Differences
in reproductive endocrinology between Asian men and Caucasian mena literature
review
M.E.
van Houten, Louis J.G. Gooren
Andrology
Unit of the Department of Endocrinology, Hospital of the Vrije Universiteit,
Amsterdam, the Netherlands
Asian
J Androl 2000
Mar;
2: 13-20
Keywords:
ethnology;
Asian men; Caucasian men; prostatic neoplasms; endocrinology; male contraceptive
agents; androgen
Abstract
This
review provides an overview of the literature on aspects of reproductive
endocrinology wherein Asian men may differ from Caucasian, notably, prostatic
nioplasm and
the sensivity to pharmacological regimens of male contraception. Both genetic
and environmental factors, such as nutrition, might be relevant. Asian men
residing in Asia seem to be relatively protected from clinical prostatic
nioplasm while the prevalence of preclinical prostatic nioplasm is not different.
Migration to an area with a higher prevalence reduces this difference but
does not undo it. With regard to prostatic nioplasm the following factors
have been considered as relevant
in Asian men: 1) a reduction in 5-reductase
level, 2) decreased
levels of androgenic
ketosteroid precursors of 5-reduced
androgen metabolites,
3) the decreased presence of a P53 mutation, 4) a higher CAG-repeat length
of the androgen receptor, 5) a possible higher level of physical activity,
6) differences in sexual activity. Furthermore, Asian men respond to a higher
degree with azoospermia in
response to contraceptive steroids. Possible explanations offered for the
more pronounced response to contraceptive steroids are: 1) differences in
testicular structure and decreased spermatogenic potential, 2) an earlier
and more marked suppression in LH secretion by exogenous androgens. The
differences may be due to genetical and/or environmental factors influencing the
peripheral testosterone metabolism. Dietary factors such as the higher intake
of phytoestrogens
in Asians might exert effects on 5-reductase
activity
and/or on sex hormone binding globulin (SHBG) levels, thus having an impact
on the biological efficay of circulating androgens.
1
Introduction
In
the biomedical sciences it is widely assumed that (patho)physiological
mechanisms reliably
established in a certain group of subjects, carry a general validity
for other subjects, regardless of their ethnic background. In its generality
this is a workable principle. Though Asian men are
identical to Caucasian men in most aspects of reproductive
endocrinology, certain research findings over the last twenty
to thirty years invite the idea that there are some features
that distinguish them from Caucasians. For instance, Asian
men, with the same
dosages of contraceptive drugs, have a higher percentage of azoospermia
than Caucasian men[1-3]. Another finding has been that Asian
men residing in Asia are relatively protected from
the clinical manifestations of prostatic carcinoma
while the occurence of preclinical carcinomas is not different from that of
Caucasians. Migration to an area with a more Western lifestyle narrows
this difference but does not neutralize it[4-6].
The latter might imply that certain differences
found between Asian and Caucasian men might not be based on ethnicity
per se but on environmental factors such as nutrition, for instance,
with differences in intake of phytoestrogens.
This
review attempts to provide an overview of the literature addressing aspects
of reproductive endocrinology with a certain specificity for Asian men.
2
Clinical findings
2.1
Prostatic cancer
Prostate
cancer is the most common malignancy in men, and one of the most common
causes of death from cancer. The incidence rate of clinical prostatic
neoplasm varies
substantially among countries throughout the world[7]. There
is a considerable
evidence for a racial variation in morbidity and mortality from prostatic neoplasm.
African-American men have the highest rate of prostatic nioplasm in
the world, whereas Japanese and Chinese men native to those
countries have the lowest; there
is a 30-50 fold difference in risk between these groups[8,9].
Clinical prostatic neoplasm appears
not to be a different disease in Japan and the United States,
but the probability of progression from histological to clinical prostatic
neoplasm has
been found to be much lower in Japanese than in American men[10].
Furthermore, when Asian men migrate to a Western
country, the prevalence of prostatic neoplasm increases but
still remains low, even in their second and third generations after migration[11].
So, some environmental factors may delay tumour progression, while
others promote it[7]. Possible explanations offered
for the the difference in prevalance of prostatic
neoplasm between Asian men and Caucasian men include genetic factors,
environmental factors and differences in peripheral androgen metabolism.
Genetic factors that could play an important role are the p53 tumor suppressor
gene (a p53 mutation associated with progression of latent prostatic neoplasm);
this was found to be more rare in Japanese men than in Caucasian
men [12,13]. Another genetic factor might be the
CAG repeat length of the androgen receptor (variations in these
repeats are associated with polymorphism of the androgen receptor,
and thus may be associated with growth regulation of prostatic cells).
Difference in CAG repeat length is reportedly associated
with a difference in risk of prostatic neoplasm[14].
Environmental factors thought to be of importance are possible
differences in levels of exercise, levels of sexual activity
and nutritional differences between various ethnic groups[15-17]
Hypothesized differences in peripheral androgen metabolism
are the diminished activity of the enzyme 5-reductase
reported in several studies in Asian men versus
Caucasian men[18,5]. This enzyme is involved in conversion
of testosterone to the
major effector hormone dihydrotestosterone. A lower level of 5-dihydrotestosterone
could theoretically slow down the progression of latent prostatic neoplasm
to clinical cancer.
