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To review the contemporary knowledge regarding the dehydroepiandrosterone and erectile function. Medline was reviewed for English-language journal articles spanning the time between January 1990 and December 2017, using the terms 'erectile function', 'dehydroepiandrosterone'. We used Journal Articles and review articles that found to be relevant to the purpose of this review. Criteria included all pertinent review articles, randomized controlled trials with tight methodological design, cohort studies and retrospective analyses. We also manually revised references from selected articles. Several interesting studies have addressed the age-related decline in dehydroepiandrosterone levels with many age-related phenomena or deterioration in various physiological functions. Particularly, aging; neurological functions including decreased well-being, cognition, and memory; increased depression, decreased bone mineral density, obesity, diabetes, increased cardiovascular morbidity, erectile dysfunction (ED), and decreased libido. Supporting this result, some trials of dehydroepiandrosterone supplementation in healthy, middle-aged, and elderly subjects have reported improvements in different aspects of well-being. Several studies had demonstrated that dehydroepiandrosterone level is declined as a part of aging. Large-scale well-designed prospective studies are warranted to better define indications and therapeutic implications of dehydroepiandrosterone in men with ED.
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INTRODUCTION
Dehydroepiandrosterone (DHEA) is a steroid prohor-
mone. By the age of 70 to 80 years, levels may be as low
as 10% to 20% of those encountered in young individu-
als [1,2]. The mechanism underlying this physiological
decline is unknown. However, this age-related decline
in DHEA levels may correlate with many age-related
phenomena or deterioration in various physiological
functions. Particularly, aging; neurological functions
including decreased well-being, cognition, and memory;
increased depression; aggressiveness; and dementia
have involved changes in body composition, decreased
bone mineral density, obesity, diabetes, increased car-
diovascular morbidity, erectile dysfunction (ED), and
decreased libido [3,4]. Supporting this result, some trials
of DHEA supplementation in healthy, middle-aged, and
elderly subjects have reported improvements in differ-
ent aspects of well-being [5].
Consistently, in our previous study we have dem-
onstrated age-related decline in testosterone level
throughout 4 years of follow-up in patients with ED.
Patients with decreasing testosterone levels were
older than patients with a steady testosterone level [6].
Received: Jan 16, 2018 Revised: Feb 24, 2018 Accepted: Feb 26, 2018 Published online May 11, 2018
Correspondence to: Ahmed I. El-Sakka https://orcid.org/0000-0001-8671-5952
Department of Urology, Faculty of Medicine, Suez Canal University, Round Road, 41111, Ismailia, Egypt.
Tel: +20-122-3456364, Fax: +20-64-3200035, E-mail: aielsakka@yahoo.com
Copyright © 2018 Korean Society for Sexual Medicine and Andrology
Review Article
pISSN: 2287-4208 / eISSN: 2287-4690
World J Mens Health Published online May 11, 2018
https://doi.org/10.5534/wjmh.180005
Dehydroepiandrosterone and Erectile Function:
A Review
Ahmed I. El-Sakka
Department of Urology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
To review the contemporary knowledge regarding the dehydroepiandrosterone and erectile function. Medline was reviewed
for English-language journal articles spanning the time between January 1990 and December 2017, using the terms ‘erectile
function’, ‘dehydroepiandrosterone’. We used original articles and review articles that found to be relevant to the purpose of
this review. Criteria included all pertinent review articles, randomized controlled trials with tight methodological design, co-
hort studies and retrospective analyses. We also manually revised references from selected articles. Several interesting studies
have addressed the age-related decline in dehydroepiandrosterone levels with many age-related phenomena or deterioration
in various physiological functions. Particularly, aging; neurological functions including decreased well-being, cognition, and
memory; increased depression, decreased bone mineral density, obesity, diabetes, increased cardiovascular morbidity, erec-
tile dysfunction (ED), and decreased libido. Supporting this result, some trials of dehydroepiandrosterone supplementation in
healthy, middle-aged, and elderly subjects have reported improvements in different aspects of well-being. Several studies had
demonstrated that dehydroepiandrosterone level is declined as a part of aging. Large-scale well-designed prospective studies
are warranted to better define indications and therapeutic implications of dehydroepiandrosterone in men with ED.
Keywords: Androgens; Dehydroepiandrosterone; Erectile dysfunction; Testosterone
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0)
which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
https://doi.org/10.5534/wjmh.180005
2www.wjmh.org
Therefore, this steady decrease in circulating DHEA
concentrations with age might initiate the speculation
that DHEA therapy have potential benefits in several
diseases associated with aging.
Recent analyses for the association between age and
ED revealed positive effects for testosterone, DHEA,
perceived general health, emotional support, intimacy
motivation, and a negative eff ect f or interleukin-6 (IL-6)
(all p<0.05). Higher testosterone and DHEA and lower
IL-6 levels buff ered against an age-related increase
in ED [7]. Furthermore, an interesting study demon-
strated that men who work nonstandard shif ts and
have poor sleep quality are at increased risk f or hypo-
gonadal symptoms and sexual dysfunction however,
no associations between sleep quality and mean serum
testosterone, free testosterone, estrogen, DHEA, follicle
stimulating hormone, and luteinizing hormome levels
were observed [8].
