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Hormonal therapy and genital tract cancer.
Wren B
Centre for the Management of the Menopause, Royal Hospital
for Women, Paddington, Sydney, NSW, Australia.
Curr Opin Obstet Gynecol (United States) Feb 1996, 8 (1)
p38-41
The use of hormonal replacement therapy following genital
tract cancer is often denied to women because of the fear of
increasing the risk of recurrence or new growth. The paucity
of articles written on this subject during the past decade is
an indication of the attitude of the medical profession to the
needs of women suffering from symptoms of sex hormone
deficiency. During 1994-1995 there were few articles published
on the use of hormonal therapy to treat menopausal symptoms
following genital tract cancer. Several articles, however,
reviewed the relationship between hormones and genital tract
cancer, some explored the value of antioestrogens in
controlling recurrent or secondary disease, and a few others
discussed the risk of developing uterine cancer when tamoxifen
was used to manage postmenopausal breast cancer. Some
suggestions are made that will allow women suffering from
symptoms of hormone deficiency to receive alternative regimens
of hormonal therapy. Maintaining quality of life without
reducing the potential length of life is paramount in reaching
a decision on the use of hormonal therapy following genital
tract cancer.
Health consequences of short- and long-term
postmenopausal hormone therapy.
Weiss NS
University of Washington, Seattle 98195, USA
nweiss@u.washington.edu
Clin Chem (United States) Aug 1996, 42 (8 Pt 2)
p1342-4
Some women take an estrogen preparation for as long as
several years to ease symptoms of the menopause. Such women
appear to have little or no alteration in their risk of
endometrial cancer, especially if they are also taking a
progestogen, and no alteration in their risk of breast cancer.
Similarly, the incidenc of fractures is unaffected by
relatively short-term hormone use. The risk of ischemic heart
disease also is reduced among women who currently take
estrogens (with or without a progestogen), but the influence
of duration of use on this association is uncertain.
Postmenopausal women who take estrogens for an extended period
of time (e.g., a decade or more) incur a sharply increased
risk of cancer of the endometrium. This is largely abated by
use of a progestogen for at least 10 days per month. Such
long-term estrogen use, whether accompanied by a progestogen
or not, may increase the risk of breast cancer slightly, but
this is an area of great controversy, at present unresolved.
The incidence of both myocardial infarction and fracture is
substantially reduced in long-term users of menopausal
hormones.
Current concepts in postmenopausal hormone
replacement therapy.
Mayeaux EJ Jr; Johnson C
Department of Family Medicine, Lousiana State University
Medical Center, Shreveport, USA.
J Fam Pract (United States) Jul 1996, 43 (1)
p69-75
As more women are living longer, there is an increasing
need for women to discuss hormone replacement therapy (HRT)
with their physicians. This task is complicated by areas of
scientific uncertainty and evolving data concerning the risks
and benefits of HRT. Benefits of HRT that are supported by
strong scientific evidence include relief from menopausal
symptoms such as hot flashes, prevention of osteoporosis,
cardioprotective effects, relief of urogenital atrophy, and
decreased urinary incontinence. Benefits supported by
observational evidence include improvement of emotional
lability and depression, improved sense of well-being in
patients with rheumatoid arthritis, increased dermal and total
skin thickness, improved verbal memory skills, and decreased
risk of colon cancer. Risks to consider include a possible
increase in the incidence of breast cancer and an increase in
endometrial cancer in women who have an intact uterus and do
not receive a progestin. Women in various risk groups, such as
those at risk for coronary artery disease, osteoporosis, or
breast cancer, must consider the risk-to-benefit ratio for
their own individual circumstances.
Regulation of estrogen/progestogen receptors in the
endometrium.
Casper RF
Department of Obstetrics and Gynecology University of
Toronto, Ontario, Canada.
