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Effects of essential
fatty acids on cyclical mastalgia and noncyclical breast
disorders.
Mansel, R.E., Pye, J.K., Hughes, L.E.
In Omega-6 Essential Fatty Acids 1990c, pp. 557-67.
Horrobon, D., Ed. New York: Wiley-Liss.
Controlled trial of the
antigonadotropin danazol in painful nodular benign breast
disease.
Mansel RE, Wisbey JR, Hughes LE.
Lancet 1982 Apr 24;1(8278):928-30
In a double-blind crossover study of the effects of the
antigonadotropin danazol on pain and nodularity in 28 women
with cyclical mastalgia danazol was given at doses of 200
mg/day and 400 mg/day, and the responses were assessed both
subjectively and objectively. Danazol caused a significant
and progressive decrease in breast pain and nodularity when
compared with placebo. Symptoms responded more quickly with
the 400 mg/day dose of danazol than with the 200 mg dose,
but the larger dose also caused greater side-effects.
Danazol is a useful addition to the range of antihormones
that can be used to suppress the symptoms of severe
hormone-related benign breast disease.
Thyroid hormones in
fibrocystic breast disease.
Martinez L, Castilla JA, Gil T, Molina J, Alarcon JL,
Marcos C, Herruzo A. Department of Obstetrics and
Gynecology, Virgen de las Nieves General Hospital, Granada,
Spain.
Eur J Endocrinol 1995 Jun;132(6):673-6
This study was undertaken to evaluate the role of
thyroid hormones in fibrocystic breast disease. The
concentrations of thyroid-stimulating hormone (TSH),
thyroxine (T4), free T4 and free triiodothyronine (T3) were
determined in serum of 50 women with fibrocystic breast
disease without macrocysts (cysts of over 3 mm diameter)
and in the serum and breast cyst fluid (BCF) of 60 women
with fibrocystic breast disease and macrocysts. Possible
relationships between thyroid hormones and estradiol,
dehydroepiandrosterone sulfate, testosterone, progesterone
and 17-hydroxyprogesterone in the BCF also were analyzed.
Serum thyroid hormone levels did not differ between the two
groups. Free T3 levels were higher in BCF than in serum (p
< 0.001), whereas T4, free T4 and TSH concentrations
were lower in BCF as compared to serum (p < 0.001).
Cysts were divided according to their K+/Na+ ratio because
a ratio above 3 represents a predictor of malignant
transformation. Free T3 concentrations were higher in BCF
than in serum, in both low K+/Na+ cysts and in cysts with a
K+/Na+ ratio above 3; those cysts with a high K+/Na+ ratio
had the highest free T3 concentration. Free T3 in cysts
correlated positively to the K+/Na+ ratio (r = 0.831; p
< 0.001). Multiple linear regression analysis
demonstrated that the concentration of free T3 in BCF was
predicted statistically by the positive regression
coefficient for the estradiol concentration. No candidate
variable was included in the model to predict
concentrations of TSH, free T4 or T4 in BCF. These data
suggest an important role of free T3 in the physiology of
fibrocystic breast disease.
Menopause: women's sex
hormones: a refresher course.
Mayo Clinic.
Mayo Clinic Women's HealthSource 2001.
Rochester, MN: Mayo Foundation for Medical Education and
Research.
Phyllodes tumor of the
breast.
Mazy, S., Hustin, J. Van Reepinghen, P.
J. Belge Radiol. (JBR-BTR) 1999 Jun; 82(3): 118.
No abstract available.
Emerging health benefits
of CLA (conjugated linoleic acid).
McBean, L.D.
Dairy Council Digest 1999. Rosement, IL: National Dairy
Council.
No abstract available.
Cyclical breast
pain--some observations and the difficulties in
treatment.
McFayden IJ, Forrest AP, Chetty U, Raab G. Longmore
Breast Unit, Western General Hospital, Edinburgh.
Br J Clin Pract 1992 Autumn;46(3):161-4
This paper describes a retrospective study of the
clinical aspects and treatment of 566 women with cyclical
breast pain over a seven-year period. Figures for the
effectiveness of simple treatments including some
homeopathic drugs are reported. The article concludes that
reassurance is the fundamental treatment. Good responses
are obtained from simple and safe drugs (oil of evening
primrose, vitamin B6) with minimal side-effects. The use of
stronger hormone drugs such as tamoxifen and danazol was
only necessary in a small proportion of patients and
resulted in a higher incidence of side-effects.
Danazol increases the
anticoagulant effect of warfarin.
Meeks ML; Mahaffey KW; Katz MD Department of Pharmacy
Services, University of Arizona Health Sciences Center,
Tucson.
Ann Pharmacother (UNITED STATES) May 1992, 26 (5)
p641-2
OBJECTIVE: To report two cases demonstrating an
interaction between danazol and warfarin, resulting in the
potentiation of warfarin's effect and bleeding
complications. DATA SOURCES: Case reports, review articles,
and studies identified by MEDLINE. STUDY SELECTION: All
published English-language reports involving danazol and
warfarin interactions were reviewed. DATA SYNTHESIS:
Danazol, a synthetic testosterone derivative, is used in
the treatment of endometriosis, fibrocystic breast disease
, menorrhagia protein C deficiency, and hemophilia. We
describe two cases including an interaction between danazol
and warfarin, resulting in bleeding complications. There
are at least two other reported cases of this interaction.
This interaction may be attributable to several mechanisms.
Danazol may inhibit the metabolism of warfarin and/or it
may have a direct effect on the coagulation and
fibrinolytic systems. CONCLUSIONS: Based on this report and
other published cases, clinicians must be aware that
danazol may increase the anticoagulant effect of warfarin.
Patients receiving warfarin who are prescribed danazol must
be monitored closely to prevent excessive anticoagulation
and subsequent bleeding. Studies are needed to determine
the frequency of this interaction and its underlying
mechanisms.
Indole-3-carbinol is a
negative regulator of estrogen receptor-alpha signaling in
human tumor cells.
Meng Q, Yuan F, Goldberg ID, Rosen EM, Auborn K, Fan S.
Department of Radiation Oncology and. Department of
Otolaryngology, Long Island Jewish Medical Center, New Hyde
Park, NY 11040, USA.
J Nutr 2000 Dec;130(12):2927-31
Estrogen, via its binding to the estrogen receptor (ER),
plays an important role in breast cancer cell proliferation
and tumor development. Indole-3-carbinol (I3C), a compound
occurring naturally in cruciferous vegetables, exhibits a
potent antitumor activity via its regulation of estrogen
activity and metabolism. This study was designed to
determine the effect of I3C on the potential to inhibit the
ER-alpha. Using a reporter gene driven by the estrogen
receptor, I3C (10-125 micromol/L) significantly repressed
the 17ss-estradiol (E2)-activated ER-alpha signaling in a
dose-dependent manner. I3C and breast cancer susceptibility
gene 1 (BRCA1) synergistically inhibited transcriptional
activity of ER-alpha. Moreover, I3C down-regulated the
expression of the estrogen-responsive genes, pS2 and
cathepsin-D, and up-regulated BRCA1. The inhibitory effects
of I3C did not contribute to its cytotoxic effects because
these activities were observed at less than toxic
concentrations. These results further suggest that
antitumor activities of I3C are associated not only with
its regulation of estrogen activity and metabolism, but
also its modulation of ER transcription activity.
