Syndrome of hyperandrogenism in adolescent girls

The diagnosis of hyperandrogenism may be based on clinical manifestations or on determining the blood level of androgens. Causes of hyperandrogenism in the peripubertal period are polycystic ovary syndrome (PCOS), non-classical forms of congenital adrenal hyperplasia (NCCAH), androgen-producing tumors, obesity, idiopathic hirsutism, and other rare causes. Physiological hyperandrogenism of peripubertal period passes within 2 years. PCOS affects from 4 to 21% of women of reproductive age and from 6 to 18% of adolescent girls. To date, there is no consensus on the diagnostic criteria for PCOS in teenage girls. At least, three symptoms are necessary: menstrual disorders, clinical and biochemical hyperandrogenism and polycystic ovaries. Diagnosis of NCCAH includes measurement of the level of 17-hydroxyprogesterone and a test with adrenocorticotropic hormone. The purpose of the treatment of these diseases is to reduce the manifestations of hyperandrogenism, regulate the menstrual cycle and improve the quality of life. Effective methods of pharmacotherapy are combined oral contraceptives and antiandrogens. An important stage is lifestyle changes in PCOS and obesity patients.

For correspondence: Laura G. Pivazyan, 

Contribution:
Adamyan L.V., Sibirskaya E.V., Pivazyan L.G., Sharkov S.M. — concept and design of the study, editing the text;
Sarkisova A.I., Ananyeva V.S. — collecting and processing material, writing the text;
Adamyan L.V., Pivazyan L.G. — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: December 22, 2023
Accepted: January 30, 2024
Published: February 28, 2024

1. Catteau-Jonard S., Cortet-Rudelli C., Richard-Proust C., Dewailly D. Hyperandrogenism in adolescent girls. Endocr. Dev. 2012; 22: 181–93. https://doi.org/10.1159/000326688

2. Fauser B.C.J.M., Genazzani A.R. Frontiers in Gynecological Endocrinology. Springer; 2015.

3. Screening and management of the hyperandrogenic adolescent: ACOG Committee Opinion, Number 789. Obstet. Gynecol. 2019; 134(4): e106–14. https://doi.org/10.1097/AOG.0000000000003475

4. Lizneva D., Gavrilova-Jordan L., Walker W., Azziz R. Androgen excess: Investigations and management. Best Pract. Res. Clin. Obstet. Gynaecol. 2016; 37: 98–118. https://doi.org/10.1016/j.bpobgyn.2016.05.003

5. Olutunmbi Y., Paley K., English J.C. 3rd. Adolescent female acne: etiology and management. J. Pediatr. Adolesc. Gynecol. 2008; 21(4): 171–6. https://doi.org/10.1016/j.jpag.2007.07.004

6. Vassalou H., Sotiraki M., Michala L. PCOS diagnosis in adolescents: the timeline of a controversy in a systematic review. J. Pediatr. Endocrinol. Metab. 2019; 32(6): 549–59. https://doi.org/10.1515/jpem-2019-0024

7. Lizneva D., Suturina L., Walker W., Brakta S., Gavrilova-Jordan L., Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil. Steril. 2016; 106(1): 6–15. https://doi.org/10.1016/j.fertnstert.2016.05.003

8. Bozdag G., Mumusoglu S., Zengin D., Karabulut E., Yildiz B.O. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. 2016; 31(12): 2841–55. https://doi.org/10.1093/humrep/dew218

9. Wolf W.M., Wattick R.A., Kinkade O.N., Olfert M.D. Geographical prevalence of polycystic ovary syndrome as determined by region and race/ethnicity. Int. J. Environ. Res. Public Health. 2018; 15(11): 2589. https://doi.org/10.3390/ijerph15112589

10. Conway G., Dewailly D., Diamanti-Kandarakis E., Escobar-Morreale H.F., Franks S., Gambineri A., et al. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur. J. Endocrinol. 2014; 171(4): 1–29. https://doi.org/10.1530/EJE-14-0253

11. Peña A.S., Witchel S.F., Hoeger K.M., Oberfield S.E., Vogiatzi M.G., Misso M., et al. Adolescent polycystic ovary syndrome according to the international evidence-based guideline. BMC Med. 2020; 18(1): 72. https://doi.org/10.1186/s12916-020-01516-x

12. Rosenfield R.L., Ehrmann D.A. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr. Rev. 2016; 37(5): 467–520. https://doi.org/10.1210/er.2015-1104

13. Rasquin L.I., Anastasopoulou C., Mayrin J.V. Polycystic ovarian disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.

