JU INSIGHT Serum Testosterone and Dihydrotestosterone and Incidence and Progression of Lower Urinary Tract Symptoms

By: James P. Daniels, MD, Cedars-Sinai Medical Center, Los Angeles, California; James Mirocha, MS, Cedars-Sinai Medical Center, Los Angeles, California; Michie Adjei, MD, Cedars-Sinai Medical Center, Los Angeles, California; Daniel Moreira, MD, The University of Illinois College of Medicine, Chicago; Stephen J. Freedland, MD, Cedars-Sinai Medical Center, Los Angeles, California, Durham VA Medical Center, North Carolina | Posted on: 19 Jan 2024

Daniels JP, Mirocha J, Adjei M, Moreira D, Freedland SJ. Serum testosterone and dihydrotestosterone and incidence and progression of lower urinary tract symptoms: results from the REDUCE study. J Urol. 2024;211(1):101-110.

Study Need and Importance

Despite multiple studies exploring the link between serum testosterone (T) and worsening lower urinary tract symptoms (LUTS), to date there is still no consensus. Most recent studies on men with very low serum androgens receiving T replacement found exogenous T does not negatively affect LUTS. We wanted to know if higher levels of endogenous serum T would be associated with benign prostatic hyperplasia (BPH) symptoms.

What We Found

In our post hoc analysis of REDUCE, on multivariable analysis we found no evidence of association between serum T or dihydrotestosterone (DHT) with any prostate measure including PSA, prostate volume, or International Prostate Symptom Score. We also found no evidence that higher serum T or DHT levels were associated with LUTS incidence or LUTS progression (Table). Additionally, when comparing rates of LUTS incidence and progression from time of randomization between quintiles of serum T and DHT, we found no difference in risk of LUTS incidence or LUTS progression.

Table. Adjusted Hazard Ratio and 95% Confidence Interval of Lower Urinary Tract Symptoms Incidence and Lower Urinary Tract Symptoms Progression by Serum Androgen Levels

	LUTS incidence				LUTS progression
	Adj-HR	95% CI	P value		Adj-HR	95% CI	P value
Testosterone	1.01	0.99-1.03	.4	Testosterone	1.00	0.99-1.01	.7
DHT	1.05	0.93-1.20	.4	DHT	1.01	0.94-1.08	.9
Abbreviations: Adj-HR, adjusted hazard ratio; DHT, dihydrotestosterone; DRE, digital rectal examination; IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptoms.

Limitations

Limitations to our study include a lack of longitudinal androgen collection and no differentiation between free T and bioavailable T. REDUCE also lacks data on estrogens and sex hormone–binding globulin. Participants in our study were primarily White (>90%). Given REDUCE recruited men at increased risk of prostate cancer, this may not be fully representative of all men at risk of BPH. Lastly, this analysis was limited to a study period of 4 years.

Interpretation for Patient Care

The null results of our study, along with the preponderance of the literature to date, suggest that serum T and DHT are not linked with BPH. These findings do not disprove the androgen-BPH hypothesis, but rather suggest that future studies should focus on prostate tissue androgen levels and not serum androgen levels.

The following variables were adjusted for: serum testosterone (continuous), serum DHT (continuous), region (North America, Europe, and Other), smoking status (never, former, current), race (White vs non-White), age at randomization (continuous), diabetes (yes vs no), natural log of prostate volume (continuous), natural log of PSA (continuous), IPSS (continuous), DRE (normal vs abnormal), and treatment (dutasteride vs placebo).