Vitamin E and benign
breast disease.
Meyer EC, Sommers DK, Reitz CJ, Mentis H. Department of
Pharmacology, University of Pretoria, South Africa.
Surgery 1990 May;107(5):549-51
Vitamin E has been used in the treatment of benign
breast disease for 25 years. To evaluate the efficacy of
treatment by means of mammography as the objective and
sensitive parameter, 105 women were randomly selected and
entered into a double-blind, placebo-controlled crossover
trial. All patients had mammographic evidence of benign
breast disease. They received 600 mg of placebo and
alpha-tocopherol acetate in 3-month treatment phases.
Breast examinations and mammography were done, after each
treatment, at approximately the same phase of the patients
menstrual cycle. No significant subjective or objective
effects after treatment were observed. We conclude that
alpha-tocopherol is not beneficial in the treatment of
benign breast disease. We would warn against the use of
alpha-tocopherol for misdirected treatment of undiagnosed
overt disease because such treatment may delay the
diagnosis of breast cancer.
Changes in levels of
urinary estrogen metabolites after oral indole-3-carbinol
treatment in humans.
Michnovicz JJ, Adlercreutz H, Bradlow HL. Rockefeller
University Hospital and The Institute for Hormone Research,
New York, NY 10016, USA.
J Natl Cancer Inst 1997 May 21;89(10):718-23
BACKGROUND: The oxidative metabolism of estrogens in
humans is mediated primarily by cytochrome P450, many
isoenzymes of which are inducible by dietary and
pharmacologic agents. One major pathway, 2-hydroxylation,
is induced by dietary indole-3-carbinol (I3C), which is
present in cruciferous vegetables (e.g., cabbage and
broccoli).
PURPOSE: Because the pool of available estrogen
substrates for all pathways is limited, we hypothesized
that increased 2-hydroxylation of estrogens would lead to
decreased activity in competing metabolic pathways.
METHODS: Urine samples were collected from subjects
before and after oral ingestion of I3C (6-7 mg/kg per day).
In the first study, seven men received I3C for 1 week; in
the second study, 10 women received I3C for 2 months. A
profile of 13 estrogens was measured in each sample by gas
chromatography-mass spectrometry.
RESULTS: In both men and women, I3C significantly
increased the urinary excretion of C-2 estrogens. The
urinary concentrations of nearly all other estrogen
metabolites, including levels of estradiol, estrone,
estriol, and 16alpha-hydroxyestrone, were lower after I3C
treatment.
CONCLUSIONS: These findings support the hypothesis that
I3C-induced estrogen 2-hydroxylation results in decreased
concentrations of several metabolites known to activate the
estrogen receptor. This effect may lower estrogenic
stimulation in women.
IMPLICATIONS: I3C may have chemopreventive activity
against breast cancer in humans, although the long-term
effects of higher catechol estrogen levels in women require
further investigation.
Nonendocrine theories
of the etiology of benign breast disease.
Minton JP, Abou-Issa H.
World J Surg 1989 Nov-Dec;13(6):680-4
This article summarizes 15 years of clinical and
laboratory studies that have continued the search for a
biochemical basis for the development and resolution of
symptomatic benign fibrocystic disease. The clinical
response to diet modifications is presented along with
simultaneous laboratory tissue and serum studies. An
ongoing study of the clinical response to complete and
total methylxanthine abstention, especially caffeine, is
presented in the initial part of the article. Following the
clinical observations, is a series of laboratory studies,
some of which actually preceded the clinical investigation
and, in fact, pointed out that a beneficial clinical
response might occur in some women following complete
abstention. In the last paragraph, we present current
information that may identify which women are susceptible
to fibrocystic breast disease development.
Clinical and
biochemical studies on methylxanthine-related fibrocystic
breast disease.
Minton JP, Abou-Issa H, Reiches N, Roseman JM.
Surgery 1981 Aug;90(2):299-304
The results of this study show that the consumption of
methylxanthines through dietary sources appears to be
associated with the etiologic development of benign
fibrocystic disease in the American woman. Complete
abstention from methylxanthine consumption resulted in
complete resolution of the disease in 82.5% and significant
improvement in 15% of those studied. Thus 97.5% showed
clinical benefit from total methylxanthine abstention. The
results of a clinical questionnaire answered by 500 women
consuming ethylxanthines, one half of whom had fibrocystic
breast disease, suggest that women with fibrocystic disease
may have a genetic predisposition for both benign breast
disease and cancer. Biochemical studies implicate increased
sensitivity of the adenylate cyclase system to
catecholamines in patients with fibrocystic disease.
Methylxanthines are known to increase circulating
catecholamines.
Caffeine, cyclic
nucleotides, and breast disease.
Minton JP, Foecking MK, Webster DJ, Matthews RH.
Surgery 1979 Jul;86(1):105-9
Methylxanthine consumption is associated with the
development of fibrocystic disease of the breast.
Methylxanthine abstention is associated with resolution of
signs and symptoms of fibrocystic disease. Abstinence from
methylxanthine consumption decreased breast biopsies and
the need for major breast surgery because of benign
disease. Methylxanthine consumption is associated with
elevated cyclic adenosine monophosphate (AMP) and cyclic
guanosine monophosphate (GMP) values in fibrocystic dsiease
over those obtained in normal breast tissue.
Noncontraceptive
benefits of oral contraceptives.
Mishell DR Jr. Department of Obstetrics and Gynecology,
University of Southern California School of Medicine, Los
Angeles 90033.
J Reprod Med 1993 Dec;38(12 Suppl):1021-9
The noncontraceptive health benefits of oral
contraceptives were initially summarized a decade ago.
Studies conducted in the last decade confirmed the findings
of earlier studies with high-dose oral contraceptives and
extended them to low-dose formulations. Among the
noncontraceptive health benefits first cited were
reductions in menorrhagia, irregular menses, endometrial
cancer, ovarian cancer, functional ovarian cysts, benign
breast disease, dysmenorrhea, premenstrual tension and
iron-deficiency anemia. In addition, women who used oral
contraceptives were less likely to develop rheumatoid
arthritis or acute salpingitis, particularly moderate or
severe forms, than were women using no method of
contraception. Despite the fact that such benefits were
identified more than 10 years ago and despite their
inclusion in oral contraceptive labeling, women today are
largely unaware of the noncontraceptive health benefits
associated with oral contraceptive use.
Efficacy of low fat
diet in the treatment of benign breast
disease.
Mishra SK, Sharma AK, Salila M, Srivastava AK, Bal S,
Ramesh V. Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Uttar Pradesh, India.
Natl Med J India 1994 Mar-Apr;7(2):60-2
BACKGROUND. Previous studies have shown that lipid
abnormalities have a role in the pathogenesis of benign
breast disease. However, few investigators have tried to
reduce dietary fat to treat this disorder.