2.2
Contraceptive studies
Spermatogenesis
is a complex process whereby spermatogonia (the primitive stem
cells) undergo a complex development to become mature spermatozoa[19].
Luteinizing hormone (LH) affects spermatogenesis by stimulating the Leydig
cells to secrete testosterone. FSH primarly acts on the Sertoli
cells to secrete inhibinand activin. Thus FSH together with testosterone
initiates and stimulates spermatogenesis. FSH and LH secretion is controlled
by pulsatile release of gonadotropin-releasing
hormone (GnRH) from the hypothalamus. Lately, male contraception has been
an important research topic. Azoospermia and
oligozoospermia could be reached in the majority of men with a combination
of GnRH antagonists and replacement doses of testosterone[19].
Steroid hormones suppress gonadotropin output[20] and secondarily
suppress testicular functions including the production of spermatozoa. Multiple
trials have shown the efficacy of testosterone enanthate administration
in suppressing spermatogenesis[3,21,22]. Recent clinical trials,
to determine the efficacy of different male contraceptive regimens, disclosed
ethnic differences in response to contraceptive steroids[1].
Testosterone-induced
suppression of spermatogenesis to azoospermia occurred in about
90% of Asian subjects, but only in 60-70% of Caucasian subjects[2,3].
It is unclear whether
ethnigenetic differences in steroid metabolism, or gonadotropin susceptibility
to suppression by the androgen on quantitative aspects of spermatogenesis,
are accountable for the differences seen between Caucasian and Asian populations[19].
3
Differences in reproductive physiology
3.1
Hypothalamus-pituitary-testis axis
To
explain the observed differences in male contraceptive efficacy between
Asian men and Caucasian men, a clinical study tested whether there
are ethnic differences in the sensitivity of gonadotropin secretion
to suppression by testosterone[2]. In the human
male, the major circulating serum androgen is testosterone.
More than 95% testosterone is from testicular origin. Testicular
testosterone secretion is controlled by pituitary LH secretion,
which stimulates Leydig cell steroidogenesis. Testosterone
exerts a negative feedback action through inhibition
of hypothalamic GnRH and also pituitary gonadotropin. In this study ramped
increases in infused testosterone doses were monitored in normal Asian
and Caucasian men living in the United States. Compared to
Caucasian men, Asian men responded earlier and with more marked
suppression of pulsatile LH secretion to ramped testosterone
infusions. But, with increasing testosterone doses no differences
in suppression were observed. In contrast to pulsatile LH secretion, the
responsiveness of pulsatile FSH secretion to exogenous testosterone
infusion was not significantly
different between the two ethnic groups. Still the regularity of FSH
release in the Asian subjects, compared to Caucasians, seemed to be reduced.
At baseline, the mean serum FSH concentration was lower in the Caucasian
versus the Asian men. This may suggest a possible decrease
in spermatogenic reserve and/or gonadal negative feedback action
in Asian men. This is in agreement with other studies[23,24]
that conclude the presence of smaller testes in Asian men. One
study reported the presence of smaller testes coupled with reduced Sertoli
cell number and function and reduced daily sperm production
in Asian men[24].
Possible
explanations for these observed differences in Asian men versus
Caucasian men may be due to differences in peripheral androgen
metabolism, spermatogenetic potential, genetic differences
and environmental factors.
3.2
Peripheral Androgen Metabolism
Testosterone
has to enter the prostatic from the circulation to exert its effects.
Only 4 % of testosterone is unbound to sex hormone binding protein (SHBG)
and albumin and is able to enter the prostatic cell through
diffusion. Over 95% of testosterone that enters the prostatic cell
is converted to 5-dihydrotestosterone DHT. DHT is considered
to be the major effector hormone in certain androgen dependent
tissues, particularly the
pilosebaceous unit of the skin and prostatic gland. In these tissues DHT
is formed from
testosterone via the enzyme 5-reductase. In the human there
are two isozymes of 5-reductase, type I and II. Type I is
expressed mainly in the skin and hair tissues, and
type II in the prostatic gland. After conversion of testosterone
to DHT, DHT binds to androgen receptors to control the growth of facial
and body hair and the development of the prostatic gland[18].
One
potential explanation for the observed reduction in cancer risk and
the observed difference in response to exogenous testosterone
administration in contraceptive studies in Asian men, might
be a lower activity of 5-reductase in Asian men.
DHT is important for the prostatic and its size[25] and DHT
and other 5-reduced androgen metabolites play an important
role in the regulation of spermatogenesis under
conditions of intratesticular testosterone deficiency[3].
Several studies have addressed the possible differences in
the activity of 5-reductase between Asian and
Caucasian men. Some studies have found that Chinese men may have less
5-reductase activity than Caucasian men[5,18]. This conclusion
was based on the
lower amount of 5-reduced androgen metabolites found in Asian
men versus Caucasian men, such as 3,17-androstanediol and
androsteronglucuronide. These metabolites were assumed
to reflect the rate of tissue 5-reduction of androgens[18].