BIOCHEMISTRY OF
DEHYDROEPIANDROSTERONE
DHEA is a steroid prohormone synthesized in the
zona reticularis of the adrenal cortex, the gonads, adi-
pose tissue, brain, and skin. In target tissue, DHEA
transf ormed through intracrine mechanisms to andro-
gens or estrogens. The secretion of DHEA follows a di-
urnal pattern like that of cortisol. While in women ad-
renal prod uction of DHEA and DHEA sulf ate (DHE AS)
contributes substantially to overall androgen produc-
tion, in men the adrenal contribution is very small [1,2].
Together DHEA and DHEAS are the most abundant
steroid in humans. The highest concentrations of these
steroids are observed in men in the second and third
decades of age, and gradually decrease by approxi-
mately 10% per decade [1].
DHEAS exists at approximately 250 times higher
than those of free DHEA in serum. In target tissues
such as the brain, bone, breast, and adipose, DHEAS
is converted to DHEA by the sulfatase enzyme, which
may then be f urther metabolized to androstenediol,
androstenedione, estrone, testosterone, dihydrotestos-
te r o ne, an d 17β-estradiol [9-11]. Meanwhile DHEA is a
prohormone, it is claimed to have several positive ef-
fects on age-related disorders. It would be theoretically
transformed according to local and general hormone
needs.
EFFECT OF
DEHYDROEPIANDROSTERONE
ON ENDOTHELIAL AND SMOOTH
MUSCLES FUNCTION
DHEA is involved in vascular smooth muscle relax-
ation. Furthermore, the general and sexual effects are
not due to the actions of DHEA alone but due to its
function as a precursor of multiple androgens, espe-
cially testosterone and estradiol as well [9,10].
Endothelial dysfunction contributes to the patho-
genesis of atherosclerosis and cardiovascular disease
and leads to the development of insulin resistance.
Since DHEA has its own receptors, primarily on endo-
thelial cells its administration has been shown to im-
prove flow-mediated dilation of the brachial artery, an
endothelium-dependent process; reduced plasminogen
activator inhibitor type 1, a suppressor of fibrinolysis
with a pathogenic role in coronary artery disease; and
improved insulin sensitivity [12]. The improvement of
endothelial function with DHEA was subsequently
confirmed in postmenopausal women [13]. Several in vitr o
experiments have confirmed the anti-atherosclerotic
actions of DHEA [13,14].
These data support the action of DHEA on the endo-
thelium, based on the rapidity of action on endothelial
nitric oxide synthase (eNOS) and failure to block endo-
thelial cell activation with selective estrogen or testos-
terone receptor antagonists [13,14]. The roles of DHEA
in vascular endothelial cell survival [15,16], prolifera-
tion/angiogenesis, and activation, including transcrip-
tional regulation of endothelin-1 were demonstrated
[17]. Although a convincing evidence from in vitro
studies for vasculoprotective effects of DHEA, human
clinical trials of DHEA replacement on metabolic and
vascular function have shown contradictory results.
Epidemiological data in men have demonstrated either
an inverse or no relationship between cardiovascular
mortality and circulating DHEAS levels [18,19].
A specif ic DHEA receptor was identified on bovine
aortic endothelial cells [20]. This receptor is primarily
coupled to Ga12 and Ga13 subtypes of the G protein
family which activates eNOS. Further study had dem-
onstrated the existence of a DHEA-specific receptor in
human vascular smooth muscle cells (VSMC) involving
ERK1 signaling pathways that contributes to remodel-
ing of blood vessels and initiation of atherosclerosis [21].
I n vitro study DHEA also inhibits VSMC proliferation
Ahmed I. El-Sakka: Dehydroepiandrosterone and Erectile Function
3
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through a mechanism independent of its transf orma-
tion into estrogens or androgens and shows minimal
affinity for estrogen and androgen receptors f ound in
VSMC cells, but binds specif ically to putative recep-
tors in the same cells. Although consistent with the
mechanism of action through conversion into testos-
terone and estradiol, these findings will enlighten our
interpretations of the biological actions of DHEA and
the control of sexual f unction, which involves many
vascular mechanisms.
DEHYDROEPIANDROSTERONE AND
NITRIC OXIDE PATHWAY
DHEA is shown to activate potassium channels
via soluble guanylate cyclase activation and enhance
endo thelial function through increased nitric oxide
(NO) synthesis and ultimately dilate arteries, block
hypoxia-induced vasoconstriction [14,22]. Through a
plasma membrane initiated mechanism, DHEA acutely
increase NO release from intact vascular endothelial
cells [23]. The decrease in cytosolic NOS enzyme activ-
ity and penile NOS is not af f ected by adrenalectomy
in castrated rats [24]. Adrenalectomy combined with
castration significantly reduced penile neuronatal NOS
(nNOS) content, in contrast to what was found with
castration or total ablation of androgen binding in the
penis [25], where NOS activity appeared to be inhibited
in the presence of constant NOS levels. The cause of
this reduction in penile nNOS content is unknown. It
may be related to a loss of nerve terminals or a true
NOS downregulation [26]. However, penile eNOS con-
tent remains unaffected af ter 1 week. The rat adrenal
gland contributes to the maintenance of the erectile
mechanism and may affect nNOS content in the rat
pen is [27 ].
