Phytoestrogens & Infertility
Nature's contraceptives
Phytoestrogens can
make animals infertile, what about people?
(Read the British Food Standards Agencies Committee on Toxicity
Report Here)
From simple laboratory mice to
the unusual case of the phytoestrogen sensitive captive cheetahs,
there is ample evidence that dietary phytoestrogens cause infertility
in a variety of animals. Why would this be? Like
the other toxins in soybeans, the phytoestrogens are present
in the soybean to ensure its survival. What better way
to discourage predators than to make sure they aren't able to
reproduce?
The ability of phytoestrogens
to prevent reproduction in animals has been known about since
the 1940's when 'clover disease' resulted in a high percentage
of infertility among the flocks of Australian sheep farmers.
Since the early reports that first defined the phytoestrogen
induced disorder, there have been numerous
studies on sheep grazed on clovers. The clovers typically
contain high levels of isoflavones, which result in a range
of estrogenic effects in grazing sheep.
The soy industry will tell that
the the infertility effects of isoflavones are unique to sheep.
Well, Soy Online Service have learnt that the soy industry are
particularly good at something: telling fibs, whoppers, porkies,
call them what you like; bare-faced lies is what they are best
at. Don't just take our word for it, read it for yourself:
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- And what about the ridiculous feeding of captive
cheetahs soy protein? It seems cheetahs
are particularly sensitive to isoflavones as well.
So if you care at all about your pet feline, take
a tip from Soy Online Service and don't expose them
to cat food containing soy. Read more on Cheetahs
and Soybeans.
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- Reproductive health in
Humans and Wildlife: are adverse trends associated
with environmental chemical exposure? Do phytoestrogens
stop the stork?
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So, if animals want to produce
according to their kind they should avoid soy. It's hardly
what they'd be eating in the wild anyway is it?
But what about humans?
Some, such as Richard
Sharpe and Theo Colborn, have suggested that the trend toward
lower male fertility is due to environmental estrogens, including
the soy phytoestrogens. But is there any evidence that
phytoestrogens may
place males at risk of reduced fertility? There is
a wealth of evidence that shows that mammals exposed to estrogens
during critical periods of sexual development can suffer a drastic
reduction in fertility. There is also strong evidence
that soy phytoestrogens such as genistein
can inhibit 17-b-hydroxysteroid oxidoreductase, an enzyme
which is required for the synthesis of testosterone and the
development of the CNS-gonadal axis. There is also evidence
that the soy isoflavones genstein and daidzein are genotoxic
to human sperm. It is quite possible, therefore, that
phytoestrogens, along with other endocrine disrupting compounds
such as DDT, may contribute to the worldwide decrease in male
fertility.
Congenital abnormalities of the
male genital tract are also increasing, and once again soy phytoestrogens
may be implicated, according to a study that found a higher
incidence of birth
defects in male offspring of vegetarian, soy-consuming mothers.
If there is still some question
that phytoestrogens may affect male fertility, the case with
women is much more clear cut. In a UK feeding study involving
premenopausal women, 60g of soy protein per day (containing
45 mg total isoflavones) for 30 days resulted in significant
biological effects. These effects were a reduction in mean
mid-cycle levels of LH and FSH to 33% and 53% respectively of
the levels observed when the women were fed control diets that
did not contain soy. Some individuals responded to the isoflavones
less than others, however, in one individual LH and FSH levels
were reduced to 17% and 32% of normal levels respectively.
In this study all of the women
still ovulated but the effects of the isoflavones continued
for three months after the diet ceased. Clearly there is potential
for women who are exposed to dietary isoflavones to suffer sufficient
reduction in LH and FSH levels that they might become anovulatory.
Additionally, in vitro genistein has been shown to block
oocyte growth and disrupt follicle morphology, which raises
a host of questions exposures at various life-stages, including
the pre-natal period.
