Is low cortisol expected during menopause?

Is Low Cortisol Expected During Menopause?

No, low cortisol is not expected during menopause—in fact, cortisol levels typically increase during the menopausal transition, particularly during the late transition stage. 1, 2

Normal Physiological Changes During Menopause

Cortisol Trajectory

• Cortisol levels rise during the late menopausal transition, specifically from 7-12 months before to 7-12 months after onset of the late transition stage 1
• This increase occurs when menstrual irregularities are greatest and is associated with rising FSH and declining estrogen levels 2
• Cortisol becomes the dominant steroid in cerebrospinal fluid after menopause, while estrogen levels decline markedly 3
• No significant cortisol changes occur during the middle menopausal transition or immediately after the final menstrual period 1

Hormonal Correlations

• Overnight cortisol levels correlate positively with estrone glucuronide (E1G), FSH, and testosterone levels during the transition 2
• The cortisol increase is also associated with elevated epinephrine and norepinephrine 2
• Women with cortisol increases >10 ng/mg creatinine experience more severe vasomotor symptoms 1

Clinical Implications of Finding Low Cortisol

If you encounter low cortisol in a perimenopausal or menopausal woman, this is abnormal and requires evaluation for adrenal insufficiency. 4

Diagnostic Workup

• Measure morning (9 AM) cortisol and ACTH to distinguish primary from secondary adrenal insufficiency 5, 4
• Consider ACTH stimulation testing if morning cortisol is indeterminate (between 3-15 μg/dL) 5
• Evaluate FSH, estrogen, LH, and testosterone in premenopausal women with fatigue, low libido, mood changes, or oligomenorrhea 5
• Check electrolytes, as primary adrenal insufficiency causes sodium retention and potassium excretion 5

Treatment Algorithm for Confirmed Adrenal Insufficiency

Mild symptoms (Grade 1):

• Initiate hydrocortisone 15-20 mg daily in divided doses (typically 2/3 morning, 1/3 early afternoon) 5, 4
• Titrate up to maximum 30 mg daily for residual symptoms 5
• Consider fludrocortisone 0.05-0.1 mg daily for primary adrenal insufficiency 5

Moderate symptoms (Grade 2):

• Start stress-dose corticosteroids at 2-3 times maintenance (hydrocortisone 30-50 mg total or prednisone 20 mg daily) 5, 4
• Taper to maintenance after 2 days 5

Severe symptoms (Grade 3-4):

• Hospitalize for IV hydrocortisone 50-100 mg every 6-8 hours 5, 4
• Provide at least 2L normal saline 5
• Taper over 5-7 days to oral maintenance 5

Critical Management Considerations

Hormone Replacement Timing

Always initiate cortisol replacement at least 1 week before starting thyroid hormone replacement to avoid precipitating adrenal crisis 5, 6

Testosterone or estrogen replacement should only be considered after adequate cortisol replacement in women with documented low sex hormone levels and symptoms 5, 6

DHEA Supplementation

• DHEA replacement may be considered in women with low libido and/or energy who are otherwise adequately replaced with cortisol 5, 6
• DHEA is a precursor to testosterone and may address residual symptoms 6

Patient Education Requirements

• Teach stress dosing protocols for illness (typically double or triple maintenance dose) 5, 4
• Provide emergency injectable hydrocortisone with instructions 5, 4
• Recommend medical alert identification for adrenal insufficiency 5, 4
• Monitor for over-replacement signs: bruising, thin skin, edema, weight gain, hypertension, hyperglycemia 5, 4

Common Pitfalls to Avoid

Using long-acting steroids (prednisone) instead of hydrocortisone carries higher risk of over-replacement, though may be necessary if adherence to multiple daily doses is problematic 5, 4

Do not attribute fatigue, mood changes, or low libido in menopausal women to "normal menopause" without checking cortisol, as these symptoms may indicate adrenal insufficiency requiring treatment 4

The physiological increase in cortisol during menopause may mask early adrenal insufficiency, so maintain clinical suspicion if symptoms are disproportionate 1, 2