Testosterone, BPH and Lower Urinary Track Symptoms

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Nelson Vergel

Founder, ExcelMale.com
An FDA mandated warning on all testosterone products states that testosterone replacement therapy (TRT) in men with benign prostate hyperplasia (BPH) “increases the risk of worsening signs and symptoms of BPH”. This warning appears to be based off the commonly held notion that prostate growth is proportional to testosterone levels, despite evidence to the contrary. In this review article we explored BPH/LUTS and its interplay with testosterone. This included an overview of the physiology of testosterone interactions with the prostate and lower urinary tract, as well as a review of literature pertaining to TRT’s effects on LUTS/BPH.

In terms of physiology, testosterone actually appears to be beneficial for the prevention of LUTS/BPH.1,2 Studies have suggested three major contributors to LUTS/BPH: nitric oxide deficiency, autonomic hypertonicity, and pelvic atherosclerosis. Among other things, these entities result in pelvic ischemia and chronic hypoxia of the bladder and prostate, which has been associated with LUTS/BPH.3-6 Sharing a similar pathway with phosphodiesterase-5 (PDE-5) inhibitors, testosterone has been shown to alleviate this hypoxia by modulating cGMP-mediated nitric oxide production.7-10

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Nelson Vergel

Founder, ExcelMale.com
Andrology. 2015 Nov;3(6):1165-72. doi: 10.1111/andr.12114. Epub 2015 Oct 9.

Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Egan KB1, Miner MM2, Suh M1, McVary K3, Ni X4, Roehrborn CG5, Wittert G6, Wong DG7, Rosen RC1.

Author information
1New England Research Institutes, Inc., Watertown, MA, USA.
2Men's Health Center, The Miriam Hospital, Providence, RI, USA.
3Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
4Global Statistical Sciences and Advanced Analytics, Eli Lilly and Company, Indianapolis, IN, USA.
5Department of Urology, University of Texas Southwestern Medical Center, Indianapolis, IN, USA.
6Freemasons Foundation Centre for Men's Health, School of Medicine, University of Adelaide, Adelaide, Australia.
7Eli Lilly and Company, Indianapolis, IN, USA.


Little is known about how total testosterone and estradiol-17&#946; influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged &#8805;18 years randomized to tadalafil 5 mg once-daily or placebo who had &#8805;6 month history of LUTS and an International Prostate Symptom Score (IPSS)&#8805;13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17&#946;, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17&#946; and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (&#916;IPSS), &#916;IPSS-V, and &#916;IPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17&#946; was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17&#946; versus those with higher baseline estradiol-17&#946;. Lower baseline estradiol-17&#946; was significantly associated with modestly improved &#916;IPSS-V (p = 0.04) and &#916;total IPSS (p = 0.05) but not with &#916;IPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict &#916;IPSS. Men with lower baseline estradiol-17&#946; levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17&#946; levels when responsiveness was measured using total IPSS and IPSS-V.
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