Clinical Case Seminar: Postmenopausal androgen excess–challenges in diagnostic work‐up and management of ovarian thecosis

Abstract

SummaryPostmenopausal hyperandrogenism can be tumour-or non-tumour-related, with pathology residing either in the ovary or adrenal gland(s). The tempo of investigation is determined by the clinical severity of hyperandrogenism (presence/absence of actual virilisation) and degree of serum testosterone elevation. When clinical or biochemical hyperandrogenism is severe, rapidly developing, or associated with hypercortisolism, screening for adrenocortical or ovarian carcinoma with crosssectional imaging should be prioritised over detailed biochemical evaluation. Adrenal hyperandrogenism is readily characterised, both biochemically and radiologically. By contrast, even a combination of high-resolution imaging with laboratory evaluation, including dynamic endocrine testing, often cannot distinguish between ovarian hyperthecosis (OH) and virilising ovarian tumour (VOT); a definitive diagnosis usually emerging only after histological examination of excised ovaries. VOTs are typically below the resolution-limit of current imaging modalities and exhibit suppression of gonadotropin-dependent androgen secretion with GnRH-analogue therapy. Thus, for well-characterised ovarian hyperandrogenism, laparoscopic bilateral salpingo-oophorectomy may serve both as a diagnostic and therapeutic procedure. Nevertheless, women unable or unwilling to undergo ovarian surgery can be reassured that malignant VOTs are exceedingly rare and that long-term medical therapy with oral antiandrogens or GnRH-analogues is safe and well-tolerated. OH is strongly associated with insulin-resistance, with hyperinsulinaemia acting synergistically with raised gonadotropin levels to stimulate thecal cell hyperplasia and androgen secretion by the postmenopausal ovary, which lacks granulosa cell aromatase activity and thus cannot convert testosterone to 17 beta estradiol. Thus, features of metabolic syndrome may indicate OH, and significant reductions in androgens can thereby potentially be achieved with lifestyle measures and/or insulin-sensitising drugs. K E Y W O R D Shirsutes, management of ovarian hyper thecosis, post-menopausal androgen excess, virilisation testosterone

Virilising ovarian tumors: a single-center experience

“…Postmenopausal HA can be tumor- or non-tumor related, with pathology residing either in the ovary or adrenal gland (6). Ovarian hyperthecosis (OH) and VOT are most common causes of HA in these patients (7).…”

Ovarian Stromal Hyperplasia: A Rare Cause of Postmenopausal Hyperandrogenism

“…New-onset hyperandrogenism in postmenopausal women is a very infrequent pathology whose aethi- ological diagnosis can sometimes be challenging [3,6].…”

“…In Cushing' s syndrome we observe elevated testosterone levels, normal or suppressed DHEA-S, and suppression of the adrenocorticotropin hormone (ACTH). The suppression test with dexamethasone would show, in Cushing' s syndrome, a serum cortisol not suppressed when low doses of dexamethasone are administered [3]. In women with hyperandrogenism, a reduction more than 40% in testosterone levels after a suppression test with low doses of dexamethasone (0.5 mg every 6 hours for 2 days) has a sensitivity of 100% and a specificity of 88% to differentiate hyperandrogenisms of tumural origin from other causes of hyperandrogenism [11].…”

“…[2]. The main feature that differentiates OHT and OSH from polycystic ovarian syndrome is age of onset (typically, polycystic ovarian syndrome occurs in peripubertal women, while OHT and OSH are more common after the menopause, when follicle formation has ceased, and the ovaries appear more solid) [3,4]. They are characterised by 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.…”

Virilising ovarian tumour in a postmenopausal woman after bilateral oophorectomy

“…Oestradiol secretion occurs in 6-23% of patients with these tumours and hyperoestrogenemia can result in irregular menstruation or postmenopausal bleeding. 11,12 Cushing's syndrome, due to ectopic ACTH or CRH production, is described in up to 10% of patients. 11 Our patient did not develop any overt clinical features of Cushing's syndrome and cortisol excess was also excluded biochemically.…”