Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats

Huhtaniemi, Ilpo; Pye, Stephen R.; Limer, K.L.; Thomson, Wendy; O'Neill, Terence W; Platt, Hazel; Payne, Debbie; John, Sally; Jiang, Min; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Adams, Judith E.; Ward, Kate A; Bártfai, György; Casanueva, Felipe F.; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E. J.; Pendleton, Neil; Punab, Margus; Silman, Alan J.; Wu, Frederick C. W.

doi:10.1210/jc.2008-0848

Cited by 122 publications

(155 citation statements)

References 44 publications

(56 reference statements)

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“…20 Although several interesting studies have elucidated the role of E 2 in male reproduction, data on the peripheral levels of sex steroids are lacking. Huhtaniemi et al 21 reported that increased oestrogen activity rather than decreased androgen activity is associated with longer androgen receptor CAG repeats. Furthermore, Saltiki et al 22 investigated the effect of oestrogen levels on endothelial function in males and concluded that endogenous oestrogen levels were associated with flow-mediated dilatation, independent of age and lipid levels, showing a protective effect in middle-aged male subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The measurement range (0.025-15.0 ng ml 21 or 0.087-52.0 nmol l 21 ) was defined by the limit of detection and the maximum of the master curve. The interassay coefficient of variation for total T at concentrations of 24-700 ng dl 21 (0.83-24.31 nmol l 21 ) was 7.4%-1.7%. Elecsys PreciControl Universal 1 and 2 were used for quality control; these reagents contain lyophilised control serum based on human serum in two concentration ranges.…”

Section: Laboratory Assessmentmentioning

confidence: 92%

“…Cronbach's alpha coefficient has also indicated a high internal consistency. 12,13 Scoring the IIEF domain of erectile function allowed the classification of each patient as having no (26)(27)(28)(29)(30), mild (17)(18)(19)(20)(21)(22)(23)(24)(25), moderate (11)(12)(13)(14)(15)(16) or severe (0-10) ED. At the same visits during which they were assessed for ED, all patients were also interviewed to gather their sociodemographic characteristics and relevant medical history.…”

Section: Ed Assessmentmentioning

confidence: 99%

“…Low T was rated as total testosterone measuring ,2.8 (2.8-8.8) ng ml 21 on three morning (8:00-11:00 a.m.) occasions (specimens were assayed individually, and the results were averaged).…”

Section: Definitionsmentioning

confidence: 99%

“…High E 2 was considered total E 2 .42.6 (7.6-42.6) pg ml 21 . Prolactin (4.1-20 ng ml 21 ); FSH (1.5-12.4 mIU ml 21 ); LH (1.7-8.6 mIU ml 21 ) A normal hormonal pattern was considered to be a normal level of both total testosterone and E 2 .…”

Section: Definitionsmentioning

confidence: 99%

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Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

El‐Sakka¹

2013

Asian J Androl

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Our aim was to assess the impact of the association between elevated oestradiol (E 2 ) and low testosterone (T) levels on erectile dysfunction (ED) severity. A total of 614 male patients with ED and a normal or low T level in association with normal or elevated E 2 levels were enrolled. Patients underwent routine laboratory investigations in addition to measurements of total T, total E 2 , follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. We compared the responses to the erectile function domain, Q3 (achieving erection) and Q4 (maintaining erection) of the International Index for Erectile Function (IIEF) score in patients with the following: normal T and E 2 levels; low T level; low T level and elevated E 2 level; and elevated E 2 level. Of the patients included, 449 (73.1%) had normal T and E 2 levels, 110 (17.9%) had a low T level, 36 (5.9%) had a low T level and an elevated E 2 level, and 19 (3.1%) had an elevated E 2 level. Increased ED severity was significantly associated with low T levels, elevated E 2 levels, and both a low T level and an elevated E 2 level. Additionally, the mean values of the EF-domain, Q3 and Q4 were significantly lower in patients with both a low T level and an elevated E 2 level compared to patients with any condition alone.In conclusion, a low T level had the primary effect on erectile function; however, a concomitantly elevated E 2 level had an additive impairment effect. Keywords: erectile dysfunction (ED); hypogonadism; testosterone; oestradiol INTRODUCTION A diminution in testicular function with a consequence of testosterone (T) depletion is a common occurrence in older men. 1,2 The multi-factorial mechanisms of this phenomenon, which involve the hypothalamic-pituitary-testicular axis, have been reported. 3 Several studies have demonstrated that T has substantial effects on cavernosal tissues and that T deficiency impairs the anatomic and physiological substrates of erectile capacity that could be partly reversed upon androgen replacement. 4,5 Oestradiol (E 2 ) possesses an opposing functional role of T; therefore, a decline in the T level will affect its physiological balance with E 2 in men. 6 As a consequence, a high E 2 level, which has a strong gonadotropin suppressive effect, may lead to secondary hypogonadism in the ageing male. 7 Despite the concomitant elevation of E 2 in hypogonadal men, the information available on the physiological role of E 2 in erectile function is insufficient to correlate the aetiology of erectile dysfunction (ED) to a high E 2 level. 8 The likelihood of E 2 affecting the T balance and the independent effect of E 2 on erectile function have not been well evaluated. 9 Furthermore, although the association between ED severity and the prospective decrease in testosterone has been investigated, 10 the impact of an elevated E 2 level on ED severity has not been well addressed. The current study was designed to assess the impact of an association between an elevated E 2 level and a low T level on ED severity.

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Section: Discussionmentioning

confidence: 99%

Section: Laboratory Assessmentmentioning

confidence: 92%

Section: Ed Assessmentmentioning

confidence: 99%

“…Low T was rated as total testosterone measuring ,2.8 (2.8-8.8) ng ml 21 on three morning (8:00-11:00 a.m.) occasions (specimens were assayed individually, and the results were averaged).…”

Section: Definitionsmentioning

confidence: 99%

Section: Definitionsmentioning

confidence: 99%

See 3 more Smart Citations

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

El‐Sakka¹

2013

Asian J Androl

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Gonadal Steroids

Manolagas¹,

Almeida²

2018

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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Androgen receptor CAG repeat polymorphism and hypothalamic‐pituitary‐gonadal function in Filipino young adult males

Ryan

McDade

Gettler

et al. 2016

American J Hum Biol

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Objectives Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic-pituitary-gonadal (HPG) axis also controls sperm production through the secretion of follicle-stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR-CAGn). The number of repeats in the AR-CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR-CAGn to be associated with higher T, LH, and FSH levels. Methods We examined the relationship between AR-CAGn and total plasma T, LH, and FSH, as well as 'bioavailable' morning (AM-T) and evening (PM-T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males. Results There was no relationship between AR-CAGn and total T, AM-T, or LH (P > 0.25 for all). We did observe a marginally non-significant (P = 0.066) correlation between AR-CAGn and PM-T in the predicted direction, and a negative correlation between AR-CAGn and FSH (P = 0.005). Conclusions Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR-CAGn on HPG regulation at best, the AR-CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues.

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Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats

Cited by 122 publications

References 44 publications

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Gonadal Steroids

Androgen receptor CAG repeat polymorphism and hypothalamic‐pituitary‐gonadal function in Filipino young adult males

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