METHODS. Between 1990 and 1993, we conducted a
prospective cohort study to find out the efficacy of a low
fat diet (less than 15% fat-derived calories) in the
treatment of benign breast disease in patients who had been
symptomatic for 6 months or more. The study was conducted
in two phases. In the first phase 36 patients were
alternately assigned to control and treatment groups for 6
months and in the second phase 121 patients (including all
those in phase I) were given treatment (median follow up 25
months, range 3 to 39 months). Detailed lipid profiles were
studied at the time of presentation and at 4 and 5
months.
RESULTS. Phase I results showed that after 6 months none
of the patients in the control group had experienced any
alteration in their symptoms and signs but in the treatment
group 12 out of 17 improved. In phase II improvement in
pain (68 out of 97; 70%), nodularity (51 out of 79; 64%)
and discharge (15 out of 19; 80%) was seen. There was a
significant decline in the mean values of total cholesterol
and high-density lipoproteins at the end of 5 months of
treatment.
CONCLUSION. A low fat diet improves the symptoms as well
as the lipid profile in patients with benign breast
disease.
In vitro hormonal
effects of soybean isoflavones.
Molteni A, Brizio-Molteni L, Persky V. Department of
Pathology, Northwestern University, Chicago, IL.
J Nutr 1995 Mar;125(3 Suppl):751S-756S
Isoflavones exhibit a multitude of biological effects
that influence cell growth and regulation, and, thus, may
have potential value in the prevention and treatment of
cancer. Isoflavones are weak estrogens and can function
both as estrogen agonists and antagonists depending on the
hormonal milieu and the target tissue and species under
investigation. Genistein, one of the two primary
isoflavones in soybeans, has attracted much attention from
the research community, not only because of its potential
antiestrogenic effects, but because it inhibits several key
enzymes thought to be involved in carcinogenesis. Although
still speculative, greater dietary incorporation of soybean
products, because of the high concentration of isoflavones,
may be a safe and effective means of reducing cancer
risk.
Gourmet treats to keep
you healthy.
Mowatt, T.
Life Extension Magazine 1998 Jun; 4(6): 22-6.
Ft. Lauderdale, FL: Life Extension Foundation.
Hippocampal perfusion
and pituitary-adrenal axis in Alzheimer's
disease.
Murialdo G, Nobili F, Rollero A, Gianelli MV, Copello F,
Rodriguez G, Polleri A. Department of Endocrinological and
Metabolic Sciences, Epidemiology Service, University of
Genova, Italy. disem@unige.it
Neuropsychobiology 2000;42(2):51-7
The hippocampus is involved in Alzheimer's disease (AD)
and regulates the hypothalamus-pituitary-adrenal axis
(HPAA). Enhanced cortisol secretion has been reported in
AD. Increased cortisol levels affect hippocampal neuron
survival and potentiate beta-amyloid toxicity. Conversely,
dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are
believed to antagonize noxious glucocorticoid effects and
exert a neuroprotective activity. The present study was
aimed at investigating possible correlations between
hippocampus perfusion - evaluated by SPECT - and HPAA
function in AD. Fourteen patients with AD and 12 healthy
age-matched controls were studied by (99m)Tc-HMPAO
high-resolution brain SPECT. Plasma adrenocorticotropin,
cortisol, and DHEAS levels were determined at 2.00, 8.00,
14.00, 20.00 h in all subjects and their mean values were
computed. Cortisol/DHEAS ratios (C/Dr) were also
calculated. Bilateral impairment of SPECT hippocampal
perfusion was observed in AD patients as compared to
controls. Mean cortisol levels were significantly increased
and DHEAS titers were lowered in patients with AD, as
compared with controls. C/Dr was also significantly higher
in patients. Using a stepwise procedure for dependent SPECT
variables, the variance of hippocampal perfusional data was
accounted for by mean basal DHEAS levels. Moreover,
hippocampal SPECT data correlated directly with mean DHEAS
levels, and inversely with C/Dr. These data show a
relationship between hippocampal perfusion and HPAA
function in AD. Decreased DHEAS, rather than enhanced
cortisol levels, appears to be correlated with changes of
hippocampal perfusion in dementia. Copyright 2000 S. Karger
AG, Basel.
Benign Breast Lumps and
Other Benign Breast Changes 2001a.
National Cancer Institute.
Bethesda, MD (http://rex.nci.nih.gov).
Understanding Breast
Changes. About Breast Lumps and Other Changes
2001b.
National Cancer Institute.
Bethesda, MD (http://cancernet.nci.nih.gov).
Benign Breast Disease:
Summary of Risk Factors for Breast Cancer
NBCC.
1999 Jul 15. Campersdown, NSW, Australia:
National Breast Cancer Centre.
Dehydroepiandrosterone
reduces serum low density lipoprotein levels and body fat
but does not alter insulin sensitivity in normal
men.
Nestler JE, Barlascini CO, Clore JN, Blackard WG.
Division of Endocrinology and Metabolism, Medical College
of Virginia/Virginia Commonwealth University, Richmond
23298.
J Clin Endocrinol Metab 1988 Jan;66(1):57-61
To assess the effects of dehydroepiandrosterone (DHEA)
on body fat mass, serum lipid levels, and tissue
sensitivity to insulin, five normal men were given placebo
and five normal men were given oral DHEA [1600 mg/day
(554.7 mmol/day)] for 28 days in a randomized, double blind
study. In the DHEA group serum DHEA-S levels rose 2.5- to
3.5-fold, and mean ( SEM) serum androstenedione rose from
4.3 0.6 to 8.6 1.2 nmol/L (P less than 0.004, by paired t
test), but serum total testosterone, free testosterone, sex
hormone-binding globulin, estradiol, and estrone levels did
not change. In the DHEA group the mean percent body fat
decreased by 31%, with no change in weight. This suggests
that the reduction in fat mass was coupled with an increase
in muscle mass. DHEA administration also resulted in a fall
in mean serum total cholesterol concentration (4.82 0.21
vs. 4.48 0.29 nmol/L; P less than 0.05), which was due
almost entirely to a fall of 7.5% in mean serum low density
lipoprotein cholesterol (3.21 0.11 vs. 2.97 0.14 nmol/L; P
less than 0.01). No changes in anthropometric parameters or
serum lipid levels occurred in the placebo group. Tissue
sensitivity to insulin, assessed by the
hyperinsulinemic-euglycemic clamp technique, did not change
in either the placebo or DHEA groups. These results suggest
that in normal men DHEA administration reduces body fat,
increases muscle mass, and reduces serum low density
lipoprotein cholesterol levels. Tissue sensitivity to
insulin was unaffected by short term DHEA
administration.
Background Information.
Indole-3-Carbinol (I3C), 700-06-1
NIEHS.
June 2000. Research Triangle Park, NC: National
Institute of Environmental Health Sciences
(http://ntp-server.nih.gov/htdocs/Chem_Background/ExecSumm/Indolecarbinol.html).
Environmental
estrogenic effects of alkylphenol ethoxylates.