Int J Fertil Menopausal Stud (United States) Jan-Feb 1996, 41
(1)p16-21
Patient acceptance of standard cyclic hormonal replacement
therapy (HRT) has been poor. One major cause of non-acceptance
is thought to be the resumption of menses as a result of
induced withdrawal bleeding. In order to prevent bleeding,
continuous combined estrogen and progestin HRT has been
utilized. However, most publications report irregular
breakthrough bleeding in a majority of patients receiving the
continuous HRT regimen. The cause of the irregular bleeding
remains unclear at present. It is known that the continuous
presence of progestin causes down-regulation of estrogen and
progestin receptors and endometrial atrophy. Endometrial
atrophy may result in withdrawal of stromal support for blood
vessels leading to dilatation and extravasation of blood. In
addition, progestin has been implicated in neovascularization,
possibly by stimulation of vascular endothelial growth factor
(VEGF). Finally, programmed cell death and apoptosis appear to
occur in endometrial stroma after prolonged exposure to
progesterone and may contribute to breakthrough bleeding. We
have developed a novel interrupted progestin HRT regimen in
which estrogen is given continuously, but with progestin
administered in a 3-days-on and 3-days-off schedule. The
rationale for this regimen is to prevent total receptor
down-regulation by allowing estrogen to up-regulate estrogen
and progestin receptors during the progestin-free periods.
Interrupting the progestin may also prove to be favorable in
reducing neo-angiogenesis. Clinically, we have demonstrated
low bleeding rates in menopausal women, and in premenopausal
women on long-term GnRH-agonist treatment for endometriosis or
severe PMS, in whom the interrupted regimen has been used for
addback HRT. Further basic and clinical studies, preferably in
prospective randomized trials, are required to demonstrate
reduced bleeding and improved patient acceptance compared to
continuous combined HRT.
Hormone replacement therapy and breast cancer
risk.
Gambrell RD Jr br> Department of Physiology and
Endocrinology, Medical College of Georgia, Augusta, USA.
Arch Fam Med (United States) Jun 1996, 5 (6)
p341-8
The role of estrogen therapy in the risk of breast cancer
has been a concern for both physicians and patients. There is
some evidence that women taking estrogen who develop breast
cancer have a better prognosis. During 8 to 18 years of
follow-up of 256 postmenopausal women with breast cancer from
our hospital, median survival time was 84 months for those who
never used estrogen, 80 months for past users, and 143 months
for current users. More than 50 studies have shown that there
is no increased risk of breast cancer even with long-term
estrogen use, while some studies suggest an increased risk.
Several studies indicate that when progestogens are added to
estrogen therapy, there is a significant reduction in the risk
of breast carcinoma. Indirect evidence is accumulating to show
why added progestogen should decrease the risk of breast
cancer. Preliminary studies further indicate that estrogen
therapy, which has been contraindicated in breast cancer
survivors in the past, may be safe, and added progestogens may
decrease recurrences and deaths. Some medical oncologists and
surgeons now advocate estrogen use in women with previous
carcinoma of the breast.
Hormone replacement therapy, hormone levels, and
lipoprotein cholesterol concentrations in elderly women.
Paganini-Hill A; Dworsky R; Krauss RM
Department of Preventive Medicine, University of Southern
California School of Medicine, Los Angeles 90031, USA.
Am J Obstet Gynecol (United States) Mar 1996, 174 (3)
p897-902
OBJECTIVE: Our purpose was to assess the relationships of
lipid and lipoprotein cholesterol levels to hormone
replacement therapy and hormone levels in elderly women.
STUDY DESIGN: A sample of 292 postmenopausal women 55 to 99
years old (mean 76 years) was drawn from Leisure World Laguna
Hills, California, an upper-middle-class, white
independent-living population. We compared 84 women receiving
unopposed estrogen replacement therapy and 38 women taking
combination hormone replacement therapy with 170 women who had
never used hormone replacement therapy. Nonparametric tests
for differences in lipid and lipoprotein cholesterol levels
among groups and multiple stepwise regression models were
used.
