What are the implications of a total testosterone level of 11 ng/dL in a female?

A Total Testosterone of 11 ng/dL in a Female is Abnormally Low and Requires Investigation

A total testosterone level of 11 ng/dL in a female is significantly below the normal reference range and warrants a thorough diagnostic workup to identify the underlying cause, as this level is associated with increased all-cause mortality and cardiovascular events.

Understanding the Clinical Significance

Normal Reference Ranges for Women

• Normal total testosterone in reproductive-age women ranges from 15-46 ng/dL (5th to 95th percentile for a 30-year-old woman), with a mean of approximately 14.1 ng/dL in women without hyperandrogenic symptoms 1, 2
• Your patient's level of 11 ng/dL falls below the 5th percentile, indicating true biochemical hypoandrogenism 1
• Free testosterone reference range is 1.2-6.4 pg/mL, and bioavailable testosterone is 1.12-7.62 ng/dL in normally cycling women 1

Prognostic Implications

• Women with testosterone levels in the lowest quintile have significantly increased mortality risk, with a hazard ratio of 0.49 (95% CI 0.33-0.74) for all-cause mortality when comparing higher quintiles to the lowest 3
• Cardiovascular event risk is also elevated in women with low testosterone, with a hazard ratio of 0.54 (95% CI 0.38-0.77) for incident CV events, independent of traditional risk factors 3
• These associations persist even after adjusting for age, BMI, and other cardiovascular risk factors 3

Diagnostic Workup Algorithm

Step 1: Confirm the Diagnosis

• Repeat morning total testosterone measurement using liquid chromatography tandem mass spectrometry (LC-MS/MS) in a certified laboratory, as immunoassays have poor accuracy at low female ranges 4
• Obtain the sample in a fasting state between 8-10 AM to account for diurnal variation 4, 5
• Measure free testosterone by equilibrium dialysis if total testosterone remains low, as this is the biologically active fraction 4, 5
• Measure sex hormone-binding globulin (SHBG) to calculate free androgen index and assess binding protein status 5, 1

Step 2: Determine the Etiology

• Measure serum LH and FSH to distinguish primary ovarian failure from secondary (hypothalamic-pituitary) causes 5
  • Elevated LH/FSH with low testosterone indicates primary ovarian insufficiency
  • Low or low-normal LH/FSH with low testosterone indicates secondary hypogonadism
• Measure serum prolactin if LH/FSH are low or low-normal to screen for hyperprolactinemia 5
• Assess for chronic illness, including HIV/AIDS, chronic kidney disease, or autoimmune conditions that can suppress androgen production 5
• Evaluate for medication effects, particularly chronic corticosteroid use, which suppresses the hypothalamic-pituitary-gonadal axis 5

Step 3: Screen for Associated Conditions

• Assess bone mineral density via DEXA scan, as low testosterone increases osteoporosis risk in women 5
• Screen for anemia with complete blood count, as testosterone deficiency can cause unexplained anemia 5
• Evaluate cardiovascular risk factors including lipid profile, fasting glucose, and blood pressure, given the increased CV mortality risk 3
• Assess for metabolic syndrome components, as low testosterone is associated with impaired glucose control and dyslipidemia 6

Clinical Symptoms to Assess

Primary Symptoms of Female Hypoandrogenism

• Decreased libido and sexual dysfunction are the most consistent symptoms of low testosterone in women 7, 8
• Fatigue and diminished sense of vitality may be present, though evidence for improvement with treatment is limited 8
• Loss of muscle mass and decreased physical strength can occur with severe testosterone deficiency 5
• Depressed mood and reduced motivation may be associated with low testosterone 5

Physical Examination Findings

• Evaluate for loss of body hair in androgen-dependent areas (axillary and pubic regions) 5
• Assess body composition, particularly increased visceral adiposity and decreased lean muscle mass 6
• Document BMI and waist circumference as markers of metabolic health 5

Treatment Considerations

Current Evidence Limitations

• There are no FDA-approved testosterone preparations for women in the United States, and evidence for testosterone therapy in women is limited primarily to postmenopausal women with hypoactive sexual desire disorder 8
• The guidelines and evidence provided focus predominantly on male hypogonadism, with minimal guidance on female testosterone replacement 8, 5

When to Consider Referral

• Refer to endocrinology if secondary hypogonadism is confirmed (low testosterone with low/normal LH/FSH) to evaluate for pituitary disorders 5
• Refer to endocrinology if prolactin is persistently elevated to screen for prolactinoma 5
• Consider referral to a sexual medicine specialist if sexual dysfunction is the primary complaint and other causes have been excluded 7

Critical Pitfalls to Avoid

Measurement Errors

• Never rely on a single testosterone measurement, as levels vary due to biological and assay variation 4
• Never use immunoassays from commercial laboratories without verification of accuracy, as they have poor sensitivity at low female ranges and often report falsely normal values 2, 4
• Never measure testosterone at random times of day, as afternoon/evening measurements will be physiologically lower 5, 6

Diagnostic Errors

• Never assume age-related decline is normal without investigating reversible causes, particularly in reproductive-age women 5
• Never diagnose hypoandrogenism based on symptoms alone without confirmed biochemical testing on at least two separate occasions 5
• Never skip the investigation for secondary causes, as conditions like hyperprolactinemia, pituitary tumors, or chronic illness require specific treatment 5

Treatment Errors

• Never initiate testosterone therapy without confirming the patient does not desire fertility, as exogenous testosterone can suppress ovulation 8
• Never use testosterone therapy as first-line treatment without addressing underlying reversible causes such as obesity, metabolic syndrome, or medication effects 8, 5