Premature puberty is also associated
with reduced fertility. Read what the American Endocrine Society
says here
http://www.emedicine.com/ped/topic1881.htm, Pseudo Puberty
by the American Endocrine Society .
Further information on Reproductive
Health can be found at
http://www.gardenoffertility.com/
Further Reading
Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic.
Chavarro JE, Toth TL, Sadio SM, Hauser R. Hum Reprod. 2008 Nov;23(11):2584-90.
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. jchavarr@hsph.harvard.edu.
These data suggest that higher intake of soy foods and
soy isoflavones is associated with lower sperm concentration. Read
the article here.
News from
Soyatech.com - A substance found in soy-based
infant formula and over-the-counter dietary supplements affects
the development of ovaries and eggs in female infant
mice, according to a study conducted by researchers at the National
Institutes of Health (NIH) and Syracuse University. Read
the article here.
Component
in Soy Products Causes Reproductive Problems in Laboratory
Mice - From NIH News (National Institutes of Health)
January 10, 2006 - Genistein, a major component of soy, was
found to disrupt the development of the ovaries in newborn
female mice that were given the product. This study adds to
a growing body of literature demonstrating the potentially
adverse consequences of genistein on the reproductive system.
Read more about this here.
Endocrine disrupters
and female reproductive health. McLachlan
JA, Simpson E, Martin M.
Department of Pharmacology,
Tulane University School of Medicine, and Environmental Endocrinology
Laboratory, Center for Bioenvironmental Research, Tulane and
Xavier Universities, New Orleans, LA 70118, USA. john.mclachlan@tulane.edu
There is growing evidence of the impact of estrogenic
contaminants in the environment. Studies have shown that male
fish in detergent-contaminated water express female characteristics,
turtles are sex-reversed by polychlorinated biphenyls (PCBs),
male frogs exposed to a common herbicide form multiple ovaries,
pseudohermaphroditic offspring are produced by polar bears,
and seals in contaminated water have an excess of uterine
fibroids. Endocrine-disrupting chemicals (those found in the
external environment that can mimic or inhibit endogenous
hormones) mostly exhibit estrogenic effects, but a few are
anti-estrogenic or anti-androgenic. Many of these compounds
are industrial contaminants, such as pesticides and plasticizers,
and others are natural phytoestrogens found in plants such
as soy and in herbal supplements. Recent work shows that human
development can also be feminized by exposure to estrogenic
chemicals. Estrogen is the key hormone in the initiation (puberty)
and the end (menopause) of reproductive life in women and
thus of considerable importance in women's health. The same
chemicals that affect wildlife may affect breast growth and
lactation, and could have a role in uterine diseases such
as fibroids and endometriosis. New studies provide a mechanism
of action for estrogenic chemicals and other endocrine disrupters
at the molecular level (called epigenetics) that may help
explain the long-term effects of endocrine disruption.
Eating
Soy Can Decrease Your Fertility
Hidden soy in fast foods have
been linked to cutting men's fertility. Read more Here
Endometrial effects of long-term
treatment with phytoestrogens: a randomized, double-blind, placebo-controlled
study.
Unfer V, Casini ML, Costabile L, Mignosa M, Gerli S, Di
Renzo GC.;
Fertil Steril. 2004 Jul;82(1):145-8.
Long-term treatment (up to 5
years) with soy phytoestrogens was associated with an increased
occurrence of endometrial hyperplasia. These findings call into
question the long-term safety of phytoestrogens with regard
to the endometrium.
Full
Abstract Here,
More Here
Neonatal exposure to
genistein induces estrogen receptor (ER)alpha expression and
multioocyte follicles in the maturing mouse ovary: evidence
for ERbeta-mediated and nonestrogenic actions.
Jefferson WN, Couse JF, Padilla-Banks E, Korach KS, Newbold
RR. Biol Reprod. 2002 Oct;67(4):1285-96.
As a functional analysis, genistein-treated
mice were superovulated and the number of oocytes was counted.
A statistically significant increase in the number of ovulated
oocytes was observed with the lowest dose, whereas a decrease
was observed with the two higher doses.
