What hormones should be tested in a female patient presenting with fatigue and low libido?

Hormonal Testing in Females with Fatigue and Low Libido

In a female patient presenting with fatigue and low libido, test morning TSH, free T4, morning cortisol, morning ACTH, FSH, LH, and estradiol as the core hormonal panel. 1

Primary Hormonal Assessment

Thyroid Function Testing

• TSH and free T4 are essential first-line tests, as thyroid dysfunction is a common cause of both fatigue and low libido 1
• Both hypothyroidism and hyperthyroidism significantly impair female sexual function, particularly affecting desire, arousal, and lubrication 2, 3
• Hypothyroidism causes fatigue in 66% of cases and is associated with sexual dysfunction even when treated with levothyroxine 1, 4
• Important caveat: TSH alone may be unreliable in certain contexts; if clinical presentation suggests hypothyroidism despite normal TSH (1-4 IU/mL), consider measuring thyroid hormones by mass spectrometry 5
• Thyroid autoimmunity (even in euthyroid states) can selectively impair sexual desire independent of thyroid hormone levels 3, 6

Adrenal Axis Evaluation

• Morning (8 AM) cortisol and ACTH should be measured to assess for adrenal insufficiency 1
• Central adrenal insufficiency presents with fatigue in the majority of patients and is characterized by low cortisol with low/normal ACTH 1
• If morning cortisol is indeterminate (between 3-15 μg/dL), perform standard-dose ACTH stimulation testing 1

Gonadal Hormone Assessment

• FSH, LH, and estradiol should be evaluated in premenopausal females presenting with fatigue, loss of libido, mood changes, or oligomenorrhea 1
• These tests help identify hypogonadism, which commonly presents with both fatigue and decreased libido 1
• Testing should be performed in the morning around 8 AM for optimal accuracy 1

Additional Considerations

DHEA Testing

• DHEA deficiency testing can be considered in women with persistent low libido and/or fatigue who are otherwise adequately hormonally replaced 1
• DHEA replacement remains controversial but may benefit select patients with documented deficiency 1

Testosterone in Women

• Obtaining testosterone levels in women in non-research settings is not recommended according to HIV primary care guidelines 1
• However, in the context of suspected hypopituitarism or adrenal insufficiency, free testosterone may be affected by elevated SHBG, which correlates with sexual dysfunction 2

Sex Hormone Binding Globulin (SHBG)

• SHBG levels are elevated in hyperthyroidism and correlate negatively with sexual function scores 2
• Elevated SHBG reduces free testosterone availability, potentially contributing to low libido 2

Clinical Algorithm

Step 1: Order morning (8 AM) blood tests:

• TSH, free T4
• Cortisol, ACTH
• FSH, LH, estradiol
• Electrolytes 1

Step 2: If cortisol is 3-15 μg/dL, proceed with ACTH stimulation testing 1

Step 3: If multiple pituitary hormone deficiencies are identified (particularly TSH or ACTH deficiency), consider MRI brain with pituitary cuts to evaluate for hypophysitis or other pituitary pathology 1

Step 4: If thyroid and adrenal function are adequately replaced but symptoms persist, consider DHEA testing 1

Important Pitfalls

• Never start thyroid hormone replacement before addressing adrenal insufficiency, as this can precipitate adrenal crisis 1
• TSH may be unreliable as a sole screening test; clinical judgment should guide further testing if symptoms are discordant with laboratory values 5
• In central hypothyroidism (low TSH with low free T4), TSH cannot be used to monitor treatment adequacy—target free T4 in the upper half of the reference range 1
• Thyroid autoimmunity can cause sexual dysfunction even in euthyroid patients, so consider thyroid antibody testing if other causes are excluded 3, 6