Muscle pain in a woman with congenital adrenal hyperplasia due to 21-hydroxylase deficiency resolved with testosterone therapy. A case report with 10 years of follow-up

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) requires lifelong glucocorticoid (GC) and mineralocorticoid therapy to prevent adrenal crises and control androgen excess. However, chronic GC overtreatment may result in sustained suppression of adrenal androgens - an underrecognized complication with significant implications for women. Androgens contribute to muscle function, mood regulation, and sexual health, yet symptoms of deficiency are easily misattributed. We report a 32-year-old woman with classical salt-wasting CAH who presented with severe muscle pain, weakness, reduced libido, and depressive symptoms. Laboratory results revealed complete suppression of adrenocorticotrophin hormone, dehydroepiandrosterone sulfate, and testosterone, with normal creatine kinase, electrolytes, metabolic and rheumatologic parameters. Extensive neuromuscular evaluation was unremarkable. Childhood medical records confirmed persistent suppression of adrenal androgens from infancy, indicating long-standing GC overtreatment as the most likely cause. Because GC dose reduction was poorly tolerated and no alternative explanation for her symptoms was identified, low-dose intramuscular testosterone (50 mg every 4-8 weeks) was introduced as compassionate therapy and subsequently stabilized at 25 mg every 4 weeks. Within three months, the patient reported substantial improvement in muscle pain, strength, libido, and mood. Over ten years of follow-up, testosterone therapy remained well tolerated, with no side effects such as virilization, erythrocytosis, hepatotoxicity, dyslipidemia, or menstrual disturbances. Bone density and trabecular microarchitecture remained stable. This case demonstrates that chronic GC overtreatment may lead to profound androgen deficiency in women with CAH, which can manifest as debilitating musculoskeletal and neurobehavioral symptoms. The patient's sustained clinical improvement underscores the physiological importance of androgens in female health and supports consideration of individualized, low-dose testosterone replacement in carefully selected cases. Recognition and targeted treatment of androgen deficiency should form part of long-term CAH management. To our knowledge, this is the first report describing the resolution of chronic myalgia after testosterone therapy in a woman with CAH and complete adrenal androgen suppression.