Histological evaluations on
Day 19 revealed a dose-related increase in multioocyte follicles
(MOFs) in genistein-treated mice.
These data taken together demonstrate
alterations in the ovary following neonatal exposure to genistein.
Given that human infants are exposed to high levels of genistein
in soy-based foods, this study indicates that the effects of
such exposure on the developing reproductive tract warrant further
investigation.
Full
Abstract Here
Soy supplements can decrease
normal sexual behaviour by as much as 70 per cent, a study of
female rats has shown. New
Scientist 17:45 14 November 03
Soya may be making men infertile.
Read an article by James Chapman published in the Daily Mirror
Here.
Reproductive effects
in male and female rats of neonatal exposure to genistein.
Nagao T, Yoshimura S, Saito Y, Nakagomi M, Usumi K,
Ono H. Reprod Toxicol 2001 Jul-Aug;15(4):399-411
Body weights of male and female
rats exposed to genistein at any dose level examined were lower
than those of controls.
The number of females showing
estrous cycle irregularities was increased by genistein treatment.
The fertility of female rats exposed neonatally to genistein
at 100 mg/kg was disrupted...
Female rats exposed neonatally
to genistein at 100 mg/kg showed histopathologic changes in
the ovaries and uterus...
The results of this study indicate
that early neonatal exposure to genistein caused dysfunction
of postpubertal reproductive performance as well as abnormal
development of gonads in female but not in male rats.
Full
Abstract Here
Acute and chronic effects
of genistein, tyrphostin and lavendustin A on steroid synthesis
in luteinized human granulosa cells.
Whitehead SA, Cross JE, Burden C, Lacey M. Hum Reprod
2002 Mar;17(3):589-94
Phytoestrogens, including genistein
and other inhibitors of tyrosine kinases (TKs), inhibit specific
steroidogenic enzymes. This study was designed to compare the
effects of genistein, with two other TK inhibitors, on steroid
synthesis in human granulosa luteal (GL) cells and to identify
which steroidogenic enzymes they may affect.
Genistein directly inhibits 3
and 17beta-hydroxysteroid dehydrogenase activity, whilst tyrphostin
has an acute stimulatory effect on aromatase activity. Over
a longer time (24 and/or 48 h period), both TK inhibitors suppress
steroid synthesis.
Full
Abstract Here
The effect of phytoestrogens
on the female genital tract.
Burton JL, Wells M. J Clin Pathol 2002 Jun;55(6):401-7
This review will discuss the
evidence from both animal studies and humans for an effect of
these ubiquitous compounds on the development of the human female
genital tract, in addition to prolonging the menstrual cycle,
alleviating symptoms of the menopause, and protecting against
the development of endometrial carcinoma.
Full
Abstract Here
Infant feeding with soy
formula milk: effects on the testis and on blood testosterone
levels in marmoset monkeys during the period of neonatal testicular
activity.
Sharpe RM, Martin B, Morris K, Greig I, McKinnell C,
McNeilly AS, Walker M. Hum Reprod 2002 Jul;17(7):1692-703.
SMA-fed males had mean testosterone
levels of 2.8-3.1 ng/ml, typical of the 'neonatal testosterone
rise', whereas SFM-fed males exhibited consistently lower mean
levels (1.2-2.6 ng/ml); paired comparison in SMA-and SFM-fed
co-twins at day 35-45 revealed 53-70% lower levels in 11 of
13 co-twins fed with SFM (P = 0.004).
Further evidence for suppression
of testosterone levels in SFM-fed males came from comparison
of the frequency of low testosterone levels (<0.5 ng/ml).
In historical controls aged 35-45 days, two out of 22 values
were <0.5 ng/ml, a similar frequency as found in control
SMA-fed males (one out of 15 values <0.5 ng/ml). In contrast,
12 out of 15 values for SFM-fed males were <0.5 ng/ml (P
< 0.001).
