What is the management approach for a 16-year-old female with a 5.1 cm ovarian cyst and hyperandrogenism (elevated testosterone levels)?

Management of 5.1 cm Ovarian Cyst with Elevated Testosterone in a 16-Year-Old

This 16-year-old requires an 8-12 week follow-up ultrasound to assess cyst persistence, combined with immediate evaluation to exclude an androgen-secreting tumor, which is the critical concern given the combination of a cyst and hyperandrogenism at this age. 1, 2

Initial Imaging and Risk Stratification

• Perform transvaginal ultrasound (if sexually active) or transabdominal ultrasound with detailed characterization of the cyst, specifically evaluating for solid components, septations, wall irregularities, and vascularity using color Doppler 2
• The 5.1 cm size falls into the premenopausal management category requiring 8-12 week follow-up if the cyst appears simple or hemorrhagic 1, 2
• If the cyst contains any solid components, immediate specialist referral is required regardless of size 1
• Apply O-RADS classification: simple unilocular cysts are O-RADS 2 (almost certainly benign, <1% malignancy risk), but any complexity increases the risk category 3, 2

Critical Testosterone Evaluation

The elevated testosterone is the most concerning feature and requires immediate attention to exclude an androgen-secreting tumor:

• Testosterone levels >150 ng/dL (>5.2 nmol/L) strongly suggest either ovarian hyperthecosis or an androgen-secreting tumor 4
• Testosterone levels >200 ng/dL (>7 nmol/L) are highly suspicious for an androgen-secreting ovarian tumor 5
• Approximately 1% of ovarian tumors can cause hyperandrogenism, including Sertoli-Leydig cell tumors, steroid cell tumors, and other sex cord-stromal tumors 5
• Assess for virilization signs: clitoromegaly, deepening voice, male-pattern baldness, increased muscle mass—these indicate severe hyperandrogenism requiring urgent evaluation 4, 5

Management Algorithm

If Cyst is Simple or Hemorrhagic (O-RADS 2):

• Schedule follow-up ultrasound in 8-12 weeks, ideally during the proliferative phase after menstruation 1, 2
• If the cyst resolves but testosterone remains elevated, this suggests a functional ovarian disorder (PCOS or hyperthecosis) rather than a tumor 6
• If the cyst persists or enlarges at follow-up, refer to gynecology or consider MRI for further characterization 3, 1

If Cyst Has Complex Features (Solid Components, Thick Septations, Nodularity):

• Immediate referral to gynecology is mandatory 1
• Measure additional androgens: DHEA-S (to exclude adrenal source), androstenedione, LH/FSH ratio 5, 6
• Check tumor markers if malignancy is suspected based on imaging (though CA-125 can be elevated in benign conditions in adolescents) 3
• Consider GnRH agonist stimulation test: androgen-secreting tumors typically do not suppress with GnRH agonist therapy, while functional hyperandrogenism does** 4, 5

If Virilization is Present:

• This constitutes an urgent indication for surgical evaluation regardless of cyst appearance 5, 7
• Proceed directly to gynecologic oncology consultation for potential surgical exploration 5
• Even benign mature cystic teratomas can rarely contain Leydig cells producing androgens 8

Common Pitfalls to Avoid

• Do not assume PCOS without excluding an androgen-secreting tumor first—while PCOS can present with large ovarian cysts and hyperandrogenism in adolescents, the combination warrants tumor exclusion 6
• Do not delay follow-up imaging beyond 12 weeks for cysts >5 cm in the setting of hyperandrogenism 1, 2
• Do not perform unnecessary surgery for simple functional cysts—most resolve spontaneously in premenopausal women, even when >5 cm 2
• Do not rely solely on tumor markers in adolescents, as they have poor sensitivity and specificity in this age group 3

Definitive Diagnosis

• If imaging and biochemical workup cannot definitively exclude a tumor, and testosterone remains significantly elevated (>150-200 ng/dL) despite several months of observation or GnRH agonist trial, laparoscopic ovarian exploration with possible cystectomy or oophorectomy may be required for both diagnosis and treatment 4, 5, 7
• Ovarian-sparing surgery (cystectomy) should be prioritized in adolescents when feasible to preserve fertility 6