Download PDF
Horm Metab Res 2020; 52(03): 179-185
DOI: 10.1055/a-1109-2630
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome

Sarantis Livadas
1   Endocrine Hospital, Unit, Metropolitan Greece, Athens, Greece
,
Christina Bothou
2   Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland
,
Christina Kanaka-Gantenbein
3   Division of Endocrinology, Metabolism and Diabetes, “Aghia Sophia” Children’s Hospital, Athens, Greece
,
Dimitrios Chiotis
3   Division of Endocrinology, Metabolism and Diabetes, “Aghia Sophia” Children’s Hospital, Athens, Greece
,
Nicholas Angelopoulos
1   Endocrine Hospital, Unit, Metropolitan Greece, Athens, Greece
,
Djuro Macut
4   Department of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
George P. Chrousos
3   Division of Endocrinology, Metabolism and Diabetes, “Aghia Sophia” Children’s Hospital, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 05 June 2019

accepted 22 January 2020

Publication Date:
19 February 2020 (online)

Also available at
    Permissions and Reprints

Abstract

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Key words

premature adrenarche - psychologic profile - premature pubarche - insulin resistance - PCOS
 

  • References

  • 1 Mäntyselkä A, Jääskeläinen J, Lindi V. et al. J Clin Endocrinol Metab 2014; 99: 3889-3894
    CrossrefPubMed
  • 2 Voutetakis A, Livadas S, Sertedaki A. et al. Insufficient adrenarche in patients with combined pituitary hormone deficiency caused by a PROP-1 gene defect. J Pediatr Endocrinol Metab 2001; 14: 1107-1111
    PubMedGoogle Scholar
  • 3 Marakaki C, Karapanou O, Gryparis A. et al. IEarly adiposity rebound and premature adrenarche. J Pediatr 2017; 186: 72-77
    CrossrefPubMedGoogle Scholar
  • 4 Noordam C, Dhir V, McNelis JC. et al. Inactivating PAPSS2 mutations in a patient with premature pubarche. N Engl J Med 2009; 361: 217
    PubMedGoogle Scholar
  • 5 Dacou-Voutetakis C, Dracopoulou M. High incidence of molecular defects of the CYP21 gene in patients with premature adrenarche. J Clin Endocrinol Metab 1999; 84: 1570-1574
    CrossrefPubMedGoogle Scholar
  • 6 Utriainen P, Laakso S, Liimatta J. et al. Premature adrenarche- a common condition with variable presentation. Horm Res Paediatr 2015; 3: 221-231
    PubMedGoogle Scholar
  • 7 Livadas S, Dracopoulou M, Vasileiadi K. et al. Elevated coagulation and inflammatory markers in adolescents with a history of premature adrenarche. Metabolism 2009; 58: 576-581
    CrossrefPubMedGoogle Scholar
  • 8 Byrne ML, Whittle S, Vijayakumar N. et al. A systematic review of adrenarche as a sensitive period in neurobiological development and mental health. Dev Cogn Neurosci 2017; 25: 12-28
    CrossrefPubMedGoogle Scholar
  • 9 Ibañez L, Potau N, Virdis R. et al. Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993; 76: 1599-1603
    PubMedGoogle Scholar
  • 10 Conway G, Dewailly D, Diamanti-Kandarakis E. et al. The polycystic ovary syndrome: A position statement from the European Society of Endocrinology. Eur J Endocrinol 2014; 171: 1-29
    CrossrefPubMedGoogle Scholar
  • 11 Ibáñez L, Dimartino-Nardi J, Potau N. et al. Premature adrenarche - Normal variant or forerunner of adult disease?. Endocr Rev 2000; 21: 671-696
    PubMedGoogle Scholar
  • 12 Meas T, Chevenne D, Thibaud E. et al. Endocrine consequences of premature pubarche in post-pubertal Caucasian girls. Clin Endocrinol (Oxf) 2002; 57: 101-106
    CrossrefPubMedGoogle Scholar
  • 13 Voutilainen R, Jääskeläinen J. Premature adrenarche: etiology, clinical findings, and consequences. J Steroid Biochem Mol Biol 2015; 145: 226-236
    CrossrefPubMedGoogle Scholar
  • 14 Paterson WF, Ahmed SF, Bath L. et al. Exaggerated adrenarche in a cohort of Scottish children: Clinical features and biochemistry. Clin Endocrinol (Oxf) 2010; 72: 496-501
    CrossrefPubMedGoogle Scholar
  • 15 Williams KM, Oberfield SE, Zhang C. et al. The relationship of metabolic syndrome and body composition in children with premature adrenarche: Is it age related?. Horm Res Paediatr 2015; 84: 401-407