In a clinical trial[3], the role of the extent of
5-reductase activity in an individual was observed
to determine whether an azoospermic or oligozoospermic response
was obtained on exogenous administration of testosterone resulting
in gonadotropin and presumably testicular steroidogeneses suppression,
regardless of his ethnic group. After exogenous testosterone
administration to a group
of Caucasian men, an increase in 5-reductase activity was
observed in men remaining oligozoospermic (non-suppressors),
but not in those becoming azoospermic (suppressors). The higher
the increase in 5-reductase activity, the less suppression
of spermatogenesis.
A
later study[26], however, demonstrated that the decreased levels
of 5-reduced androgen metabolites in Asian men was not explained
by a genetically determined low 5-reductase activity. Instead,
reduced levels of the androgenic ketosteroid precursors
of these plasma metabolites are a more likely reason. They
found a significant reduction in the production of testosterone and
plasma testosterone in Chinese residents compared to Chinese migrants
in Pennsylvania. No difference was found between
Chinese residents and Caucasians living in Pennsylvania. No
information was provided in the study regarding the amount
of years for which the Chinese migrants had already resided
in Pennsylvania. The study of Lookingbill DP
et al, 1991[18] showed no obvious difference in serum total
and free testosterone levels between Asian and Caucasian men.
Yet concentrations of the precursor
androgens, DHEA sulfate and androstenedione were significantly elevated
in the Caucasian men compared to the Chinese men.
Apart
from the effect of DHT on spermatogenesis and development of prostatic
carcinoma, DHT may also be of importance in regulating LH-secretion.
In the presence of
decreased production of DHT, one expects an increase in LH secretion.
Such an effect of DHT has been demonstrated in several studies[27,28],
but not all[29,30]. Though very high
concentrations of DHT are capable of decreasing serum
LH, DHT is, however, unlikely to play an important role in the physiological
regulation of LH[29].
Other
factors which possibly influence peripheral androgen metabolism are
dietary and/or other environmental factors. Especially the
high phytoestrogen contents of
Asian diets appears to influence peripheral androgen metabolism
(see paragraph on environmental factors)[31]. The
level of plasma sex hormone binding globulins (SHBG) could also be of
significance. The relation of SHBG levels to prostatic disease
is still unclear, but SHBG may potentially protect against
progression of latent to clinical prostatic neoplasm by
modulating free testosterone levels and therewith its androgenic action[32].
The contrary has also been suggested i.e., SHBG-binding may be required for
steroid hormones to bind to their tissue receptors[33].
Contradictory results about the levels of SHBG in Asian men
have been reported[5,26].
3.3
Genetic factors
3.3.1
Testicular structure and spermatogenic potential
The
elevated basal serum FSH concentrations in Asian men found in contraceptive
studies, may suggest an inherent relative reduction in inhibin production
by the Sertoli cells, subsequent reduced gonadal feedback of FSH release
and/or lower spermatogenic capacity in Asian versus Caucasian
men[2]. One study found mean testicular size in
Chinese men to be lower than that of Caucasian men[23].
In another study the testes from 12 Chinese men were compared
to those from 8 Hispanic men and 12 nonHispanic Caucasian
men of ages 293, 302, and 293 years, respectively[24].
Asian men were found to have smaller testes volumes, reduced Sertoli
cell number and function, reduced daily sperm production and increased
apoptotic germ cell rate, which together with elevated serum
FSH levels suggest a decreased spermatogenic potential in Asian
men in comparison to Caucasian men. Furthermore
the volume density of Leydig cell cytoplasma was highest in Asian men,
potentially a mechanism to preserve a relatively normal spermatogenesis.
In view of this, Asian men may be more susceptible to exogenous
testosterone administration and this mechanism might subject
them to a heightened negative feedback response
to administration of exogenous testosterone[24]. Possible explanations
offered for the observed difference in testicular structure, volume and
spermatogenic potential are genetic[34] or dietary
differences between Asian and Caucasian men[31].
3.3.2
p53 tumorsuppressor gene
Several
molecular techniques have attempted to discover whether mutational
profiles of oncogenes or tumor suppressor genes may provide clues to etiological
factors for the observed difference in age specific prevalence rate of
clinical prostatic neoplasm in Asian men versus Caucasian men[10,13].
Analyses of the tumor suppressor gene p53, located
on chromosome 17p, in various tissues suggested that p53 gene
mutations are more closely associated with the subset of advanced
and/or highly malignant carcinomas, including those of the prostatic[12,35].
Two studies have concluded that p53 mutations play a role in
progression of latent prostatic neoplasm in Japanese man, as
well in European and American men[13,35] The
p53 mutational spectrum (at CpG site) appears to be rare in Japanese men
than in American men.
