Treatment of Hyperandrogenism with Normal Metabolic Parameters
For a patient with hyperandrogenism and normal thyroid/glucose function, spironolactone 50-100 mg daily is the first-line medical treatment, with combined oral contraceptives as an alternative or adjunctive therapy. 1
Initial Diagnostic Considerations
Before initiating treatment, you must exclude serious causes of hyperandrogenism:
- Rule out androgen-secreting adrenal tumors urgently, particularly if virilization symptoms are present, as approximately 60% of androgen-secreting adrenocortical tumors demonstrate evidence of adrenal steroid hormone excess 2, 3
- Obtain adrenal CT imaging immediately if rapidly progressive virilization is present, as delay can be catastrophic when malignancy is the underlying cause 2, 3
- Measure serum total and/or free testosterone, DHEA-S, and consider LH/FSH if PCOS is suspected 1
- Screen for Cushing's syndrome if clinical features suggest it (buffalo hump, moon facies, hypertension, abdominal striae) 1
Critical pitfall: Never delay imaging when virilization symptoms are rapidly progressive—this pattern strongly suggests malignancy requiring urgent intervention 2, 3
Medical Management Algorithm
First-Line Hormonal Therapy
Spironolactone monotherapy:
- Start with 50-75 mg daily for patients with mild-to-moderate hyperandrogenism 4, 5
- Can increase to 100 mg daily if needed for more severe cases 1
- Expect clinical response in approximately 61% of patients, with incomplete response in 26% 4
- Monitor for the major side effect: polymenorrhea (changes in menstrual pattern) 4
- Other side effects include increased diuresis, fatigability, and rarely acne aggravation 5
- Potassium monitoring is of low usefulness in patients without risk factors for hyperkalemia (older age, medical comorbidities, concurrent medications) 1
Mechanism: Spironolactone inhibits the binding of androgens to their receptor and causes statistically significant reduction in testosterone, LH, and prolactin values 4, 6
Alternative or Adjunctive Therapy
Combined oral contraceptives:
- Suppress androgen secretion by the ovaries and increase sex hormone binding globulin 1
- Reduce risk of endometrial cancer (important in chronic anovulation) 1
- Can be used alone or in combination with spironolactone 1
When to use combination therapy: Consider adding oral contraceptives to spironolactone if the patient has:
- Irregular menstrual cycles requiring regulation 1
- Need for contraception 1
- Inadequate response to spironolactone alone after 4-6 months 4
Expected Timeline and Monitoring
- Clinical improvement in acne occurs in approximately 80% of affected patients (4 of 5 in studies) 6
- Hirsutism improvement is slower, with approximately 20% showing improvement initially, increasing to 54% reduction in hirsutism scores after one year 4, 5
- Reassess response at 4-6 months, as spironolactone effects accrue gradually 4
- Some patients may ovulate and restore fertility during treatment—6 of 18 patients with sterility became pregnant within one year after treatment in one study 4
Special Considerations for PCOS
If PCOS is the underlying diagnosis (most common cause of hyperandrogenism in this clinical scenario):
- Screen for type 2 diabetes with fasting glucose followed by 2-hour glucose level after 75-gram glucose load, even though your patient's current glucose is normal 1
- Screen for dyslipidemia with fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides 1
- Calculate BMI and waist-hip ratio 1
- Emphasize lifestyle modifications: regular exercise and weight control before considering additional drug therapy 1
Important caveat: The high prevalence of physiological peripubertal hirsutism, anovulation, and polycystic ovarian morphology results in mislabeling many patients as having PCOS—use strict criteria of age-specific anovulation, hyperandrogenism, and duration to avoid stigmatization 7
When Medical Management is Insufficient
If elevated DHEA levels are documented and medical management fails: