- André P van Beek, MD, PhD
André P van Beek, MD, PhD
- Associate Professor
- Department of Endocrinology
- University Medical Center Groningen
- University of Groningen, the Netherlands
- Section Editors
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- William F Crowley, Jr, MD
William F Crowley, Jr, MD
- Section Editor — Female Reproductive Endocrinology
- Daniel K Podolsky Professor of Medicine
- Harvard Medical School
The term hyperthecosis refers to the presence of nests of luteinized theca cells in the ovarian stroma due to differentiation of the ovarian interstitial cells into steroidogenically active luteinized stromal cells (picture 1). These nests or islands of luteinized theca cells are scattered throughout the stroma of the ovary, rather than being confined to areas around cystic follicles as in the polycystic ovary syndrome (PCOS). The result is greater production of androgens. The precise etiology of ovarian hyperthecosis is still unclear.
The clinical presentation, diagnosis, and treatment of ovarian hyperthecosis are discussed here. The clinical presentation and diagnosis of PCOS are reviewed separately. (See "Clinical manifestations of polycystic ovary syndrome in adults" and "Diagnosis of polycystic ovary syndrome in adults".)
Ovarian hyperthecosis, a disorder characterized by severe hyperandrogenism and insulin resistance, is seen primarily in postmenopausal women [1-3]. Women typically present with slowly progressive acne and hirsutism (eg, excessive male pattern hair growth), and they are likely to be virilized . Thus, many have clitoral enlargement, male pattern baldness, deepening of the voice, and a male habitus.
In almost all cases, insulin resistance and hyperinsulinemia are present [3,5], and women are at increased risk for type 2 diabetes and cardiovascular disease . Additional physical findings may include central obesity, skin tags, and acanthosis nigricans.
The ovarian secretion of large amounts of androgens in women with hyperthecosis means that peripheral estrogen production is increased. As a result, the risk of endometrial hyperplasia and endometrial carcinoma is increased, especially in postmenopausal women [2,6].
- Goldman JM, Kapadia LJ. Virilization in a postmenopausal woman due to ovarian stromal hyperthecosis. Postgrad Med J 1991; 67:304.
- Nagamani M, Hannigan EV, Dinh TV, Stuart CA. Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer. J Clin Endocrinol Metab 1988; 67:144.
- Barth JH, Jenkins M, Belchetz PE. Ovarian hyperthecosis, diabetes and hirsuties in post-menopausal women. Clin Endocrinol (Oxf) 1997; 46:123.
- Geist SH, Gains JA. Diffuse luteinization of the ovaries associated with masculinization syndrome. Am J Obstet Gynecol 1942; 43:975.
- Krug E, Berga SL. Postmenopausal hyperthecosis: functional dysregulation of androgenesis in climacteric ovary. Obstet Gynecol 2002; 99:893.
- Zhang C, Sung CJ, Quddus MR, et al. Association of ovarian hyperthecosis with endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women: a clinicopathological study of 238 cases. Hum Pathol 2017; 59:120.
- Meldrum DR, Abraham GE. Peripheral and ovarian venous concentrations of various steroid hormones in virilizing ovarian tumors. Obstet Gynecol 1979; 53:36.
- Friedman CI, Schmidt GE, Kim MH, Powell J. Serum testosterone concentrations in the evaluation of androgen-producing tumors. Am J Obstet Gynecol 1985; 153:44.
- O'Driscoll JB, Mamtora H, Higginson J, et al. A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia. Clin Endocrinol (Oxf) 1994; 41:231.
- Derksen J, Nagesser SK, Meinders AE, et al. Identification of virilizing adrenal tumors in hirsute women. N Engl J Med 1994; 331:968.
- Nagamani M, Stuart CA. Specific binding sites for insulin-like growth factor I in the ovarian stroma of women with polycystic ovarian disease and stromal hyperthecosis. Am J Obstet Gynecol 1990; 163:1992.
- Nagamani M, Lingold JC, Gomez LG, Garza JR. Clinical and hormonal studies in hyperthecosis of the ovaries. Fertil Steril 1981; 36:326.