    CrossrefPubMedGoogle Scholar
  • 16 Livadas S, Chaskou S, Kandaraki AA. et al. Anxiety is associated with hormonal and metabolic profile in women with polycystic ovarian syndrome. Clin Endocrinol (Oxf) 2011; 75: 698-703
    CrossrefPubMedGoogle Scholar
  • 17 Zehr JL, Culbert KM, Sisk CL. et al. An association of early puberty with disordered eating and anxiety in a population of undergraduate women and men. Horm Behav 2007; 52: 427-435
    CrossrefPubMedGoogle Scholar
  • 18 Sontag-Padilla LM, Dorn LD, Tissot A. et al. Executive functioning, cortisol reactivity, and symptoms of psychopathology in girls with premature adrenarche. Dev Psychopathol 2012; 24: 211-223
    CrossrefPubMedGoogle Scholar
  • 19 Whittle S, Simmons JG, Byrne ML. et al. Associations between early adrenarche, affective brain function and mental health in children. Soc Cogn Affect Neurosci 2015; 10: 1282-1290
    CrossrefPubMedGoogle Scholar
  • 20 Idkowiak J, Lavery GG, Dhir V. et al. Premature adrenarche: Novel lessons from early onset androgen excess. Eur J Endocrinol 2011; 165: 189-207
    CrossrefPubMedGoogle Scholar
  • 21 Likitmaskul S, Cowell CT, Donaghue KK. et al. “Exaggerated adrenarche” in children presenting with premature adrenarche. Clin Endocrinol (Oxf) 1995; 42: 265-272
    CrossrefPubMedGoogle Scholar
  • 22 Liimatta J, Utriainen P, Voutilainen R. et al. Girls with a history of premature adrenarche have advanced growth and pubertal development at the age of 12 years. Front Endocrinol (Lausanne) 2017; 8: 291
    CrossrefPubMedGoogle Scholar
  • 23 Macut D, Bjekić-Macut J, Rahelić D. et al. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract 2017; 130: 163-170
    CrossrefPubMedGoogle Scholar
  • 24 Livadas S, Kollias A, Panidis D. et al. Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome. Eur J Endocrinol 2014; 171: 301-309
    CrossrefPubMedGoogle Scholar
  • 25 Uçar A, Saka N, Baş F. et al. Reduced atherogenic indices in prepubertal girls with precocious adrenarche born appropriate for gestational age in relation to the conundrum of DHEAS. Endocr Connect 2013; 2: 1-10
    CrossrefPubMedGoogle Scholar
  • 26 Ibáñez L, Potau N, Chacon P. et al. Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche. Diabetologia 1998; 41: 1057-1063
    CrossrefPubMedGoogle Scholar
  • 27 Battaglia C, Regnani G, Mancini F. et al. Isolated premature pubarche: Ultrasonographic and color Doppler analysis–a longitudinal study. J Clin Endocrinol Metab 2002; 87: 3148-3154
    PubMedGoogle Scholar
  • 28 Pere A, Perheentupa J, Peter M. et al. Follow up of growth and steroids in premature adrenarche. Eur J Pediatr 1995; 154: 346-352
    CrossrefPubMedGoogle Scholar
  • 29 Oron T, Lebenthal Y, de Vries L. et al. Interrelationship of extent of precocious adrenarche in appropriate for gestational age girls with clinical outcome. J Pediatr 2012; 160: 308-313
    CrossrefPubMedGoogle Scholar
  • 30 Miller D, Emans SJ, Kohane I. Follow-up study of adolescent girls with a history of premature pubarche. J Adolesc Health 1996; 18: 301-305
    CrossrefPubMedGoogle Scholar
  • 31 Ibañez L, Virdis R, Potau N. et al. Natural history of premature pubarche: An auxological study. J Clin Endocrinol Metab 1992; 74: 254-257
    PubMedGoogle Scholar
  • 32 Alvarez-Blasco F, Botella-Carretero JI, San Millán JL. et al. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med 2006; 166: 2081-2086
    CrossrefPubMedGoogle Scholar
  • 33 Legro RS, Arslanian SA, Ehrmann DA. et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013; 98: 4565-4592
    CrossrefPubMedGoogle Scholar
  • 34 Macut D, Bačević M, Božić-Antić I. et al. Predictors of subclinical cardiovascular disease in women with polycystic ovary syndrome: Interrelationship of dyslipidemia and arterial blood pressure. Int J Endocrinol. 2015: 812610
    PubMedGoogle Scholar