Androgen-Secreting Ovarian Tumour

Androgen secreting ovarian tumours are rare ovarian neoplasms producing testosterone or its precursors and causing rapid virilisation. Most are Sertoli-Leydig cell tumours, with steroid cell tumours and hilus cell tumours less common.

They make up under 0.5% of ovarian tumours. Sertoli-Leydig cell tumours occur in women aged 20 to 40 years (and in girls), and hilus cell tumours in postmenopausal women. Most are unilateral and low stage at diagnosis.

DICER1 germline variants are associated with Sertoli-Leydig cell tumours in young women, with a risk of thyroid and other tumours.

Pathophysiology.

Tumour cells autonomously secrete testosterone and androstenedione, which suppress LH and FSH (and ovulation) and cause virilisation. Oestrogen may also be produced by peripheral conversion.

Androgen levels rise quickly, in contrast to the slow course of polycystic ovary syndrome.

• Rapid onset (months) of hirsutism, acne, voice deepening, clitoromegaly, temporal balding, muscle increase and amenorrhoea or oligomenorrhoea. Breast atrophy.
• Pelvic mass, pain or abdominal swelling in some.

Red flags.

• Rapid virilisation with a pelvic mass.
• Ascites, weight loss or an extra-ovarian mass (malignancy).

• Total testosterone markedly raised (usually over 5 to 7 nmol/L, 150 to 200 ng/dL) with LH and FSH suppressed. Dehydroepiandrosterone sulphate normal or mildly raised, which separates it from adrenal tumours. 17-hydroxyprogesterone, prolactin, cortisol and thyroid function to exclude other causes.
• Transvaginal ultrasound and pelvic MRI. Small tumours (such as hilus cell tumours) may be missed, and CT or MRI of the adrenals is used to exclude an adrenal source.
• Inhibin and anti-Müllerian hormone as tumour markers. Selective ovarian and adrenal vein sampling if imaging is negative and testosterone is very high.
• DICER1 testing in young women with Sertoli-Leydig cell tumour.

Differential diagnosis.

• Polycystic ovary syndrome and ovarian hyperthecosis (gradual onset, testosterone less raised).
• Non-classic congenital adrenal hyperplasia and Cushing syndrome.
• Virilising adrenal tumour and exogenous androgens or danazol.
• Pregnancy luteoma and androgen secreting pituitary or other tumours.

• Surgery: unilateral salpingo oophorectomy with staging for young women wishing fertility and stage IA tumours; hysterectomy with bilateral salpingo oophorectomy for older women or advanced disease.
• Chemotherapy (bleomycin, etoposide and cisplatin) for advanced, recurrent or poorly differentiated tumours.
• Testosterone usually falls within days to weeks of surgery, and hirsutism improves over months. Voice change and clitoromegaly may persist.
• Persistent hirsutism: spironolactone 100 to 200 mg daily with reliable contraception, or cosmetic measures.
• DICER1 carriers: surveillance and genetic counselling.

Special groups. Pregnancy: androgens can virilise a female foetus. Women wishing fertility: preserve the uterus and contralateral ovary where possible.

Monitoring. Testosterone at 6 weeks after surgery, then inhibin or anti-Müllerian hormone and testosterone every 3 to 6 months for 2 years, with pelvic imaging, and yearly after.

Referral and escalation. Gynaecological oncology and endocrinology for all cases.