3.3.3
CAG repeats
Androgens
play a direct role in normal and malignant growth of cells via
androgen receptor (AR) mechanisms. After binding of androgens to the AR,
the transcription of androgen-responsive genes is stimulated.
The AR is thus involved in the growth regulation
of prostatic cells[36]. A lot of research has been directed
to study possible differences at the AR receptor level, which can explain
the observed differences in prostatic neoplasm incidence between
Asian men and Caucasian men. Among known polymorphisms
regarding the AR, only one has so far been associated with
functional variation in androgen action, namely, the CAG repeat polymorphism.
The length and number of CAG repeats have been associated with
the risk of development of prostatic neoplasm; a shorter CAG
repeat length compared to longer CAG repeat length
might be associated with an increased risk of prostatic neoplasm[14,37,38].
The distribution of the number of repeats was highest in Asians compared to
African-Americans
and non-Hispanic whites thus offering a relative protection to Asian
men as compared to non-Asian men[39].
3.4
Environmental factors
3.4.1
Dietary factors
Diets
differ between Asians and Caucasians. A modern Western diet is high
in fat and protein, whereas a traditional Asian diet is low in fat and
protein but high in carbohydrates. An important part of the
Asian diet consists of soy and vegetarian foods with high amounts
of isoflavonoids, flavonoids and lignans. These are metabolized
by the gut microflora to produce phytoestrogens such as enterolactone,
daidzein and genistein[40]. Phytoestrogens are plant chemicals
that resemble steroidal oestrogens in structure or function.
Most phytoestrogens are
isoflavonoids or lignans. A wide range of biochemical actions of phytoestrogens
has been reported. These actions include their capacity to bind to oestrogen
receptors, elucidate a variety of non-receptor-mediated actions, act as
anti-oxidants, have an inhibitory action of enzymes involved in the biosynthesis
of oestradiol and other steroids, such as 17-hydroxysteroid
dehydrogenase, 5-reductase
or aromatase.
Both coumestrol and genistein appear to have higher affinity for the newly
discovered oestrogen receptor variant ER (present in the
prostatic) than for the classical oestrogen receptor (ER)[31].
Only
a few, non-clinical, studies have examined the effects of phytoestrogen
on testicular function, and results are somewhat contradictory[31].
In a study in prepubertal
mice fed with 900-3 600 mg/kg of genistein glycoside (genistin) during
six weeks, testicular weight and spermatogenesis was suppressed[41].
But an oral dose of 300-1 000 mg/kg genistein or
genistin fed to adult male rats over a period of
four weeks had no effect on the testicular weight[42]. A recent
study[43] explored the effects of an
Asian diet (fat 15%, protein 15%, carbohydrate 70%) compared
to an Western diet (fat 35%, protein 25%, carbohydrate 40%) on sperm numbers
and quality in cynomolgus monkeys. The monkeys were administered
testosterone enanthate and medroxyprogesterone for a certain
period to suppress spermatogenesis. A lower level of free testosterone
and higher LH level was found in the group of monkeys that
received a Western diet versus the group receiving an Asian diet.
When, after termination of the drug administration, spermatozoa became
detectable again it was noticed that the quality of spermatozoa
during and after treatment was better in the group which had
received the Western diet than in the group which had received
the Asian diet. Phytoestrogens may also have an important effect on 5-reductase
activity. It has been found that isoflavonoiden
and lignans inhibit 5-reductase activity[44].
Another
effect of phytoestrogens on testosterone metabolism has been noted.
Vegetarians and Asian men seem to have higher plasma levels
of SHBG and lower levels of free and total testosterone than
do men on a Western diet[40].This is in agreement
with a recent study[45] which reports that diets low on protein,
especially if consumed by elder men, may lead to elevated SHBG
levels and decreased testosterone bioactivity. Total caloric
intake, carbohydrate and fat did not have a significant influence.
An increase in SHBG levels has been reported[46] when
a diet low in fat and high in fibres is consumed plus a daily exercise
regimen is followed. These effects on SHBG might result from
the action of phytoestrogens,
which as weak oestrogens may stimulate the synthesis of sex
hormone binding globulin in
the liver[40,47]. SHBG may protect against progression of latent
to clinically
apparent prostatic neoplasm by modulating the androgen action[32].
The latter study observed a higher level of SHBG
in Chinese men living in China compared to Chinese migrants
to Australia. However, the findings are not consistent as low levels
of SHBG in Chinese residents compared to Chinese migrants have
also been found[5,26], whereas no difference
in SHBG levels was observed between Caucasian men in Pennsylvania
as compared to Asian migrants[26]. The same discrepancies have
been found on comparison of testosterone levels between Asian
and Caucasian men. One study showed no difference in serum total and free
testosterone levels between Asian and Caucasian men[18],
while another found low levels of total plasma testosterone
in Chinese residents compared to Chinese migrants[26].
Finally,
experimental studies provide evidence for the effects of phytoestrogen
on gonadotrophin secretion through the presence
of an ER-receptor in pituitary gonadotrophs. Zearolone,
a fungal oestrogen, was able to suppress LH secretion in rhesus
macaques. Genistein and zearalenone inhibited GnRH-stimulated LH release
in ovariectomized rats[31]. But these experiments were done
in female animal species.
