What are the evaluation and treatment options for elevated androstenedione levels?

Evaluation and Management of Elevated Androstenedione Levels

Elevated androstenedione levels require thorough endocrinological evaluation to determine the source and appropriate treatment, with referral to an endocrinologist being the most appropriate first step for comprehensive management.

Causes of Elevated Androstenedione

• Polycystic Ovary Syndrome (PCOS) is a common cause of elevated androstenedione in women, affecting approximately 4-6% of the general female population and 10-25% of women with temporal lobe epilepsy 1
• Adrenal disorders, including adrenal tumors, can cause elevated androstenedione levels 2
• Ectopic ACTH syndrome can present with disproportionately elevated androstenedione levels 2
• Ovarian sources - the ovary can be the major source of excess androgen production in women with PCOS, as indicated by the ratio of androstenedione to 11-OHA 3

Diagnostic Evaluation

Initial Assessment

• Measure serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to help establish the etiology of hormonal imbalance 1
• Assess menstrual regularity in women using a menstrual chart for at least 6 months to identify patterns such as oligomenorrhea (>35 days) or polymenorrhea (<23 days) 1
• Evaluate for clinical signs of hyperandrogenism such as hirsutism, acne, and male-pattern baldness 1

Laboratory Testing

• Measure testosterone levels, as androstenedione is a major precursor to testosterone 4
• Measure serum estradiol, especially in patients presenting with breast symptoms or gynecomastia 1
• Assess DHEAS (dehydroepiandrosterone sulfate) levels to evaluate adrenal androgen production 1
• Consider measuring 11-beta-hydroxyandrostenedione (11-OHA) to help differentiate between ovarian and adrenal sources of excess androgen production 3
• Evaluate cortisol levels to rule out Cushing syndrome, particularly if clinical features suggest hypercortisolism 1
• Measure prolactin levels, especially if LH levels are low or low/normal 1

Imaging Studies

• Pelvic ultrasound in women to assess for polycystic ovaries (>10 peripheral cysts, 2-8 mm diameter in one ultrasound plane, thickening of ovarian stroma) 1
• Consider adrenal imaging (CT or MRI) if adrenal pathology is suspected 1
• Pituitary MRI if prolactin levels are elevated or if there are other signs of pituitary dysfunction 1

Treatment Approaches

For PCOS-Related Elevated Androstenedione

• Lifestyle modifications including weight loss for overweight/obese patients 1
• Oral contraceptives to regulate menstrual cycles and reduce androgen production 1
• Anti-androgen medications may be considered for symptomatic management of hirsutism and acne 1

For Adrenal-Related Elevated Androstenedione

• If due to adrenal tumor:

  • Surgical removal (adrenalectomy) for benign or malignant adrenal tumors causing hormonal excess 1
  • Laparoscopic approach is preferred for benign tumors when feasible 1
  • Open adrenalectomy for suspected malignant tumors 1

• If due to adrenal hyperplasia:

  • Medical management with appropriate hormonal therapy 1
  • Consider adrenal vein sampling to distinguish between unilateral and bilateral disease if surgical intervention is being considered 1

For Ectopic ACTH-Related Elevated Androstenedione

• Identify and remove the ectopic source if possible 2
• Medical management with adrenostatic agents such as ketoconazole if surgical removal is not possible 1

For Men with Elevated Androstenedione

• Evaluate for testosterone deficiency, which may be related to androstenedione metabolism issues 1
• If testosterone deficiency is present, consider appropriate testosterone replacement therapy after thorough evaluation 1
• For men interested in fertility, reproductive health evaluation should be performed before any hormonal treatment 1

Special Considerations

• Androstenedione supplements are available without prescription but should be avoided as they may have unpredictable effects on hormone levels 5
• In postmenopausal women, oral androstenedione administration can significantly increase serum testosterone and estrone levels, with considerable individual variability 6
• Patients with elevated androstenedione should be monitored for potential metabolic complications including insulin resistance and dyslipidemia 1
• For women with persistent symptoms despite optimized conventional treatment, a trial of DHEA replacement (10-50 mg daily) may be considered under medical supervision 1

Follow-up and Monitoring

• Regular monitoring of androgen levels to assess treatment efficacy 1
• Periodic evaluation of metabolic parameters including glucose tolerance and lipid profile 1
• For patients on hormonal treatments, monitoring for potential side effects based on the specific therapy 1
• Adjustment of treatment based on clinical response and laboratory findings 1