RESULTS: Estrogen users (with and without progestin) had
lower total and low-density lipoprotein cholesterol and higher
high-density lipoprotein and high-density lipoprotein
subfraction types 2, 2a, and 2b cholesterol levels. High
density lipoprotein type 3 subfractions were lower in
combination hormone replacement therapy users but higher in
unopposed estrogen users relative to nonusers. The conjugated
equine estrogen dose was negatively correlated with total (p =
0.0009) and low-density lipoprotein cholesterol (p <0.0001)
levels and positively correlated to high-density lipoprotein
cholesterol (p = 0.002) and its subfractions. The
medroxyprogesterone acetate dose showed no consistent effect
on cholesterol levels.
CONCLUSION: The associations found here reaffirm the
significant role of estrogen replacement therapy on lipid and
lipoprotein cholesterol levels and provide no evidence of a
reduction in the beneficial effect of estrogen with the
addition of a progestational agent to the replacement
regimen.
Hormone replacement therapy as treatment of breast
cancer--a phase II study of Org OD 14 (tibilone).
O'Brien M; Montes A; Powles TJ
Breast Unit, Royal Marsden Hospital, Sutton, Surrey,
UK.
Br J Cancer (England) May 1996, 73 (9) p1086-8
Org OD 14 (tibilone) is a synthetic steroid, designed to
combine the favourable effects of oestrogens, progestagens and
androgens into a single substance for use as hormone
replacement therapy (HRT). Given its antiovulatory properties,
the ability to control menopausal symptoms and blocking action
on progesterone receptors, Org OD 14 was considered as an
agent with potential anti-cancer activity while at the same
time helping existing menopausal symptoms. In this phase II
study, 14 post-menopausal women with advanced or metastatic
breast cancer, who had failed on tamoxifen, were treated with
Org OD 14. The median duration of treatment was 12 weeks and
all patients stopped because of progressive disease with or
without toxicity. Vaginal bleeding occurred in four patients,
three of whom had recently stopped tamoxifen. One response was
seen: an 82-year-old patient had a partial response in an
axillary soft tissue mass, improvement in liver function tests
and an improvement in her performance status that lasted over
6 months. One patient with progressive disease on Org OD 14
improved on stopping the drug. In view of the vaginal
bleeding, Org OD 14 should not be given to patients who have
recently stopped tamoxifen.
Postmenopausal hormone therapy and breast
cancer.
Speroff L
Department of Obstetrics and Gynecology, Oregon Health
Sciences University, Portland, USA.
Obstet Gynecol 1996 Feb;87(2 Suppl):44S-54S
Given the magnitude of the older female population, the
possibility that postmenopausal hormone therapy is associated
with an increased risk of breast cancer is an issue of great
public and individual importance. Epidemiologic evidence
indicates the possibility of a slightly increased risk of
breast cancer associated with long durations of postmenopausal
estrogen use. However, in a review of the literature, it is
apparent that the epidemiologic data are contradictory and do
not yield uniform and consistent results. It is further
apparent that adding a progestin to a postmenopausal hormone
program does not alter the findings compared with the use of
estrogen alone. Reasons for this disagreement and lack of
definitive evidence are detailed, and it is suggested that any
impact of postmenopausal hormone therapy on the risk of breast
cancer is unlikely to be great. Finally, the question of
whether a woman who has had breast cancer should use
postmenopausal hormones is addressed.
Future aspects of hormone-replacement therapy
Huber J.C.
Abt Gynakologische Endokrinologie, Sterilitatsbehandlung,
Universitatskli nik Frauenheilkunde, Wahringer Gurtel 18-20,
A-1090 Wien Austria
Acta Chirurgica Austriaca (Austria), 1996, 28/5
(282-284)
Background: The last 30 years' hormon-replacement therapy
has mostly been directed towards substituting estrogen and
progestogen.
Methods: A survey trying to demonstrate the therapeutic
significance of replacing other hormones is given.
Results: The third sexual hormone, testosterone, was
largely disregarded. As this steroid has a number of
physiologic functions to fulfill it should be made use of in
future replacement therapies. Another future aspect is to
substitute not only sexual hormones but other hormones, which
diminish with increasing age, as well. Among them are the
growth hormone, dehydroepiandrosterone, and melatonin.