14. Shorakae S., Ranasinha S., Abell S., Lambert G., Lambert E., de Courten B., et al. Inter-related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS. Clin. Endocrinol. (Oxf.). 2018; 89(5): 628–33. https://doi.org/10.1111/cen.13808

15. Adamyan L.V., Makiyan Z.N., Glybina T.M., Sibirskaya E.V., Ploshkina A.A. Features of diagnostics and treatment of polycystic ovary syndrome in adolescent girls (analytical review). Reproduktivnoe zdorov’e detey i podrostkov. 2014; (3): 16–22. https://elibrary.ru/smgqwf (in Russian)

16. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod. 2004; 19(1): 41–7. https://doi.org/10.1093/humrep/deh098

17. Meczekalski B., Niwczyk O., Kostrzak A., Maciejewska-Jeske M., Bala G., Szeliga A. PCOS in adolescents-ongoing riddles in diagnosis and treatment. J. Clin. Med. 2023; 12(3): 1221. https://doi.org/10.3390/jcm12031221

18. Milewicz A., Kudła M., Spaczyński R.Z., Dębski R., Męczekalski B., Wielgoś M., et al. The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of gynaecologists and obstetricians, and the Polish Society of gynaecological endocrinology. Endokrynol. Pol. 2018; 69(4). https://doi.org/10.5603/EP.2018.0046

19. Teede H.J., Tay C.T., Laven J.J.E., Dokras A., Moran L.J., Piltonen T.T., et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Eur. J. Endocrinol. 2023; 189(2): G43–64. https://doi.org/10.1093/ejendo/lvad096

20. Villarroel C., López P., Merino P.M., Iñiguez G., Sir-Petermann T., Codner E. Hirsutism and oligomenorrhea are appropriate screening criteria for polycystic ovary syndrome in adolescents. Gynecol. Endocrinol. 2015; 31(8): 625–9. https://doi.org/10.3109/09513590.2015.1025380

21. Tsukui Y., Kitahara Y., Hasegawa Y., Kobayashi M., Osuka S., Iwase A. Anti-Müllerian hormone levels in the diagnosis of adolescent polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr. J. 2022; 69(8): 897–906. https://doi.org/10.1507/endocrj.EJ22-0081

22. Abdolahian S., Tehrani F.R., Amiri M., Ghodsi D., Yarandi R.B., Jafari M., et al. Effect of lifestyle modifications on anthropometric, clinical, and biochemical parameters in adolescent girls with polycystic ovary syndrome: a systematic review and meta-analysis. BMC Endocr. Disord. 2020; 20(1): 71. https://doi.org/10.1186/s12902-020-00552-1

23. Goodman N.F., Cobin R.H., Futterweit W., Glueck J.S., Legro R.S., Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome – part 1. Endocr. Pract. 2015; 21(11): 1291–300. https://doi.org/10.4158/EP15748.DSC

24. Jungari M., Choudhary A., Gill N.K. Comprehensive management of polycystic ovary syndrome: effect of pharmacotherapy, lifestyle modification, and enhanced adherence counseling. Cureus. 2023; 15(2): e35415. https://doi.org/10.7759/cureus.35415

25. Witchel S.F., Teede H.J., Peña A.S. Curtailing PCOS. Pediatr. Res. 2020; 87(2): 353–61. https://doi.org/10.1038/s41390-019-0615-1

26. Rodríguez A., Ezquieta B., Labarta J.I., Clemente M., Espino R., Rodriguez A., et al. Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia. An. Pediatr. (Barc.). 2017; 87(2): 116.e1–10. https://doi.org/10.1016/j.anpedi.2016.12.002 (in Spanish)

27. Esquivel-Zuniga M.R., Kirschner C.K., McCartney C.R., Burt Solorzano C.M. Non-PCOS hyperandrogenic disorders in adolescents. Semin. Reprod. Med. 2022; 40(1-02): 42–52. https://doi.org/10.1055/s-0041-1742259

28. Adamyan L.V., Bogdanova E.A., Sibirskaya E.V., Glybina T.M., Garunova M.B. Reproductive health of girls with congenital adrenal hyperplasia. Rossiyskiy vestnik perinatologii i pediatrii. 2014; 59(2): 43–7. https://elibrary.ru/sggywn (in Russian)