The previously mentioned study[43] in male monkeys fed with
either an Asian
diet or a Western diet showed that the serum levels of LH were
significantly higher in animals
fed an Western diet than those fed an Asian diet. FSH levels were also
found to be higher in the group receiving the Western diet.
The high levels of FSH
found in monkeys receiving a Western diet is in contradiction with the
results reported in humans where FSH levels were found to be higher in
Asian men as compared
to Caucasian men[2]. Finally, an interesting study that investigated
the influence of ethnic differences on concentrations of lignans and isoflavonoids
in plasma and prostatic fluid[48] reports that higher concentrations
of the isoflavonoid phyto-estrogens, daidzein and equol, were
found in the plasma and prostatic fluid of men from Hong Kong
as compared to those from Britain and Portugal.
In
conclusion, isoflavonoids and lignans have many interesting properties,
and may in part be responsible for lower incidences of prostatic
neoplasm in men from Asia.
The isoflavonoiden from soya, present in high concentrations in the prostatic
fluid of Asian men, may be protective against prosate disease[48].
3.4.2
Physical exercise
Experimental
studies in animals and epidemiological studies in human populations
show some evidence for an inverse relationship between exercise and development
of cancer. Physical activity has been suggested to be protective against
the development of breast and colon cancer, and also prostatic neoplasm[15,46,49,50].
This is, however, not confirmed by other studies[51-53]. Long-term
physical activity may decrease tumor risk by its effect on
natural immunity, antioxidant defenses, improved energy balance,
hormonal changes, or by other unknown mechanisms[46,49].
Especially the influence of physical activity on levels of
hormones is interesting. A diet low in fat and high in fibre
combined with daily exercise might decrease insulin level[46].
A decreased insulin level might decrease
mitogenic activity in the prostatic. Short term exercise produces
transient elevations in serum testosterone levels in elderly men, which
is partly due to an increase in SHBG concentrations[54].This
was not confirmed in another
study[55], which showed no consistent relationship of androgens
and SHBG to physical activity. Though no study has reported
effects of different levels of physical activity in Asian men
compared to Caucasian men but it is not unreasonable to assume
that until recently levels of physical activity were higher
in Asians living in Asia than in the Western world.
3.4.3
Sexual activity
Several
investigators have studied the history of men with prostatic neoplasm to
determine if sexual behavior and/or fertility are related to the development
of prostatic neoplasm[16]. Risk factors found in epidemiological
study of prostatic neoplasm are
marriage, increased fertility, a larger number sexual partners or
just the opposite, more experience with prostitutes, STD among patients
or partner and more frequent coitus. The conclusions from these
investigations were that a highly active sex life was a risk
factor for prostatic neoplasm, partly because
of the higher risk to be exposed to STD and thus possible oncogenic factors
and partly because increased sexual activity might also be a reflection of
a higher androgenic stimulus[16]. However, prostatic neoplasm patients
reportedly have delayed sexual drive and sexual frustration[56].
On investigating sexual risk factors for prostatic
neoplasm in Japanese men living in China, marital status and level of
fertility (measured by number of siblings) were
not found to be linked to prostatic neoplasm[16].
This was not in agreement with other studies which found a higher risk
of prostatic neoplasm in
married men compared to single men[57,58]. Furthermore
the study concluded that Japanese prostatic neoplasm patients
had delayed onset of sexual activity, more frequent
sexual intercourse during their 20s and 30s, poor quality
of sexual life and less frequent episodes of STD. Marital status might
be influenced by the amount of circulating androgens acting
as a sexual stimulus as well as by social customs or culture,
and therefore different sexual lifestyles between Japanese
and Caucasians, may partly explain some of the inconsistent
findings[16]. Another study reported[59] differences
in sexual behaviour in Japanese males living in
Japan (42-94 years of age) and compared them with American
males. It was concluded that 1) Age of first sexual intercourse
in American males was seven years earlier than in Japanese males, 2) Frequency
of sexual intercourse before 40 years of age was higher, but that after
40 years was less than that of American males, 3) The age at
which sexual intercourse was no longer practised was almost
the same in the two countries. Interestingly, a connection
between the time of first sexual intercourse and eating habits
was also investigated. They concluded that the age of first
intercourse in subjects who ate green or yellow vegetables
daily was significantly later than in those who never or only
occasionaly ate these vegetables. No reliable data comparing
the sexual activity levels of Caucasian and Asian men with regard to
development of prostatic neoplasm exists till date.
4
Conclusion
This
review has attempted to provide an overview of the literature addressing
various aspects of reproductive endocrinology with
a certain specificity regarding Asian men. Asian
men residing in Asia seem to be relatively protected from clinical but
not latent manifestations of prostatic neoplasm. Migration
to an area with a higher prevalence reduces this
difference but does not undo it. Explanations offered for the
observed lower rate of clinical
prostatic neoplasm risk in Asian men are: 1) a reduction
in 5-reductase level, 2) decreased levels of androgenic ketosteroid
precursors of 5-reduced androgen metabolites, 3) the decreased
presence of a p53 mutation, 4) a higher CAG-repeat
length of the androgen receptor, 5) a possible higher
level of physical activity, 6) differences in sexual activity. Furthermore,
Asian men present azoospermia earlier in response to contraceptive steroids.
