madman
Super Moderator
Premature Ejaculation and Its Association with Serum Testosterone Levels: A Comprehensive Review (2022)
Robert H. Drury,* Jacob W. Greenberg, Megan Lerner, and Wayne J.G. Hellstrom
Abstract
Premature ejaculation (PE) is the most common form of male sexual dysfunction. Various hormonal and nutritional deficiencies have been implicated in PE, although conflicting data exist. We sought to determine if androgen levels, particularly testosterone, correlate with PE. A comprehensive narrative review was performed by using PubMed. Exclusion criteria included review articles and articles addressing nonandrogenic hormones. Sixty articles met our inclusion criteria and 165 were excluded. Relatively high testosterone levels were associated with PE, including men with specific medical histories (e.g., emotional trauma and infertility). On a molecular level, increased trinucleotide CAG repeats within the androgen receptor gene contributed to the relationship between high testosterone and PE. Elevated fetal androgen exposure was also linked to an increased risk of PE, although the data were contradictory. In addition, although not explicitly related to high testosterone, lowering testosterone via various interventions was associated with PE improvement. Conversely, relatively low testosterone was also associated with an increased risk of PE, especially when increasing testosterone through medical or surgical treatments helped alleviate PE in both human- and animal-based models. Finally, numerous studies showed no association between testosterone levels and PE, including in patients with normal or low testosterone, concurrent sexual pathologies (e.g., infertility and chronic prostatitis), comorbid chronic diseases, or various nutritional deficiencies or toxicities. The association between testosterone and PE remains controversial. Relatively high and low testosterone both appear to be associated with PE, although strong evidence exists that PE is not affected by testosterone levels. Thus, the physiologic mechanism behind PE is multifactorial and cannot be attributed solely to testosterone levels.
Introduction
Premature ejaculation (PE) is the most common form of male sexual dysfunction.1,2 Some sources estimate that >25% of patients presenting for treatment of sexual dysfunction have PE.3,4 PE is defined as ejaculation consistently occurring within 1 min of vaginal penetration, causing great personal distress.5,6 In patients without PE, normal intravaginal ejaculatory latency time (IELT) ranges from 5 to 20 min.7
There are four subtypes of PE (Table 1). Primary/ lifelong PE patients experience symptoms from the start of their sexual maturity, while those with secondary/ acquired PE develop the disease over the course of their life span. In terms of prevalence within the general population, primary or variable PE appears to be the most common subtype.4,11 PE may occur in sexually active men of any age. In one study, accounting for all PE subtypes, the mean age of men presenting with PE was the mid-thirties, although ages ranged from 24 to 52 years.11 Contradictory evidence exists on whether PE increases or decreases in prevalence with increasing age.4,12
PE is associated with several pathologies, including prostatitis, obesity, smoking, and the presence of multiple comorbidities.4,13 In addition, numerous hormonal (e.g., leptin, melatonin, thyroid hormone, oxytocin, and prolactin) and nutritional (e.g., folate, vitamin D, magnesium, and nickel) imbalances have been implicated in PE.14–35 Androgen levels, particularly testosterone, have also been analyzed for their role in ejaculatory physiology and PE.36,37
Currently, all medications used for PE treatment are considered off-label.38,39 Standard treatment for all subtypes includes selective serotonin reuptake inhibitors (SSRIs) (e.g., ‘‘on-demand’’ dapoxetine), topical anesthetics, and cognitive-behavioral therapy.19,40–43
However, certain SSRIs may negatively impact fertility or be too expensive, causing discontinuance.44,45 In addition, some men experience PE that is refractory to SSRIs.46 Several alternative treatments for PE have been explored with mixed results, including phenoxybenzamine, epelsiban, tadalafil, antiandrogen medications, cligosiban, and exercise.47–52 Although many treatments exist, their beneficial mechanism often proves elusive.53
A better understanding of PE’s etiologies will help improve treatment. The objective of this study was to determine the role of androgens, particularly testosterone, in PE.
*Elevated testosterone and its association with PE
*Decreased testosterone and its association with PE
*Testosterone levels are not associated with PE
*Fetal androgen exposure and its association with PE
Conclusion
Contemporary evidence for the association between testosterone and PE remains controversial. This may, in part, be due to the large patient heterogeneity and poor PE subtyping within the published literature. In addition, many studies use relative values for determining high versus low testosterone in patients with PE rather than using laboratory-based testosterone ranges. This makes it difficult to determine a specific value that would qualify as low or high testosterone when assessing risk for PE.
