madman
Super Moderator
Male Sex Hormones in Andrology Today (2022)
Nicola Bianchi, Olga Prontera, Mauro Dicuio, Sergio Concetti, Alessandra Sforza, and Giovanni Corona
19.1 Introduction
Male sexual function is the result of the communication among organic relational and intrapsychic components, which mutually interact to support and maintain a satisfying sexual relationship [1–9]. Endocrine and nervous systems represent the key messengers connecting and regulating all the involved phases. Both systems detect all the environmental changes affecting the body and work together to provide the best appropriate response to such events. The nervous system is based on electrical stimulations to communicate, whereas hormones a heterogeneous group of steroid or peptide-derived molecules, produce a messenger system regulating distant target organs.
Sexual sensations collected through the sense organs such as sight, hearing, smell, and touch are detected by peripheral nerves and the codified information reaches the most important centers within the central nervous system, including the septal nuclei, the amygdala, and the hippocampus [5, 10, 11]. The latter are brain areas widely interconnected with each other and with other regulatory centers of endocrine activity, such as the hypothalamus. At the appropriate time, the symphonic activity of hormones and neurotransmitters determines the readiness towards sexuality, which eventually results in intense vascularization of the corpora cavernosa and, eventually in penile erection.
Several hormonal pathways are involved in the latter process. Testosterone (T) represents the most important hormonal regulator of male sexuality acting either at the central or peripheral level [11, 12]. The thyroid system seems to be more involved in the regulation of the ejaculatory reflex, although a possible contribution to sexual desire as well as in penile erection has also been supposed [12–15]. Prolactin (PRL) is mainly involved in the modulation of sexual desire, whereas its contribution to the pathogenesis of erectile dysfunction (ED) is more conflicting [12, 16]. Similarly, the role of other hormonal pathways in the regulation of male sexual response appears negligible [12].
In the following sections, the available evidence supporting the role endocrine system in the regulation of male sexual response will be summarized and critically discussed. In particular, the specific contribution on sexual desire erectile function, and ejaculation will be analyzed in detail.
19.2 Steroids
Testosterone (T) is the main circulating sex steroid in males, essentially derived from testis production (daily production of 5–10 mg) with a negligible contribution from the adrenal glands [17–19].
About 6–8% of daily T production is reduced into the more potent androgen, dihydrotestosterone (DHT), through the action of two distinct 5 α reductase (5αR) isoforms, 5αR type 1 and 2 [19]. In addition, T and its precursor, Δ4 androstenedione, can be actively transformed, through P450 aromatase, to other bioactive metabolites, such as estrone and 17-β-estradiol (E2) (daily production about 45 μg), which activate estrogen receptors (ERs)
19.2.1 Sexual Desire
T represents the fuel of the sex drive and it is the most important determinant of the motivation to seek sexual contact (Table 19.1).
19.2.2 Erectile Function
Data derived from animal models and in vitro studies have documented that T controls most of the signaling pathways involved in the control of penile erection, including nitric oxide (NO) production and degradation, adenosine signaling, calcium sensitization through the RhoA-ROCK pathway, and even penile smooth muscle differentiation [52] (Table 19.1)
19.2.3 Ejaculation
As previously reported for erectile function and sexual desire, T is deeply involved also in the modulation of ejaculatory reflex acting either at the central or peripheral level [15, 65] (Table 19.1).
19.3 Prolactin
PRL is a polypeptide secreted by the anterior pituitary and mainly regulated through tonic hypothalamic inhibition, by dopamine (DA) secretion [71, 72].
19.3.1 Sexual Desire
PRL receptors (PRLR) are expressed in the brain, testis, accessory glands, and even at the penis level [16].
19.3.2 Erectile Dysfunction
The role of PRL in the regulation of the erectile process is more conflicting (Table 19.1).
19.3.3 Ejaculation
Several observational studies have reported a PRL increase following male orgasm [84–86], supporting a possible role of PRL in the regulation of the postorgasmic refractory period [16].
19.4 Thyroid Hormones
Free fractions (FT3 and FT4) represent the biological active fraction of the thyroid hormones (TH) produced by thyroid glands under thyroid-stimulating hormone (TSH) control [15]. TH is involved in regulating protein, fat, and carbohydrate metabolism so that no organs or tissues can be unaffected by thyroid diseases [87]. Accordingly, thyroid receptors are widely expressed within the male genitalia tract, although the specific role of TH on male sexual function is still conflicting.