In pulmonary artery tissue from DHEA-treated rats,
soluble guanylate cyclase, but not eNOS, levels were
increased [28]. However, in other experiments, DHEA /
DHEAS did not af f ect relaxation induced by acetylcho-
line or sodium nitroprusside, and relaxation responses
were not changed by treatment with methylene blue
[29 ]. N e v e r t h e less, in vitr o studies supporting proper in-
trinsic functions have shown that DHEA may directly
increase NO production from intact endothelial cells,
probably through G protein-dependent activation of
endothelial NO synthetase [23].
DEHYDROEPIANDROSTERONE AND
ERECTILE DYSFUNCTION
DHEA plays an important role in sexual function.
Low levels of DHEA were associated with a higher risk
for ED in men [30,31] and low sexual responsiveness
in women [32]. It has also been speculated that DHEA
plays a role in the process of erection. The Massachu-
setts Male Aging Study investigated 17 hormones, and
DHEAS was the only one inversely correlated to ED
prevalence [31]. This data was later confirmed by an-
other study, which demonstrated that DHEAS levels
were signif icantly lower in men with ED in comparison
to age-matched normal controls [33]. The same group
had demonstrated that DHEA treatment was associ-
ated with higher mean scores for each of the five do-
mains of International Index of Erectile Function (IIEF)
sc o re [34].
In a more recent study, 79 men with sexual dysfunc-
tion and androgen deficiency had received oral testos-
terone undecanoate (80 mg twice daily), DHEA (50 mg
twice daily), or placebo. There were no significant dif-
ferences in sexual performance outcomes between pla-
cebo or intervention, as assessed by IIEF, the Androgen
Deficiency in the Aging Male, Aging Male Symptom
Scale, and Global Assessment Questionnaire [35].
Lacking evidence-based data to show involvement
of DHEA in ED is obvious, however promising data
supporting the possibility of DHEA-specific receptors
availability on vascular endothelial and smooth muscle
cells allows the postulation of its possible involvement
in the vascular mechanisms of erection [21]. DHEA is
only a weak androgen by itself that does not have any
restorative effect on the erectile response in adrenal-
ectomized or castrated animals [36,37]. Furthermore,
DHEA is involved in conditions associated with aging,
immune suppression, and major diseases. In addition,
DHEA enhances the feeling of well-being, but not libi-
do in older men [36,37]. The positive effect of DHEA on
erection supports the notion that adrenal corticoids are
involved in this process. Clinical studies showed that
oral DHEA treatment increased total serum testoster-
one levels, libido, sexual activity, and sexual satisfac-
tion in postmenopausal women [38]. More recent study
reported that higher endogenous levels of testosterone
and DHEA are beneficially related to sexual health in
men and seem to ameliorate the age-related ED [39].
Furthermore, testosterone and DHEA might exert
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their positive effects on erectile f unction via their va-
sodilative and molecular properties. Additionally, lower
levels of IL-6 were associated with age-related increase
of ED, which f urther confirms the hypothesis of an as-
sociation between inflammation and ED. The levels of
several proinflammatory cytokines are also elevated in
cardiac dysf unction, and the administration of phos-
phodiesterase type 5 inhibitor such as sildenafil was
reported to cause a sustained reduction of proinflam-
matory cytokines, linking the inf luence of proinflam-
matory cytokines on vasculogenic function and ED [40].
DEHYDROEPIANDROSTERONE
AS A TREATMENT FOR ERECTILE
DYSFUNCTION
Several studies have reported decreased serum
DHEAS levels in patients with ED and denoted that
decreased secretions of DHEA and DHEAS are impor-
tant risk factors f or ED in aging men [41]. DHEA levels
reach their peak in the third decade of age in men. The
serum DHEAS levels were significantly lower in the
younger patients with ED compared with non-ED pa-
tients. Diminished DHEAS levels, especially in young
Table 1. Summary of different clinical trials that assessed DHEA in ED and other conditions
Authors Year Subjects Duration Comments
Feldman
et al [31]
1994 1,265/total 1,709 men in the MMAS
study
8 y follow-up In the MMAS, DHEA sulfate was the only hormone that
showed a negative correlation to the prevalence of
ED among 17 investigated hormones, including T and
estradiol.
Reiter et al [33] 2000 309 patients with ED and 133
healthy volunteers
- Until the age of 60 years, the mean serum level of DHEAS is
lower in patients with ED than in healthy volunteers.
Reiter et al [34] 2001 27 patients with hypertension, 24
patients with diabetes mellitus,
6 patients with neurological
disorders, and 28 patients with no
organic etiology were treated with
50 mg DHEA.
6 mo Oral DHEA-treatment may be of benefit to patients with ED
who have hypertension or to patients with ED without
organic etiology.
Morales
et al [35]
2009 86 men received: oral T (n=29) 80 mg
twice daily, DHEA (n=28) 50 mg
twice daily, or placebo (n=29)
No clinical benefit of T or DHEA supplementation in men
with hypoandrogenism and SD.
Munarriz
et al [38]
2002 Women with sexual dysfunction Androgen replacement therapy with DHEA is a safe and
effective treatment for androgen insufficiency with
female sexual dysfunction.
Nair et al [43] 2006 Placebo-controlled, randomized,
double-blind; 87 men and 57
elderly women
2 y Neither DHEA nor low-dose testosterone replacement in
elderly people has physiologically relevant beneficial
effects on body composition, physical performance,
insulin sensitivity, or quality of life.
