Androgen Excess Disorders in Women pp 107-119

Part of the Contemporary Endocrinology book series (COE)

Pregnancy-Related Androgen Excess

  • Howard D. McClamrock

Abstract

Pregnancy-related androgen excess and virilization almost always arise from conditions occurring during pregnancy. It is often stressful and challenging for the clinician because of the need for a timely diagnosis in order to estimate the likelihood of virilization of an unborn female fetus. Androgen excess in pregnancy is relatively rare; the two most common causes are gestational luteoma and hyperreactio luteinalis (theca-lutein cysts of the ovaries). Increases in androgen production in pregnant women may cause hirsutism and virilization of the mother and at times virilization of a female fetus. The risk to the fetus depends on a number of factors, including the onset of increased maternal androgen production, the severity of the increase, and the condition causing the increase. Luteoma should be suspected in women with unilateral or bilateral (47%) solid ovarian masses, whereas Krukenberg tumor remains a possibility, especially in those with bilateral lesions. The natural course of the luteoma is regression and disappearance of the lesion after delivery, and it appears that elevated cord levels of testosterone and/or androstenedione are necessary for virilization of a female fetus based on a few reported cases. Hyperreactio luteinalis should be suspected in pregnancies complicated by androgen excess with bilateral cystic ovaries noted on exam or ultrasound. This condition does not appear to put the female fetus at risk for virilization even in situations in which circulating maternal androgens are high. As with luteoma, these cysts normally regress after delivery and should not require surgical therapy. Consideration should always be given to exogenous hormone therapy in pregnancies complicated by androgen excess. Unilateral solid ovarian lesions in pregnancies complicated by androgen excess increase the risk of malignancy. Current management is mostly limited to evaluating the risk to the fetus rather than implementing intervention that may alter the course of the pregnancy.

Key Words

Gestational hyperandrogenism androgen excess in pregnancy maternal/fetal masculinization virilization virilization hyperreactio luteinalis (theca-lutein cysts) luteoma pregnancy complication 

