What is the management approach for a female patient of reproductive age with elevated testosterone levels but no symptoms of hyperandrogenism?

Management of Elevated Testosterone Without Hyperandrogenism Symptoms

When elevated testosterone levels are found in a reproductive-age female without any clinical signs or symptoms of hyperandrogenism, this likely represents either isolated polycystic ovaries (a benign finding requiring no treatment), laboratory interference requiring verification, or rarely a selective tissue response to androgens—but you must still systematically exclude serious causes like androgen-secreting tumors before reassurance. 1

Understanding the Clinical Scenario

The absence of hyperandrogenism symptoms despite elevated testosterone is uncommon but recognized:

• Isolated polycystic ovaries occur in 17-22% of women in the general population and represent polycystic ovarian changes without symptoms, pathological signs, or hormonal consequences requiring treatment 2
• This differs fundamentally from PCOS, which is defined as hyperandrogenic chronic anovulation with clinical manifestations 2
• Rare cases demonstrate selective peripheral tissue response where some tissues respond to elevated androgens (suppressing ovulation) while others do not (no virilization) 3

Critical First Step: Verify the Laboratory Result

Before proceeding with extensive workup, confirm the testosterone elevation is real:

• Repeat testosterone measurement on at least two separate occasions using early morning samples, as random levels are unreliable 1
• If levels remain elevated without clinical signs, suspect laboratory interference and request diethyl-ether extraction prior to immunoassay to exclude heterophile antibodies or other assay interference 3
• This step is crucial because discrepancies between laboratory results and clinical presentation often reflect technical issues rather than true pathology 3

Mandatory Exclusion of Serious Pathology

Even without symptoms, certain dangerous conditions must be ruled out:

Androgen-Secreting Tumors

• Testosterone >2-3 times the upper limit of normal (typically >8.7 nmol/L or 250 ng/dL) warrants urgent investigation for ovarian or adrenal tumors, even without virilization 1, 4
• However, the positive predictive value of elevated testosterone alone for neoplasm is only 9%, with specificity of 98% 4
• Obtain pelvic ultrasound to evaluate for ovarian masses if testosterone is significantly elevated 1
• Measure DHEA-S levels: values >16.3 μmol/L (6000 ng/ml) or >600 mg/dL suggest adrenal cortical adenoma and require adrenal imaging 1, 4

Other Endocrine Disorders

Complete the hormonal panel to identify treatable causes 1:

• LH and FSH to distinguish ovarian versus central causes
• Prolactin if LH is low or low-normal, as hyperprolactinemia can present with hyperandrogenism without obvious symptoms 1, 5
• Early morning 17-hydroxyprogesterone (17-OHP) to screen for non-classical congenital adrenal hyperplasia, which commonly presents with elevated androgens 1, 5
• ACTH levels to determine adrenal versus ectopic androgen sources 1

Management Based on Findings

If No Pathology Identified (Isolated Finding)

• No treatment is required for isolated polycystic ovaries without symptoms, hormonal abnormality, or metabolic consequences 2
• Reassure the patient that this represents a benign variant requiring only monitoring 2
• Screen for metabolic complications including lipid profile and glucose tolerance testing, as elevated testosterone associates with cardiovascular risk factors even without symptoms 1
• Monitor annually with repeat testosterone levels and clinical assessment for development of symptoms 6

If PCOS Criteria Met Despite Minimal Symptoms

Even with minimal symptoms, if 2 of 3 criteria are present (androgen excess, ovulatory dysfunction, polycystic ovaries), treatment may be warranted 1:

• Combined oral contraceptives (17β-estradiol-based formulations preferred) as first-line therapy 1
• Lifestyle modifications including weight loss and increased physical activity to reduce testosterone levels 1
• Metformin if metabolic abnormalities or insulin resistance are present 1

If Tumor Identified

• Immediate referral to endocrinology and surgical oncology 1
• Surgical resection is curative, with testosterone normalizing within 24 hours post-operatively 3

Important Clinical Caveats

• Hypothalamic amenorrhea can cause oligomenorrhea and infertility in the absence of hyperandrogenism signs, affecting 12% of women with temporal lobe epilepsy versus 1.5% of the general population 2
• Drug effects must be considered: valproate and other antiepileptic drugs can cause modest testosterone elevation without typical PCOS features 2
• The absence of hirsutism, acne, or virilization does not exclude significant pathology—tumors can present with isolated biochemical findings 3
• Fertility implications should be discussed, as elevated testosterone can suppress ovulation even without other symptoms 1, 3

Monitoring Strategy

For patients with confirmed isolated elevation without identified pathology 6, 1:

• Recheck testosterone, DHEA-S at 1-2 months after initial evaluation
• Monitor hematocrit/hemoglobin for polycythemia, as elevated androgens increase these values 6
• Assess blood pressure regularly for cardiovascular risk 1
• Annual follow-up with clinical examination and laboratory monitoring once stable 6