Løvås et al [47] 2003 Thirty-nine women 9 mo No evidence of beneficial effects of DHEA on subjective
health status and sexuality in adrenal failure.
Hunt et al [48] 2000 A randomized, double blind study in
which 39 patients with Addison’s
disease
12 wk DHEA then
4-wk washout
period, then
12 wk of placebo
DHEA replacement corrects this steroid deficiency
effectively and improves some aspects of psychological
function.
Yoshida
et al [58]
2010 419 individuals; 208 males and 211
females
- DHEAS is inversely associated with sex dependent diverse
carotid atherosclerosis such as increased maximum and
mean intima-media thickness in males and decreased
common carotid arteries-blood flow volume in females.
Genazzani
et al [63]
2011 48 healthy postmenopausal women
randomized into three groups
received DHEA, daily oral estradiol
plus dihydrogesterone,
or daily oral tibolone
12 mo Daily oral DHEA therapy, hormonal replacement therapy
and tibolone all provided a significant improvement in
sexual function and in frequency of sexual intercourse in
early postmenopausal women
DHEA: dehydroepiandrosterone, ED: erectile dysfunction, MMAS: Massachusetts Male Aging Study, DHEAS: DHEA and DHEA sulfate, T: testoster-
one, SD: sexual dysfunction.
Ahmed I. El-Sakka: Dehydroepiandrosterone and Erectile Function
5
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men with ED, may either be an etiologic factor f or
ED or a negative consequence of it. However, patients
treated with DHEA had a statistically significant in-
crease in all domains of the IIEF in contrast to the
placebo group. Interestingly, the serum DHEAS levels
increased significantly after sildenafil citrate treat-
ment in the ED group (especially in patients younger
than 50 years). Also, patient age was an important f ac-
tor af fecting the sildenaf il citrate response [42].
The f irst clinical effects were reported af ter 8 weeks
of DHEA treatment and a remarkable improvement
in maintaining the erection after 16 weeks. Prostate
volume, postvoid residual, prolactin and PSA were not
significantly changed after DHEA therapy [34]. Despite
the evidence that has questioned the validity of im-
provement in sexual f unction when treatment relied
solely on DHEA administration [43], several previous
studies had demonstrated the usefulness of DHEA in
treating sexual dysfunction associated with testoster-
one or DHEA deficiency [34]. A nice explanation of
that eff ect was demonstrated as both testosterone and
DHEA are considered central neurosteroids and have
been found to modulate endothelial f unction, which ul-
timately influence libido and penile erections [44]. Sev-
eral studies on other organs support the protective role
of DHEA and DHEAS i.e ., reduction of vascular steno-
sis in heterotopic heart transplants [45]. Because there
is also some experimental evidence f or direct effects on
the brain, the possibility of a central effect of DHEA
might be evident. An interesting mechanism that could
better define the role of DHEA in sexual performance
is that administration of DHEA results in biosynthesis
of active androgens by tissue targets without represen-
tation in the peripheral circulation [10].
Although experimental studies had demonstrated
that DHEA has direct genomic and nongenomic ef-
fects on the vascular endothelium, however its clinical
effect as a facilitator of penile erections is not evident
[46]. Most of the literature had not confirmed the role
of DHEA in the field of sexual medicines [43,47]. Addi-
tionally, other studies questioned the concept of DHEA
as a neurosteroid with a central putative effect on libi-
do [48], although this hormone had been found to inf lu-
ence self-esteem and mood in younger individuals [49].
Furthermore, the evidence-based studies supporting an
anti-aging, anti-inflammatory, antiatherosclerotic ac-
tions, and antidepressant effect of DHEA supplemen-
tation are often poor [50,51] (Table 1).
DEHYDROEPIANDROSTERONE
DECLINE AND AGE-RELATED
DISORDERS
Although the underlying mechanism of organic ED
in both middle-age and older men is basically the same,
the middle-aged men’s ED is assumed to have some dif-
ference from older men’s ED [52]. The relation between
biological, psychosocial, and lifestyle factors in terms
of the age-related increase in ED seems to be best
explained by their concomitant inf luence on general
health [53]. This notion is supported by the recent re-
sults, which indicate that perceived general health, as
a proxy of general health, is associated with a buffered
age-related increase in ED [7,54].
Reduction of DHEA with aging is clinically relevant
and has been related to a variety of age-related condi-
tions [54]. A positive relationship between diminution
of DHEA levels and decline in muscle mass, muscle
strength, as well as mobility and a higher risk f or falls,
has been reported with aging [55,56]. The relationship
between DHEA levels and cardiovascular risk factors
such as dyslipidemia and hyperglycemia are inconsis-
tent [54]. Nevertheless, studies have shown that low
DHEA levels are related to a higher risk for athero-
sclerosis, heart failure, cardiovascular complications,
and overall mortality [57-59]. A meta-analysis of endog-
enous DHEA on cardiovascular disease risk indicates
the variations in metabolic effects of DHEA and sug-
gests inconsistency in the positive effects of DHEA on
cardiovascular disease [60].
The relationship between low level of DHEA and
mood disorders and depression symptoms were more
obvious in the literature [61]. Furthermore, DHEA
supplementation has shown positive effects on mood as
well as sexual f unction both f or men and f or women
[62,6 3 ].