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References

  1. 1.
    Bammann BL, Coulan CB, Jiang N-S. Total and free testosterone during pregnancy. Am J Obstet Gynecol 1980;137:293.PubMedGoogle Scholar
  2. 2.
    Berger NG, Tepke JT, Woodrull JD. Markedly elevated serum testosterone in pregnancy without fetal virilization. Obstet Gynecol 1984;63:260.PubMedGoogle Scholar
  3. 3.
    Dawood MT, Saxena BB. Testosterone and dihydrotestosterone in maternal and cord blood and in amniotic fluid. Am J Obstet Gynecol 1977;129;37.Google Scholar
  4. 4.
    Mizuno M, Lobotsky J, Lloyd CW, Kobayashi T, Murasawa Y. Plasma androstenedione and testosterone during pregnancy and in the newborn. J Clin Endocrinol Metab 1968;28:1133.PubMedCrossRefGoogle Scholar
  5. 5.
    Rivarola MA, Forest MG, Migeon CJ. Testosterone, androstenedione and dehydroepiandrosterone in plasma during pregnancy and at delivery: Concentration and protein binding. J Clin Endocrinol Metab 1968;28:34.PubMedGoogle Scholar
  6. 6.
    Saez JM, Forest MG, Morera A, Bertrand J. Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, in hyperthyroidism. J Clin Invest 1972;51:1226.PubMedCrossRefGoogle Scholar
  7. 7.
    Castracane VD, Stewart DR, Gimpel T, et al. Maternal serum and androgens in human pregnancy: early increases with the cycle of conception. Human Reprod 1998;13:460.CrossRefGoogle Scholar
  8. 8.
    Anderson DC, Lasley BL, Fisher RA, Shepherd JH, Newlam L, Hendrickx AG. Transplacental gradients of sex-hormone-binding globulin in human and simian pregnancy. J Clin Endocrinol Metab 1976;5:657.Google Scholar
  9. 9.
    Vermeulen A, Verdonch L, an Der Straeten M, Orie N. Capacity of the testosterone-binding globulin in human plasma and influence of specific binding of testosterone on its metabolic clearance rates. J Clin Endocrinol Metab 1969;29:1470.Google Scholar
  10. 10.
    Pearlman WH, Crepy O, Murphy M. Testosterone-binding levels in the serum of women during normal menstrual cycle, pregnancy and the post-partum period. J Clin Endocrinol Metab 1967;27:1012.PubMedGoogle Scholar
  11. 11.
    Tulchinsky D, Ryan KJ. Maternal-Fetal Endocrinology. Philadephia: W.B. Saunders, 1980.Google Scholar
  12. 12.
    Treloar OL, Wolf RC, Meyer RK. The corpus luteum of the rhesus monkey during late pregnancy. Endocrinology 1972;91:665.PubMedGoogle Scholar
  13. 13.
    Milewich L, Gomez-Sanchez C, Madden JD, et al. Dehydroisoandrosterone sulfate in peripheral blood premenopausal, pregnant and postmenopausal women and men. J Steroid Biochem 1978;9:1159.PubMedCrossRefGoogle Scholar
  14. 14.
    McClamrock HD, Adashi EY. Gestational hyperandrogenism. In: Adashi EY, Rock JA, Rosenwaks Z, eds. Reproductive Endocrinology, Surgery, and Technology: A Textbook in Reproductive Medicine. Philadelphia: Lipincott-Raven Publishers, 1966:1599.Google Scholar
  15. 15.
    Edman CD, Toofanian A, MacDonald PC, Gant NF. Placental clearance rate of maternal plasma androstenedione through placental estradiol formation: an indirect method of assessing uteroplacental blood flow. Am J Obstet Gynecol 1981;141:1029.PubMedGoogle Scholar
  16. 16.
    Hensleigh PA, Carter RP, Grotjan HE Jr. Fetal protection against masculinization with hyperreactio luteinalis and virilization. J Clin Endocinol Metab 1975;40:816.Google Scholar
  17. 17.
    Shozu M, Akasofu K, Harada T, Kubota Y. A new cause of female pseudohermaphroditism: placental aromatase deficiency. J Clin Endocrinol Metab 1991;72:560.PubMedGoogle Scholar
  18. 18.
    Conte FA, Gumbach MM, Ito Y, et al. A syndrome of female pseudohermaphroditism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab 1994;78:1287.PubMedCrossRefGoogle Scholar
  19. 19.
    Nagamani M, Gomez LG, Garza J. In vivo steroid studies in luteoma of pregnancy. Obstet Gynecol 1982;59:105S.PubMedGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    Jewelewicz R, Perkins RP, Dyrenfurth I, Vande Wiele RL. Luteomas of pregnancy: a cause for maternal virilization. Am J Obstet Gynecol 1971;109(1):24.PubMedGoogle Scholar
  22. 22.
    Galle PC, McCool JA, Elsner CW. Arrhenoblastoma during pregnancy. Obstet Gynecol 1978;51:359.PubMedCrossRefGoogle Scholar
  23. 23.
    .Barkan A, Cassorla F, Loriaux DL, Marshall JC. Pregnancy in a patient with virilizing arrhenoblastoma. Am J Obstet Gynecol 1984;149:901.Google Scholar
  24. 24.
    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.PubMedGoogle Scholar
  25. 25.
    Kirk JMW, Perry LA, Shand WR, Kirby RS, Besser GM, Savage MO. Female pseudohermaphroditism due to a maternal adrenocortical tumor. J Clin Endocrinol Metab 1990;70:1280.PubMedGoogle Scholar
  26. 26.
    Buescher MA, McClamrock HD, Adashi EY. Cushing syndrome in pregnancy. Obstet Gynecol 1992;79;130.PubMedGoogle Scholar
