madman
Super Moderator
Abstract
Introduction
Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libidoand erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood.
Objectives
To understand the mechanisms and treatment of androgen deficiency–related ED.
Methods
A literature search in the past 10 years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency.
Results
Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway(nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy.
Conclusions
Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.
Introduction
Androgens, which are steroid hormones, include testosterone,dihydrotestosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Androgens are produced mainly by the testes, ovaries, adrenal glands, placenta, brain, and skin.1 The testes and ovaries are the main organs that produce testosterone, which is metabolized in target tissues by the enzyme alpha-reductase to produce the more reactive dihydrotestosterone.2 Androgen production at different sites is regulated by different factors. The hypothalamic-pituitary-gonadal (HPG) axis has an important role in regulating androgen production. Gonadotropin releasing hormone is secreted by the hypothalamus; it acts on the pituitary via the hypothalamic-pituitary portal circulation to stimulate the secretion of gonadotropins,mainly luteinizing hormone and follicle-stimulating hormone. Luteinizing hormone acts on the Leydig cells of the testes and the membranous cells of the ovaries in a way that causes them to produce testosterone, which negatively regulates the hypothalamus and the pituitary gland.3 Although androgens play roles in many organs throughout the body, their mosti mportant role is the regulation of sexual and reproductive development. Hypogonadism can lead to androgen deficiency.4 Androgens help maintain and regulate the growth and function of a range of cells in penile tissue. Endothelial progenitor cells, smooth muscle cells, and cavernous sinusoids are significantly reduced in the cavernous body of the penis of denuded rats, and testosterone supplementation restores the number and function of these cells.5,6 Androgen deficiency also leads to alterations in signaling pathways such as the nitric oxide (NO) pathway in penile tissues, as well as to a decrease in elastic fibers and a significant increase in collagen fibers, both of which ultimately lead to erectile dysfunction (ED).7,8 ED refers to the persistent inability to achieve and maintain sufficient erectile capacity to achieves atisfactory sexual behavior.9 Therefore, understanding the causes of androgen deficiency and its effects on erectile function can help prevent and treat ED due to androgen deficiency.
Results and discussion
*Causes of androgen deficiency and its effect on erectile function
As one of the most important classes of sex hormones in the body, androgens are regulated centrally and peripherally and are usually maintained in a relatively balanced state. Androgen deficiency may result when certain diseases affect the central nervous system or the sex organs. The prevalence of androgen deficiency is as high as 20% in adolescent and young adult males, and androgen levels tend to decrease over time.10 There are many causes of androgen deficiency (Table 1).
-Hypothalamic-pituitary lesions and injuries
-Testicular diseases and injuries
-Endocrine and metabolic disorders
-Side effects of medication
-Aging
*Molecular mechanisms of ED due to androgen deficiency
The process of male penile erection is complex in that it requires blood vessels, nerves, and muscles to work together;thus, the structural and functional integrity of these tissues plays an important role in penile erection. Under conditions of sexual stimulation, nerve endings release diastolic factor, which acts on vascular endothelial cells and smooth muscle cells, leading to arterial vasodilatation and congestion; the congested arteries further prevent venous blood from returning to the venous sinus, which ultimately leads to penile erection.41 The NO/cyclic guanosine monophosphate(NO/cGMP) signaling pathway may be the most important pathway that acts on the penile vasculature and smooth muscle; it also plays an important regulatory role in the erectile process. Nerve cells and endothelial cells in the corpus cavernosum produce and release NO synthase (NOS), which activates guanylyl cyclase and produces cGMP; this reduces the inward flow of Ca+, leading to smooth muscle relaxation and penile erection.42 Androgen deficiency can affect endothelial and smooth muscle cells by affecting endothelial NOS (eNOS) activity, the opening and closing of ion channels, oxidative stress, apoptosis, and fibrosis through a variety of pathways leading to ED (Figure 1).
-Androgen deficiency inhibits the NOS/NO/cGMP pathway
-Androgen deficiency alters ion channel protein expression
-Androgen deficiency induces alterations, including oxidative stress, cell death, and tissue fibrosis, in penile corpus cavernosum cells
*Treatment of low androgen-induced ED
*Improved maintenance of erectile function in a low androgen state
Introduction
Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libidoand erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood.