- Rousset P, Gompel A, Christin-Maitre S, et al. Ovarian hyperthecosis on grayscale and color Doppler ultrasound. Ultrasound Obstet Gynecol 2008; 32:694.
- Nagamani M, Chilvers R. Ultrasonography and diagnosis of polycystic ovary syndrome. In: Ultrasonography in Reproductive Medicine and Infertility, Rizk B (Ed), Cambridge University Press, New York 2010. p.75.
- Yance VRV, Marcondes JAM, Rocha MP, et al. Discriminating between virilizing ovary tumors and ovary hyperthecosis in postmenopausal women: clinical data, hormonal profiles and image studies. Eur J Endocrinol 2017; 177:93.
- 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; 19:41.
- Bühler-Christen A, Tischler V, Diener PA, Brändle M. New onset alopecia and hirsutism in a postmenopausal women. Gynecol Endocrinol 2009; 25:324.
- Hall DA, McCarthy KA, Kopans DB. Sonographic visualization of the normal postmenopausal ovary. J Ultrasound Med 1986; 5:9.
- Sherman ME, Lacey JV, Buys SS, et al. Ovarian volume: determinants and associations with cancer among postmenopausal women. Cancer Epidemiol Biomarkers Prev 2006; 15:1550.
- Rosenkrantz AB, Popiolek D, Bennett GL, Hecht EM. Magnetic resonance imaging appearance of ovarian stromal hyperplasia and ovarian hyperthecosis. J Comput Assist Tomogr 2009; 33:912.
- Fujii S, Kiyokawa T, Tsukihara S, et al. Magnetic resonance imaging findings of ovarian stromal hyperthecosis. Acta Radiol 2009; 50:954.
- Pascale MM, Pugeat M, Roberts M, et al. Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours. Clin Endocrinol (Oxf) 1994; 41:571.
- Vollaard ES, van Beek AP, Verburg FA, et al. Gonadotropin-releasing hormone agonist treatment in postmenopausal women with hyperandrogenism of ovarian origin. J Clin Endocrinol Metab 2011; 96:1197.
- Chico A, García JL, Matías-Guiu X, et al. A gonadotrophin dependent stromal luteoma: a rare cause of post-menopausal virilization. Clin Endocrinol (Oxf) 1995; 43:645.
- Picón MJ, Lara JI, Sarasa JL, et al. Use of a long-acting gonadotrophin-releasing hormone analogue in a postmenopausal woman with hyperandrogenism due to a hilus cell tumour. Eur J Endocrinol 2000; 142:619.
- Kaltsas GA, Mukherjee JJ, Kola B, et al. Is ovarian and adrenal venous catheterization and sampling helpful in the investigation of hyperandrogenic women? Clin Endocrinol (Oxf) 2003; 59:34.
- Petersons CJ, Burt MG. The utility of adrenal and ovarian venous sampling in the investigation of androgen-secreting tumours. Intern Med J 2011; 41:69.
- Brown DL, Henrichsen TL, Clayton AC, et al. Ovarian stromal hyperthecosis: sonographic features and histologic associations. J Ultrasound Med 2009; 28:587.
- Baldini M, Semprini E, Orsatti A, et al. Reduction of insulin resistance after correction of nonneoplastic ovarian virilization. J Endocrinol Invest 1993; 16:285.
- Manieri C, Di Bisceglie C, Fornengo R, et al. Postmenopausal virilization in a woman with gonadotropin dependent ovarian hyperthecosis. J Endocrinol Invest 1998; 21:128.
- Pelusi C, Forlani G, Zanotti L, et al. No metabolic impact of surgical normalization of hyperandrogenism in postmenopausal women with ovarian androgen-secreting tumours. Clin Endocrinol (Oxf) 2013; 78:533.
- Steingold KA, Judd HL, Nieberg RK, et al. Treatment of severe androgen excess due to ovarian hyperthecosis with a long-acting gonadotropin-releasing hormone agonist. Am J Obstet Gynecol 1986; 154:1241.
- Parr JH, Abraham RR, Seed M, et al. The treatment of a hyperandrogenic and virilizing state in an elderly female with a synthetic LHRH agonist. J Endocrinol Invest 1988; 11:433.
- Kolterman OG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. J Clin Invest 1980; 65:1272.