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Causes of gestational hyperandrogenism

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


Hyperandrogenism and virilization during pregnancy are nearly always the result of conditions arising during pregnancy. The reason for this is that hyperandrogenism in a nonpregnant woman usually results in anovulation and infertility, even if the androgen excess is not clinically evident as hirsutism or virilization.

This topic will review these and other rarer causes of this problem (table 1). The diagnosis and treatment of these conditions are discussed elsewhere. (See "Diagnosis and management of gestational hyperandrogenism".)


Normal pregnancy is characterized by a progressive increase in serum total testosterone concentrations, due primarily to an increase in serum sex hormone-binding globulin concentrations, and a late increase in serum free testosterone and androstenedione concentrations (table 2).

The incidence of hyperandrogenism during pregnancy is low, although the incidence of some of the ovarian diseases that can cause it is higher [1]. The two most common causes of gestational hyperandrogenism are luteomas and theca-lutein cysts of the ovary.

An increase in androgen production in a pregnant woman can cause hirsutism in both the woman and her fetus. The extent of fetal virilization varies, depending on the time of onset of the increased maternal androgen production, its severity, and unknown factors (table 3). For example, fetal virilization is common in virilized pregnant women with luteomas, but extremely rare in those with theca-lutein cysts.


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Literature review current through: Mar 2017. | This topic last updated: Jun 12, 2015.
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  1. McClamrock HD, Adashi EY. Gestational hyperandrogenism. Fertil Steril 1992; 57:257.
  2. Wang YC, Su HY, Liu JY, et al. Maternal and female fetal virilization caused by pregnancy luteomas. Fertil Steril 2005; 84:509.
  3. Joshi R, Dunaif A. Ovarian disorders of pregnancy. Endocrinol Metab Clin North Am 1995; 24:153.
  4. Garcia-Bunuel R, Berek JS, Woodruff JD. Luteomas of pregnancy. Obstet Gynecol 1975; 45:407.
  5. Shortle BE, Warren MP, Tsin D. Recurrent androgenicity in pregnancy: a case report and literature review. Obstet Gynecol 1987; 70:462.
  6. 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.
  7. Nagamani M, Gomez LG, Garza J. In vivo steroid studies in luteoma of pregnancy. Obstet Gynecol 1982; 59:105S.
  8. 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.
  9. 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.
  10. GRUMBACH MM, DUCHARME JR. The effects of androgens on fetal sexual development: androgen-induced female pseudohermaphrodism. Fertil Steril 1960; 11:157.
  11. Illingworth PJ, Johnstone FD, Steel J, Seth J. Luteoma of pregnancy: masculinisation of a female fetus prevented by placental aromatisation. Br J Obstet Gynaecol 1992; 99:1019.
  12. Baxi L, Holub D, Hembree W. Bilateral luteomas of pregnancy in a patient with diabetes. Am J Obstet Gynecol 1988; 159:454.
  13. Ben-Chetrit A, Greenblatt EM. Recurrent maternal virilization during pregnancy associated with polycystic ovarian syndrome: a case report and review of the literature. Hum Reprod 1995; 10:3057.
  14. 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.
  15. 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.
  16. Wajda KJ, Lucas JG, Marsh WL Jr. Hyperreactio luteinalis. Benign disorder masquerading as an ovarian neoplasm. Arch Pathol Lab Med 1989; 113:921.
  17. Berger NG, Repke JT, Woodruff JD. Markedly elevated serum testosterone in pregnancy without fetal virilization. Obstet Gynecol 1984; 63:260.
  18. Hensleigh PA, Carter RP, Grotjan HE Jr. Fetal protection against masculinization with hyperreactio luteinalis and virilization. J Clin Endocrinol Metab 1975; 40:816.
  19. 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.
  20. 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.
  21. 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.
  22. Duck SC, Katayama KP. Danazol may cause female pseudohermaphroditism. Fertil Steril 1981; 35:230.
  23. GRUMBACH MM, DUCHARME JR, MOLOSHOK RE. On the fetal masculinizing action of certain oral progestins. J Clin Endocrinol Metab 1959; 19:1369.
  24. 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.
  25. Shozu M, Akasofu K, Harada T, Kubota Y. A new cause of female pseudohermaphroditism: placental aromatase deficiency. J Clin Endocrinol Metab 1991; 72:560.
  26. Conte FA, Grumbach MM, Ito Y, et al. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab 1994; 78:1287.
  27. Bracken MB. Oral contraception and congenital malformations in offspring: a review and meta-analysis of the prospective studies. Obstet Gynecol 1990; 76:552.
  28. 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.
  29. Silva PD, Porto M, Moyer DL, Lobo RA. Clinical and ultrastructural findings of an androgenizing Krukenberg tumor in pregnancy. Obstet Gynecol 1988; 71:432.
  30. Novak DJ, Lauchlan SC, Mccawley JC, et al. Virilization during pregnancy. Case report and review of literature. Am J Med 1970; 49:281.
  31. Fayez JA, Bunch TR, Miller GL. Virilization in pregnancy associated with an ovarian cystadenoma. Am J Obstet Gynecol 1974; 120:341.
  32. 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.
  33. Kirk JM, Perry LA, Shand WS, et al. Female pseudohermaphroditism due to a maternal adrenocortical tumor. J Clin Endocrinol Metab 1990; 70:1280.
  34. Galle PC, McCool JA, Elsner CW. Arrhenoblastoma during pregnancy. Obstet Gynecol 1978; 51:359.
  35. Barkan A, Cassorla F, Loriaux DL, Marshall JC. Pregnancy in a patient with virilizing arrhenoblastoma. Am J Obstet Gynecol 1984; 149:909.
  36. 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.
  37. Ritter DB, McGill FM, Greston WM. Krukenberg tumor part II: Identification during pregnancy. Female Patient 1999; 24:19.
  38. Sir-Petermann T, Maliqueo M, Angel B, et al. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 2002; 17:2573.
  39. Buescher MA, McClamrock HD, Adashi EY. Cushing syndrome in pregnancy. Obstet Gynecol 1992; 79:130.
  40. Hatjis CG. Nonimmunologic fetal hydrops associated with hyperreactio luteinalis. Obstet Gynecol 1985; 65:11S.
  41. Daane TA, Lurie AO, Barton RK. Ovarian lutein cysts associated with an otherwise normal pregnancy. Report of a case. Obstet Gynecol 1969; 34:655.
  42. Caspi E, Schreyer P, Bukovsky J. Ovarian lutein cysts in pregnancy. Obstet Gynecol 1973; 42:388.
  43. KLEIN J. Delayed appearance and rupture of lutein cysts with hydatidiform mole. Report of a case. Obstet Gynecol 1963; 21:30.