madman
Super Moderator
* The role of hormones in male sexual desire
Testosterone
In conclusion, preclinical and clinical evidence suggest that AR activation is not the only determinant of male sexual desire and that androgen aromatization to estrogen may play a relevant role (see below).
Estrogens
Overall, theevidence suggests that E2 in the brain might participate in regulating sexual desire in men. However, epidemiological studies did not show significant relationships between circulating E2 and sexual desire in men.17,20-22 A possible explanation ist hat brain estrogen levels, which affect sexual desire, are most probably formed locally from T through ARO rather than originating from circulating E2, which consequently does not accurately describe the intracerebral estrogen amount. In contrast with this view, a secondary analysis of the treatment arm of the aforementioned TTrials20 showed that changes in circulating E2 measured by mass spectrometry correlated better than changes in total T levels with changes in sexual desire, with an apparent threshold at 22 pg/mL.54
Dihydrotestosterone
In the aforementioned secondary analysis of the treatmentarm of the TTrials, besides E2, changes in DHT levels were significantly associated with changes in sexual desire.54 Accordingly, a meta-analysis of placebo-controlled trials for benign prostate hyperplasia with 5α-reductase inhibitors (5ARI) indicated a more than 50% increased risk of MHSDD in the treatment arm, with the risk decreased as a function of shorter trial follow-up.55
* Role of DHEA and other adrenal hormones
The European Registry on Cushing’s syndrome documented that cortisol excess was associated with a 35% and 21% reduced libido in men younger or older than 65 years, respectively.60 However, whether cortisol plays a direct role in the regulation of male sexual desire, or the latter relationshipis the result of cortisol excess-associated morbidities, including hypogonadism and mood disturbances, is unknown.6
Prolactin
Dopamine agonists (bromocriptine and cabergoline) are the first-line treatment for hyperprolactinemia, particularly when derived from prolactin-secreting adenomas.69 Cabergoline, even more than bromocriptine or quinagolide, effectively lowers prolactin levels and reduces the adenoma size.69 In prolactin-secreting adenomas, surgery may also be considereda first-line option if the risk of invasion of the cavernoussinus is low; otherwise, it generally represents a second-line choice.69
According to a recent meta-analysis of three studies assessing the change in prevalence of reduced sexual desire before and after medical or surgical treatment, the probability of remission was dramatic, with a prevalence almost 60-fold lower after therapy.68
* The role of hormones in arousal/erection
Testosterone
- Summary of evidence from preclinical studies.
- Summary of evidence from clinical studies.
Estrogens
Dihydrotestosterone
Prolactin
* Other hormones involved in the pathophysiology of male sexual desire and arousal/erection
Thyroid hormones
Growth hormone – IGF1
Oxytocin
Melanocortins
Kisspeptin
Although more data are needed, kisspeptin treatment could potentially be a pharmacological target to treatmen with low sexual desire; however, it should be considered that continuous stimulation of the GPR54 receptor is able to cause severe hypogonadotropic hypogonadism.215 Therefore,a possible chronic treatment may not be possible, or a suitable timing of administration should be considered.
Conclusions
Several hormones are involved in modulating or regulating sexual behavior in men. Therefore, it is not surprising that endocrine abnormalities are common in patients with sexual dysfunction. Epidemiological and interventional trials confirm the pivotal role of T in inducing and maintaining sexual desire and erection. Also, the role of increased prolactin levels in reducing male sexual desire is convincing. For other hormones, data are weaker, scanty, or conflictual. For hypothalamic neurohormones, such as OT, αMSH, and kisspeptin, there is room for further research due to preliminary data on theirpossible therapeutic use. However, the current pilot studies lead to inconsistent data on their efficacy or disappointing . Therefore, so far, evidence-based recommendationsmay be provided for the assessment of some but not all the hormones that are here discussed as possible modulators of male sexual function.
Testosterone
In conclusion, preclinical and clinical evidence suggest that AR activation is not the only determinant of male sexual desire and that androgen aromatization to estrogen may play a relevant role (see below).
Estrogens
Overall, theevidence suggests that E2 in the brain might participate in regulating sexual desire in men. However, epidemiological studies did not show significant relationships between circulating E2 and sexual desire in men.17,20-22 A possible explanation ist hat brain estrogen levels, which affect sexual desire, are most probably formed locally from T through ARO rather than originating from circulating E2, which consequently does not accurately describe the intracerebral estrogen amount. In contrast with this view, a secondary analysis of the treatment arm of the aforementioned TTrials20 showed that changes in circulating E2 measured by mass spectrometry correlated better than changes in total T levels with changes in sexual desire, with an apparent threshold at 22 pg/mL.54
Dihydrotestosterone
In the aforementioned secondary analysis of the treatmentarm of the TTrials, besides E2, changes in DHT levels were significantly associated with changes in sexual desire.54 Accordingly, a meta-analysis of placebo-controlled trials for benign prostate hyperplasia with 5α-reductase inhibitors (5ARI) indicated a more than 50% increased risk of MHSDD in the treatment arm, with the risk decreased as a function of shorter trial follow-up.55
* Role of DHEA and other adrenal hormones
The European Registry on Cushing’s syndrome documented that cortisol excess was associated with a 35% and 21% reduced libido in men younger or older than 65 years, respectively.60 However, whether cortisol plays a direct role in the regulation of male sexual desire, or the latter relationshipis the result of cortisol excess-associated morbidities, including hypogonadism and mood disturbances, is unknown.6
Prolactin
Dopamine agonists (bromocriptine and cabergoline) are the first-line treatment for hyperprolactinemia, particularly when derived from prolactin-secreting adenomas.69 Cabergoline, even more than bromocriptine or quinagolide, effectively lowers prolactin levels and reduces the adenoma size.69 In prolactin-secreting adenomas, surgery may also be considereda first-line option if the risk of invasion of the cavernoussinus is low; otherwise, it generally represents a second-line choice.69
According to a recent meta-analysis of three studies assessing the change in prevalence of reduced sexual desire before and after medical or surgical treatment, the probability of remission was dramatic, with a prevalence almost 60-fold lower after therapy.68
* The role of hormones in arousal/erection
Testosterone
- Summary of evidence from preclinical studies.
- Summary of evidence from clinical studies.
Estrogens
Dihydrotestosterone
Prolactin
* Other hormones involved in the pathophysiology of male sexual desire and arousal/erection
Thyroid hormones
Growth hormone – IGF1
Oxytocin
Melanocortins
Kisspeptin
Although more data are needed, kisspeptin treatment could potentially be a pharmacological target to treatmen with low sexual desire; however, it should be considered that continuous stimulation of the GPR54 receptor is able to cause severe hypogonadotropic hypogonadism.215 Therefore,a possible chronic treatment may not be possible, or a suitable timing of administration should be considered.
Conclusions
Several hormones are involved in modulating or regulating sexual behavior in men. Therefore, it is not surprising that endocrine abnormalities are common in patients with sexual dysfunction. Epidemiological and interventional trials confirm the pivotal role of T in inducing and maintaining sexual desire and erection. Also, the role of increased prolactin levels in reducing male sexual desire is convincing. For other hormones, data are weaker, scanty, or conflictual. For hypothalamic neurohormones, such as OT, αMSH, and kisspeptin, there is room for further research due to preliminary data on theirpossible therapeutic use. However, the current pilot studies lead to inconsistent data on their efficacy or disappointing . Therefore, so far, evidence-based recommendationsmay be provided for the assessment of some but not all the hormones that are here discussed as possible modulators of male sexual function.