Increased DHEA concentrations under hypoglycemic
conditions denotes stimulation of the hypothalamic-
pituitary-adrenal axis on hypoglycemic stress. There-
fore, decline of androgen may have deleterious effects
on glycemic control and ultimately therapeutic effect
in type 2 diabetes mellitus (DM).
In one of our previous studies, we have assessed the
pattern of type-2 DM-associated androgen alteration
in patients with ED. We have shown that there were
signif icant associations between low levels of total tes-
tosterone or DHEAS and poor control of DM [64]. Fur-
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thermore, in a consequent study we have demonstrated
that there were significant associations between good
control of DM, decreased fasting blood sugar, and
achievement of normal levels of testosterone at 3- and
6-month follow-up visits. However, no signif icant as-
sociations were detected between controls of DM or de-
creased fasting blood sugar and change in DHEAS and
insulin levels [65]. In addition, administration of testos-
terone to hypogonadal men improves insulin sensitiv-
ity and glucose homeostasis [66]. Earlier study reported
no significant linear correlations between total or free
testosterone with fasting plasma glucose; however,
total testosterone was negatively correlated with glyco-
sylated hemoglobin levels [67]. Among other research-
ers, we expanded the current knowledge regarding, the
percentage of patients with type 2 DM with subnormal
levels of total testosterone or DHEAS is much higher
than that observed with subnormal levels of these
androgen in patients without DM. Further study had
shown that the existence of chronic diseases subtracts
10% to 15% from the values of androgens found in men
without chronic diseases [68]. Other study had shown
also, no positive effects on erectile f unction were f ound
when conditions such as diabetes or neurological disor-
ders were present [34].
The mechanisms of androgen alteration in men with
DM have not been completely discovered. It has been
shown that androgen deficiency in type 2 DM is com-
monly associated with hypogonadotropic hypogonadism
[67]. A more recent study showed that in middle-aged
pre-diabetic men, the more severe lower urinary tract
symptoms were associated with low total testosterone
and DHEAS, while in elderly men were associated with
low free testosterone and DHEAS [69].
FUTURE THERAPEUTIC
SUPPLEMENTATION OF
DEHYDROEPIANDROSTERONE
DHEA has gained a lot of attention and media inter-
est as a dietary supplement and sold over the counter
in some countries as in the USA. In Europe, it is either
forbidden as in France or subjects to medical prescrip-
tion as in Switzerland. Since long time, alleviation of
aging consequences was a dream to obtain durable
and healthy life and to sustain a better quality of life.
DHEA is recently proposed as an antiaging medicine
and is considered as a “fountain of youth” hormone.
As DHEA is claimed to have several positive effects on
age-related disorders. It would be theoretically trans-
formed according to local and general hormone needs.
As a potential f uture therapy, DHEA supplementa-
tion in specific indications such as osteoporosis, mood
and cognitive disorders, sexual well-being and reha-
bilitation protocols, needs to be better studied in more
prospective multicenter and larger studies. We believe
that the route to achieve an ideal antiaging supple-
mentation, which should be readily available, ef f ective
and safe, is still long. Therefore, physicians prescribing
DHEA should consider and inf orm their patients of
the f act that long-term effects not only concerning ef-
ficiency, but also saf ety, remains uncertain [70].
CONCLUSIONS
Several studies had demonstrated that DHEA
level is declined as a part of aging. It is not yet clear
whether this decline should be considered as a physi-
ologic reflection of the aging process or whether active
administration of DHEA might help to prevent and
treat age-related disorders. Furthermore, large-scale
well-designed prospective studies are warranted to bet-
ter define indications and therapeutic implications of
DHEA in men with ED [71,72].
Disclosure
The authors have no potential conflicts of interest to disclose.
Author Contribution
Review conception & design: El-Sakka AI. Data acquisition:
El-Sakka AI. Data interpretation: El-Sakka AI. Draf ting of the
manuscript: El-Sakka AI. Critical revision of the manuscript: El-
Sakka AI. Approval of final manuscript: El-Sakka AI.
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... By the age of 50 to 60 years, serum DHEAS may be decreased by 70% compared with the 20-to 30-year-old peak values (The et al., 1989;Labrie et al., 1997). Previous epidemiologic, prospective studies and reviews associated the age-related decrease of DHEAS levels with higher prevalence of degenerative disorders, obesity, diabetes, sexual dysfunction, decreased bone mineral density, increased frailty and mortality from all causes in the elderly, attributing to DHEAS anti-ageing properties (Gurnell and Chatterjee, 2001;Johnson et al., 2002;Lois et al., 2014b;Mannella et al., 2018;El-Sakka, 2018;Corona et al., 2013;Zhou and Glowacki, 2018). By contrast, cortisol secretion does not decline with age or may even increase, especially in women (Laughlin and Barrett-Connor, 2000;Heaney et al., 2012;Otte et al., 2005). ...
... Growing evidence suggests that Klotho deficiency has a crucial role in the pathophysiology of age-related disorders, including diabetes, cancer, arteriosclerosis and chronic kidney disease (Kuro-o, 2019). Similarly, the ageing process involves a sharp decline of circulating DHEAS and testosterone plasma levels, which is associated with several age-related disorders and risk of mortality (Gurnell and Chatterjee, 2001;Johnson et al., 2002;Lois et al., 2014b;Mannella et al., 2018;El-Sakka, 2018;Corona et al., 2013;Zhou and Glowacki, 2018;Shores and Matsumoto, 2014;Yeap et al., 2012;Brand et al., 2010;Ding et al., 2006;Sievers et al., 2010;Bianchi, 2018;Corona et al., 2018). Our results could contribute to a better understanding of the well-known anti-ageing properties of DHEAS and testosterone, which may partly explain by an increase of S-Klotho plasma levels production via androgen receptor. ...