Robert H. Drury,* Jacob W. Greenberg, Megan Lerner, and Wayne J.G. Hellstrom
Abstract
Premature ejaculation (PE) is the most common form of male sexual dysfunction. Various hormonal and nutritional deficiencies have been implicated in PE, although conflicting data exist. We sought to determine if androgen levels, particularly testosterone, correlate with PE. A comprehensive narrative review was performed by using PubMed. Exclusion criteria included review articles and articles addressing nonandrogenic hormones. Sixty articles met our inclusion criteria and 165 were excluded. Relatively high testosterone levels were associated with PE, including men with specific medical histories (e.g., emotional trauma and infertility). On a molecular level, increased trinucleotide CAG repeats within the androgen receptor gene contributed to the relationship between high testosterone and PE. Elevated fetal androgen exposure was also linked to an increased risk of PE, although the data were contradictory. In addition, although not explicitly related to high testosterone, lowering testosterone via various interventions was associated with PE improvement. Conversely, relatively low testosterone was also associated with an increased risk of PE, especially when increasing testosterone through medical or surgical treatments helped alleviate PE in both human- and animal-based models. Finally, numerous studies showed no association between testosterone levels and PE, including in patients with normal or low testosterone, concurrent sexual pathologies (e.g., infertility and chronic prostatitis), comorbid chronic diseases, or various nutritional deficiencies or toxicities. The association between testosterone and PE remains controversial. Relatively high and low testosterone both appear to be associated with PE, although strong evidence exists that PE is not affected by testosterone levels. Thus, the physiologic mechanism behind PE is multifactorial and cannot be attributed solely to testosterone levels.
Introduction
Premature ejaculation (PE) is the most common form of male sexual dysfunction.1,2 Some sources estimate that >25% of patients presenting for treatment of sexual dysfunction have PE.3,4 PE is defined as ejaculation consistently occurring within 1 min of vaginal penetration, causing great personal distress.5,6 In patients without PE, normal intravaginal ejaculatory latency time (IELT) ranges from 5 to 20 min.7
There are four subtypes of PE (Table 1). Primary/ lifelong PE patients experience symptoms from the start of their sexual maturity, while those with secondary/ acquired PE develop the disease over the course of their life span. In terms of prevalence within the general population, primary or variable PE appears to be the most common subtype.4,11 PE may occur in sexually active men of any age. In one study, accounting for all PE subtypes, the mean age of men presenting with PE was the mid-thirties, although ages ranged from 24 to 52 years.11 Contradictory evidence exists on whether PE increases or decreases in prevalence with increasing age.4,12
PE is associated with several pathologies, including prostatitis, obesity, smoking, and the presence of multiple comorbidities.4,13 In addition, numerous hormonal (e.g., leptin, melatonin, thyroid hormone, oxytocin, and prolactin) and nutritional (e.g., folate, vitamin D, magnesium, and nickel) imbalances have been implicated in PE.14–35 Androgen levels, particularly testosterone, have also been analyzed for their role in ejaculatory physiology and PE.36,37
Currently, all medications used for PE treatment are considered off-label.38,39 Standard treatment for all subtypes includes selective serotonin reuptake inhibitors (SSRIs) (e.g., ‘‘on-demand’’ dapoxetine), topical anesthetics, and cognitive-behavioral therapy.19,40–43
However, certain SSRIs may negatively impact fertility or be too expensive, causing discontinuance.44,45 In addition, some men experience PE that is refractory to SSRIs.46 Several alternative treatments for PE have been explored with mixed results, including phenoxybenzamine, epelsiban, tadalafil, antiandrogen medications, cligosiban, and exercise.47–52 Although many treatments exist, their beneficial mechanism often proves elusive.53
A better understanding of PE’s etiologies will help improve treatment. The objective of this study was to determine the role of androgens, particularly testosterone, in PE.
*Elevated testosterone and its association with PE
*Decreased testosterone and its association with PE
*Testosterone levels are not associated with PE
*Fetal androgen exposure and its association with PE
Conclusion
Contemporary evidence for the association between testosterone and PE remains controversial. This may, in part, be due to the large patient heterogeneity and poor PE subtyping within the published literature. In addition, many studies use relative values for determining high versus low testosterone in patients with PE rather than using laboratory-based testosterone ranges. This makes it difficult to determine a specific value that would qualify as low or high testosterone when assessing risk for PE.