Conclusions: Sexual steroids are involved in many biologic
compartments. Intensified, future, interdisciplinary
cooperation with other fields could create therapeutic
possibilities for a causative treatment of immunologic,
dermatologic and ophthalmologic diseases that have so far not
been linked with sexual steroids.
Neuroendocrine aspects of the menopause and hormone
replacement therapy
Genazzani A.R.; Stomati M.; Spinetti A.; Bertolini S.; Nappi
L.; Taponeco F.; Cela V.; D'Ambrogio G.; Hesch
Dept. of Obstetrics and Gynaecology, University of Pisa, Pisa
Italy
Journal of Cardiovascular Pharmacology (USA), 1996, 28/Suppl.
5 (S58-S60)
Hypergonadotrophic hypogonadism in postmenopausal women
induces neuroendocrine changes involving hypothalamic
functions and secretion of pituitary hormones. Specific
receptors for oestrogen, progestogen, and androgen are
localized in the central nervous system, and sex steroid
hormones exert a modulatory effect on the synthesis, release,
and metabolism of neuroactive transmitters and their
receptors. In particular, noradrenaline, dopamine, serotonin,
acetylcholine, GABA, opioid peptides, neuropeptide Y, galanin,
melatonin, and corticotrophin-releasing factor are influenced
by sex steroids. Several disturbances originate from the
withdrawal of sex steroids which, in the menopause, is
associated with vasomotor instability, anxiety, insomnia, mood
changes, migraine/headache, depression, loss of libido,
reduced motor activity, loss of memory, and Alzheimer's
disease. These represent possible clinical expressions of
neuroendocrine modifications. There is particular interest in
the higher prevalence of Alzheimer's dementia in
postmenopausal women than in men. Hormone replacement therapy
improves the cognitive performance and short- term memory of
women with Alzheimer's type dementia. In fact, oestrogens
increase the activity of acetylcholine transferase, which is
the most important enzyme in the synthesis of acetylcholine.
Therefore, the levels of acetylcholine are reduced, which is
an important sign of Alzheimer's disease. Moreover, oestrogens
improve dopaminergic tone, playing a protective role against
Parkinson's disease in postmenopausal women.
Hormone therapy and phytoestrogens
Lien L.L.; Lien E.J.
Dept. of Pharmaceutical Sciences, USC School of Pharmacy, Los
Angeles, CA 90033 USA
Journal of Clinical Pharmacy and Therapeutics (United
Kingdom), 1996, 21/2 (101-111)
As ageing progresses the levels of sex hormones decrease in
the human body. In the male population, the decrease or
absence of testosterone leads to decreased strength and
stamina, thin bones and a low sex drive
(1). In the female population, the immediate symptoms of
menopause include irregular periods, painful sexual
intercourse due to vaginal dryness, hot flushes and night
sweats
(2). Lack of oestrogen also leads to the risk of developing
osteoporosis and cardiovascular diseases. In this report, the
authors will mainly discuss the effects of hormone therapy
(HT) in menopausal women. Available current clinical data on
the effects of calcium supplementation with and without HT,
exercise, exercise plus calcium and exercise with HT on bone
loss are presented. The effects of transdermal and oral
oestrogen therapy (OT) on serum lipids are discussed.
Commercially-available HT products, their indications,
dosages, contra-indications, side-effects and drug
interactions are compared. Alternative therapies for
menopausal symptoms with Chinese traditional herbs, and a
comparison of the molecular structures of phytoestrogens with
estradiol and diethylstilbestrol are examined
(3, 4). A list of medicinal herbs and foods reported
toelicit an oestrogenic response in animals is compiled.
The effects of hormone replacement therapy on
plasma vitamin E levels in post-menopausal women
Wu J.; Norris L.A.; Wen Y.C.; Sheppard B.L.; Feely J.; Bonnar
J.
