madman
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Updates on androgen replacement therapy and lower urinary tract symptoms: a narrative review (2022)
Raed M. Al-Zoubi, Mustafa Alwani, Omar M. Aboumarzouk, Mai Elaarag, Ahmad R. Al-Qudimat, Laxmi Ojha & Aksam Yassin
ABSTRACT
Lower urinary tract symptoms (LUTS) are caused by higher tension at the bladder neck level (due to fibrosis or stiffness) or benign prostatic hyperplasia, which causes static obstruction of the bladder outlet. Both forms cause a group of symptoms such as hesitancy, intermittency, weak stream, nocturia, urine frequency, and urgency. Additionally, LUTS (obstructive or irritative symptoms) are common in elderly men with hypogonadism, identified as the reduced testes capability in producing sex steroids and sperm, and are categorized as testosterone deficiency. Even though the mode of action (MoA) of testosterone therapy (TTh) on hypogonadal men needs more research and understanding, the effectiveness of TTh in the development of male genital organs has been reported in several studies. This review shows the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages.
Introduction
The earth’s population is indeed aging, and there are many age-related health concerns in men have become obvious over the last two decades. One of the current attracting awareness is the significant incidence of symptoms in aging males with hypogonadism such as weariness, loss of libido, lack of physical strength, erectile dysfunction (ED), depression, and visceral obesity, which are all known to be caused by testosterone deficiency (TD) [1–4]. In aging men, there is a steady reduction in the levels of testosterone [5]. This has been shown to lead to many clinical and major biological conditions that have been associated with low levels of testosterone (T) such as ischemic heart disease, hypertension, diabetes mellitus, hypercholesterolemia, and osteoporosis (Figure 1) [6–9].
Lower urinary tract symptoms (LUTS) are sequences of benign prostatic enlargement (BPE), or dynamic tension at bladder neck level leading to symptoms (obstructive, irritative, or both), The symptoms include intermittency, weak stream, hesitancy, urine frequency, nocturia, and urgency [10,11]. Many researchers have investigated testosterones’ role in male genital organs in terms of differentiation and development in prolonging good physical health [12].
Even though several investigations were studied on the association between sex hormones and benign prostatic hyperplasia (BPH), few of them have reported the association between LUTS symptoms and circulating testosterone. Hypogonadism was observed in 20% of aging men with LUTS, but without any effect on the status of symptoms [7,13]. For instance, Litman et al. published a survey study on the possible association between testosterone and LUTS symptoms. Even though they reported good findings in terms of sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and oestradiol (E2), it was concluded that circulating levels of sex hormones are not significant predictors of urological symptoms and perhaps other factors control the pathophysiology of LUTS in hypogonadal men [14]. Furthermore, looking at LUTS and serum sex steroid hormones, there seems to be no associations between LUTS symptoms with total and calculated free testosterone, however, there seem to be some links with androstanediol glucuronide, a dihydrotestosterone metabolite, and estradiol [11].
Low T levels were found to be inversely correlated with urethral closure and detrusor pressure with maximum flow in patients with clinical bladder outlet blockage and also increased detrusor overactivity [15].
Overall, it was proven to be difficult to link plasma testosterone (T) and LUTS. However, it is worth noting that in elderly males, both symptoms and signs of TD do not correlate consistently to testosterone concentrations [16]. This could be explained (in part) by androgen receptor characteristics that were believed to be influenced by the number of CAG repetitions [17].
The side effects of TD and the positive effects of testosterone therapy may be oblique. This review aims to show the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages. It shows the positive effect of regulating levels of testosterone in elderly men on metabolic syndrome (MetS) variables as well as the International Prostate Symptoms Score (IPSS) [18] scores and with no scientific evidence that TTh could worse LUTS in men with hypogonadism.
Areas of concentration
Metabolic syndrome and LUTS
Even though the exact association and link between LUTS and MetS is still not completely clear, findings of fast-developed LUTS symptoms or normal BPE surgery with men experiencing metabolic alterations support this possible hypothesis.