Nimrod AC, Benson WH. Department of Pharmacology and
Environmental Toxicology Research Program/RIPS School of
Pharmacy, University of Mississippi, University 38677,
USA.
Crit Rev Toxicol 1996 May;26(3):335-64
Alkylphenol ethoxylates (APEs) and related compounds
recently have been reported to be estrogenic because it has
been demonstrated in laboratory studies that they mimic the
effects of estradiol both in vitro and in vivo. Chemicals
referred to as "environmental estrogens" are suspected of
causing health effects in both humans and wildlife through
disruption of the endocrine system. In this review, the
occurrence, environmental fate, and biological effects of
APEs are presented. To provide understanding of the
potential for endocrine disruption due to environmental
estrogens, the physiology of estrogens in mammals and fish
is also reviewed. The estrogenic potency of other
environmental estrogens is compared to the potency of APE
degradation products. The reproductive effects of
estrogenic compounds are considered when evaluating the
potential health effects of APEs. Given the reported
environmental concentrations and bioconcentration factors
of APE products, the potential for these compounds to
produce estrogenic effects in the environment appears low.
Although questions concerning the physiological effects of
APEs and other environmental estrogens remain unanswered,
there are indications that research is in progress that
will lead to better understanding of the risks to humans
and wildlife.
Benign breast pain in
women: a practical approach to evaluation and
treatment.
Norlock FE. Cook County Hospital, USA.
J Am Med Womens Assoc 2002 Spring;57(2):85-90
The literature on breast pain etiology, practical
approaches to evaluating benign breast pain, and effective
treatments was reviewed. Medline, the Cochrane Database of
Systematic Reviews, and Cancerlit were searched for 1975 to
2001. Researchers have found no clear hormonal or specific
pathological processes that explain cyclical breast pain.
Some investigations did find associations between breast
pain and premenstrual syndrome, fibrocystic breast disease,
and caffeine intake. Initial treatment with reassurance, a
well-fitted brassiere, caffeine reduction, and primrose oil
should be tried before prescribing pharmaceutical agents.
Medications such as danazol, bromocriptine, and tamoxifen
are effective, but often have side effects and
contraindications. Future studies should indude
double-blind, randomized, controlled trials of
selective-serotonin reuptake inhibitors and primrose oil
and single-blind, randomized, controlled trials advising
caffeine reduction.
Breast biopsy for
mammographically detected non-palpable lesions using a
vacuum-assisted biopsy device (Mammotome) and an
upright-type stereotactic mammography unit.
Ohsumi S, Takashima S, Aogi K, Ishizaki M, Mandai K.
Department of Surgery, National Shikoku Cancer Center, 13
Hori-no-uchi, Matsuyama, Ehime 790-0007, Japan.
sosumi@shikoku-cc.go.jp
Jpn J Clin Oncol 2001 Nov;31(11):527-31
BACKGROUND: It is planned to start screening mammography
throughout Japan in the near future. However, a minimally
invasive biopsy procedure for mammographically detected
non-palpable breast lesions is not available in almost all
Japanese hospitals. It is crucial to develop a useful
minimally invasive biopsy method which can be applied
without difficulty. METHODS: Eighty-nine biopsies for 88
mammographically detected non-palpable breast lesions,
consisting of 70 lesions with microcalcifications alone,
eight masses without calcifications and 10 with both masses
and microcalcifications, were performed using the
combination of a vacuum-assisted biopsy device (Mammotome)
and an upright-type stereotactic mammography unit. RESULTS:
Microcalcifications were confirmed radiographically in the
tissue obtained from 78 biopsies among 81 biopsies for the
lesions with microcalcifications (96.3%). All the lesions
without calcifications were considered to be biopsied
successfully. Five patients complained of nausea or fainted
during the localization or biopsy procedure and an
additional patient suffered from hyperventilation syndrome.
Five cases experienced mild subcutaneous bleeding in the
breasts. CONCLUSIONS: The biopsy technique using the
combination of a vacuum-assisted biopsy device and an
upright-type stereotactic mammography unit is a
cost-effective, safe and very useful method for
mammographically detected non-palpable breast lesions. It
is expected to be a standard method of biopsy for such
lesions in many developed countries other than the USA.
However, it is important to make the patients relaxed
during the biopsy to prevent mental strain.
Mammographic
parenchymal patterns: a marker of breast cancer
risk.
Oza AM, Boyd NF. Department of Medicine, Princess
Margaret Hospital and Ontario Cancer Institute, Toronto,
Canada.
Epidemiol Rev. 1993;15(1):196-208.
There is now a large amount of evidence showing that
mammographic densities are an indicator of increased risk
of breast cancer. There is as yet no generally agreed upon
and recognized method of classifying these densities,
although the available evidence shows that quantitative
description of densities creates larger gradients of risk
than Wolfe's classification and larger risk gradients than
most other risk factors for breast cancer. It seems likely
that improved methods of describing densities
quantitatively, and possibly other methods of
characterizing the tissue changes that are responsible for
the densities, will allow greater discrimination. However,
it is already clear that breast cancer develops in a large
number of women who do not have radiologic changes
indicating increased risk, and that it is unlikely that
mammographic pattern, or any other risk factor for breast
cancer identified to date, will be useful for the selection
of women for mammographic screening. Although mammographic
densities are associated with an increased risk of
developing histologic changes that are risk factors for
breast cancer, the histologic feature most consistently
associated with mammographic densities is stromal fibrosis.
We suggest that the relation between stromal fibrosis and
risk of breast cancer can be explained by the known actions
of a variety of growth factors that are thought to play a
role in a number of aspects of breast development and
carcinogenesis. The association between mammographic
densities and several other risk factors for breast cancer
suggests that these factors may also modulate the activity
of growth factors in breast tissue, and that this may be
the means by which they influence breast cancer risk.
Further research is needed to determine whether differences
in the activity of growth factors in breast tissue can be
found in association with radiologic and other risk factors
for breast cancer. The available evidence indicates,
therefore, that mammographic parenchymal patterns do, at
least in part, meet the criteria outlined in the
introduction of this paper. Some mammographic appearances
are associated with a substantial increase in the risk of
breast cancer, and, as shown by observations on the effects
of hormone use, are capable of change. Mammographic
densities have also been found to be associated with
biochemical characteristics of possible relevance to
carcinogenesis. The appearances that are related to risk
may, therefore, be most useful as a means of investigating
the etiology of breast cancer and of testing hypotheses
about potential preventive strategies.
Mammographic and
ultrasonographic study of changes in the breast related to
HRT.
Ozdemir A, Konus O, Nas T, Erbas G, Cosar S, Isik S.
Department of Radiology, University of Gazi, School of
Medicine, Besevler, Ankara, Turkey.
aozdemir@med.gazi.edu.tr
Int J Gynaecol Obstet 1999 Oct;67(1):23-32
OBJECTIVE: To determine the frequency and degree of
change in mammographic densities, and new solid or cystic
formations in the breast tissue, during different types of
hormone replacement therapy (HRT).
