Treatment of Female Hyperandrogenism (High Testosterone)
For a female with hyperandrogenism, combined oral contraceptives are the first-line treatment, with spironolactone added for persistent hirsutism or acne. 1
Initial Diagnostic Approach
Before initiating treatment, confirm the diagnosis and identify the underlying cause:
- Measure total testosterone as the first-line test using radioimmunological assay following sample extraction, or mass spectrometry when available 2
- If testosterone is twice the upper limit of normal (>100 ng/dL), measure DHEAS to distinguish adrenal from ovarian sources 2
- Screen for nonclassic congenital adrenal hyperplasia with 17-hydroxyprogesterone testing 3
- Assess for PCOS in adolescents and reproductive-age women, though diagnosis can be challenging due to overlap with normal pubertal changes 3
Physical Examination Priorities
Evaluate the following specific findings:
- Body mass index and waist circumference to assess for metabolic syndrome 1
- Blood pressure for hypertension associated with hyperandrogenism 3
- Severity of hirsutism and acne using standardized scales 1, 3
- Signs of virilization including clitoromegaly, androgenic alopecia, and voice deepening 1
- Menstrual history for oligomenorrhea or amenorrhea 4
First-Line Medical Treatment
Combined oral contraceptives (COCs) are the primary treatment for most women with hyperandrogenism:
- COCs suppress ovarian androgen production and increase sex hormone-binding globulin (SHBG), reducing free testosterone 1
- Treatment should not be withheld during ongoing evaluation for the underlying cause 3
- Set realistic expectations: improvement in hirsutism takes 6-12 months; acne responds faster 3
Second-Line and Adjunctive Therapy
Add spironolactone for persistent symptoms despite COC therapy:
- Typical dosing: 50-200 mg daily 1
- Spironolactone blocks androgen receptors and inhibits androgen synthesis 1
- Potassium monitoring is unnecessary in patients without risk factors for hyperkalemia (older age, renal disease, medications affecting potassium) 1
- Must be combined with reliable contraception due to risk of feminization of male fetuses 1
Treatment of Specific Manifestations
For Acne
- Topical retinoids are recommended as foundational therapy 1
- Intralesional corticosteroids for larger papules or nodules at risk of scarring 1
- Consider isotretinoin for severe acne or psychosocial burden, with mandatory pregnancy prevention and monitoring of liver function tests and lipids only 1
For Hirsutism
- Mechanical hair removal methods (laser, electrolysis) can be used adjunctively 1
- Eflornithine cream may slow facial hair growth 1
Critical Pitfalls to Avoid
Do not misinterpret normal testosterone with low SHBG as normal androgenic status:
- SHBG is reduced in overweight patients, metabolic syndrome, and family history of diabetes 2
- In these cases, free testosterone may be elevated despite normal total testosterone 2
- Calculate or measure free testosterone when clinical hyperandrogenism is present with normal total testosterone 4, 3
Avoid contamination artifacts in testosterone measurement:
- If a patient is using testosterone gel (unlikely in hyperandrogenic females but possible in gender-affirming care), ensure phlebotomy is performed away from application sites 5
Rule out serious causes before assuming functional hyperandrogenism:
- Testosterone >200 ng/dL (twice upper limit) requires imaging to exclude androgen-secreting tumors 2
- Rapid onset of virilization suggests tumor rather than PCOS 1
When to Refer
Refer to endocrinology when:
- Testosterone exceeds twice the upper limit of normal 2
- DHEAS >600 μg/dL suggesting adrenal tumor 2
- Rapid progression of virilization 1
- Suspected Cushing's syndrome or other complex endocrinopathy 4