECTIVE: Our objectives were to quantify the prevalence of PCOS with FOH and to evaluate whether the presence of FOH may distinguish different clinical and biochemical phenotypes. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational study at an academic hospital that included 148 PCOS women and 22 healthy age-matched normal-weight control women. MAIN OUTCOME MEASURES: A hormone profile was taken at baseline and in response to (1-24)ACTH and to a GnRH agonist, buserelin, administered during dexamethasone suppression. RESULTS: Based on the data obtained in the control subjects, the PCOS patients were divided into two groups, one with a normal (NR-PCOS, n = 78) and one with a high 17-hydroxyprogesterone response (HR-PCOS, n = 70) to buserelin. The two groups of PCOS subjects had similar anthropometric parameters and clinical signs of hyperandrogenism. Age and body weight at menarche were significantly lower and higher, respectively, in the HR-PCOS group than the NR-PCOS group. Moreover, the HR-PCOS group had higher basal testosterone (P < 0.001), free androgen index (P < 0.01), 17-hydroxyprogesterone (P < 0.05), estrogens (P < 0.05), area under the curve for insulin (insulin(AUC)) (P < 0.05), and C-peptide(AUC) (P < 0.01) and lower insulin sensitivity (as composite insulin sensitivity index) (P < 0.05) than the NR-PCOS group. The response of 17-hydroxyprogesterone to (1-24)ACTH (as percent variation) was lower in the HR-PCOS group with respect to the NR-PCOS group (P < 0.05), whereas the response of cortisol, androstenedione, and dehydroepiandrosterone was similar. Finally, the HR-PCOS group had lower percent suppression of androstenedione (P < 0.001) and 17-hydoxyprogesterone (P < 0.05) to dexamethasone. In a multiple regression model applied in all PCOS women, insulin(AUC) but not androgens or markers of insulin resistance predicted the 17-hydroxyprogesterone response to buserelin to a highly significant extent (t = 3.269; P < 0.01). CONCLUSIONS: This study indicates that the paradigm that FOH is a specific feature of the PCOS status can no longer be sustained. We have shown that women with an exaggerated 17-hydroxyprogesterone response to a GnRH agonist, buserelin, are characterized by more severe hyperandrogenemia, glucose-stimulated beta-cell insulin secretion, and worse insulin resistance than those without evidence of FOH. Our data may be consistent with the hypothesis that excess insulin may represent a candidate factor responsible for FOH in these women, through the overactivation of the cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) enzyme pathway. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/17785360/17_hydroxyprogesterone_responses_to_gonadotropin_releasing_hormone_disclose_distinct_phenotypes_of_functional_ovarian_hyperandrogenism_and_polycystic_ovary_syndrome_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2007-0870 DB - PRIME DP - Unbound Medicine ER -