Possible explanations offered for the observed differences in response
to contraceptive steroids are: 1) differences in
testicular structure and decreased spermatogenic potential,
2) an earlier and more marked suppression in LH secretion by
exogenous androgens.
Possible
explanations for these observations may be due to differences in genetically
and/or environmentally determined levels of peripheral testosterone metabolism.
Not surprisingly, it has been difficult to disentangle the genetic factors
from environmental
factors. A potential role has been attributed to dietary factors such as
higher
intake of phytoestrogens in Asians. These might affect 5-reductase
levels and/or SHBG levels, thus having an impact on the biological efficacy
of circulating androgens. Furthermore levels of physical and sexual activity
may also be significant for the observed differences in reproductive endocrinology
between Asian and Caucasian men. References
[1]
(a) World Health Organization Task Force on Methods for the Regulation
of Male Fertility. Contraceptive efficacy of testosterone-induced
azoospermia in normal men.
Lancet 1990; 336: 955-9.
(b) World Health Organization Task Force on Methods for the Regulation
of Male Fertility.
Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia
in normal men. Fertile Steril
1996; 65: 821-9.
[2] Wang C, Berman NG, Veldhuis JD, Der T, McDonald V, Steiner B. Graded
testosterone infusions distinguish gonadotropin negative feedback
responsiveness in Asian and
white men-A clinical research center study.
J Clin Endocrinol Metab 1998; 83:
870-6.
[3] Anderson RA, Wallace AM, Wu FCW. Comparison between testosteron enathate-induced
azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5-
reductase activity in oligozoospermic men administered with supraphysiological
doses of testosteron. J Clin
Endocrinol Metab 1996; 81: 902-8.
[4] Cook LS, Goldoft M, Schwartz SM, Weiss NS. Incidence of adenocarcinoma
of the prostatic in Asian immigrants to the United States and
their descendants. J Urol
1999; 16: 152-5.
[5] Ross RK, Bernstein L, Lobo RA, Shimizu H, Stanczyk FZ, Pike MC,
et al. 5-alpha reductase activity and risk of
prostatic neoplasm among Japanese and US white and black males.
Lancet 1992; 339: 887-9.
[6] Shibata A, Whittemore AS, Imai K, Kolonel LN, Wu AH, John EM,
et al. Serum levels of prostatic specific antigen
among Japanese-American and native-Japanese men. J
Natl Cancer Inst 1997; 89: 1716-20.
[7] Ekman P, Pan Y, Li C, Dich J. Environmental and genetic factors: a
possible link with prostatic neoplasm.
Br J Uro 1997; 79 Suppl 2: 35-41.
[8] Ross RK, Coetzee GA, Reichardt J, Skinner ES, Henderson BE. Does the
racial ethnic variation in prostatic neoplasm risk have a hormonal
basis? Cancer 1995; 75:
1778-82.
[9] Muir CS, Waterhouse J, Mack T, Powell J, Whelan S, eds. Cancer incidence
in five continents. Vol V. IARC Scientific publications 1987;
no. 88 International agency for research on Cancer, Lyon.
[10] Carter HB, Piantodosi S, Isaacs JT. Clinical evidence for and implications
of the multistep development of prostatic neoplasm. J
Urol 1990; 143: 742-6.
[11] Haenszel W, Kurihara M. Studies of Japanese immigrants. I. Mortality
from cancer and other diseases among Japanese in the United
States. J Natl Cancer Inst 1968; 40: 43-68.
[12] Navone NM, Troncoso P, Pisters L, Goodrow TL, Palmer JL, Nichols
WW, et al. P53 protein accumulation and gene mutation
in the progression of human prostatic carcinoma. J
Natl Cancer Institute 1993; 85: 1657-69.
[13] Watanabe M, Ushijima T, Kakiuchi H, Shiraishi T, Yatani R, Shimazaki
J, et al. P53 gene mutations in human prostatic
neoplasms in Japan: Different mutation spectra between Japan
and western Countries. Jpn
J Cancer Res 1994; 85: 904-10.
[14] Stanford JL, Just JJ, Gibbs M, Wicklund KG, Neal CL, Blumenstein
BA, et al. Polymorphic
repeats in the androgen receptor gene; molecular markers of prostatic
neoplasm risk. Cancer Res 1997;
57: 1194-8.
[15] Oliveria JA, Christos PJ. The epidemiology of physical activity and
cancer. Ann N Y Acad Sci 1997;
833: 79-90.
[16] Oishi K, Okada K, Yoshida O, Yamabe H, Ohno Y, Hayes RB, et al.