Article
Background: α-Klotho is a recently discovered gene that accelerates ageing when disrupted and extends lifespan when overexpressed. The age-related decline in DHEAS and testosterone secretion and the increase in cortisol are associated with a rise of frailty and mortality. Objective: To investigate the association of DHEAS, cortisol and testosterone plasma levels with S-Klotho plasma levels in healthy sedentary middle-aged adults. Methods: 73 (39 women) healthy middle-aged sedentary adults (45–65years old) were recruited for the present study. The blood samples were collected in the morning after fasting for 12h. Results: DHEAS was positively associated with S-Klotho in men (β=0.521, R⁠2=0.248, P=0.002), whereas no association was observed in women (P≥ 0.201). Testosterone was positively associated with S-Klotho in both men and women (β=0.360, R⁠2=0.099, P=0.047; β=0.431, R⁠2=0.161, P=0.010, respectively). No association was found between cortisol and S-Klotho neither in men nor in women (all P≥ 0.141). The association between DHEAS and testosterone with S-Klotho in men disappeared after adjusting by age (all P≥ 0.151). Nevertheless, the association between testosterone (β=0.397, R⁠2=0.423, P=0.011) and S-Klotho in women remained after adjusting by age. Conclusions: DHEAS and testosterone were positively associated with S-Klotho in healthy sedentary middle-aged men while only testosterone was positively associated in women.
... According to the 1994 Dietary Supplement Health Education Act, DHEA was recognized and marketed as a dietary supplement. Currently, DHEA is easily available as a nutritional supplement or an OTC drug (El-Sakka, 2018;Park et al., 2017;Rutkowski et al., 2014). The sexual effects resulted not from the actions of DHEA alone, but also its function as a precursor of multiple androgens, especially testosterone and estradiol (El-Sakka, 2018). ...
... Currently, DHEA is easily available as a nutritional supplement or an OTC drug (El-Sakka, 2018;Park et al., 2017;Rutkowski et al., 2014). The sexual effects resulted not from the actions of DHEA alone, but also its function as a precursor of multiple androgens, especially testosterone and estradiol (El-Sakka, 2018). DHEA also enhances athletic performance because of the potential doping or anabolic effect of DHEA. ...
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The Ministry of Food and Drug Safety (MFDS) has identified that numerous dietary supplements contain unapproved (hidden, undeclared, and unauthorized) ingredients that could be unsafe. The aim of this study is to summarize the presence of unapproved ingredients in dietary supplements based on the warning dataset released by the MFDS from 2010 to 2019. The warning data were extracted from the alert system on the MFDS’s website. The highest number (ratio) of products found in the dataset were marketed for sexual enhancement [770 (43.3%)], weight-loss [690 (38.8%)], muscular strengthening [243 (13.7%)], or relaxing [76 (4.3%)]. A total of 1,779 products contained one or more unapproved ingredients. The most common unauthorized compounds were icariin, sildenafil, and tadalafil for sexual enhancement, yohimbine, sibutramine, and sennoside for weight loss, and yohimbine and icariin for muscular strengthening, and melatonin and 5-hydroxytryptophan for relaxing products, respectively. Unapproved ingredients continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after warnings by regulatory authorities. The unauthorized compounds in these dietary supplements have potential adverse health effects on consumers owing to accidental misuse, overuse, interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement. Our study reviewed potential health issues concerning the main unapproved ingredients to contribute to the understanding of adulteration in dietary supplements. The result of this study can be used to elucidate adulteration trends of unapproved ingredients in dietary supplements.
... A 2013 meta-analysis of 25 randomized controlled trials studying DHEA use in over 1,300 men found that DHEA supplementation was associated with small improvements in body fat composition, but no improvements were noted in total serum testosterone, glucose or lipid profiles, bone mineral density, or mental or physical quality of life outcomes (38). Additionally, studies have shown that DHEA supplementation does not improve erectile function (39). ...
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Testosterone deficiency is defined as a total testosterone level <300 ng/dL confirmed on two early morning lab draws. Testosterone therapy has historically been offered to men with symptomatic testosterone deficiency in the form of injections, gels, or pellets. However, these treatments are invasive or have undesirable effects including the risk of drug transference. Additionally, testosterone therapy has been associated with increases in hematocrit and controversy remains regarding the risk of cardiovascular and thromboembolic events while on testosterone therapy. As such, much interest has recently been focused on alternative treatment options for testosterone deficiency in the form of orally-administered medications with more favorable side effect profiles. Lifestyle modifications and varicocelectomy have been shown to raise endogenous testosterone production. Similarly, SERMs and aromatase inhibitors (AIs) have been shown to raise testosterone levels safely and effectively. Human chorionic gonadotropin (hCG) remains the only FDA-approved non-testosterone treatment option for testosterone deficiency in men. However, this medication is expensive and requires patient-administered injections. Over the counter herbal supplements and designer steroids remain available though they are poorly studied and are associated with the potential for abuse as well as increased hepatic and cardiovascular risks. This review aims to discuss the existing treatment alternatives to traditional testosterone therapy, including efficacy, safety, and side effects of these options. The authors suggest that the SERM clomiphene citrate (CC) holds the greatest promise as a non-testosterone treatment option for testosterone deficiency.
