Can Korlym (Mifepristone) Affect Serum Testosterone Levels?
Yes, mifepristone increases serum testosterone levels in both men and women through its glucocorticoid receptor antagonism, which disrupts the hypothalamic-pituitary-adrenal axis feedback mechanisms.
Mechanism and Clinical Evidence
Mifepristone consistently elevates testosterone levels as a direct pharmacologic consequence of its mechanism of action:
In women, mifepristone administration (200 mg) significantly increased serum testosterone levels in both serum and decidual tissue 1. This effect was observed within 12-24 hours of administration and represents a measurable hormonal change 1.
In men with Cushing's disease, the Endocrine Society guidelines note that mifepristone does not cause hypogonadism, unlike ketoconazole, making it a potentially preferable option from an endocrine standpoint 2. This is a key clinical advantage when selecting medical therapy for male patients.
The elevation occurs alongside other hormonal changes: Mifepristone treatment increases ACTH, cortisol, estradiol, and testosterone levels as part of its glucocorticoid receptor blockade 3. These increases reflect the body's compensatory response to perceived glucocorticoid insufficiency at the receptor level.
Clinical Significance for Monitoring
The testosterone elevation with mifepristone has important monitoring implications:
Cortisol levels remain elevated during mifepristone treatment and cannot be used to monitor treatment efficacy or adrenal insufficiency—only clinical features can guide management 4, 2. This same principle applies to testosterone monitoring.
The hormonal changes are dose-dependent: In controlled trials, mean serum cortisol and ACTH levels increased dose-dependently with mifepristone treatment at doses of 300 mg, 600 mg, and 1200 mg 5.
Thyroid function should be closely monitored and thyroid hormone replacement adjusted as needed during mifepristone therapy, as hormonal perturbations extend beyond the cortisol-testosterone axis 4.
Key Clinical Caveats
When prescribing mifepristone, be aware of these testosterone-related considerations:
The testosterone increase is generally not clinically problematic in the context of Cushing's disease treatment, where the primary concern is controlling hypercortisolism 4.
In women, the anti-progesterone activity causes endometrial hypertrophy and irregular menstrual bleeding, which may be more clinically relevant than testosterone elevation 4.
Mifepristone should only be prescribed by clinicians with extensive experience in Cushing's disease management due to the complex hormonal effects and inability to use standard biochemical monitoring 2, 6.