Department of Obstetrics/Gynaecology, Trinity College Centre,
St. James's Hospital, Dublin 8 Ireland
European Journal of Obstetrics Gynecology and Reproductive
Biology (Ireland), 1996, 66/2 (151-154)
Objective: To measure vitamin E levels in post-menopausal
women before and after HRT, compared with levels in
pre-menopausal women.
Design: Post-menopausal women (n = 21) had plasma vitamin E
levels measured before treatment and after 6 and 12 months
treatment with HRT (2 mg 17-beta-oestradiol and 1 mg
norethisterone acetate). The pre-menopausal group (n = 20) had
plasma vitamin E levels measured at day 15-18 of the menstrual
cycle.
Results: There was no significant difference in vitamin E
levels between the pre-menopausal group and the
post-menopausal group. Plasma vitamin E levels were not
significantly altered by 12 months HRT, Conclusion:
Post-menopausal women did not have altered levels of vitamin E
compared with pre-menopausal women. Similarly HRT has no
effect on plasma vitamin E levels. We conclude therefore that
HRT does not reduce vitamin E levels in a similar manner to
oral contraceptives and consequently post-menopausal women are
unlikely to need a vitamin E supplement.
Effects of hormonal therapies and dietary soy
phytoestrogens on vaginal cytology in surgically
postmenopausal macaques
Cline J.M.; Paschold J.C.; Anthony M.S.; Obasanjo I.O.; Adams
M.R.
Department of Comparative Medicine, Bowman Gray School of
Medicine, Medical Center Boulevard, Winston-Salem, NC
27157-1040 USA
Fertility and Sterility (USA), 1996, 65/5
(1031-1035)
Objective: To evaluate the effects of conjugated equine
estrogens, medroxyprogesterone acetate (MPA), conjugated
equine estrogens combined with MPA, tamoxifen, and soybean
estrogens on vaginal cytology in surgically postmenopausal
cynomolgus macaques (Macaca fascicularis).
Design: Randomized long-term experimental trial.
Setting: Cytologic samples were taken from animals in two
long-term randomized studies of the effects of hormonal and
dietary effects on atherosclerosis.
Patients: Surgically postmenopausal cynomolgus macaques.
Interventions: Conjugated equine estrogens, MPA, conjugated
equine estrogens combined with MPA, tamoxifen, and soybean
estrogens were given via the diet, at doses scaled from those
given to women.
Main Outcome Measure: Vaginal cytologic maturation
index.
Results: Conjugated equine estrogens elicited a marked
maturation effect, which was antagonized partially by the
addition of MPA. Tamoxifen produced a lesser estrogenic
response. The cytologic pattern in animals given soybean
estrogens or MPA alone did not differ from that of
controls.
Conclusion: Soybean estrogens at the doses given do not
exert an estrogenic effect on the vagina of macaques.
Conjugated equine estrogens are potent inducers of vaginal
keratinization in this model; tamoxifen has a lesser effect.
Medroxyprogesterone acetate partially antagonizes the effects
of conjugated equine estrogens, and has no effect when given
alone. The results support the possibility that soybean
estrogens may be a 'tissue-selective' estrogen with minimal
effects on the reproductive tract.
Dietary and behavioral determinants of
menopause
Gold E.B.
Community/International Health Dept., School of Medicine,
University of California, Davis, CA 95616 USA
Clinical Consultations in Obstetrics and Gynecology (USA),
1996, 8/1 (21-26)
1. Black and Hispanic women have been observed to
experience natural menopause at an earlier age than white
women, despite increased body mass, whereas Asian women have
been observed to have a lower frequency of hot flushes than
white women, despite lower serum estradiol levels.
2. Women who smoke have consistently been shown to
experience menopause earlier than nonsmokers and to have a
shorter perimenopause, and a dose-response relationship in
this association has been shown. Little is known about the
relationship of passive smoke exposure to age at menopause or
whether smoking increases the frequency or severity of
menopausal symptoms.
3. Although some studies show that increased body mass and
upper body fat are associated with later age at menopause,
some studies do not confirm this. Further research is needed
on the independent effects of body mass and composition on
frequency and severity of menopausal symptoms.
