How to assess and treat low testosterone in premenopausal women?

Assessment and Treatment of Low Testosterone in Premenopausal Women

Free testosterone measurement is the preferred method for assessing testosterone status in premenopausal women, with morning samples being essential due to significant diurnal variation in levels. 1

Diagnostic Evaluation

Initial Assessment

• Measure free testosterone (preferred) or calculate free testosterone index (total testosterone/SHBG ratio) as SHBG can affect total testosterone readings 1
• Collect blood samples in the morning (8-10 AM) due to significant diurnal variation in testosterone levels 2
• A free testosterone index <0.3 indicates hypogonadism 1
• Two separate measurements are recommended to confirm low testosterone levels 2, 3

Additional Testing

• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine the etiology of testosterone deficiency 2, 4
• Measure serum prolactin in patients with low testosterone and low/normal LH levels to screen for hyperprolactinemia 1, 4
• Consider pituitary MRI if testosterone is very low with low/normal LH levels 3, 4
• Measure serum estradiol, particularly if there are menstrual irregularities or other evidence of hypogonadism 1
• Assess for conditions that may cause secondary hypogonadism: obesity, diabetes, pituitary dysfunction, adrenal insufficiency 4, 5

Clinical Presentation

• Common symptoms of low testosterone in premenopausal women include:
  • Reduced energy and physical performance 2, 6
  • Fatigue and depression 2, 6
  • Poor concentration and memory 2
  • Decreased libido and sexual function 6, 7
  • Decreased bone mineral density 6, 7

Treatment Approach

First-line Treatment

• Transdermal testosterone therapy (10 mg/day) has shown significant improvements in well-being, mood, and sexual function in premenopausal women with low libido and low testosterone 6
• Target testosterone levels to the mid-normal range for premenopausal women 2, 3

Monitoring During Treatment

• Monitor testosterone levels to ensure they remain within the normal range and avoid supraphysiologic levels 2, 3
• Assess for potential side effects including hirsutism, acne, and breast symptoms 3, 7
• If breast symptoms develop, measure serum estradiol 3, 4

Precautions and Contraindications

• Be aware that testosterone therapy may affect fertility; discuss this with patients desiring pregnancy 3
• Monitor hemoglobin/hematocrit as testosterone therapy can increase these values 3, 4

Special Considerations

Adrenal Function

• Consider measuring DHEA-S levels, as decreased levels have been found in women with low libido, suggesting potential adrenal dysfunction 5
• 70% of women with decreased sexual desire may have decreased total testosterone, free testosterone, and DHEA-S 5

Evidence Limitations

• Limited long-term studies evaluating safety and effectiveness of testosterone therapy in premenopausal women 7, 8
• Some studies have failed to show a significant association between testosterone serum levels and libido in premenopausal women 8

Lifestyle Modifications

• Weight loss through low-calorie diets may improve testosterone levels in overweight patients 2
• Regular physical activity may provide modest improvements in testosterone levels 2

Treatment Efficacy

• Testosterone therapy has shown improvements in well-being, mood, and sexual function in controlled studies of premenopausal women with low libido and low testosterone 6
• However, evidence is mixed, with some studies showing limited or inconsistent benefits 8