Effects of testosterone on LUTS
Testosterone may not be the "primary mover" behind the effects of testosterone on urinary tract systems that are functionally and physically linked to LUTS. The indirect association could obscure the interrelationship between symptoms of LUTS and testosterone levels that is biologically feasible.
Nitric oxide synthase in the urinary tract
Nitric oxide synthase in the urinary tract Nitric oxide (NO), known as a non-cholinergic neurotransmitter, is reported to relax smooth muscles in both animals and humans and is found in the genital tissues and the urinary tract [44].
LUTS, androgens, and prostatic inflammation
Several immune cells exist in the prostate tissue that is immunocompetent such as granulocytes, lymphocytes, and macrophages, which upon activation can introduce a chronic immune response to persisting inflammations.
Temporary interruption of TTh
LUTS are known to be associated with hypogonadism in addition to other common conditions such as obesity, Ed, hypertension, CVD, and depression.
Improving LUTS independent of prostate size
Prostatic enlargement secondary to benign hyperplasia is one of the major causes of LUTs. The relationship between LUTs and testosterone is well-documented.
Conclusion
Men tend to experience LUTS and other alignments like erectile dysfunction (ED) and metabolic syndrome very commonly and particularly in the aging male population. The association between LUTS and testosterone levels on an epidemiological level may be indirect. However, the autonomic nervous system overactivity may be related to the connection of LUTS to metabolic syndrome. Additionally, LUTS can be related to the genitourinary anatomical/pathophysiological characteristics, which is why it may become severe because of the autonomic nervous system overactivity. Long-term testosterone is found to be effective and safe for males’ metabolic outcomes. This review showed the positive effect of normalizing levels of testosterone in aging men on metabolic syndrome variables as well as the IPSS scores and with no scientific evidence that TTh could worsen LUTS in men with hypogonadism. TTh has been used worldwide as a therapy to treat testosterone deficiency with increasing evidence and benefits. Nevertheless, more randomized and controlled research and clinical trials are needed to further support the use of TTh in treating men with both severe LUTS and testosterone deficiency.
Raed M. Al-Zoubi, Mustafa Alwani, Omar M. Aboumarzouk, Mai Elaarag, Ahmad R. Al-Qudimat, Laxmi Ojha & Aksam Yassin
ABSTRACT
Lower urinary tract symptoms (LUTS) are caused by higher tension at the bladder neck level (due to fibrosis or stiffness) or benign prostatic hyperplasia, which causes static obstruction of the bladder outlet. Both forms cause a group of symptoms such as hesitancy, intermittency, weak stream, nocturia, urine frequency, and urgency. Additionally, LUTS (obstructive or irritative symptoms) are common in elderly men with hypogonadism, identified as the reduced testes capability in producing sex steroids and sperm, and are categorized as testosterone deficiency. Even though the mode of action (MoA) of testosterone therapy (TTh) on hypogonadal men needs more research and understanding, the effectiveness of TTh in the development of male genital organs has been reported in several studies. This review shows the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages.
Introduction
The earth’s population is indeed aging, and there are many age-related health concerns in men have become obvious over the last two decades. One of the current attracting awareness is the significant incidence of symptoms in aging males with hypogonadism such as weariness, loss of libido, lack of physical strength, erectile dysfunction (ED), depression, and visceral obesity, which are all known to be caused by testosterone deficiency (TD) [1–4]. In aging men, there is a steady reduction in the levels of testosterone [5]. This has been shown to lead to many clinical and major biological conditions that have been associated with low levels of testosterone (T) such as ischemic heart disease, hypertension, diabetes mellitus, hypercholesterolemia, and osteoporosis (Figure 1) [6–9].
Lower urinary tract symptoms (LUTS) are sequences of benign prostatic enlargement (BPE), or dynamic tension at bladder neck level leading to symptoms (obstructive, irritative, or both), The symptoms include intermittency, weak stream, hesitancy, urine frequency, nocturia, and urgency [10,11]. Many researchers have investigated testosterones’ role in male genital organs in terms of differentiation and development in prolonging good physical health [12].
