UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Approach to the patient with gestational hyperandrogenism

Author
Howard D McClamrock, MD
Section Editors
Robert L Barbieri, MD
William F Crowley, Jr, MD
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Hyperandrogenism in pregnant women may cause hirsutism and virilization in the woman and virilization of female fetuses. This topic will review the diagnostic approach and management of pregnant women presenting with new hyperandrogenism. The major causes and clinical features of gestational hyperandrogenism are discussed in detail elsewhere (table 1 and table 2). The management of the virilized infant is also reviewed separately. (See "Causes and clinical features of gestational hyperandrogenism" and "Management of the infant with atypical genitalia (disorder of sex development)".)

DIAGNOSTIC APPROACH

Hyperandrogenism in pregnant women may cause hirsutism and virilization of the mother and, more variably, virilization of any female fetuses. The fetal risk depends on a number of factors including the timing of the excess maternal androgen production, the severity of this increase, and the condition(s) causing the increase.

The possibility of androgen excess usually arises when a pregnant woman presents with the rapid onset of masculinization (virilization). Affected women may have a variety of symptoms including hirsutism (at times requiring shaving), acne, temporal balding, clitoromegaly, and deepening of the voice.

There may also be a palpable abdominal mass due to a tumor or cyst. Causes of the masses include luteomas, theca-lutein cysts, other ovarian tumors, and adrenal tumors. No masses would be expected when the etiology is exposure to exogenous hormones or placental aromatase deficiency. (See "Causes and clinical features of gestational hyperandrogenism".)

At other times, gestational hyperandrogenism is first suspected at the time of delivery of a virilized female infant. If the investigation begins after delivery, one must keep in mind that luteomas and theca-lutein cysts undergo spontaneous regression after delivery, ie, maternal surgical intervention is not required. (See "Causes and clinical features of gestational hyperandrogenism".)

