Co-administration of 5α-reductase inhibitors worsens the adverse metabolic effects of prescribed glucocorticoids.

Othonos, Nantia, Marjot, Thomas, Woods, Conor, Hazlehurst, Jonathan M, Nikolaou, Nikolaos, Pofi, Riccardo, White, Sarah, Bonaventura, Ilaria, Webster, Craig, Duffy, Joanne, Cornfield, Thomas, Moolla, Ahmad, Isidori, Andrea M, Hodson, Leanne and Tomlinson, Jeremy W (2020) Co-administration of 5α-reductase inhibitors worsens the adverse metabolic effects of prescribed glucocorticoids. The Journal of clinical endocrinology and metabolism. ISSN 1945-7197. This article is available to all UHB staff and students via Ask Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://academic.oup.com/jcem

Abstract

CONTEXT

Glucocorticoids (GC) are commonly prescribed, but their use is associated with adverse metabolic effects. 5a-reductase inhibitors (5aRI) are also frequently prescribed, mainly to inhibit testosterone conversion to dihydrotestosterone. However, they also prevent the inactivation of GCs.

OBJECTIVE

We hypothesised that 5aRIs may worsen the adverse effects of GCs.

DESIGN

Prospective, randomised study.

PATIENTS

19 healthy male volunteers (age; 45±2 years, BMI; 27.1±0.7kg/m2).

INTERVENTIONS

Participants underwent metabolic assessments; 2-step hyperinsulinemic, euglycemic clamp incorporating stable-isotopes, adipose tissue microdialysis and biopsy. Participants were then randomised to either prednisolone (10mg daily) or prednisolone (10mg daily) plus a 5aRI (finasteride 5mg daily or dutasteride 0.5mg daily) for 7 days; metabolic assessments were then repeated.

MAIN OUTCOME MEASURES

Ra glucose, glucose utilization (M-value), glucose oxidation, non-esterified fatty acids (NEFA) levels.

RESULTS

Co-administration of prednisolone with a 5aRI increased circulating prednisolone levels (482±96 vs. 761±57nmol/L, p=0.029). Prednisolone alone did not alter Ra glucose (2.55±0.34 vs 2.62±0.19mg/kg/min, p=0.86), M-value (3.2±0.5 vs 2.7±0.7mg/kg/min, p=0.37), or glucose oxidation (0.042±0.007 vs 0.040±0.004mmol/hr/kg/min, p=0.79). However, co-administration with a 5aRI increased Ra glucose (2.67±0.16 vs. 3.05±0.18mg/kg/min, p<0.05) and decreased M-value (4.0±0.5 vs. 2.6±0.4mg/kg/min, p<0.05), and oxidation (0.043±0.003 vs. 0.036±0.002mmol/hr/kg, p<0.01). Similarly, prednisolone did not impair insulin-mediated suppression of circulating NEFA (43.1±28.9 vs. 36.8±14.3μmol/L, p=0.81), unless co-administered with a 5aRI (49.8±8.6 vs. 88.5±13.5μmol/L, p<0.01).

CONCLUSIONS

We have demonstrated that 5aRIs exacerbate the adverse effects of prednisolone. This study has significant translational implications, including the need to consider GC dose adjustments, but also the necessity for increased vigilance for the development of adverse effects.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via Ask Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
WK Endocrine system. Endocrinology
Divisions: Ambulatory Care > Endocrinology
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 08 Jul 2020 11:30
Last Modified: 08 Jul 2020 11:30
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3235

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