4. Shorter and more variable menstrual cycles in early
adulthood and increased parity and oral contraceptive use have
all been associated with later age at menopause.
5. Age at menarche, previous spontaneous abortions, age at
first birth, and history of breast- feeding have all been
shown not to be associated with age at menopause.
6. The effect of physical activity on age at menopause is
unknown, but participation in an exercise program reduced the
vasomotor symptoms associated with menopause.
7. Lower social class has been associated with earlier
menopause, but nothing is known about the relationship of
occupational exposures to age at menopause or frequency or
severity of menopausal symptoms.
8. Dietary phytoestrogens have estrogenic activity and may
compete with estradiol for binding to estrogen receptors and
affect plasma estradiol, FSH and LH levels in premenopausal
women and have been shown to reduce hot flashes in one small
study of postmenopausal women.
A review of the clinical effects of
phytoestrogens
Knight D.C.; Eden J.A.
Frank Rundle House, Royal Hospital for Women, 188 Oxford
Street, Paddington, NSW 2021 Australia
Obstetrics and Gynecology (USA), 1996, 87/5 II Suppl.
(897-904)
Objective: To review the sources, metabolism, potencies,
and clinical effects of phytoestrogens on humans.
Data Sources: The MEDLINE data base for the years 1980-1995
and reference lists of published articles were searched for
relevant English-language articles concerning phytoestrogens,
soy products, and diets with high-phytoestrogen content.
Methods of Study Selection: We identified 861 articles as
being relevant. Human cell line studies, human epidemiologic
studies (case-control or cohort), randomized trials, and
review articles were included. Animal studies regarding
phytoestrogens were included when no human data were available
concerning an important clinical area.
Tabulation, Integration, and Results: Included were studies
containing information considered pertinent to clinical
practice in the areas of growth and development, menopause,
cancer, and cardiovascular disease. When findings varied,
those presented in this study reflect consensus. All studies
concurred that phytoestrogens are biologically active in
humans or animals. These compounds inhibit the growth of
different cancer cell lines in cell culture and animal models.
Human epidemiologic evidence supports the hypothesis that
phytoestrogens inhibit cancer formation and growth in humans.
Foods containing phytoestrogens reduce cholesterol levels in
humans, and cell line, animal, and human data show benefit in
treating osteoporosis.
Conclusion: This review suggests that phytoestrogens are
among the dietary factors affording protection against cancer
and heart disease in vegetarians. With this epidemiologic and
cell line evidence, intervention studies are now an
appropriate consideration to assess the clinical effects of
phytoestrogens because of the potentially important health
benefits associated with the consumption of foods containing
these compounds.
Molecular effects of genistein on estrogen receptor
mediated pathways
Wang T.T.Y.; Sathyamoorthy N.; Phang J.M.
Lab Nutritional Molecular Regulation, NCI-Frederick Cancer
Res Dev Ctr, NIH, Frederick, MD 21702-1201 USA
Carcinogenesis (United Kingdom), 1996, 17/2
(271-275)
Genistein, a component of soy products, may play a role in
the prevention of breast and prostate cancer. However, little
is known about the molecular mechanisms involved. In the
present study, we examined the effects of genistein on the
estrogen receptor positive human breast cancer cell line
MCF-7. We observed that genistein stimulated
estrogen-responsive pS2 mRNA expression at concentrations as
low as 10-8 M and these effects can be inhibited by tamoxifen.
We also showed that genistein competed with (3H)estradiol
binding to the estrogen receptor with 50% inhibition at 5 X
10-7 M. Thus, the estrogenic effect of genistein would appear
to be a result of an interaction with the estrogen receptor.