SUBJECTS AND METHODS: This prospective study included
118 postmenopausal women, 88 under hormone replacement
therapy and 30 control subjects. Four types of hormone
therapies were compared for their effects on mammograms and
sonograms obtained before and during therapy. Mean duration
of follow-up was 16.92 7.65 months in the treated and 21.56
11.49 months in the control group. Density changes on
mammograms were evaluated subjectively.
RESULTS: Density increase was recorded in 34% of the
patients receiving HRT and in none of the control subjects
(P < 0.01). Highest frequency of density increase was
found in the groups treated with estrogen plus cyproterone
acetate (46%) and with estrogen plus medroxyprogesterone
acetate (43%). Frequencies of density increase in the
tibolone users, and in estrogen alone users were 28% and
18%, respectively. Degree of density increase was evidently
minimal in tibolone users, compared to others. New cysts
occurred in six patients receiving HRT (6%) which was not
statistically different from the control group (16%) (P
> 0.05). New cyst formation was not related to the
degree of density increase. New solid mass formation was
not observed.
CONCLUSION: Our findings show that mammographic density
changes related to HRT are dependent on the selected
hormone regimen. Formations of breast cysts or solid
lesions do not seem to be related to HRT.
Management of cyclical
mastalgia.
Pain JA, Cahill CJ. King's College Hospital, London.
Br J Clin Pract 1990 Nov;44(11):454-6
In order to establish the current treatment of cyclical
mastalgia, a postal questionnaire was sent to 276
consultant general surgeons (over 25% of the UK total),
randomly selected from the 12 UK regional health
authorities. Surgeons were questioned about their choices
of treatment for cyclical mastalgia, after initial
resassurance, and for persistent pain. Two hundred and
forty-five (89%) responded, out of whom 219 saw patients
with breast disease. Twenty-three (11%) of these surgeons
were identified as having a major interest in breast
disease. Danazol, used by 75% of surgeons, was the drug
most commonly prescribed. Initial treatments by
non-specialist surgeons included danazol (31%), analgesia
(19%) and diuretics (17%), and by breast surgeons evening
primrose oil (30%), tamoxifen (13%) and vitamin B6 (13%).
For persistent pain 46% of non-specialist surgeons
prescribed danazol and 18% surgery, whereas 65% of breast
surgeons prescribed danazol and 30% bromocriptine. A wide
variety of therapies are used, but danazol is the most
common. For persistent unresponsive pain, local excision
biopsy surgery is frequently considered by non-specialist
surgeons. Breast specialist tend initially to use other
methods that are associated with fewer side-effects and
reserve other treatments such as danazol and bromocriptine
for persistent cases.
Estrogen replacement
therapy and fibrocystic breast disease.
Pastides H, Najjar MA, Kelsey JL. Division of Public
Health, University of Massachusetts School of Health
Sciences, Amherst 01003.
Am J Prev Med 1987 Sep-Oct;3(5):282-6
In a hospital-based case-control study conducted in New
Haven, Connecticut, women experiencing estrogen replacement
therapy were found to be at twice the risk of nonusers for
histologically confirmed fibrocystic breast disease (odds
ratio = 2; 95 percent confidence limits = 1-3.9) if their
menopause was natural. No excess risk was found for women
experiencing a surgical menopause. The highest risk for
fibrocystic disease was observed for women with more than
three years of estrogen replacement therapy. When therapy
occurred was not significantly related to the risk of
disease once duration of use was controlled for. These
results suggest an etiologic role of estrogen replacement
therapy in the development or promotion of fibrocystic
breast disease.
Female
pseudohermaphroditism with somatic chromosomal anomaly in
association with in utero exposure to danazol
Peress M.R.; Kreutner A.K.; Mathur R.S.; Williamson H.O.
Sect. Reprod. Endocrinol. Infertil., Dept. Obstet.
Gynecol., Med. Univ. South Carolina, Charleston, SC 29425
United States
American Journal of Obstetrics and Gynecology 1982,
142/6 I (708-709)
Female pseudohermaphroditism is characterized by XX
karyotype, female internal reproductive organs, but
ambiguous external genitals, usually as a result of in
utero exposure to excess androgens. Such androgens may be
of exogenous, fetal, or maternal origin. Congenital adrenal
hyperplasia (CAH) with excessive fetal androgen production
is the most common underlying disorder causing female
pseudohermaphroditism. Masculinization of the female fetus
as a result of increased maternal androgen production is
rare but has been reported with luteoma of pregnancy and
arrhenoblastoma. Female pseudohermaphroditism has also been
reported after prenatal exposure to synthetic progestogens,
stilbestrol, and prenatal vitamins containing
methyltestosterone. Williamson reported a female
pseudohermaphrodite with CAH and incidental in utero
exposure to medroxyprogesterone acetate. More recently,
Duck and associates reported the association of female
pseudohermaphroditism with in utero exposure to danazol.
This compound has been used in the treatment of
endometriosis, fibrocystic breast disease , precocious
puberty, dysfunctional uterine bleeding, and angioneurotic
edema.
MR-Guided vacuum biopsy
of 206 contrast-enhancing breast lesions.
Perlet C, Schneider P, Amaya B, Grosse A, Sittek H,
Reiser MF, Heywang-Kobrunner SH. Institut fur Klinische
Radiologie, Klinikum der Universitat Grosshadern,
Munchen.
Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2002
Jan;174(1):88-95
Abstract. PURPOSE: To detemine the accuracy and clinical
use of MR-guided vacuum biopsy (VB) of enhancing breast
lesions. MATERIAL AND METHODS: 254 lesions were referred to
MR-guided vacuum-assisted breast biopsy. In 43 (16 %)
patients the indication was dropped because the lesions
could not be identified at the time VB was scheduled. This
was due to hormonal influences (n = 37), to too strong
compression (n = 3) or to misinterpretation of the initial
diagnostic MRI (n = 3). In 5 cases (2 %) VB was not
performed due to obesity (n = 2); problems of access (n =
2) or a defect of the MR-unit (n = 1). VB was performed on
altogether 206 lesions. In 4 cases (2 %) VB was
unsuccessful. This was immediately realized on the
post-interventional images. Thus a false negative diagnosis
was avoided. Verification included excision of the cavity
in cases with proven malignancy or atypical ductal
hyperplasia (ADH) and (for benign lesions) retrospective
correlation of VB-histology with pre-and postinterventional
MRI and subsequent follow-up. RESULTS: 51/202 successful
biopsies proved malignancy. In 7 cases ADH and in 144 cases
a benign lesion was diagnosed. One DCIS was underestimated
as ADH. All other benign or malignant diagnoses proved to
be correct. CONCLUSION: MR-guided VB allows reliable
histological work-up of contrast-enhancing small lesions
which are not visible by any other modality.
Dementia: a
neuroendocrine perspective.
Polleri A, Gianelli MV, Murialdo G. Department of
Endocrinological and Metabolic Sciences, University of
Genoa, Italy.