  27. 27.
    Ben-Chetrit A, Greenblatt EM. Recurrent maternal virilization during pregnancy associated with polycystic ovary syndrome: a case report and review of the literature. Hum Reprod 1995;10:3057.PubMedGoogle Scholar
  28. 28.
    Sir-Petermann T, Maliqueo M, Angel B, Laura HE, Perez-Bravo F, Recabarren SE. Maternal serum androgens in pregnant women with polycystic ovary syndrome: possible implications in prenatal androgenization. Hum Reprod 2002;17:2573.PubMedCrossRefGoogle Scholar
  29. 29.
    Sir-Petermann T, Devoto L, Maliqueo M, Peirano P, Recabarren SE, Wildt L. Resumption of ovarian function during lactational amenorrhea in breastfeeding women with polycystic ovary syndrome: endocrine aspects. Hum Reprod 2001;16:1603.PubMedCrossRefGoogle Scholar
  30. 30.
    Wilkins L, Jones Jr HW, Holman GH, Stempfel RS. 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.PubMedGoogle Scholar
  31. 31.
    Grumbach MM, Ducharme JR, Moloshok RE. On the fetal masculinizing action of certain oral progestins. J Clin Endocrinol Metab 1959;19:1369.PubMedGoogle Scholar
  32. 32.
    Holt HB, Medbak S, Kirk D, et al. Recurrent severe hyperandrogenism during pregnancy: a case report. J Clin Pathol 2005;58(4):439.PubMedCrossRefGoogle Scholar
  33. 33.
    Sternberg WH: Non-functioning ovarian neoplasma. In: Grady HG, Smith DE, eds. The Ovary. International Academy of Pathologists, monogram 3. Baltimore: Williams & Wilkins, 1963:289.Google Scholar
  34. 34.
    Garcia-Bunuel R, Berek JS, Woodruff JD. Luteomas of pregnancy. Obstet Gynecol 1975;45:407.PubMedGoogle Scholar
  35. 35.
    Garcia-Bunuel R, Berek JS, Woodruff JD. Tumors, including endometriosis: luteomas of pregnancy. Obstet Gynecol Surv 1975;45:635.CrossRefGoogle Scholar
  36. 36.
    Joshi R, Dunaif A. Ovarian disorders of pregnancy. Endocrinol Metab Clin North Am 1995;24:153.PubMedGoogle Scholar
  37. 37.
    McClamrock HD, Adashi EY. Gestational hyperandrogenism. Fertil Steril 1992;57:257.PubMedGoogle Scholar
  38. 38.
    Wolff E, Glasser M, Gordon GG, et al. Virilization luteoma of pregnancy. Report of a case with measurements of testosterone and testosterone binding in plasma. Am J Med 1973;54:229.PubMedCrossRefGoogle Scholar
  39. 39.
    Grumbach MM, Ducharme JR. The effects of androgens on fetal sexual development: Androgen-induced female pseudohermaphroditism. Fertil Steril 1960;11:157.PubMedGoogle Scholar
  40. 40.
    Illingworth PJ, Johnstone FD, Steel J, Seth J. Luteoma of pregnancy: masculinization of a female fetus preventd by placental aromatization. Br J Obstet Gynaecol 1992;99(12):1019.PubMedGoogle Scholar
  41. 41.
    Baxi L, Holub D, Hembree W. Bilateral luteomas of pregnancy in a patient with diabetes. Am J Obstet Gynecol 1988;159:454.PubMedGoogle Scholar
  42. 42.
    Bradshaw KD, Santos-Ramos R, Rawlins SC, et al. Endocrine studies in pregnancy complicated by ovarian theca lutein cysts and hyperreactio luteinalis. Obstet Gynecol 1986;67:66S.PubMedGoogle Scholar
  43. 43.
    Muechler EK, Fichter J, Zongrone J. Human chorionic gonadotropin, estradiol, testosterone changes in two pregnancies with hyperreactio luteinalis. Am J Obstet Gynecol 1987;157:1126.PubMedGoogle Scholar
  44. 44.
    Wajda KJ, Lucas JG, Marsh WL. Hyperreactio luteinalis. Arch Pathol Lab Med 1989;113;921.Google Scholar
  45. 45.
    Bilowus M, Abbassi V, Gibbons MD. Female pseudohermaphroditism is a neonate born to a mother with polycystic ovary disease. J Urol 1986;136:1098.PubMedGoogle Scholar
  46. 46.
    Ritter DB, McGill FM, Greston WM. Krukenberg tumor part II: identification during pregnancy. Female Patient 1999;24:19.Google Scholar
  47. 47.
    Duck SC, Katayama DP. Danazol may cause female pseudohermaphroditism. Fertil Steril 1981;35:230.PubMedGoogle Scholar
  48. 48.
    Bongiovanni AM, DiGeorge AM, Grumbach MM. Masculinization of the female infant associated with estrogenic therapy alone during gestation: four causes. J Clin Endocrinol Metab 1959;19:1004.CrossRefGoogle Scholar
  49. 49.
    Bracken MB. Oral contraception and congenital malformations in offspring: a review and meta-analysis of the prospective studies. Obstet Gynecol 1990;76;552.Google Scholar
  50. 50.
    Vandekerckhove D. A Propus de l’ administration de methylandrostendiol pendant la grossesse. Ann Endocrinol (Paris) 1954;15;513.Google Scholar
  51. 51.
    Montz FJ, Schlaerth JB, Morrow CP. The natural history of theca-lutein cysts. Obstet Gynecol 1988;72:247.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Howard D. McClamrock
    • 1
  1. 1.Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, and Reproductive SciencesUniversity of Maryland School of MedicineBaltimore

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