Characterization of Functionally Typical and Atypical Types of Polycystic Ovary Syndrome

Hirshfeld-Cytron, Jennifer; Barnes, Randall B.; Ehrmann, David A.; Caruso, Anthony J.; Mortensen, Monica; Rosenfield, Robert L.

doi:10.1210/jc.2008-2248

Cited by 35 publications

(21 citation statements)

References 54 publications

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“…Our findings are consistent with previous published reports that showed in PCOS and normal women minimal and non-significant changes of 17-OHP and adrenal androgens following acute injection of ACTH(8, 12, 13). In contrast, Lachelin et al observed increases of 17-OHP and DHEA following a 2 hour infusion of ACTH in women with PCOS that were significantly greater than those noted for normal controls(13).…”

Section: Discussionsupporting

confidence: 94%

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

Maas

Chuan

Harrison

et al. 2016

Fertility and Sterility

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Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues.

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Section: Discussionsupporting

confidence: 94%

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

Maas

Chuan

Harrison

et al. 2016

Fertility and Sterility

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“…Our results are not surprising as amplified 17-OHP responses to GnRH agonist stimulation in PCOS women were reported to be unaltered despite ovarian suppression for one month (Gilling-Smith et al, 1997). In addition, after 3 months of ovarian suppression by long acting GnRH agonist, women with PCOS exhibited 17-OHP responses to hCG that remained greater than those of normal women albeit at substantially lower circulating values (Hirsh-feld-Cytron et al, 2009). Collectively, these results suggest that endogenous gonadotropin secretion contributes to basal androgen secretion and, even in the presence of lowered gonadotropin levels, maintains ovarian androgen synthesis and responsiveness to gonadotropin stimulation.…”

Section: Theca Cell Androgen Productionmentioning

confidence: 99%

Disordered follicle development

Chang

Cook-Andersen

2013

Molecular and Cellular Endocrinology

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Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells.

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“…Desensitization involves down-regulation of LH receptor expression and steroidogenesis. Because steroidogenic down-regulation is primarily exerted on 17,20-lyase activity, which converts 17alpha-hydroxycorticoids to 17-ketosteroids, 17-hydroxyprogesterone levels rise in response to increased LH levels, but there is only a limited rise in androgens (Hirshfeld-Cytron et al, 2009; McCartney et al, 2004; Mortensen et al, 2009). …”

Section: The Case For Pcos Being Unique In Its Relationships Amongmentioning

confidence: 99%

“…3) (Du et al, 2009; Ehrmann et al, 1995; Hirshfeld-Cytron et al, 2009; Nelson et al, 1999; Rosenfield, 1999). The ovarian hyperandrogenism is “functional” because it is gonadotropin-dependent; however, LH excess does not seem to ordinarily be the fundamental stimulus to hyperandrogenism.…”

Section: The Case For Pcos Being Unique In Its Relationships Amongmentioning

confidence: 99%

Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

Rosenfield

Bordini

2010

Brain Research

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Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty.

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Characterization of Functionally Typical and Atypical Types of Polycystic Ovary Syndrome

Abstract: Typical PCOS is characterized by intrinsic ovarian hypersensitivity to hCG to which excessive paracrine FSH signaling via inhibin-B may contribute. Atypical PCOS is due to a unique type of ovarian dysfunction that is relatively gonadotropin hyposensitive.

Cited by 35 publications

References 54 publications

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome

Disordered follicle development

Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

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