                            
To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Sep 27, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. McClamrock HD, Adashi EY. Gestational hyperandrogenism. Fertil Steril 1992; 57:257.
  2. McClamrock HD, Adashi EY. Gestational hyperandrogenism. In: Reproductive Endocrinology, Surgery, and Technology, Adashi EY, Rock JA, Rosenwaks Z (Eds), Lippincott-Raven, Philadelphia 1996. p.1612.
  3. Burandt E, Young RH. Pregnancy luteoma: a study of 20 cases on the occasion of the 50th anniversary of its description by Dr. William H. Sternberg, with an emphasis on the common presence of follicle-like spaces and their diagnostic implications. Am J Surg Pathol 2014; 38:239.
  4. Wadzinski TL, Altowaireb Y, Gupta R, et al. Luteoma of pregnancy associated with nearly complete virilization of genetically female twins. Endocr Pract 2014; 20:e18.
  5. Masarie K, Katz V, Balderston K. Pregnancy luteomas: clinical presentations and management strategies. Obstet Gynecol Surv 2010; 65:575.
  6. Caspi E, Schreyer P, Bukovsky J. Ovarian lutein cysts in pregnancy. Obstet Gynecol 1973; 42:388.
  7. Magendantz HG, Jones DE, Schomberg DW. Virilization during pregnancy associated with polycystic ovary disease. Obstet Gynecol 1972; 40:156.
  8. Wajda KJ, Lucas JG, Marsh WL Jr. Hyperreactio luteinalis. Benign disorder masquerading as an ovarian neoplasm. Arch Pathol Lab Med 1989; 113:921.
  9. Lo YM, Tein MS, Lau TK, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998; 62:768.
  10. Lo YM, Patel P, Wainscoat JS, et al. Prenatal sex determination by DNA amplification from maternal peripheral blood. Lancet 1989; 2:1363.
  11. Bianchi DW, Simpson JL, Jackson LG, et al. Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn 2002; 22:609.
  12. Johnson KL, Dukes KA, Vidaver J, et al. Interlaboratory comparison of fetal male DNA detection from common maternal plasma samples by real-time PCR. Clin Chem 2004; 50:516.
  13. Jorgez CJ, Dang DD, Wapner R, et al. Elevated levels of total (maternal and fetal) beta-globin DNA in maternal blood from first trimester pregnancies with trisomy 21. Hum Reprod 2007; 22:2267.
  14. Devaney SA, Palomaki GE, Scott JA, Bianchi DW. Noninvasive fetal sex determination using cell-free fetal DNA: a systematic review and meta-analysis. JAMA 2011; 306:627.
  15. Montz FJ, Schlaerth JB, Morrow CP. The natural history of theca lutein cysts. Obstet Gynecol 1988; 72:247.
  16. Garcia-Bunuel R, Berek JS, Woodruff JD. Luteomas of pregnancy. Obstet Gynecol 1975; 45:407.
  17. Shortle BE, Warren MP, Tsin D. Recurrent androgenicity in pregnancy: a case report and literature review. Obstet Gynecol 1987; 70:462.
  18. Wolff E, Glasser M, Gordon GG, et al. Virilizing luteoma of pregnancy. Report of a case with measurements of testosterone and testosterone binding in plasma. Am J Med 1973; 54:229.
  19. Nagamani M, Gomez LG, Garza J. In vivo steroid studies in luteoma of pregnancy. Obstet Gynecol 1982; 59:105S.
  20. Spitzer RF, Wherrett D, Chitayat D, et al. Maternal luteoma of pregnancy presenting with virilization of the female infant. J Obstet Gynaecol Can 2007; 29:835.
  21. Joshi R, Dunaif A. Ovarian disorders of pregnancy. Endocrinol Metab Clin North Am 1995; 24:153.
  22. Verkauf BS, Reiter EO, Hernandez L, Burns SA. Virilization of mother and fetus associated with luteoma of pregnancy: a case report with endocrinologic studies. Am J Obstet Gynecol 1977; 129:274.
  23. GRUMBACH MM, DUCHARME JR. The effects of androgens on fetal sexual development: androgen-induced female pseudohermaphrodism. Fertil Steril 1960; 11:157.
  24. Bradshaw KD, Santos-Ramos R, Rawlins SC, et al. Endocrine studies in a pregnancy complicated by ovarian theca lutein cysts and hyperreactio luteinalis. Obstet Gynecol 1986; 67:66S.
  25. Muechler EK, Fichter J, Zongrone J. Human chorionic gonadotropin, estriol, and testosterone changes in two pregnancies with hyperreactio luteinalis. Am J Obstet Gynecol 1987; 157:1126.
  26. Berger NG, Repke JT, Woodruff JD. Markedly elevated serum testosterone in pregnancy without fetal virilization. Obstet Gynecol 1984; 63:260.
  27. Hensleigh PA, Carter RP, Grotjan HE Jr. Fetal protection against masculinization with hyperreactio luteinalis and virilization. J Clin Endocrinol Metab 1975; 40:816.
  28. Simsek Y, Celen S, Ustun Y, et al. Severe preeclampsia and fetal virilization in a spontaneous singleton pregnancy complicated by hyperreactio luteinalis. Eur Rev Med Pharmacol Sci 2012; 16:118.
  29. Tanaka Y, Yanagihara T, Ueta M, et al. Naturally conceived twin pregnancy with hyperreactio luteinalis, causing hyperandrogenism and maternal virilization. Acta Obstet Gynecol Scand 2001; 80:277.
  30. Verhoeven AT, Mastboom JL, van Leusden HA, van der Velden WH. Virilization in pregnancy coexisting with an (ovarian) mucinous cystadenoma: A case report and review of virilizing ovarian tumors in pregnancy. Obstet Gynecol Surv 1973; 28:597.
  31. Silva PD, Porto M, Moyer DL, Lobo RA. Clinical and ultrastructural findings of an androgenizing Krukenberg tumor in pregnancy. Obstet Gynecol 1988; 71:432.
  32. Novak DJ, Lauchlan SC, Mccawley JC, et al. Virilization during pregnancy. Case report and review of literature. Am J Med 1970; 49:281.
  33. Fayez JA, Bunch TR, Miller GL. Virilization in pregnancy associated with an ovarian cystadenoma. Am J Obstet Gynecol 1974; 120:341.
  34. Duska LR, Flynn C, Goodman A. Masculinizing sclerosing stromal cell tumor in pregnancy: report of a case and review of the literature. Eur J Gynaecol Oncol 1998; 19:441.
  35. Kirk JM, Perry LA, Shand WS, et al. Female pseudohermaphroditism due to a maternal adrenocortical tumor. J Clin Endocrinol Metab 1990; 70:1280.
  36. Galle PC, McCool JA, Elsner CW. Arrhenoblastoma during pregnancy. Obstet Gynecol 1978; 51:359.
  37. Barkan A, Cassorla F, Loriaux DL, Marshall JC. Pregnancy in a patient with virilizing arrhenoblastoma. Am J Obstet Gynecol 1984; 149:909.
  38. Widschwendter M, Meduri G, Loosfelt H, et al. Fulminant recurrence of a Sertoli-Leydig cell tumour during pregnancy. Br J Obstet Gynaecol 1999; 106:284.
  39. Ritter DB, McGill FM, Greston WM. Krukenberg tumor part II: Identification during pregnancy. Female Patient 1999; 24:19.
  40. Fuller PJ, Pettigrew IG, Pike JW, Stockigt JR. An adrenal adenoma causing virilization of mother and infant. Clin Endocrinol (Oxf) 1983; 18:143.
  41. Abiven-Lepage G, Coste J, Tissier F, et al. Adrenocortical carcinoma and pregnancy: clinical and biological features and prognosis. Eur J Endocrinol 2010; 163:793.
  42. Raffin-Sanson ML, Abiven G, Ritzel K, et al. [Adrenocortical carcinoma and pregnancy]. Ann Endocrinol (Paris) 2016; 77:139.
  43. Morris LF, Park S, Daskivich T, et al. Virilization of a female infant by a maternal adrenocortical carcinoma. Endocr Pract 2011; 17:e26.
  44. WILKINS L, JONES HW Jr, HOLMAN GH, STEMPFEL RS Jr. Masculinization of the female fetus associated with administration of oral and intramuscular progestins during gestation: non-adrenal female pseudohermaphrodism. J Clin Endocrinol Metab 1958; 18:559.
  45. Duck SC, Katayama KP. Danazol may cause female pseudohermaphroditism. Fertil Steril 1981; 35:230.
  46. GRUMBACH MM, DUCHARME JR, MOLOSHOK RE. On the fetal masculinizing action of certain oral progestins. J Clin Endocrinol Metab 1959; 19:1369.
  47. Bongiovanni AM, DiGeorge AM, Grumbach MM. Masculinization of the female infant associated with estrogenic therapy alone during gestation: four cases. J Clin Endocrinol Metab 1959; 19:1004.
  48. Bracken MB. Oral contraception and congenital malformations in offspring: a review and meta-analysis of the prospective studies. Obstet Gynecol 1990; 76:552.
  49. Shozu M, Akasofu K, Harada T, Kubota Y. A new cause of female pseudohermaphroditism: placental aromatase deficiency. J Clin Endocrinol Metab 1991; 72:560.