Initial Treatment for Female Hyperandrogenism (Elevated Testosterone)
Combined oral contraceptives (COCs) are the first-line treatment for hyperandrogenism in women, as they effectively regulate menstrual cycles and reduce androgen excess. 1, 2
Diagnostic Confirmation Before Treatment
Before initiating therapy, confirm the diagnosis with appropriate testing:
- Measure morning total testosterone (8-10 AM) and repeat if elevated to confirm hyperandrogenism, using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for highest accuracy 1, 2
- Obtain free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), especially in obese patients 1
- Measure LH and FSH to distinguish primary from secondary causes 1
- Check serum prolactin to exclude hyperprolactinemia, which can cause similar symptoms 1, 2
- Perform pelvic ultrasonography to evaluate for polycystic ovaries or ovarian tumors 1, 2
Critical caveat: If testosterone levels are very high (>150-200 ng/dL) or symptoms developed rapidly with virilization (clitoromegaly, voice deepening), immediately evaluate for androgen-secreting tumors before starting medical therapy, as these require surgical management. 2, 3, 4
First-Line Medical Treatment
Combined oral contraceptives (COCs) serve as the cornerstone of therapy for non-tumorous hyperandrogenism:
- COCs regulate menstrual cycles, suppress ovarian androgen production, and increase SHBG (which reduces free testosterone) 1, 2
- Select formulations containing low-androgenic progestins to maximize benefit and reduce cardiovascular risk 5
- This approach is particularly effective for polycystic ovary syndrome (PCOS), the most common cause affecting 4-6% of women 2
Adjunctive Antiandrogen Therapy
If COCs alone provide insufficient symptom control (particularly for hirsutism or acne), add antiandrogen medications:
- Spironolactone (androgen receptor antagonist) 6
- Cyproterone acetate (not available in US) 6
- Flutamide (potent but requires hepatic monitoring due to potential toxicity) 7, 6
- Finasteride (5α-reductase inhibitor, blocks conversion of testosterone to more potent dihydrotestosterone) 6
Important warning: Antiandrogens should always be combined with reliable contraception due to teratogenic potential. 7
Metabolic Management
Screen for and aggressively manage metabolic complications:
- Assess fasting glucose and 2-hour oral glucose tolerance test to screen for diabetes and insulin resistance 2
- Check fasting lipid panel to evaluate cardiovascular risk 2
- Recommend lifestyle modifications including diet and exercise for overweight/obese patients, as weight loss alone can significantly improve hyperandrogenism 1, 2
- Consider insulin-sensitizing agents (metformin) for patients with documented insulin resistance 6
Specific Etiologies Requiring Different Approaches
Non-classical congenital adrenal hyperplasia (NCCAH): If 17-hydroxyprogesterone is elevated (>200 ng/dL baseline or >1000 ng/dL after ACTH stimulation), glucocorticoid replacement is indicated rather than COCs alone. 3
Cushing's syndrome: If suspected based on signs of hypercortisolism, perform overnight dexamethasone suppression test or 24-hour urinary free cortisol before initiating standard hyperandrogenism treatment. 3
Androgen-secreting tumors: Surgical resection is curative and the only appropriate treatment. 2, 4
Monitoring and Follow-up
- Reassess hormone levels 3-6 months after treatment initiation to confirm therapeutic response 1
- Monitor for treatment side effects including thrombotic risk with COCs and hepatotoxicity with flutamide 7, 5
- Address psychological impact of hyperandrogenism symptoms as part of comprehensive care 2
- Consider fertility implications when selecting treatment, as some therapies may affect future reproductive capacity 1
Common pitfall to avoid: Do not use antiandrogen monotherapy without concurrent contraception in women of reproductive age, as these medications can cause feminization of male fetuses. 7