J Endocrinol Invest 2002 Jan;25(1):73-83
The etiology of Alzheimer's disease (AD) has not been as
yet completely defined. Genetic, environmental and
neurophysiological aspects should all be taken into
account. The disease has also neuroendocrine implications,
some of which are discussed in this review. It is known
that stress and glucocorticoids may affect neurone
survival. On the contrary, some data indicate that DHEA and
DHEAS exert a neuroprotective action. In AD, changes in
hypothalamic-pituitary-adrenal axis function have been
reported. Experimental and clinical evidence indicates that
glucocorticoid hypersecretion and DHEAS levels decrement
may add to hippocampal dysfunction in aging and in AD.
Glucocorticoid and beta-amyloid concur in the mechanism of
neurone damage, as well as excitatory amino acids (EAA),
Ca++ and reactive oxygen species (ROS). The neuroprotective
effects exerted by IGFs are also hindered in aging and even
more in AD. Production and biological actions of IGFs are
negatively influenced by cortisol hypersecretion and DHEAS
decrease in patients with AD.
Clinical experience of
drug treatments for mastalgia.
Pye JK, Mansel RE, Hughes LE.
Lancet 1985 Aug 17;2(8451):373-7
Results of randomised trials and open studies in 291
patients with severe persistent breast pain in whom breast
cancer had been excluded showed that drug therapy produced
a good or useful result in 77% of those with cyclical
mastalgia and 44% of those with non-cyclical mastalgia. In
patients with cyclical mastalgia good or useful responses
were obtained with danazol in 70%, with bromocriptine in
47%, and with evening-primrose oil in 45%. The equivalent
response rates in patients with non-cyclical mastalgia were
31%, 20%, and 27% respectively. Progestagens were not
effective in either group. Failure to respond to one drug
did not preclude response to a different drug. Patients
with Tietze's syndrome did not respond to drug therapy, but
7 out of 10 responded to injection of lignocaine and
hydrocortisone around the affected costochondral
junction.
Complex carbohydrates:
they're the best thing since sliced bread.
Quagliani, D.
Better Homes &amp; Gardens 1997 May.
No abstract available.
A cohort study of oral
contraceptive use and risk of benign breast
disease.
Rohan TE, Miller AB. Department of Public Health
Sciences, University of Toronto, Canada.
tom.rohan@utoronto.ca
Int J Cancer 1999 Jul 19;82(2):191-6
The purpose of the cohort study reported here was to
investigate the association between oral contraceptive use
and risk of benign breast disease (BBD), overall and by
histological subtype, within the 56,537 women in the
Canadian National Breast Screening Study (NBSS) who
completed self-administered lifestyle and dietary
questionnaires. The NBSS is a randomized controlled trial
of screening for breast cancer in women aged 40-59 at
recruitment. Cases were the 2,116 women in the dietary
cohort who were diagnosed with biopsy-confirmed incident
BBD. For comparative purposes, a subcohort consisting of a
random sample of 5,681 women (including 197 subjects with
incident BBD) was selected from the full dietary cohort.
After exclusions for various reasons, the analyses were
based on 2,116 cases and 5,338 non-cases. There was an
inverse association between use of oral contraceptives and
risk of all types of BBD combined. The reduction in risk
was confined largely to proliferative forms of BBD (BPED),
and in particular, to those forms of BPED without
histological atypia, in whom there was a progressive
reduction in risk with increasing duration of use (the IRR
(95% CI) for use of more than 7 years was 0.64
(0.47-0.87)); risk of BPED with atypia was increased
somewhat in association with oral contraceptive use (the
IRR (95% CI) for use of more than 7 years was 1.43
(0.68-3.01 )), but not in a dose-dependent manner. The
results were similar when examined separately in the
screened and control arms of the NBSS and for
screen-detected and interval-detected BPED.
Why grass makes for
better milk.
Roloff, J.
Science News 1997 Oct 11.
No abstract available.
Effect of a low-fat
diet on hormone levels in women with cystic breast disease.
I. Serum steroids and gonadotropins.
Rose DP, Boyar AP, Cohen C, Strong LE.
J Natl Cancer Inst 1987 Apr;78(4):623-6
For examination of the effect of a low-fat diet on serum
estrogen, progesterone, and gonadotropin levels, 16
patients with cystic breast disease and cyclic mastalgia
were studied before dietary intervention and at 2 and 3
months thereafter. Four-day food diaries indicated that
total fat intake was reduced from a prediet average of 69 g
(35% of total kilocalories/day) to an average of 32 g (21%
of total kilocalories) after 3 months. Highly significant
reductions (P less than .001) occurred in dietary
cholesterol and less changes occurred in protein and total
kilocalorie consumption (P less than .05); fiber intakes
were not affected. After 3 months on this low-fat diet,
there were significant reductions in luteal-phase serum
total estrogens (P less than .001), estrone (P less than
.005), and estradiol (P less than .01); progesterone,
luteinizing hormone, and follicle-stimulating hormone
levels were unchanged. Two of the 16 patients were excluded
from the hormone statistical analyses because the serum
progesterone levels were not consistent with sampling in
the luteal phase of the menstrual cycle. It is concluded
that a reduction of dietary fat intake to 20% of the total
kilocalories will result in significant decreases in
circulating estrogens in benign breast disease patients and
that this effect is achievable without increasing dietary
fiber consumption. Absence of changes in serum progesterone
and gonadotropins during the dietary intervention is
consistent with altered enterohepatic circulation of
estrogens rather than with effects on the pituitary-ovarian
axis.
Effect of a low-fat
diet on hormone levels in women with cystic breast disease.
II. Serum radioimmunoassayable prolactin and growth hormone
and bioactive lactogenic hormones.
Rose DP, Cohen LA, Berke B, Boyar AP.
J Natl Cancer Inst 1987 Apr;78(4):627-31
For investigation of the bioactivity of circulating
prolactin and growth hormone (lactogenic hormones) in
symptomatic benign breast disease, serum was assayed by the
Nb2 lymphoma cell method in premenopausal patients with
cystic breast disease and cyclic mastalgia and in normal
premenopausal women. The results were compared with serum
prolactin and growth hormone concentrations determined by
radioimmunoassay. The serum bioassayable hormone levels in
the benign breast disease patients (74.0 77.6 ng/ml) were
significantly higher (P less than .001) than in normal
women (23.8 10.7 ng/ml). There were no significant
differences in the radioimmunoassayable prolactin or growth
hormone levels between the 2 groups. When 16 cystic breast
disease patients were placed on a low-fat (20% of total
kilocalories) diet for 3 months, there were significant
reductions in the serum bioassayable hormone levels (P less
than .02). It is concluded that the bioactivity of
prolactin may be elevated in the serum of patients with
cystic breast disease and cyclic mastalgia, without
corresponding increases in levels determined by
radioimmunoassay; that this abnormality is reversible by a
reduction in dietary fat consumption to 20% of the total
kilocalories; and that serum prolactin may provide a
valuable biomarker in clinical trials of a low-fat diet in
women at high breast cancer risk.
Breast cancer and the
consumption of coffee.
Rosenberg L, Miller DR, Helmrich SP, Kaufman DW,
Schottenfeld D, Stolley PD, Shapiro S.
