Androgen Profiling by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) in Healthy Normal-Weight Ovulatory and Anovulatory Late Adolescent and Young Women

Fanelli, Flaminia; Gambineri, Alessandra; Belluomo, Ilaria; Repaci, Andrea; Lallo, Valentina Diana Di; Dalmazi, Guido Di; Mezzullo, Marco; Prontera, Olga; Cuomo, Gaia; Zanotti, Laura; Paccapelo, Alexandro; Morselli-Labate, Antonio Maria; Pagotto, Uberto; Pasquali, Renato

doi:10.1210/jc.2013-1381

Cited by 56 publications

(37 citation statements)

References 38 publications

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“…The diagnosis of PCOS in adolescents is controversial, since anovulatory cycles can be observed even in the sixth year after menarche [50]. Moreover, normal menstruating girls often show elevated LH levels and androgen imbalance [51], suggesting predisposition to developing PCOS later in life. Thus, persistent oligomenorrhea, especially over 2 years beyond menarche, associated with hyperandrogenism can be considered a possible early sign of PCOS in adolescents [38, 39].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Faienza

Brunetti

Acquafredda³

et al. 2017

Horm Res Paediatr

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Background/Aims: Gonadotropin-releasing hormone analogues (GnRHa) represent the gold standard treatment for central precocious puberty (CPP). We aimed to assess the effects of GnRHa treatment on metabolic outcomes, bone status, and polycystic ovary syndrome (PCOS) prevalence in young girls with idiopathic CPP (ICPP). Methods: We enrolled 94 ICPP girls who were at least 2 years after menarche and had already attained adult height at the time of the study: 56 previously treated with depot triptorelin (3.4 ± 0.6 years) and 38 untreated. Auxological parameters, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), bone state, and prevalence of PCOS were assessed. Results: The 2 groups were similar for body mass index (BMI) and waist circumference. HOMA-IR, dehydroepiandrosterone sulfate, and Δ4-androstenedione were higher in the treated than in the untreated subjects (p < 0.001). Significant differences were found for amplitude-dependent speed of sound (p < 0.03) and bone transmission time z-scores (p < 0.01). The prevalence of PCOS was higher in the treated than in the untreated subjects (p < 0.04). Conclusion: GnRHa therapy is associated with hyperandrogenism and an increase in insulin resistance and PCOS prevalence, but not with increased BMI or lipid profile alterations. Long-term evaluations at the time of expected peak bone mass achievement are needed to understand the persistent or transient nature of subtle bone abnormalities.

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Section: Discussionmentioning

confidence: 99%

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Faienza

Brunetti

Acquafredda³

et al. 2017

Horm Res Paediatr

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“…Several recent studies have shown that extremely accurate and sensitive technologies in the detection and analysis of steroids, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) (8), have significantly improved the definition of the androgenemic blood pattern in women with PCOS (11,12,13,14,15,16,17,18). These studies have clearly shown that a steroid profile, including not only testosterone blood levels but also androstenedione and the free androgen index (FAI), may optimize the diagnosis of hyperandrogemia in women with PCOS, therefore improving our understanding on the heterogeneity of its phenotypes.…”

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

“…In these girls, body mass index (BMI) may represent the best predictor of unbound testosterone levels, much more than luteinizing hormone (LH) and insulin levels, and the Tanner stage (27). Large population-based studies have also shown that half of oligomenorrheic girls may have significantly increased LH and androgen levels (28), although this finding still remains controversial, since other studies performed in healthy normal-weight girls with anovulatory regular menses showed that they were characterized by a significantly higher androgen levels in comparison with those with ovulatory menses (29). Intriguingly, longitudinal studies have shown that adolescent serum androgen levels may be preserved into adulthood and are associated with menstrual dysfunction, which suggests a potential risk to develop PCOS (30).…”

Section: Arguments In Favor Of the Definition Of Secondary Pcosmentioning

confidence: 99%

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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“…Distinction between normal, heterozygotes, non-classic and classic CAH forms by measuring 17-OHP after ACTH stimulation was first described by Maria New and then others 93,94 This has not been repeated with modern MS assays though basal reference ranges according to age and gender have been reported. 82,83,90 An equivalent chart for GC-MS analysis is shown in Figure 2 with results closer to LC-MS/ MS methods than IA methods. As a guide, 17-OHP after ACTH stimulation is >30 nmol/L (10 ng/mL) in NC-CAH.…”

Section: -Ohp Assay Performancementioning

confidence: 99%

17-Hydroxyprogesterone in children, adolescents and adults

Honour

2014

Ann Clin Biochem

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17-Hydroxyprogesterone (17-OHP) is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase. An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentrations of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotrophic hormone. The classical congenital adrenal hyperplasia (CAH) presents usually with virilisation of a girl at birth. Affected boys and girls can have renal salt loss within a few days if aldosterone production is also compromised. Diagnosis can be delayed in boys. A non-classical form of congenital adrenal hyperplasia (NC-CAH) presents later in life usually with androgen excess. Moderately raised or normal 17-OHP concentrations can be seen basally but, if normal and clinical suspicion is high, an ACTH stimulation test will show 17-OHP concentrations (typically >30 nmol/L) above the normal response. NC-CAH is more likely to be detected clinically in females and may be asymptomatic particularly in males until families are investigated. The prevalence of NC-CAH in women with androgen excess can be up to 9% according to ethnic background and genotype. Mutations in the 21-hydroxylase genes in NC-CAH can be found that have less deleterious effects on enzyme activity. Other less-common defects in enzymes of cortisol synthesis can be associated with moderately elevated 17-OHP. Precocious puberty, acne, hirsutism and subfertility are the commonest features of hyperandrogenism. 17-OHP is a diagnostic marker for CAH but opinions differ on the role of 17OHP or androstenedione in monitoring treatment with renin in the salt losing form. This review considers the utility of 17-OHP measurements in children, adolescents and adults.

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Androgen Profiling by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) in Healthy Normal-Weight Ovulatory and Anovulatory Late Adolescent and Young Women

Abstract: This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.

Cited by 56 publications

References 38 publications

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

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

17-Hydroxyprogesterone in children, adolescents and adults

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