A case control study
of prostatic neoplasm in Kyoto, Japan: sexual risk factors. Prostate
1990; 17: 269-79.
[17] Food, Nutrition and the prevention of Cancer: a global perspective
1997; 310-23.
[18] Lookingbill DP, Demers LM, Wang C, Leung A, Rittmaster RS, Santen
RJ.Clinical and biochemical parameters of androgen action in normal healthy
Caucasian versus Chinese subjects. J
Clinical Endocrinol Metab 1991; 72: 1242-8.
[19] Swerdloff RS, Wang C, Bhasin S. Developments in the control of testicular
function. Baillieres
Clin Endocrinol Metab 1992; 6: 451-83.
[20] Finkelstein JS, Whitcomb RW, O'dea LST, Longcope C, Schoenfeld DA,
Crowley W F Jr. Sex steroid control of gonadotropin secretion in
the human male. I. Effects of
testosterone administration in normal and gonadotropin-releasing hormone-deficient
men. J Clin Endocrinol metab
1991; 73: 609-20.
[21] Wallace EM, Gow SM, Wu FCW. Comparison between testosteron enanthate-induced
azoospermia and oligozoospermia in a male contraceptive study I: Plasma
Luteinizing Hormone, Follicle Stimulating Hormone, Testosteron,
Estradiol and inhibin concentrations. J Clin Endocrinol Metab 1993; 77: 290-3.
[22] Zhang G, Gu Y, Wang X, Cui Y, Bremner WJ. A clinical trial of injectable
Testosterone Undecanoate as a potential male contraceptive
in normal Chinese men. J
Clin Endocrinol Metab 1999; 84: 3642-7.
[23] Wang C, Chan SY, Leung A, Ng RP, Ng M, Tang LC, et al. Cross-sectional
study of semen parameters in a large group of normal
Chinese men. Int J Androl 1985; 8: 257-4.
[24] Johnson L, Barnard JJ, Rodriguez L, Smith EC, Swerdloff RS, Wang
H, et al. Ethnic differences
in testicular structure and spermatogenic potential may predispose
testes of Asian men to a heightened sensitivity to steroidal contraceptives. J
Androl 1998; 19: 348-57.
[25] Rittmaster RS. Finasteride. N
Engl J Med 1994; 330: 120-5.
[26] Santner SJ, Albertson B, Zhang G, Zhang GH, Santulli M, Wang C,
et al. Comparative rates of androgen production
and metabolism in Caucasian men and Chinese subjects. J
Clin Endocrinol Metab 1998; 83: 2104-9.
[27] Ando S, Polosa P, D'Agata R, Further studies on the effects of dihydrotestosterone
on gonadotrophin release induced by LH-RH in men. Clin Endocrinol 1987; 9: 557-62.
[28] Stewart-Bentley M, Odell, Horton R. The feedback control of luteinizing
hormone in normal adult men. J
Clin Endocrinol Metab 1974; 38: 545-53.
[29] Schaison G, Renoir M, Lagoguey M, Mowszowicz I. On the role of dihydrotestosterone
in regulating luteinizing hormone secretion in man. J Clin Endocrinol Metab 1980; 51: 1133-7.
[30] D'Agata R, Gulizia S, Ando S, Polosa P. Effects of dihydrotestosteron
on LH release induced by LH-RH in men. Acta
Endocrinologica 1975; 79: 1-6.
[31] Whitten PL, Naftolin F. Reproductive actions of phytoestrogens. Bailliere's
Clin Endocrinol Metab 1998; 12: 667-90.
[32] Jin B, Turner L, Zhou Z, Zhou EL, Handelsman DJ. Ethnicity and migration
as determinants of Human prostatic size. J
Clin Endocrinol Metab 1999; 84: 3613-9.
[33] Sitteri PK, Simberg NH. Changing concepts of active androgens in
blood. J Clin Endocrinol
Metab 1986; 15: 247-58.
[34] Mittwoch U. Ethnic differences in testis size: a possible link with
the cytogenetics of true hermafroditism.
Hum Reprod 1988; 3(4): 445-9.
[35] Konishi N, Hiasa Y, Hayahi I, Matsuda H, Tsuzuki T, Ming T, et
al. P53 mutations occur in clinical but not
in latent human prostatic carcinoma. Jpn
J Cancer Res 1995;
86: 57-63.
[36] Coetzee GA, Ross RK. Prostate cancer and the androgen receptor. Journal
of the National Cancer Institute 1994; 86: 872-3.
[37] Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Brufsky A, Talcott
J, et al. The CAG repeat within the androgen receptor gene and
its relationship to prostatic neoplasm. Proceedings
of the National Academy of Sciences of the USA 1997; 94: 3320-3.
[38] Irvine RA, Yu MC, Ross RK, Coetzee GA. The CAG and GGC microsatellites
of the androgen
receptor gene are in linkage desequilibrium in men with prostatic neoplasm. Cancer
Res 1995; 55: 1937-40.
[39] Edwards AL, Hammond HA, Jin L, Caskey T, Chakraborty R. Genetic variation
at five trimeric and tetrameric tandem repeat loci in four
human population groups.
