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Androgen resistance syndrome — Clinical Guidelines

Overview

Androgen resistance syndrome encompasses conditions where the body fails to respond appropriately to androgens due to genetic mutations or other factors, leading to symptoms akin to androgen deficiency despite normal or elevated androgen levels. 3

Diagnosis

Low cortisol with elevated ACTH levels suggests ACTH resistance syndromes like familial glucocorticoid deficiency (FGD). 3

Genetic analysis of MC2R, MRAP, and AAAS genes can identify specific mutations in patients with ACTH resistance. 3

Plasma testosterone levels may be normal or elevated in androgen resistance, complicating diagnosis based solely on hormonal assays. 2 6

Management

No specific first-line treatments universally recommended for androgen resistance syndrome due to limited evidence; management often focuses on addressing symptoms and underlying causes. 2 4

In women with androgen deficiency symptoms, judicious testosterone supplementation may alleviate symptoms if bioavailable testosterone levels are low. 6

Monitoring and supportive care for associated conditions like adrenal insufficiency are crucial. 3

Special Populations

Elderly: Androgen deficiency in aging males impacts bone density, muscle mass, sexual function, and psychological health; careful assessment and individualized treatment plans are recommended. 4

Comorbidities: No specific guidance provided in abstracts for managing androgen resistance in the context of comorbidities; general principles of symptom management apply. 2 4

Key Recommendations

Avoid diagnosing androgen deficiency syndrome in healthy women due to lack of well-defined syndrome and insufficient data correlating androgen levels with specific symptoms. (Evidence: Strong 2)

Genetic testing of MC2R, MRAP, and AAAS genes is recommended in patients suspected of having ACTH resistance syndromes to identify specific mutations. (Evidence: Moderate 3)

Consider testosterone supplementation in postmenopausal women with symptoms of androgen deficiency and confirmed low bioavailable testosterone levels. (Evidence: Moderate 6)

References

1 D'Andrea S, Martorella A, Coccia F, Castellini C, Minaldi E, Totaro M et al.. Relationship of Vitamin D status with testosterone levels: a systematic review and meta-analysis. Endocrine 2021. link 2 Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH et al.. Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism 2014. link 3 Collares CV, Antunes-Rodrigues J, Moreira AC, Franca SN, Pereira LA, Soares MM et al.. Heterogeneity in the molecular basis of ACTH resistance syndrome. European journal of endocrinology 2008. link 4 McClure RD. Androgen deficiency and the aging male: new urologic perspectives. Current urology reports 2001. link 5 Hauptmann H, Paulus B, Kaiser T, Herdtweck E, Huber E, Luppa PB. Concepts for the syntheses of biotinylated steroids. Part I: testosterone derivatives as immunochemical probes. Bioconjugate chemistry 2000. link 6 Davis SR. Androgen treatment in women. The Medical journal of Australia 1999. link 7 Sutton JR, Coleman MJ, Casey J, Lazarus L. Androgen responses during physical exercise. British medical journal 1973. link

Androgen resistance syndrome