Am J Epidemiol 1985 Sep;122(3):391-9
The hypothesis has been raised that coffee consumption
may increase the incidence of breast cancer, based on the
report that fibrocystic breast disease, a risk factor for
breast cancer, regresses after abstention from coffee and
other methylxanthines. The relation between recent coffee
consumption and the risk of breast cancer was evaluated in
a case-control study, based on interviews conducted
1975-1982 at several mainly eastern US teaching and
community hospitals. The responses of 2,651 women with
newly diagnosed breast cancer were compared with those of
1,501 controls with nonmalignant conditions and 385
controls with cancers at other sites. The relative risk
estimates for levels of coffee drinking up to seven or more
cups daily, relative to none, approximated 1.0 with narrow
95% confidence intervals. After allowance for confounding,
the relative risk estimate for drinking at least five cups
a day was 1.2 (95% confidence interval, 0.9-1.6) using the
noncancer controls and 1.1 (0.7-1.6) using the cancer
controls. Coffee consumption was not associated with an
increase in the risk of breast cancer among women with a
history of fibrocystic breast disease, nor were tea or
decaffeinated coffee associated with an increase in the
risk of breast cancer. The results suggest that the recent
consumption of coffee does not influence the incidence of
breast cancer.
Caffeine restriction as
initial treatment for breast pain.
Russell LC. Department of Surgery, Duke University
Medical Center, Durham, N.C.
Nurse Pract 1989 Feb;14(2):36-7, 40
The effects of methylxanthines (caffeine, theophylline
and theobromine) on the symptoms associated with
fibrocystic breast disease were studied in 147 patients.
Disease was documented by mammography, physical examination
and clinical symptoms. Only those individuals with breast
pain (n = 138) were included in the study. Questionnaires
were presented and explained to all patients by the same
nurse examiner. Patients reported their degree of caffeine
consumption as either light (two cups per day or less of
caffeine-containing beverages or foods), moderate (more
than two cups, but less than six cups per day), or heavy
(six cups per day or more of caffeine-containing products).
They additionally reported breast pain as mild, moderate or
severe. Past medical and family histories were reported as
well as medication intake. All patients were counseled to
abstain from or reduce caffeine consumption and were given
a list of commonly used caffeine-containing products. The
results at the end of one year indicated that compliance
was high, with 113 patients (81.9 percent) reducing their
caffeine intake substantially and, of those, 69 (61
percent) reporting a decrease or absence of breast pain.
This study supports the findings of others in that caffeine
restriction is an effective means of management of breast
pain associated with fibrocystic disease.
The use of silymarin in
the treatment of liver diseases.
Saller R, Meier R, Brignoli R. Abteilung Naturheilkunde,
University Hospital Zurich, Switzerland.
Drugs 2001;61(14):2035-63
The high prevalence of liver diseases such as chronic
hepatitis and cirrhosis underscores the need for efficient
and cost-effective treatments. The potential benefit of
silymarin (extracted from the seeds of Silybum marianum or
milk thistle) in the treatment of liver diseases remains a
controversial issue. Therefore, the objective of this
review is to assess the clinical efficacy and safety of
silymarin by application of systematic approach. 525
references were found in the databases, of which 84 papers
were retained for closer examination and 36 were deemed
suitable for detailed analysis. Silymarin has metabolic and
cell-regulating effects at concentrations found in clinical
conditions, namely carrier-mediated regulation of cell
membrane permeability, inhibition of the 5-lipoxygenase
pathway, scavenging of reactive oxygen species (ROS) of the
R-OH type and action on DNA-expression, for example, via
suppression of nuclear factor (NF)-kappaB. Pooled data from
case record studies involving 452 patients with Amanita
phalloides poisoning show a highly significant difference
in mortality in favour of silibinin [the main isomer
contained in silymarin] (mortality 9.8% vs 18.3% with
standard treatment; p < 0.01). The available trials in
patients with toxic (e.g. solvents) or iatrogenic (e.g.
antispychotic or tacrine) liver diseases, which are mostly
outdated and underpowered, do not enable any valid
conclusions to be drawn on the value of silymarin. The
exception is an improved clinical tolerance of tacrine. In
spite of some positive results in patients with acute viral
hepatitis, no formally valid conclusion can be drawn
regarding the value of silymarin in the treatment of these
infections. Although there were no clinical end-points in
the four trials considered in patients with alcoholic liver
disease, histological findings were reported as improved in
two out of two trials, improvement of prothrombin time was
significant (two trials pooled) and liver transaminase
levels were consistently lower in the silymarin-treated
groups. Therefore, silymarin may be of use as an adjuvant
in the therapy of alcoholic liver disease. Analysis was
performed on five trials with a total of 602 patients with
liver cirrhosis. The evidence shows that, compared with
placebo, silymarin produces a nonsignificant reduction of
total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 -
1.1)]; but that, on the other hand, the use of silymarin
leads to a significant reduction in liver-related mortality
of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual
trial reported a reduction in the number of patients with
encephalopathy of -8.7% (p = 0.06). In one study of
patients with cirrhosis-related diabetes mellitus, the
insulin requirement was reduced by -25% (p < 0.01). We
conclude that available evidence suggests that silymarin
may play a role in the therapy of (alcoholic) liver
cirrhosis. Silymarin is has a good safety record and only
rare case reports of gastrointestinal disturbances and
allergic skin rashes have been published. This review does
not aim to replace future prospective trials aiming to
provide the 'final' evidence of the efficacy of
silymarin.
Beta-carotene
supplementation associated with intermittent retinol
administration in the treatment of premenopausal
mastodynia.
Santamaria L, Dell'Orti M, Bianchi Santamaria A.
Boll Chim Farm 1989 Sep;128(9):284-7
Twenty-five women, 23-41 year old, suffering from
premestrual cyclical mastodynia linked or otherwise to
benign breast disease (BBD), with moderate or severe pain
at least seven days before each menstrual period, were
treated with daily beta-carotene (BC) supplementation
associated with intermittent administration of retinol
(all-trans-retinol 300,000 IU per day). In this therapy
retinol was given for 7 days immediately before each
menstrual period. After 6 months' treatment, the results
revealed marked reduction in breast pain, and sometime
recovery, in 23-41 year old women with no toxic side
effects. But no such advantages in 5 women with
non-cyclical mastodynia treated as above were found. Above
this age range, the advantages appear to be absent. All the
women developed a healthy look because of a slight tanning
of the skin due to beta-carotene supplementation. These
data demonstrated a therapeutic synergism between BC and
retinol.
Methylxanthines and
benign breast disease.
Schairer C, Brinton LA, Hoover RN.
Am J Epidemiol 1986 Oct;124(4):603-11
The relation between methylxanthine consumption and
biopsied benign breast disease was investigated by using
data from a case-control study which included 1,569 cases
and 1,846 controls identified between 1973 and 1980 through
a nationwide screening program. There was no evidence of an
association between methylxanthine consumption and benign
breast disease in the total study population. When
histologic types of benign breast disease were examined,
there were no trends in risk according to methylxanthine
consumption among the 813 cases with fibrocystic disease,
the 508 cases for whom detailed pathology data were not
available, the 172 cases with benign neoplasms, or the 156
cases with other benign conditions. When cases with
fibrocystic disease were examined according to presence of
atypia, hyperplasia, sclerosing adenosis, or cysts, there
was, again, no association between methylxanthine
consumption and risk of disease. In addition, no relation
was found between methylxanthine consumption and menstrual
breast tenderness among premenopausal women with
fibrocystic disease or unknown conditions.
