Increased Adrenal Androgens in Overweight Peripubertal Girls

Solorzano, Christine M. Burt; Helm, Kristin D.; Patrie, James T.; Shayya, Rana F.; Cook-Andersen, Heidi; Chang, R. Jeffrey; McCartney, Christopher R.; Marshall, John C.

doi:10.1210/js.2017-00013

Cited by 16 publications

(11 citation statements)

References 45 publications

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“…Davio et al [ 24 ] found that 11-KT is the dominant circulating bioactive androgen during normal and premature adrenarche and that concentrations do not seem to decline in women as they age. Ovarian-derived testosterone is higher in peripubertal girls with obesity [ 25 ]. However, in premenarchal daughters of women with PCOS, 11-oxyandrogens were not elevated relative to age-matched controls [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

Taylor

Ware

Breslow

et al. 2022

Journal of the Endocrine Society

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Background/context Polycystic ovary syndrome (PCOS) is common and diagnosis requires an elevated testosterone. The clinical importance of adrenal 11-oxyandrogens in PCOS is unclear. We sought to determine if 11-oxyandrogens: 1) better identify PCOS diagnosis compared to testosterone 2) predict clinical comorbidities of PCOS, 3) are altered with combined oral contraceptive pill (COCP) or metformin therapy. Methods Data from 200 adolescent females aged 12-21 years, most with obesity, enrolled across 6 studies in pediatric endocrinology were included: 70 non-PCOS controls, 115 untreated PCOS, 9 PCOS+obesity treated with COCP, 6 PCOS+obesity treated with metformin. 11-hydroxyandrostenedione (11OHA4), 11-hydroxytestosterone (1-OHT), 11-ketotestosterone (11KT) and testosterone were measured with LC/MSMS. Data between 1) untreated PCOS and controls and 2) untreated PCOS and the 2 treatment groups were compared. Results Untreated girls with PCOS had higher 11OHA4 (p=0.003) and 11OHT (p=0.005) compared to controls, but not 11KT (p=0.745). Elevated 11OHA4 remained significant after controlling for obesity. Testosterone better predicted PCOS status compared to 11-oxyandrogens (ROC analysis: 11OHA4 AUC=0.620, 11OHT AUC=0.638; testosterone AUC=0.840). Among untreated PCOS, all three 11-oxyandrogens correlated with hirsutism severity. 11KT (p=0.039) and testosterone (p<0.006) was lower in those on COCP treatment compared to untreated PCOS). Metformin treatment had no effect on 11-oxyandrogens, although testosterone was lower (p=0.01). Conclusions/Relevance While 11-oxyandrogens do not aid in the diagnosis of PCOS, they relate to excess hair growth. COCP treatment may related to 11-KT, however, further work is needed to determine causality, relationship with metabolic outcomes, and the clinical utility of measuring these androgens in PCOS.

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Section: Discussionmentioning

confidence: 99%

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

Taylor

Ware

Breslow

et al. 2022

Journal of the Endocrine Society

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“…It is known that girls with obesity have relatively higher androgen levels and are consequently prone for an increased AS, which might have influenced the results. 36 However, we could only speculate on the theory, since no analysis stratified by sex was performed, since the number of participants assigned to a subgroup stratified by sex and Tanner stage was too small to analyze. In addition, the observed difference in BMI may have limited the influence of Tanner stage on AS.…”

Section: Discussionmentioning

confidence: 99%

Increased Arterial Stiffness in Adolescents With Obesity

Lentferink

Kromwijk

et al. 2019

Global Pediatric Health

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Increased arterial stiffness (AS) is an early sign of cardiovascular disease. Influence of weight, puberty, and insulin resistance (IR) on AS in adolescents is unclear. Therefore, this study compared AS, assessed with pulse wave velocity (PWV) and augmentation index (AIx), of adolescents with and without obesity and evaluated the influence of puberty and IR on AS. Sixty-two lean and 61 adolescents with obesity were included. Significantly higher PWV was observed in adolescents with obesity (4.1 ms −1 [2.4 to 5.6 ms −1 ] vs 3.6 ms −1 [0.4 to 6.1 ms −1 ]; P = .01), while AIx was not significant different. However, significantly higher AIx was observed in adolescents with obesity and IR (3.0 [−17.5% to 28.5%] vs −3.0 [−19.0% to 13.0%]; P = .01). For Tanner stages, no differences were observed. The higher PWV in adolescents with obesity and higher AIx in adolescents with obesity and IR both indicate an increased AS. Consequently, measurement of AS should be considered in adolescents with obesity and IR as part of cardiovascular risk assessment.

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“…19 The precise source of such T increases is unclear, but may be of adrenal origin early in puberty, with increasing ovarian contribution by mid to late puberty. 20 It has been recently recognized that 11-oxygenated C19 androgens—generated in part via aldo-keto reductase family 1 member C3 (AKR1C3) activity in the adrenal gland and adipose tissue—are important contributors to androgen excess in adolescent girls and women. Such androgens include 11-ketotestosterone (11-KT), which binds and activates the androgen receptor with the same affinity as T. 11-KT levels are elevated in girls with premature adrenarche, congenital adrenal hyperplasia (CAH), PCOS, and obesity.…”

Section: Defining Hyperandrogenemia In Adolescentsmentioning

confidence: 99%

“…79 By late puberty, girls with obesity demonstrate fourfold higher post-dexamethasone levels of free T and twofold higher A4 and free T responses to cosyntropin, suggesting both ovarian and adrenal contributions to obesity-associated hyperandrogenemia in later puberty. 20…”

Section: Obesity-related Hyperandrogenemiamentioning

confidence: 99%

Non-PCOS Hyperandrogenic Disorders in Adolescents

et al. 2022

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Hyperandrogenism—clinical features resulting from increased androgen production and/or action—is not uncommon in peripubertal girls. Hyperandrogenism affects 3 to 20% of adolescent girls and often is associated with hyperandrogenemia. In prepubertal girls, the most common etiologies of androgen excess are premature adrenarche (60%) and congenital adrenal hyperplasia (CAH; 4%). In pubertal girls, polycystic ovary syndrome (PCOS; 20–40%) and CAH (14%) are the most common diagnoses related to androgen excess. Androgen-secreting ovarian or adrenal tumors are rare (0.2%). Early pubic hair, acne, and/or hirsutism are the most common clinical manifestations, but signs of overt virilization in adolescent girls—rapid progression of pubic hair or hirsutism, clitoromegaly, voice deepening, severe cystic acne, growth acceleration, increased muscle mass, and bone age advancement past height age—should prompt detailed evaluation. This article addresses the clinical manifestations of and management considerations for non-PCOS-related hyperandrogenism in adolescent girls. We propose an algorithm to aid diagnostic evaluation of androgen excess in this specific patient population.

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Increased Adrenal Androgens in Overweight Peripubertal Girls

Cited by 16 publications

References 45 publications

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

Increased Arterial Stiffness in Adolescents With Obesity

Non-PCOS Hyperandrogenic Disorders in Adolescents

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