19.4.1 Sexual Desire
However, it should be important to recognize that no association between low TH and sexual desire has been reported in a larger series of subjects either from the general population or from patients seeking medical care for sexual dysfunction [14]. Hence, more studies are advisable to better clarify the role of TH on sexual desire (Table 19.1).
19.4.2 Erectile Dysfunction
Similar to what was reported for sexual desire, the role of TH in regulating male erectile function is still conflicting (Table 19.1).
19.4.3 Ejaculation
More robust data have supported a possible role of TH in the regulation of the ejaculatory reflex (Table 19.1).
19.5 Other Hormones
Oxytocin (OT): is a short peptide synthesized in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and released by the posterior pituitary. OT in men is released during sexual activity and orgasm and it can activate the secretion of ET-1 and OT itself in the epididymis, creating a reciprocal and synergic cross-activation of contractile factors involved in the regulation of male genitalia tract contractility favoring sperm progression [15]. Despite this evidence, the role of OT in regulating penile erection is limited and still conflicting [12] (Table 19.1).
Other hormones: Limited evidence has documented a possible contribution of other hormones in the regulation of male sexual functioning, including growth hormone [99] and melanocortin [100]; however, available data are too preliminary and not supported by robust evidence-based data [12] (Table 19.1).
19.6 Conclusions
A large body of evidence supports the crucial role of T in the regulation of male sexual response. PRL is mainly involved in modulating sexual desire, whereas TH plays a major role in regulating ejaculatory reflexes. All available guidelines strongly encourage investigating T levels in all subjects complaining of sexual dysfunction [18, 22–24]. TRT can improve all aspects of sexual function and should be considered the first treatment, especially in hypogonadal patients with milder forms of ED. Dopaminergic drugs are highly effective in restoring male sexual desire in subjects with severe hyperprolactinemia, whereas the treatment of underlying thyroid diseases can improve ejaculatory problems. Further studies are advisable to better characterize the role of other hormones.
Nicola Bianchi, Olga Prontera, Mauro Dicuio, Sergio Concetti, Alessandra Sforza, and Giovanni Corona
19.1 Introduction
Male sexual function is the result of the communication among organic relational and intrapsychic components, which mutually interact to support and maintain a satisfying sexual relationship [1–9]. Endocrine and nervous systems represent the key messengers connecting and regulating all the involved phases. Both systems detect all the environmental changes affecting the body and work together to provide the best appropriate response to such events. The nervous system is based on electrical stimulations to communicate, whereas hormones a heterogeneous group of steroid or peptide-derived molecules, produce a messenger system regulating distant target organs.
Sexual sensations collected through the sense organs such as sight, hearing, smell, and touch are detected by peripheral nerves and the codified information reaches the most important centers within the central nervous system, including the septal nuclei, the amygdala, and the hippocampus [5, 10, 11]. The latter are brain areas widely interconnected with each other and with other regulatory centers of endocrine activity, such as the hypothalamus. At the appropriate time, the symphonic activity of hormones and neurotransmitters determines the readiness towards sexuality, which eventually results in intense vascularization of the corpora cavernosa and, eventually in penile erection.
Several hormonal pathways are involved in the latter process. Testosterone (T) represents the most important hormonal regulator of male sexuality acting either at the central or peripheral level [11, 12]. The thyroid system seems to be more involved in the regulation of the ejaculatory reflex, although a possible contribution to sexual desire as well as in penile erection has also been supposed [12–15]. Prolactin (PRL) is mainly involved in the modulation of sexual desire, whereas its contribution to the pathogenesis of erectile dysfunction (ED) is more conflicting [12, 16]. Similarly, the role of other hormonal pathways in the regulation of male sexual response appears negligible [12].
In the following sections, the available evidence supporting the role endocrine system in the regulation of male sexual response will be summarized and critically discussed. In particular, the specific contribution on sexual desire erectile function, and ejaculation will be analyzed in detail.
19.2 Steroids
Testosterone (T) is the main circulating sex steroid in males, essentially derived from testis production (daily production of 5–10 mg) with a negligible contribution from the adrenal glands [17–19].