Based on the average isoflavone
content of the SFM brand used, intake of isoflavones was estimated
at 1.6-3.5 mg/kg/day in the SFM-fed marmosets which is 40-87%
of that reported in 4 month human infants fed on a 100% SFM
diet. It is therefore considered likely that similar, or larger,
effects to those shown here in marmosets may occur in human
male infants fed with SFM. Whether the changes described result
in longer-term effects is under investigation.
Full
Abstract Here
Effects of the dietary
phytoestrogens daidzein and genistein on the incidence of vulvar
carcinomas in 129/J mice.
Thigpen JE, Locklear J, Haseman JK, Saunders H, Grant MF, Forsythe
DB.
Cancer Detect Prev 2001;25(6):527-32
Within one month, the incidence
of vulvar carcinomas in mice fed the AIN-76A modified soy protein
diet was significantly (P < .05) increased over those of
mice fed the AIN-76A modified casein diet, the #5K96, or the
# 5058 diet. At three months, the incidence of vulvar carcinomas
in mice fed the soy protein diet was significantly (P < .05)
increased over those of mice fed the NIH-31 diet or the PMI
#5K96 diet.
We concluded that dietary
levels of daidzein and genistein were associated with an increase
in the incidence of vulvar carcinomas in mice
Soy isoflavone supplements
antagonize reproductive behavior and estrogen receptor alpha-
and beta-dependent gene expression in the brain.
Patisaul HB, Dindo M, Whitten PL, Young LJ. Endocrinology
2001 Jul;142(7):2946-52
Supplement treatment also resulted
in a significant decrease in receptive behavior in estrogen-
and progesterone-primed females. The observed disruption of
sexual receptivity by the isoflavone supplement is probably
due to antiestrogenic effects observed in the brain.
Full
Abstract Here
Neurobehavioral actions
of coumestrol and related isoflavonoids in rodents.
Whitten PL, Patisaul HB, Young LJ. Neurotoxicol Teratol
2002 Jan-Feb;24(1):47-54
Treatment of rat dams with a
100-ppm coumestrol diet from birth to postnatal day (PND) 21
induced premature anovulation in female offspring, and treatment
from birth to PND 10 suppressed sexual behavior in male offspring.
Full
Abstract Here
Cross-species and interassay
comparisons of phytoestrogen action.
Whitten PL, Patisaul HB. Environ Health Perspect 2001
Mar;109 Suppl 1:5-20
In vivo data show that phytoestrogens
have a wide range of biologic effects at doses and plasma concentrations
seen with normal human diets. Significant in vivoresponses have
been observed in animal and human tests for bone, breast, ovary,
pituitary, vasculature, prostate, and serum lipids. The doses
reported to be biologically active in humans (0.4--10 mg/kg
body weight/day) are lower than the doses generally reported
to be active in rodents (10--100 mg/kg body weight/day), although
some studies have reported rodent responses at lower doses.
Full
Abstract Here
Combined effects of dietary
phytoestrogen and synthetic endocrine-active compound on reproductive
development in Sprague-Dawley rats: genistein and methoxychlor.
You L, Casanova M, Bartolucci EJ, Fryczynski MW, Dorman
DC, Everitt JI, Gaido KW, Ross SM, Heck Hd H. Toxicol Sci 2002
Mar;66(1):91-104
An acceleration of vaginal opening
(VO) in the exposed female offspring was the only observed effect
of genistein at 300 ppm. Exposure to 800 ppm genistein or 800
ppm methoxychlor caused accelerated VO and also altered estrous
cyclicity toward persistent estrus in the female offspring.
The estrogenic responses to genistein and methoxychlor administered
together were apparently accumulative of the effects associated
with each compound alone.
Data from this study indicate
that phytoestrogens are capable of altering the toxicological
behaviors of other EACs, and the interactions of these compounds
may involve complexities that are difficult to predict based
on their in vitro steroid receptor reactivities.
Full
Abstract Here
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