The effect of genistein on growth of MCF-7 cells was also
examined. Genistein produced a concentration-dependent effect
on the growth of MCF-7 cells. At lower concentrations
(10-8-10-6 M) genistein stimulated growth, but at higher
concentrations (>10-5 M) genistein inhibited growth. The
effects of genistein on growth at lower concentrations
appeared to be via the estrogen receptor pathway, while the
effects at higher concentrations were independent of the
estrogen receptor. We also found that genistein, though
estrogenic, can interfere with the effects of estradiol. In
addition, prolonged exposure to genistein resulted in a
decrease in estrogen receptor mRNA level as well as a
decreased response to stimulation by estradiol.
Rationale for the use of genistein-containing soy
matrices in chemoprevention trials for breast and prostate
cancer
Barnes S.; Peterson T.G.; Coward L.
Department of Pharmacology, Birmingham Medical Center,
University of Alabama, 1670 University Boulevard, Birmingham,
AL 35294-0019 USA
J Cell Biochem Suppl 1995;22:181-7
Pharmacologists have realized that tyrosine kinase
inhibitors (TKI) have potential as anti-cancer agents, both in
prevention and therapy protocols. Nonetheless, concern about
the risk of toxicity caused by synthetic TKIs restricted their
development as chemoprevention agents. However, a naturally
occurring TKI (the isoflavone genistein) in soy was discovered
in 1987. The concentration of genistein in most soy food
materials ranges from 1-2 mg/g. Oriental populations, who have
low rates of breast and prostate cancer, consume 20-80 mg of
genistein/day, almost entirely derived from soy, whereas the
dietary intake of genistein in the US is only 1-3 mg/day.
Chronic use of genistein as a chemopreventive agent has an
advantage over synthetic TKIs because it is naturally found in
soy foods. It could be delivered either in a purified state as
a pill (to high-risk, motivated patient groups), or in the
form of soy foods or soy-containing foods. Delivery of
genistein in soy foods is more economically viable ($1.50 for
a daily dose of 50 mg) than purified material ($5/day) and
would require no prior approval by the FDA. Accordingly,
investigators at several different sites have begun or are
planning chemoprevention trials using a soy beverage product
based on SUPRO(TM), an isolated soy protein manufactured by
Protein Technologies International of St. Louis, MO. These
investigators are examining the effect of the soy beverage on
surrogate intermediate endpoint biomarkers (SIEBs) in patients
at risk for breast and colon cancer, defining potential SIEBs
in patients at risk for prostate cancer, and determining
whether the soy beverage reduces the incidence of cancer
recurrence. These studies will provide the basis for formal
Phase I, Phase II and Phase III clinical trials of genistein
and soy food products such as SUPRO(TM) for cancer
chemoprevention.
Dietary flour supplementation decreases
post-menopausal hot flushes: Effect of soy and wheat
Murkies A.L.; Lombard C.; Strauss B.J.G.; Wilcox G.; Burger
H.G.; Morton M.S.
Brighton Medical Clinic, 26 Carpenter St., Brighton, Vic.
3186 Australia
Maturitas (Ireland), 1995, 21/3 (189-195)
Plants contain compounds with oestrogen-like action called
phytoestrogens. Soy contains daidzin, a potent phytoestrogen,
and wheat flour contains less potent enterolactones. We aimed
to show in 58 postmenopausal women (age 54, range 30-70 years)
with at least 14 hot flushes per week, that their daily diet
supplemented with soy flour (n = 28) could reduce flushes
compared with wheat flour (n = 30) over 12 weeks when
randomised and double blind. Hot flushes significantly
decreased in the soy and wheat flour groups (40% and 25%
reduction, respectively <0.001 for both) with a significant
rapid response in the soy flour group in 6 weeks (P <
0.001) that continued. Menopausal symptom score decreased
significantly in both groups (P < 0.05). Urinary daidzein
excretion confirmed compliance. Vaginal cell maturation,
plasma lipids and urinary calcium remained unchanged. Serum
FSH decreased and urinary hydroxyproline increased in the
wheat flour group.
Soy and experimental cancer: Animal studies
Hawrylewicz E.J.; Zapata J.J.; Blair W.H.
Department of Research, Mercy Hospital/Medical Center,
Chicago, IL 60616 USA
Journal of Nutrition (USA) , 1995, 125/3 SUPPL.