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To investigate serum estradiol, progesterone and dehydroepiandrosterone levels on FSD in females having urinary incontinence (UI), we studied 150 females [100 having UI (50 with FSD and 50 without FSD) and 50 controls]. There were significant lower estradiol and progesterone and higher DHEA serum levels in patients than controls (P = 0.001for all). In UI patients, females having sexual disruption had significantly low levels of estradiol (p = 0.001). Low estradiol serum level represented an isolated predictive factor for sexual dysfunction in incontinent female patients (p = 0.001). A low estradiol serum level might be a possible risk factor for FSD in women having UI.
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Objectives To define the characteristics of patients with late‐onset hypogonadism based on endocrinological findings. Methods We assessed age, body mass index, laboratory/endocrinological profiles and symptom‐specific questionnaire scores of 967 men with late‐onset hypogonadism symptoms. The patients comprised four groups by testosterone and luteinizing hormone concentrations: normal group, compensated hypogonadism group, primary hypogonadism group and secondary hypogonadism group. We compared characteristics between the normal group and compensated hypogonadism group in men with normal testosterone concentration, and the primary hypogonadism group and secondary hypogonadism group in hypogonadal men after age adjustment. Results The normal group, compensated hypogonadism group, primary hypogonadism group and secondary hypogonadism group accounted for 83.6%, 3.4%, 0.8% and 12.2% of patients, respectively. Despite age adjustment, serum dehydroepiandrosterone sulfate and insulin‐like growth factor 1 concentrations were significantly lower in the compensated hypogonadism group than the normal group. Only the Aging Males' Symptoms scale mental subscore was significantly different. Serum testosterone and dehydroepiandrosterone sulfate concentrations were significantly lower in the primary hypogonadism group than the secondary hypogonadism group. Only the Aging Males' Symptoms scale sexual subscore was significantly different. Conclusions Most patients with late‐onset hypogonadism symptoms are in the normal group, with secondary hypogonadism being much more frequent than primary hypogonadism. Current symptomatic differences among these groups are minor. Classifying patients by testosterone and luteinizing hormone levels might provide useful information for follow up.
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Background: Hidradenitis suppurativa (HS) can cause considerable impact on several aspects of quality of life. Sexuality is a central aspect of quality of life. In recent years there has been an increase in the number of articles on HS and sexuality. Objectives: To synthesize the available scientific evidence on HS and sexual health. Methods: A systematic review was conducted in February 2020. The clinical databases used included Medline and Embase. All types of epidemiological articles were included; reviews, guidelines, protocols, conference abstracts and case report articles were excluded. Results: Eleven studies were included for review, representing 42729 patients with HS. The most common study design was cross-sectional with or without comparison group(s), conducted in an outpatient setting or through surveys. Prevalence of sexual dysfunction ranged between 51%-62%, and in the case of erectile dysfunction, a specific kind of sexual dysfunction affecting penile erection, it ranged from between 52%-60% of patients studied using validated questionnaires. Potential risk factors for sexual dysfunction among men and women were identified, mainly related to disease activity, symptoms and partners. Mood disorders like depression and anxiety appear to be associated with sexual dysfunction. Women were more affected by sexual distress. HS patients with sexual dysfunction had a decreased overall quality of life. With respect to treatment, surgery did not improve sexual function and there is no scientific evidence regarding medical treatments. Patients stated that they would like to treat their sexual problems with healthcare professionals. Conclusions: Sexual and erectile dysfunction are common in HS patients, and negatively affect their quality of life. There are clinical factors potentially associated with this which should be identified and treated by dermatologists in the comprehensive care of HS patients. Prospective studies are needed to provide more scientific evidence on this unmet need.
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Background: Hidradenitis suppurativa (HS) has a high impact on quality of life. However, sexual health has scarcely been investigated. Objective: To describe the frequency of sexual dysfunction (SD) in women and erectile dysfunction (ED) in men with HS and to explore potential risk factors. Patients and methods: We conducted a cross-sectional study using a crowd-sourced online questionnaire spread by the Spanish hidradenitis suppurativa patients' association (ASENDHI). Results: In total, 393 participants answered the questionnaire. SD was found in 51% (95% CI 45-57%) of women and ED in 60% (95% CI 49-70%) of men. Factors related to SD were education status, patient's global assessment for disease activity, numeric rating scale for pain and unpleasant odour and the absence of a stable relationship. Factors related to ED were increasing age, the presence of active lesions in the genital area and the number of areas affected by active lesions. Conclusions: There is a high prevalence of SD and ED in HS patients. Being in a stable relationship has been a protective factor of SD in women. The results suggest that sexual impairment in HS patients is due, at least in part, to disease activity, symptoms and active lesions.