29. Kurtoğlu S., Hatipoğlu N. Non-classical congenital adrenal hyperplasia in childhood. J. Clin. Res. Pediatr. Endocrinol. 2017; 9(1): 1–7. https://doi.org/10.4274/jcrpe.3378

30. Carmina E., Dewailly D., Escobar-Morreale H.F., Kelestimur F., Moran C., Oberfield S., et al. Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. Hum. Reprod. Update. 2017; 23(5): 580–99. https://doi.org/10.1093/humupd/dmx014

31. Yesiladali M., Yazici M.G.K., Attar E., Kelestimur F. Differentiating polycystic ovary syndrome from adrenal disorders. Diagnostics (Basel). 2022; 12(9): 2045. https://doi.org/10.3390/diagnostics12092045

32. Adriaansen B.P.H., Schröder M.A.M., Span P.N., Sweep F.C.G.J., van Herwaarden A.E., Claahsen-van der Grinten H.L. Challenges in treatment of patients with non-classic congenital adrenal hyperplasia. Front. Endocrinol. (Lausanne). 2022; 13: 1064024. https://doi.org/10.3389/fendo.2022.1064024

33. Gardner D.G., Shoback D. Greenspan’s Basic & Clinical Endocrinology. New York: McGraw Hill; 2018: 609–22.

34. Itriyeva K. The effects of obesity on the menstrual cycle. Curr. Probl. Pediatr. Adolesc. Health Care. 2022; 52(8): 101241. https://doi.org/10.1016/j.cppeds.2022.101241

35. Dobbie L.J., Pittam B., Zhao S.S., Alam U., Hydes T.J., Barber T.M., et al. Childhood, adolescent, and adulthood adiposity are associated with risk of PCOS: a Mendelian randomization study with meta-analysis. Hum. Reprod. 2023; 38(6): 1168–82. https://doi.org/10.1093/humrep/dead053

36. Sultan C., Gaspari L., Maïmoun L., Kalfa N., Paris F. Management of Adolescent Hyperandrogenism: Still a Challenge? In: Berga S., Genazzani A., Naftolin F., Petraglia F., eds. Menstrual Cycle Related Disorders. ISGE Series. Cham: Springer; 2019. https://doi.org/10.1007/978-3-030-14358-9_7

37. Unluhizarci K., Hacioglu A., Taheri S., Karaca Z., Kelestimur F. Idiopathic hirsutism: Is it really idiopathic or is it misnomer? World J. Clin. Cases. 2023; 11(2): 292–8. https://doi.org/10.12998/wjcc.v11.i2.292

38. Brzana J., Yedinak C.G., Hameed N., Plesiu A., McCartney S., Fleseriu M. Polycystic ovarian syndrome and Cushing’s syndrome: a persistent diagnostic quandary. Eur. J. Obstet. Gynecol. Reprod. Biol. 2014; 175(1): 145–8. https://doi.org/10.1016/j.ejogrb.2013.12.038

39. Iezzi M.L., Lasorella S., Varriale G., Zagaroli L., Ambrosi M., Verrotti A. Clitoromegaly in childhood and adolescence: behind one clinical sign, a clinical sea. Sex. Dev. 2018; 12(4): 163–74. https://doi.org/10.1159/000489385

40. Glintborg D., Altinok M.L., Petersen K.R., Ravn P. Total testosterone levels are often more than three times elevated in patients with androgen-secreting tumours. BMJ Case Rep. 2015; 2015: bcr2014204797. https://doi.org/10.1136/bcr-2014-204797

41. Papadakis G., Kandaraki E.A., Tseniklidi E., Papalou O., Diamanti-Kandarakis E. Polycystic ovary syndrome and NC-CAH: Distinct characteristics and common findings. A Systematic Review. Front. Endocrinol. (Lausanne). 2019; 10: 388. https://doi.org/10.3389/fendo.2019.00388

42. Speiser P.W., Arlt W., Auchus R.J., Baskin L.S., Conway G.S., Merke D.P., et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2018; 103(11): 4043–88. https://doi.org/10.1210/JC.2018-01865

43. Nakhleh A., Saiegh L., Shehadeh N., Weintrob N., Sheikh-Ahmad M., Supino-Rosin L., et al. Screening for non-classic congenital adrenal hyperplasia in women: New insights using different immunoassays. Front. Endocrinol. (Lausanne). 2022; 13: 1048663. https://doi.org/10.3389/fendo.2022.1048663