(698S-708S)
Studies are reviewed that report consumption of soy protein
diets inhibits the growth of various tumors in rats. The
inhibitory effect has been attributed to the phytoestrogens
(genistein and diadzein) or protein kinase inhibitor in soy
protein products. Recent studies indicate that additional
factors in soy protein products may also contribute to the
inhibition of tumorigenesis, namely the deficiency of the
essential amino acid methionine. Metastatic growth to the
lungs of a primary rhabdomyosarcoma tumor was inhibited by
feeding a soy protein diet. The effect was reversed by
methionine fortification of the diet. Carcinogen-induced
mammary tumor development was inhibited during the promotional
phase in rats fed soy protein isolate diet and reversed with a
methionine-supplemented diet. Additional studies demonstrated
that after excision of the primary mammary tumor, growth of
additional tumors was inhibited when the diet was changed from
casein to soy protein isolate. Histopathologic evaluation of
the mammary tumors revealed more benign fibroadenomas and
lower-grade adenocarcinomas in the soy protein group. Before
carcinogen administration (at 7 weeks of age), ornithine
decarboxylase activity and polyamine concentrations in the rat
mammary epithelium were significantly lower in the soy protein
group. These data suggest an inhibitory effect on mammary
epithelial growth in the soy-protein-fed group.
Aromatase in bone cell: Association with
osteoporosis in postmenopausal women
Nawata H.; Tanaka S.; Tanaka S.; Takayanagi R.; Sakai Y.;
Yanase T.; Ikuyama S.; Haji M.
Third Dept. of Internal Medicine, Faculty of Medicine, Kyushu
University, Maidashi 3-1-1, Fukuoka 812 Japan
Journal of Steroid Biochemistry and Molecular Biology (United
Kingdom), 1995, 53/1-6 (165-174)
To clarify the possible action of adrenal androgen on bone
cell, the existence, characteristics and regulation of
aromatase in human osteoblast-like osteosarcoma cells (HOS)
and primary cultured osteoblast-like cells from normal human
bones (HO) were examined in this study. Significant positive
correlation between bone mineral density (BMD) and serum
dehydroepiandrosterone sulfate (DHEA-S) was found in 120
postmenopausal women (51-99 years old) but no correlation was
seen between BMD and serum estradiol (E2). In subset analysis,
strongly positive correlation of serum DHEA-S and estrone (E1)
with BMD was observed in postmenopausal women aged less than
69 years old. Administration of DHEA to ovariectomized rat
significantly increased BMD and decreased relative osteoid
volume in femur. These in vivo findings strongly suggested
that serum adrenal androgen may be converted to estrogen in
peripheral organ, especially, osteoblast and be important
steroids to maintain BMD. (3H)DHEA was converted to
(3H)androstenedione and (3H)androstenedione to (3H)estrone in
primary cultured human osteoblast. Osteoblast-like cells
showed aromatase activity, and an apparent K(m) and the V(max)
were 4.74 plus or minus 0.78 nM (mean plus or minus SD, n = 3)
and 0.83 plus or minus 0.79 fmol/mg protein/h for HOS, and 4.6
plus or minus 2.9 nM and 279 plus or minus 299 fmol/mg
protein/h (mean plus or minus SD, n = 19) for HO,
respectively. The aromatase activity was significantly
increased by dexamethasone in a dose-dependent manner. Reverse
transcription-polymerase chain reaction analysis revealed that
dexamethasone increased the transcript of P450(AROM) gene.
Osteoblast-specific promoters were also determined.
Dexamethasone and 1alpha,25-dihydroxyvitamin D3
synergistically enhanced aromatase activity and P450(AROM)
mRNA expression. These results demonstrate that adrenal
androgen, DHEA, is converted to E1 in osteoblast by P450(AROM)
which is positively regulated by glucocorticoid and
1alpha,25-dihydroxyvitamin D3 and important to maintain BMD in
the 6 to 7th decade, after menopause.
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