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Sexual health severely decreases with age. For males older than 40 years, erectile dysfunction (ED) is the most common sexual disorder. Although physical and psychological risk factors for ED have been identified, protective factors are yet to be determined. To date, no study has examined endocrine and psychosocial factors in parallel with regard to their modifying effect on the age-related increase in ED. Two hundred and seventy-one self-reporting healthy men aged between 40 and 75 years provided both psychometric data on sexual function and a set of potential psychosocial protective factors, and saliva samples for the analysis of steroid hormones and proinflammatory cytokines. Around 35% of the participants reported at least a mild form of ED. Direct associations with ED were identified for perceived general health, emotional support, relationship quality, intimacy motivation but not for steroid hormones or proinflammatory markers. Moderation analyses for the association between age and ED revealed positive effects for testosterone (T), dehydroepiandrosterone (DHEA), perceived general health, emotional support, intimacy motivation, and a negative effect for interleukin-6 (all p < .05; f² > .17). Group differences between older men with and without ED emerged for T, DHEA, and psychometric measures such as perceived general health, emotional support, satisfaction with life, and intimacy motivation (all p < .05; d > .3). Both psychosocial and endocrine parameters moderated the association between age and sexual health. Perceived general health, emotional support, intimacy motivation, and relationship quality emerged as psychosocial protective factors against ED. Higher T and DHEA and lower interleukin-6 levels also buffered against an age-related increase in ED.
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Objectives: Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) are common in diabetic men. The aim of this study was to investigate hormonal determinants, the prevalence and severity of ED and LUTS in middle-aged and elderly men with prediabetes (PD). Methods: We investigated 176 men with PD and 184 healthy peers. PD was defined according American Diabetes Association. ED according IIEF scale and LUTS according IPSS scale were assessed. Total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor 1 (IGF-1) were measured. Results: The prevalence of ED in patients with PD was higher than in control group (30 versus 24%) as well as the prevalence and severity of ED and LUTS in elderly (60-80 years) and middle-aged (40-59 years) men with PD was higher than in healthy peers. In middle-aged pre-diabetic men, the more severe LUTS symptoms were associated with low TT and DHEAS, while in elderly men with low cFT and DHEAS. The higher prevalence of ED in middle-aged men with PD was associated with cFT and DHEAS, while in elderly pre-diabetic men with TT and IGF-1. Conclusions: The prevalence and severity of LUTS and ED symptoms were higher in pre-diabetic men than in healthy peers. Hormonal determinants of these symptoms are different in middle-aged and elderly patients with PD.
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Full-text available
Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA) in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders, cardiovascular health and sexual activity. We also provide information on the efficiency and safety of hormone replacement protocols in aging patients. Finally, we argue on future perspectives of such protocols as part of everyday practice.
Article
Objectives: To investigate the impact of sleep quality in hypogonadal symptoms and sexual function in men working non-standard shifts. Methods: Men treated at a single andrology clinic between July-October 2014 completed questionnaires assessing sleep quality, hypogonadal symptoms (Androgen Deficiency in the Aging Male - ADAM/qADAM), and sexual function (International Index of Erectile Function - IIEF). Serum hormone levels were assessed at the time of survey completion. Results: 182 men were identified as working non-standard shifts (work that starts before 7am or after 2pm, rotates, or regularly includes hours outside of the standard 7am to 6pm work day) with a mean±SD age of 41.1±10.8 years. Of men working non-standard shifts, those with better sleep quality had fewer hypogonadal symptoms and better sexual function. Multivariate regression analysis revealed significant linear associations between sleep quality and qADAM score (p=0.008), positive ADAM responses (p=0.003), and IIEF score (p=0.0004) were observed. When comparing individual groups, men who were "very satisfied" (n=60) with sleep quality had higher qADAM scores than men who were "somewhat dissatisfied" (p=0.02), and men who were "very dissatisfied" had significantly lower IIEF scores than men who were "very satisfied" (p=0.001) and "somewhat satisfied" (p=0.005). No associations between sleep quality and mean serum testosterone (T), free T, estrogen, DHEA, FSH, and LH levels were observed. Conclusions: Men who work non-standard shifts and have poor sleep quality are at increased risk for hypogonadal symptoms and sexual dysfunction.
Chapter
Current demographic statistics show that modern societies are rapidly aging. Aging in general is accompanied by an increased susceptibility to physical and mental disease as well as an increased risk of mortality. Health care costs are expected to rise enormously. Therefore, successful aging with less disease burden and dependency is emerging as one of the most crucial health care goals of the upcoming decades. Over the last 20 years, research on successful aging in men has increasingly focused on age-related hormonal changes. A gradual reduction in testosterone and dehydroepiandrosterone beginning around the age of 40 has been well documented. At the same age, other steroid hormones including estradiol and cortisol also show an age-dependent progressive change. These changing patterns of steroid hormone secretion play an essential role for general health and psychological well-being in males over 40. In the following chapter, we will discuss the underlying biological mechanisms of age-related hormonal alterations and elucidate their influence in the context of psychological, sexual, cognitive and physical areas of life in aging men. Considering these widespread consequences due to age-related hormonal changes, we will also discuss the clinical implications for men facing these conditions. Apparent good health or specific lifestyle factors were shown to slow down age-related hormonal changes. Since clinical conditions cannot be prevented for every male by maintaining good health or establishing a healthier lifestyle, hormone replacement represents a reasonable opportunity to overcome certain psychological, sexual, cognitive and physical impairments caused by age-related steroid alterations. Besides individual psychological support for the successful management of severe symptoms of age-related hormonal changes, targeted psychoeducation at a population-based level would, in the long term, be one possibility to inform men about their options and to support them in countering these largely neglected disorders.
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