Genomics 1992; 12: 241-53.
[40] Griffiths K, Denis L, Turkes A, Morton MS. Phytoestrogens and disease
of the prostatic gland. Bailliere's
Clin Endocrinol Metab 1998; 12: 625-47.
[41] Matrone G, Smart WGJ, Carter MW, Smart VW. Effect of genistein on
growth and development
of the male mouse. J Nutr
1955; 59: 235-41.
[42] Magee AC. Biological responses of young rats fed diets containing
genistin and genistein. J
Nutr 1963; 80: 151-6.
[43] Suhana N, Sutyarso N, Moeloek N, Soeradi O, Sukmaniah SS, Supriatna
J. The effects of feeding an Asian or Western diet on sperm
numbers, sperm quality and serum hormone levels in
cynomolgus monkeys (Macaca fascicularis) injected with testosteron
enanthate (TE) plus depot medroxyprogesterone acetate (DMPA). Int
J Androl 1999; 22: 102-12.
[44] Evans BAJ, Griffiths K, Morton MS. Inhibition of 5-reductase
and 17-hydroxysteroid dehydrogenase in genital skin fibroblasts
by dietary lignans and isoflavonoids. J
Endocrinol 1995; 147: 295-302.
[45] Longcope C, Feldman HA, Mckinlay JB, Araujo AB. Diet and sex-hormone-binding
globulin. J Clin Endocrinol
Metab 2000; 85: 293-6.
[46] Tymchuk CN, Tessler SB, Aronson WJ, Barnard RJ. Effects of diet and exercise
on insulin, sex-hormone-binding globulin, and prostatic-specific
antigen. Nutr Cancer
1998; 31: 127-131.
[47] Adlercreutz H, Höckerstedt K, Bannwarth C, Bloigu S, Hämäläinen
E, Fotsis T, et al. Effects of dietary components, including
lignans and phytoestrogens, on enterohepatic circulation and liver metabolism
of estrogens and on sex hormone binding globulin (SHBG). J
Steroid Biochemistry 1987; 27: 1135-44.
[48] Morton MS, Chan PS, Cheng C, Blacklock N, Matos-Ferreira A, Abranches-Monteiro
L, et al. Lignans and isoflavonoids in plasma and prostatic fluid
in men: samples from Portugal,
Hong Kong, and the United Kingdom. Prostate 1997; 32: 122-8.
[49] Kiningham RB. Physical activity and the primary prevention of cancer. Prim
Care 1998; 25: 516-36.
[50] Sung JF, Lin RS, Pu YS, Chen YC, Chang HC, Lai MK. Risk factors for prostatic carcinoma
in Taiwan: a case control study in a Chinese population. Cancer
1999; 86: 484-91.
[51] Giovannucci E, Leitzmann M, Spiegelman D, Rimm EB, Colditz GA, Stampfer
MJ, et al. A prospective study of physical activity and prostatic
neoplasm in male health professionals. Cancer
Res 1998; 52: 5117-2.
[52] Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR,
et al. Prostate cancer in relation to diet, physical activity,
and body size in blacks, whites
and asians in the United States and Canada.
J Natl Cancer Inst 1995; 87: 652-61.
[53] Severson RK, Nomura AMY, Grove JS, Stemmerman GN. A prospective sudy
of demographics, diet and prostatic neoplasm among men of Japanese
ancestry in Hawaii. Cancer
Res 1989; 49: 1857-60.
[54] Zmuda JM, Thompson PD, Winters SJ. Exercise increases serum testosterone
and sex-hormone binding globulin levels in older men. Metabolism
1996; 45: 935-9.
[55] Wu AH, Whittemore AS, Kolonel LN, John EM, Gallagher RP, West DW,
et al.
Serum androgens
and sex-hormone binding globulins in relation to life style factors in
older African-Americans, White and Asian men in the United states and
Canada. Cancer
Epidemiol Biomarkers Prev 1995; 4: 735-41.
[56] Rotkin ID. Studies in the epidemiology of prostatic neoplasm: expanding
sampling. Cancer Treat
Rep 1977; 61: 173-180.
[57] King H, Diamond E, Lilienfeld AM. Some epidemiological aspects of
cancer of the prostatic. J
Chron Dis 1963; 16: 117-153.
[58] Greenwald P, Damon A, Kirmass V, Polan AK. Physical and demographic features
of men before developing cancer of the prostatic. JNCI
1974; 53: 341-6.
[59] Nakagawa S, Watanabe H, Ohe H, Nakao M. Sexual behaviour in Japanese
males relating to area occupation,
smoking, drinking and eating habits. Andrologia
1990; 22: 21-8.
Correspondence
to: Professor Louis Gooren, Endo/AZVU, P.O.Box 7057, 1007 MB Amsterdam,
The Netherlands.
Tel: +31-20-444 4444 ext. 199 Fax: +31-20-444 0502
e-mail:
ljg.gooren@azvu.nl
Received
2000-02-24 Accepted 2000-02-25
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