17-Hydroxyprogesterone Responses to Gonadotropin-Releasing Hormone Disclose Distinct Phenotypes of Functional Ovarian Hyperandrogenism and Polycystic Ovary Syndrome

Pasquali, Renato; Patton, Laura; Pocognoli, Patrizia; Cognigni, Graçiela Estela; Gambineri, Alessandra

doi:10.1210/jc.2007-0870

Cited by 41 publications

(35 citation statements)

References 28 publications

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“…They may also refer to a subset of PCOS women with a primary ovarian functional hyperandrogenism, since overproduction of androstenedione from both the ovaries and the adrenals has been demonstrated (53). However, this finding may also disclose a specific subset of women with PCOS, characterized by decreased aromatase activity in the ovarian tissues, as suggested by previous studies (54) and recent genetic findings on the activity of this enzyme in PCOS (55).…”

Section: Effect Of Weight Loss On Pcos: Lifestyle and Bariatric Surgerymentioning

confidence: 74%

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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PCOS is a clinical heterogeneous entity of female androgen excess diagnosed by exclusion of other disorders responsible for androgen excess. The concept of secondary PCOS implies that there is a primary well-defined cause leading to the PCOS phenotype with underlying androgen overproduction, regardless of the origin. In these cases, we presume the term of 'secondary PCOS' could be used. In all these conditions, the potential complete recovery of the hyperandrogenemic state as well as the remission of the PCOS phenotype should follow the removal of the cause. If accepted, these concepts could help clinicians to perform in-depth investigations of the potential factors or disorders responsible for the development of these specific forms of secondary PCOS. Additionally, this could contribute to develop further research on factors and mechanisms involved in the development of the classic and the nonclassic PCOS phenotypes. Invited author's profileRenato Pasquali is full professor of Endocrinology & Metabolism and Director of the division of Endocrinology of the S.Orsola-Malpighi Hospital, Bologna, Italy. He also heads the School of Specialization in Endocrinology and Metabolism, University Alma Mater Studiorum of Bologna, Italy. He is a member of numerous national and international scientific societies and serves on the editorial boards of international journals. His scientific interests relate to (i) the pathophysiology and treatment of the polycystic ovary syndrome; (ii) the endocrinology of obesity (sex hormones, the hypothalamic-pituitary-adrenal axis, and the endocannabinoid system).

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Section: Effect Of Weight Loss On Pcos: Lifestyle and Bariatric Surgerymentioning

confidence: 74%

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Pasquali

Diamanti-Kandarakis

Gambineri

2016

European Journal of Endocrinology

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“…High androstenedione concentrations in women who still presented PCOS after weight loss may imply an excess production rate of androgens from both the ovarian theca cells and/or the adrenals (19), which may be relatively independent of the presence of excess weight or obesity and therefore may predict the classic hyperandrogenic PCOS status (20). It may also refer to a subset of PCOS women with a primary ovarian functional hyperandrogenism, in whom the coexistence (12). However, this finding may also disclose a specific subset of women with PCOS characterized by decreased aromatase activity in the ovarian tissues, as suggested by previous studies (21) and recent genetic findings on the activity of this enzyme in PCOS (22).…”

Section: Discussionmentioning

confidence: 99%

“…Anthropometry and clinical evaluation Body weight, waist and hip circumferences, and systolic and diastolic blood pressure and pulse rate were carefully measured, according to standardized procedures (12). The ratio between waist and hip circumference (WHR) was used as an index of body fat distribution.…”

Section: Subjectsmentioning

confidence: 99%

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Heterogeneity in the responsiveness to long-term lifestyle intervention and predictability in obese women with polycystic ovary syndrome

Pasquali

Gambineri²,

Cavazza³

et al. 2011

European Journal of Endocrinology

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Background: Treatment of obesity improves all features of the polycystic ovary syndrome (PCOS). There is, however, a heterogeneous response to weight loss, and predictive factors are unknown.Objective: This follow-up study aimed to investigate obese women with PCOS treated with a long-term lifestyle program to evaluate responsiveness and predictability. Methods: One hundred PCOS women meeting the criteria for selection were invited to participate and 65 of them agreed. Lifestyle intervention had consisted of a 1200-1400 kcal/day diet for 6 months, followed by mild calorie restriction and physical activity. The protocol, which was similar at baseline and follow-up, included anthropometry, clinical evaluation, pelvic ultrasound, and laboratory investigations. The mean follow-up period was 20.4G12.5 months. Results: After the follow-up period, women were reclassified into three groups according to the persistence (group 1, 15.4%), partial (group 2, 47.7%), or complete (group 3, 36.9%) disappearance of the categorical features of PCOS (hyperandrogenism, menses, and ovulatory dysfunctions). Duration of the follow-up and extent of weight loss were similar among the three groups, as were fasting and glucose-stimulated insulin and indices of insulin resistance. Baseline waist circumference, waist to hip ratio (WHR), and androstenedione blood levels were negatively correlated with a better outcome in the univariate analysis. However, only basal androstenedione values persisted to a highly significant extent (P!0.001) in the multivariate analysis. Conclusions: Responsiveness to weight loss in overweight/obese PCOS women varies considerably and more than one third of women may achieve full recovery. These findings add new perspectives to the impact of obesity on the pathophysiology of PCOS.

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“…Moreover, DHEAS levels, are generally elevated in most women with PCOS, suggesting a prevalent adrenal contribution to this hyperandrogenic condition because of the unique adrenal origins of the conjugated steroid (14). While hyperandrogenic adrenal responses to ACTH in PCOS women are not necessarily accompanied by other remarkable adrenal abnormalities of the zona glomerulosa and zona fasciculata, or the hypothalamic-pituitary-adrenal axis (16,17), some PCOS studies suggest a generalized hypersecretion of adrenal steroids (15), or ACTH hyperresponsiveness to corticotropin releasing hormone (CRH) (18,19). The latter, however, may reflect diminished somatostatin release in PCOS women (20), particularly since somatostatin treatment reduces CRH-mediated ACTH release in PCOS women (21).…”

Section: Introductionmentioning

confidence: 99%

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

Abbott¹,

Zhou²,

Bird

et al. 2008

Disorders of the Human Adrenal Cortex

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Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of DHEAS, typical of PCOS women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

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17-Hydroxyprogesterone Responses to Gonadotropin-Releasing Hormone Disclose Distinct Phenotypes of Functional Ovarian Hyperandrogenism and Polycystic Ovary Syndrome

Cited by 41 publications

References 28 publications

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

MANAGEMENT OF ENDOCRINE DISEASE: Secondary polycystic ovary syndrome: theoretical and practical aspects

Heterogeneity in the responsiveness to long-term lifestyle intervention and predictability in obese women with polycystic ovary syndrome

Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

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