About 6–8% of daily T production is reduced into the more potent androgen, dihydrotestosterone (DHT), through the action of two distinct 5 α reductase (5αR) isoforms, 5αR type 1 and 2 [19]. In addition, T and its precursor, Δ4 androstenedione, can be actively transformed, through P450 aromatase, to other bioactive metabolites, such as estrone and 17-β-estradiol (E2) (daily production about 45 μg), which activate estrogen receptors (ERs)
19.2.1 Sexual Desire
T represents the fuel of the sex drive and it is the most important determinant of the motivation to seek sexual contact (Table 19.1).
19.2.2 Erectile Function
Data derived from animal models and in vitro studies have documented that T controls most of the signaling pathways involved in the control of penile erection, including nitric oxide (NO) production and degradation, adenosine signaling, calcium sensitization through the RhoA-ROCK pathway, and even penile smooth muscle differentiation [52] (Table 19.1)
19.2.3 Ejaculation
As previously reported for erectile function and sexual desire, T is deeply involved also in the modulation of ejaculatory reflex acting either at the central or peripheral level [15, 65] (Table 19.1).
19.3 Prolactin
PRL is a polypeptide secreted by the anterior pituitary and mainly regulated through tonic hypothalamic inhibition, by dopamine (DA) secretion [71, 72].
19.3.1 Sexual Desire
PRL receptors (PRLR) are expressed in the brain, testis, accessory glands, and even at the penis level [16].
19.3.2 Erectile Dysfunction
The role of PRL in the regulation of the erectile process is more conflicting (Table 19.1).
19.3.3 Ejaculation
Several observational studies have reported a PRL increase following male orgasm [84–86], supporting a possible role of PRL in the regulation of the postorgasmic refractory period [16].
19.4 Thyroid Hormones
Free fractions (FT3 and FT4) represent the biological active fraction of the thyroid hormones (TH) produced by thyroid glands under thyroid-stimulating hormone (TSH) control [15]. TH is involved in regulating protein, fat, and carbohydrate metabolism so that no organs or tissues can be unaffected by thyroid diseases [87]. Accordingly, thyroid receptors are widely expressed within the male genitalia tract, although the specific role of TH on male sexual function is still conflicting.
19.4.1 Sexual Desire
However, it should be important to recognize that no association between low TH and sexual desire has been reported in a larger series of subjects either from the general population or from patients seeking medical care for sexual dysfunction [14]. Hence, more studies are advisable to better clarify the role of TH on sexual desire (Table 19.1).
19.4.2 Erectile Dysfunction
Similar to what was reported for sexual desire, the role of TH in regulating male erectile function is still conflicting (Table 19.1).
19.4.3 Ejaculation
More robust data have supported a possible role of TH in the regulation of the ejaculatory reflex (Table 19.1).
19.5 Other Hormones
Oxytocin (OT): is a short peptide synthesized in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and released by the posterior pituitary. OT in men is released during sexual activity and orgasm and it can activate the secretion of ET-1 and OT itself in the epididymis, creating a reciprocal and synergic cross-activation of contractile factors involved in the regulation of male genitalia tract contractility favoring sperm progression [15]. Despite this evidence, the role of OT in regulating penile erection is limited and still conflicting [12] (Table 19.1).
Other hormones: Limited evidence has documented a possible contribution of other hormones in the regulation of male sexual functioning, including growth hormone [99] and melanocortin [100]; however, available data are too preliminary and not supported by robust evidence-based data [12] (Table 19.1).
19.6 Conclusions
A large body of evidence supports the crucial role of T in the regulation of male sexual response. PRL is mainly involved in modulating sexual desire, whereas TH plays a major role in regulating ejaculatory reflexes. All available guidelines strongly encourage investigating T levels in all subjects complaining of sexual dysfunction [18, 22–24]. TRT can improve all aspects of sexual function and should be considered the first treatment, especially in hypogonadal patients with milder forms of ED. Dopaminergic drugs are highly effective in restoring male sexual desire in subjects with severe hyperprolactinemia, whereas the treatment of underlying thyroid diseases can improve ejaculatory problems. Further studies are advisable to better characterize the role of other hormones.