Even though several investigations were studied on the association between sex hormones and benign prostatic hyperplasia (BPH), few of them have reported the association between LUTS symptoms and circulating testosterone. Hypogonadism was observed in 20% of aging men with LUTS, but without any effect on the status of symptoms [7,13]. For instance, Litman et al. published a survey study on the possible association between testosterone and LUTS symptoms. Even though they reported good findings in terms of sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and oestradiol (E2), it was concluded that circulating levels of sex hormones are not significant predictors of urological symptoms and perhaps other factors control the pathophysiology of LUTS in hypogonadal men [14]. Furthermore, looking at LUTS and serum sex steroid hormones, there seems to be no associations between LUTS symptoms with total and calculated free testosterone, however, there seem to be some links with androstanediol glucuronide, a dihydrotestosterone metabolite, and estradiol [11].
Low T levels were found to be inversely correlated with urethral closure and detrusor pressure with maximum flow in patients with clinical bladder outlet blockage and also increased detrusor overactivity [15].
Overall, it was proven to be difficult to link plasma testosterone (T) and LUTS. However, it is worth noting that in elderly males, both symptoms and signs of TD do not correlate consistently to testosterone concentrations [16]. This could be explained (in part) by androgen receptor characteristics that were believed to be influenced by the number of CAG repetitions [17].
The side effects of TD and the positive effects of testosterone therapy may be oblique. This review aims to show the latest updates of TTh in LUTS including potential adverse effects, advantages, and disadvantages. It shows the positive effect of regulating levels of testosterone in elderly men on metabolic syndrome (MetS) variables as well as the International Prostate Symptoms Score (IPSS) [18] scores and with no scientific evidence that TTh could worse LUTS in men with hypogonadism.
Areas of concentration
Metabolic syndrome and LUTS
Even though the exact association and link between LUTS and MetS is still not completely clear, findings of fast-developed LUTS symptoms or normal BPE surgery with men experiencing metabolic alterations support this possible hypothesis.
Effects of testosterone on LUTS
Testosterone may not be the "primary mover" behind the effects of testosterone on urinary tract systems that are functionally and physically linked to LUTS. The indirect association could obscure the interrelationship between symptoms of LUTS and testosterone levels that is biologically feasible.
Nitric oxide synthase in the urinary tract
Nitric oxide synthase in the urinary tract Nitric oxide (NO), known as a non-cholinergic neurotransmitter, is reported to relax smooth muscles in both animals and humans and is found in the genital tissues and the urinary tract [44].
LUTS, androgens, and prostatic inflammation
Several immune cells exist in the prostate tissue that is immunocompetent such as granulocytes, lymphocytes, and macrophages, which upon activation can introduce a chronic immune response to persisting inflammations.
Temporary interruption of TTh
LUTS are known to be associated with hypogonadism in addition to other common conditions such as obesity, Ed, hypertension, CVD, and depression.
Improving LUTS independent of prostate size
Prostatic enlargement secondary to benign hyperplasia is one of the major causes of LUTs. The relationship between LUTs and testosterone is well-documented.
Conclusion
Men tend to experience LUTS and other alignments like erectile dysfunction (ED) and metabolic syndrome very commonly and particularly in the aging male population. The association between LUTS and testosterone levels on an epidemiological level may be indirect. However, the autonomic nervous system overactivity may be related to the connection of LUTS to metabolic syndrome. Additionally, LUTS can be related to the genitourinary anatomical/pathophysiological characteristics, which is why it may become severe because of the autonomic nervous system overactivity. Long-term testosterone is found to be effective and safe for males’ metabolic outcomes. This review showed the positive effect of normalizing levels of testosterone in aging men on metabolic syndrome variables as well as the IPSS scores and with no scientific evidence that TTh could worsen LUTS in men with hypogonadism. TTh has been used worldwide as a therapy to treat testosterone deficiency with increasing evidence and benefits. Nevertheless, more randomized and controlled research and clinical trials are needed to further support the use of TTh in treating men with both severe LUTS and testosterone deficiency.