Objectives
To understand the mechanisms and treatment of androgen deficiency–related ED.
Methods
A literature search in the past 10 years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency.
Results
Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway(nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy.
Conclusions
Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.
Introduction
Androgens, which are steroid hormones, include testosterone,dihydrotestosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Androgens are produced mainly by the testes, ovaries, adrenal glands, placenta, brain, and skin.1 The testes and ovaries are the main organs that produce testosterone, which is metabolized in target tissues by the enzyme alpha-reductase to produce the more reactive dihydrotestosterone.2 Androgen production at different sites is regulated by different factors. The hypothalamic-pituitary-gonadal (HPG) axis has an important role in regulating androgen production. Gonadotropin releasing hormone is secreted by the hypothalamus; it acts on the pituitary via the hypothalamic-pituitary portal circulation to stimulate the secretion of gonadotropins,mainly luteinizing hormone and follicle-stimulating hormone. Luteinizing hormone acts on the Leydig cells of the testes and the membranous cells of the ovaries in a way that causes them to produce testosterone, which negatively regulates the hypothalamus and the pituitary gland.3 Although androgens play roles in many organs throughout the body, their mosti mportant role is the regulation of sexual and reproductive development. Hypogonadism can lead to androgen deficiency.4 Androgens help maintain and regulate the growth and function of a range of cells in penile tissue. Endothelial progenitor cells, smooth muscle cells, and cavernous sinusoids are significantly reduced in the cavernous body of the penis of denuded rats, and testosterone supplementation restores the number and function of these cells.5,6 Androgen deficiency also leads to alterations in signaling pathways such as the nitric oxide (NO) pathway in penile tissues, as well as to a decrease in elastic fibers and a significant increase in collagen fibers, both of which ultimately lead to erectile dysfunction (ED).7,8 ED refers to the persistent inability to achieve and maintain sufficient erectile capacity to achieves atisfactory sexual behavior.9 Therefore, understanding the causes of androgen deficiency and its effects on erectile function can help prevent and treat ED due to androgen deficiency.
Results and discussion
*Causes of androgen deficiency and its effect on erectile function
As one of the most important classes of sex hormones in the body, androgens are regulated centrally and peripherally and are usually maintained in a relatively balanced state. Androgen deficiency may result when certain diseases affect the central nervous system or the sex organs. The prevalence of androgen deficiency is as high as 20% in adolescent and young adult males, and androgen levels tend to decrease over time.10 There are many causes of androgen deficiency (Table 1).
-Hypothalamic-pituitary lesions and injuries
-Testicular diseases and injuries
-Endocrine and metabolic disorders
-Side effects of medication
-Aging
*Molecular mechanisms of ED due to androgen deficiency
The process of male penile erection is complex in that it requires blood vessels, nerves, and muscles to work together;thus, the structural and functional integrity of these tissues plays an important role in penile erection. Under conditions of sexual stimulation, nerve endings release diastolic factor, which acts on vascular endothelial cells and smooth muscle cells, leading to arterial vasodilatation and congestion; the congested arteries further prevent venous blood from returning to the venous sinus, which ultimately leads to penile erection.41 The NO/cyclic guanosine monophosphate(NO/cGMP) signaling pathway may be the most important pathway that acts on the penile vasculature and smooth muscle; it also plays an important regulatory role in the erectile process. Nerve cells and endothelial cells in the corpus cavernosum produce and release NO synthase (NOS), which activates guanylyl cyclase and produces cGMP; this reduces the inward flow of Ca+, leading to smooth muscle relaxation and penile erection.42 Androgen deficiency can affect endothelial and smooth muscle cells by affecting endothelial NOS (eNOS) activity, the opening and closing of ion channels, oxidative stress, apoptosis, and fibrosis through a variety of pathways leading to ED (Figure 1).
-Androgen deficiency inhibits the NOS/NO/cGMP pathway
-Androgen deficiency alters ion channel protein expression
-Androgen deficiency induces alterations, including oxidative stress, cell death, and tissue fibrosis, in penile corpus cavernosum cells
*Treatment of low androgen-induced ED
*Improved maintenance of erectile function in a low androgen state
