Assessment of Frailty and Association with Progression of Benign Prostatic Hyperplasia Symptoms and Serious Adverse Events among Men Using Drug Therapy

Scott R. Bauer, Louise C. Walter, Kristine E. Ensrud, Anne M. Suskind, John C. Newman, William A. Ricke, Teresa T. Liu, Kevin T. McVary, Kenneth Covinsky

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Importance: Benign prostatic hyperplasia (BPH) in older men can cause lower urinary tract symptoms (LUTS), which are increasingly managed with medications. Frailty may contribute to both symptom progression and serious adverse events (SAEs), shifting the balance of benefits and harms of drug therapy.

Objective: To assess the association between a deficit accumulation frailty index and clinical BPH progression or SAE.

Design, Setting, and Participants: This cohort study used data from the Medical Therapy of Prostatic Symptoms trial, which compared placebo, doxazosin, finasteride, and combination therapy in men with moderate-to-severe LUTS, reduced urinary flow rate, and no prior BPH interventions, hypotension, or elevated prostate-specific antigen. Enrollment was from 1995 to 1998, and follow-up was through 2001. Data were assessed in February 2021.

Exposures: A frailty index (score range, 0-1) using 68 potential deficits collected at baseline was used to categorized men as robust (score ≤0.1), prefrail (score 0.1 to <0.25), or frail (score ≥0.25).

Main Outcomes and Measures: Primary outcomes were time to clinical BPH progression and time to SAE, as defined in the parent trial. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regressions adjusted for demographic variables, treatment group, measures of obstruction, and comorbidities.

Results: Among 3047 men (mean [SD] age, 62.6 [7.3] years; range, 50-89 years) in this analysis, 745 (24%) were robust, 1824 (60%) were prefrail, and 478 (16%) were frail at baseline. Compared with robust men, frail men were older (age ≥75 years, 12 men [2%] vs 62 men [13%]), less likely to be White (646 men [87%] vs 344 men [72%]), less likely to be married (599 men [80%] vs 342 men [72%]), and less likely to have 16 years or more of education (471 men [63%] vs 150 men [31%]). During mean (SD) follow-up of 4.0 (1.5) years, the incidence rate of clinical BPH progression was 2.2 events per 100 person-years among robust men, 2.9 events per 100 person-years among prefrail men (AHR, 1.36; 95% CI, 1.02-1.83), and 4.0 events per 100 person-years among frail men (AHR, 1.82; 95% CI, 1.24-2.67; linear P = .005). Larger point estimates were seen among men who received doxazosin or combination therapy, although the test for interaction between frailty index and treatment group did not reach statistical significance (P for interaction = .06). Risk of SAE was higher among prefrail and frail men (prefrail vs robust AHR, 1.81; 95% CI, 1.48-2.23; frail vs robust AHR, 2.86; 95% CI, 2.21-3.69; linear P < .001); this association was similar across treatment groups (P for interaction = .76).

Conclusions and Relevance: These findings suggest that frailty is independently associated with greater risk of both clinical BPH progression and SAEs. Older frail men with BPH considering initiation of drug therapy should be counseled regarding their higher risk of progression despite combination therapy and their likelihood of experiencing SAEs regardless of treatment choice.

Original languageEnglish (US)
Article number34427
JournalJAMA Network Open
Issue number11
StatePublished - Nov 24 2021

Bibliographical note

Funding Information:
Funding/Support: This work was supported by grants from the National Institute of Diabetes, Digestive, and Kidney Disorders (grant 1K12DK111028 to Dr Bauer, the National Institute on Aging (grant 1R03AG067937 to Dr Bauer) and the UCSF Claude D. Pepper Older Americans Independence Center funded by National Institute on Aging (grant P30 AG044281 to Dr Covinsky).

Funding Information:
Disclaimer: The Medical Therapy of Prostatic Symptoms (MTOPS) study was conducted by the MTOPS Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the MTOPS study reported here were supplied by the NIDDK Central Repository. This manuscript was not prepared in collaboration with Investigators of the MTOPS study (except Dr Kevin T. McVary) and does not necessarily reflect the opinions or views of the MTOPS study, the NIDDK Central Repository, or the NIDDK.

Publisher Copyright:
© 2021 BMJ Publishing Group. All rights reserved.


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