What is the management for a female patient with hyperandrogenism (elevated testosterone)?

Management of Elevated Testosterone in Female Patients

For women with elevated testosterone, initiate spironolactone 50-200 mg daily as first-line anti-androgenic therapy after excluding androgen-secreting tumors and other serious causes through targeted diagnostic evaluation. 1

Initial Diagnostic Workup

Before initiating treatment, you must exclude life-threatening causes:

• Measure morning total and free testosterone using liquid chromatography with tandem mass spectrometry (LC-MS/MS), as this is the most accurate method 1
• Check DHEAS and androstenedione to distinguish adrenal from ovarian sources; DHEAS >3800 ng/ml (age 20-29) or >2700 ng/ml (age 30-39) suggests adrenal pathology 2
• Obtain LH and FSH levels to differentiate primary from secondary causes; an LH/FSH ratio >2 suggests PCOS 2, 1
• Measure 17-hydroxyprogesterone if non-classical congenital adrenal hyperplasia is suspected 3
• Check prolactin levels to exclude hyperprolactinemia, which can present with hyperandrogenism and oligomenorrhea 2, 3

Critical red flags requiring immediate imaging: Total testosterone >2.5 nmol/l warrants consideration of ovarian or adrenal tumors, particularly if accompanied by rapid virilization (clitoromegaly, voice deepening, male-pattern baldness) 2, 3, 4, 5. Androstenedione >10.0 nmol/l specifically suggests tumor 2.

Treatment Algorithm by Etiology

For PCOS (Most Common Cause)

PCOS accounts for the majority of hyperandrogenism cases and is diagnosed by chronic anovulation with hyperandrogenism after exclusion of other causes. 2, 3

• Start combination oral contraceptive pills as first-line therapy; these suppress ovarian androgen secretion and increase sex hormone-binding globulin 2
• Add spironolactone 50 mg daily, titrating up to 200 mg daily based on response for additional anti-androgenic effects 1
• Monitor potassium levels due to spironolactone's potassium-sparing effects 1
• Screen for type 2 diabetes with fasting glucose followed by 2-hour glucose tolerance test (75g load), as PCOS significantly increases diabetes risk 2
• Obtain fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides, as dyslipidemia is common 2
• Measure mid-luteal progesterone (day 21 of cycle); levels <6 nmol/l indicate anovulation 2

For Hirsutism Management

• Spironolactone 50-200 mg daily is the primary pharmacologic treatment 1
• Finasteride 5 mg daily can be used as an alternative, as it blocks conversion of testosterone to dihydrotestosterone 1
• Both medications are teratogenic; ensure reliable contraception in women of reproductive age 1

For Non-Classical Congenital Adrenal Hyperplasia

• Perform ACTH stimulation test if basal 17-hydroxyprogesterone is elevated 3
• Initiate glucocorticoid therapy if confirmed by stimulation testing 3

For Suspected Tumors

Any woman with testosterone >2-3 standard deviations above normal reference range, rapid onset virilization, or very high DHEAS requires urgent imaging. 4, 5

• Order pelvic ultrasound or MRI to evaluate for ovarian tumors (Sertoli-Leydig cell tumors, steroid cell tumors) 5
• Order adrenal CT or MRI if DHEAS is markedly elevated 5
• Surgical resection is definitive treatment for androgen-secreting tumors 4, 5

Monitoring and Follow-Up

• Reassess clinical symptoms every 3-6 months including hirsutism score, acne severity, and menstrual regularity 1
• Recheck testosterone levels to ensure adequate suppression on therapy 1
• Monitor potassium in patients on spironolactone, particularly those with renal impairment or on ACE inhibitors 1
• Calculate body mass index and waist-hip ratio at each visit, as weight loss improves outcomes in PCOS 2

Critical Pitfalls to Avoid

Never prescribe exogenous testosterone therapy to women with hyperandrogenism, as this will dramatically worsen symptoms 1. This seems obvious but bears emphasis given the increasing use of testosterone in various clinical contexts.

Do not assume PCOS without excluding other causes. While PCOS is most common, missing a Cushing's syndrome, tumor, or late-onset CAH has serious consequences 3, 5. The pattern is key: PCOS typically presents with gradual onset after menarche, while tumors cause rapid virilization 3, 4.

Laboratory interference can occur with testosterone assays. If testosterone levels are extremely high (>2-3 SD above normal) but clinical virilization is absent, suspect assay interference and consider diethyl ether extraction prior to immunoassay 4.

In women with epilepsy on valproate, recognize that this medication can cause or worsen PCOS; testosterone elevation may be drug-induced 2.