Quantification and identification of pharmacological and psychological components of the androgen withdrawal syndrome in men: a community-dwelling cross-sectional study

Bonnie Grant; Joseph Kean; de Silva Nipun Lakshitha; Maha Gumssani; Oliver Quinton; James McVeigh; Dhillo Waljit S.; Anne Lingford-Hughes; Jayasena Channa N.

doi:10.1530/endoabs.109.OC3.3

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Endocrine Abstracts (2025) 109 OC3.3 | DOI: 10.1530/endoabs.109.OC3.3

SFEBES2025 Oral Communications Reproductive and Neuroendocrinology (6 abstracts)

Quantification and identification of pharmacological and psychological components of the androgen withdrawal syndrome in men: a community-dwelling cross-sectional study

Bonnie Grant ¹ , Joseph Kean ² , Nipun Lakshitha de Silva ^1,3 , Maha Gumssani ¹ , Oliver Quinton ¹ , James McVeigh ⁴ , Waljit S. Dhillo ¹ , Anne Lingford-Hughes ⁵ & Channa N. Jayasena ¹

Author affiliations

¹Section of Investigative Medicine, Imperial College London, London, United Kingdom; ²Bradford Metropolitan District Council, Bradford, United Kingdom; ³Department of Clinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka; ⁴Change Grow Live, Manchester, United Kingdom; ⁵Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom

Background: A recent meta-analysis estimated that men <30 years old have a 6% lifetime prevalence rate of androgen abuse. Androgen abuse increases mortality 3-fold by exposing men to cardiovascular and psychiatric diseases, suicide and violent crime. Up to 30% of men abusing androgens develop a dependency syndrome causing high relapse rates within the first year of cessation. However, clinical and biochemical characteristics of androgen withdrawal have not been quantified previously.

Methods: Ethics-approved cross-sectional study of 286 community-dwelling men: no androgen use (Control; n=50); current androgen abuse (Current; n=125); cessation of androgen abuse within previous year (Withdrawal; n=111). Total International Index of Erectile Function-15 (IIEF-15), Beck Depression Inventory-II (BDI-II), Generalised Anxiety Disorder-7 (GAD-7) and 36-item Short Form Survey (SF-36) questionnaires, fasting morning blood sampling and urine toxicology testing were performed.

Results: Men stopping androgen abuse within the previous year had worse sexual function (IIEF-15: 69.0 [IQR 62.0, 73.0], Controls; 62.0 [IQR 47.0, 71.0], Withdrawal; P=0.0135), depression (BDI-II: 3.0 [0.0, 8.0], Controls; 8.0 [2.0, 18.0], Withdrawal; P=0.0005), and anxiety (GAD-7 1.0 [0.0, 3.0], Controls; 2.0 [0.01, 6.0], Withdrawal; P=0.0271) scores compared with healthy men. Lower total testosterone levels were linearly correlated with worsened sexual function (P<0.05). Multivariable analysis suggested that androgen cessation (coefficient -10.8 [95% CI -5.6, -17.2]; P<0.001) and psychiatric comorbidity (coefficient -6.5 [95% CI -13.0, -1.3] P=0.03) were independently associated with poor sexual function, and that pre-diagnosed psychiatric illnesses (OR 2.39 [95% CI 1.60, 3.57]; P<0.001) and lower serum total testosterone (OR 0.85 [95% CI 0.88, 0.94]; P=0.002) were independently associated with depression.

Conclusions: This study provides the first quantitation of acute androgen abuse withdrawal symptoms in men. Our data reveal potential pharmacological and psychological components of androgen withdrawal, which could be targeted to develop novel therapies supporting androgen withdrawal, none of which currently exist.