Oral contraceptives in
the 90s.
Scott, P.M.
Physician Assist. 1993; 17(12): 19-28.
No abstract available.
Adipose tissue as a
source of hormones.
Siiteri PK.
Am J Clin Nutr 1987 Jan;45(1 Suppl):277-82
Obesity is known to increase the risk for cancer of the
reproductive tract in women. The mechanism underlying this
association can be explained by increased estrogenic
stimulus to estrogen-target tissues as the result of three
factors. First, increased adrenal secretory activity makes
more androgen precursors available for conversion to
estrogen in peripheral tissues. Second, the efficiency of
conversion of androstenedione (A) to estrone (E1), is
elevated in obese subjects because adipose tissue is the
major tissue site of conversion. Third, plasma levels of
SHBG, which binds estradiol (E2), are depressed in obese
subjects and greater than normal amounts of serum estradiol
are therefore available to target tissues from the
circulation. Recent studies have shown that the levels of
estrogens and other steroid hormones in breast fluids are
much higher than in serum, which may be the result of local
synthesis or increased uptake from the circulation. No
differences in estrogen levels of breast fluid have been
found between normal women and those with breast disease. A
possible explanation may be differences in the levels of
estrogen antagonists, such as progesterone.
Aromatization of
androgens in women: current concepts and
findings.
Simpson ER. Prince Henry's Institute of Medical
Research, Clayton, Victoria, Australia
Fertil Steril 2002 Apr;77 Suppl 4:6-10
OBJECTIVE: To review the role of circulating C(19)
steroids as precursors of estrogens in postmenopausal
women.DESIGN: Review of current published
literature.RESULT(S): In postmenopausal women as in men,
estradiol no longer functions as a circulating hormone,
because it ceases to be formed by the ovaries at the time
of menopause. Estradiol continues to be formed in a number
of extragonadal sites, however, including breast, bone,
vascular smooth muscle, and various sites in the brain. At
these sites of formation, local estradiol levels can be
quite high, but the production rate is insufficient to
affect the body in a global fashion; thus, estrogen action
at these extragonadal sites of synthesis is primarily at a
local level and serves a paracrine or even intracrine
role.Because of this, in postmenopausal women as in men,
circulating estrogen levels do not drive growth and
development of target tissues. Instead, they reflect the
metabolism of estradiol at these extragonadal sites.
Estrogen that is not metabolized at these sites reenters
the circulation, and, consequently, circulating levels of
estradiol reflect its synthesis and action in extragonadal
sites. Thus, they are reactive instead of proactive. An
important difference between estrogen production at these
extragonadal sites and estrogen that is synthesized in the
ovary is that the former is absolutely dependent on a
supply of circulating C(19) androgenic
substrate.CONCLUSION(S): Circulating levels of testosterone
begin to decline in the mid-reproductive years, and the
levels of adrenal androgenic steroids, namely
adrostenedione and DHEA, decrease throughout postmenopausal
life. Therefore, the circulating levels of these adrogenic
steroids may serve an important role in the maintenance of
local estrogen synthesis, for example, in the bone and
brain where estrogen has a profound influence on the
maintenance of mineralization on the one hand, and possible
cognitive function on the other.
Epidemiologic study of
central obesity, insulin resistance and associated
disturbances in the urban population of North
India.
Singh RB, Niaz MA, Agarwal P, Beegum R, Rastogi SS,
Singh NK. Heart Research Laboratory, Medical Hospital and
Research Centre, Moradabad, India.
Acta Cardiol 1995;50(3):215-25
Central obesity in association with insulin resistance
is a strong predictor of coronary artery disease (CAD) in
South Asians; however the prevalence of central obesity and
insulin resistance in Indians are unknown. Anthropometric
measurements, dietary intakes, physical activity and
prevalence of risk factors and CAD were obtained in 152
adults between 26-65 years of age (80 males, 72 females)
selected by random sampling from urban population of
Moradabad. The overall prevalence of central obesity was
539 per 1000 adults including 56.2% in males and 51.3% in
females. The prevalence of glucose intolerance, diabetes
mellitus, hypertension, hypertriglyceridemia and CAD were
significantly higher in the higher quintiles of WHR above
0.88 compared to lower quintiles. Fasting and postprandial
glucose, plasma insulin and triglycerides as well s total
cholesterol and blood pressure were significantly higher in
each of the upper quintile of WHR with increase in WHR
compared to lowest quintile of WHR below 0.81. These
findings indicate the existence of a modest degree of
insulin resistance with a modest tendency to central
obesity in the urban population of North India. The
prevalence of CAD was significantly (p < 0.01) higher
among subjects with central obesity than in non-obese
subjects (21.5 vs 3.2%). Underlying these findings, the
prevalence of central obesity was significantly greater
among sedentary and mild activity group compared to
moderate and heavy activity group and per day energy
expenditure during activity in the upper quintiles with WHR
> 0.88 was significantly less compared to energy
expenditure in lower quintiles of WHR. Similarly dietary
fat intake in the upper quintiles of WHR was also
significantly higher than in the lower quintiles of WHR.
These findings suggest that populations with higher
prevalence of central obesity and CAD may be benefited with
an aim to decrease central obesity.
Benign breast disease
I: hormonal investigation.
Sitruk-Ware R, Sterkers N, Mauvais-Jarvis P.
Obstet Gynecol 1979 Apr;53(4):457-60
One hundred eighty-four patients with benign breast
disease (BBD) were studied and compared with 50 normal
women. All of the women had ovulatory cycles according to a
biphasic basal body temperature and a plasma prolactin in
the normal range. Their corpus luteum function was
evaluated by way of plasma progesterone (P) and estradiol
(E2) determinations at days 5, 7, and 9 of the hyperthermic
phase. In the 184 patients, plasma P over plasma E2 ratio
during the luteal phase was found significantly lower than
in normal women. When the patients were grouped according
to type of breast lesions, it appeared that plasma P was
constantly lower in all groups than in the normal women,
while plasma E2 was either normal or elevated in the groups
of patients with adenosis tumors and increased nodularity
of both breasts. From these results it may be postulated
that an imbalance in the secretion of E2 and P by the
corpus luteum is a constant finding in women with benign
breast disease.
Dehydroepiandrosterone
(DHEA) as a possible source for estrogen formation in bone
cells: correlation between bone mineral density and serum
DHEA-sulfate concentration in postmenopausal women, and the
presence of aromatase to be enhanced by
1,25-dihydroxyvitamin D3 in human osteoblasts.
Takayanagi R, Goto K, Suzuki S, Tanaka S, Shimoda S,
Nawata H. Department of Geriatric Medicine, Graduate School
of Medical Sciences, Kyushu University, Maidashi 3-1-1,
Higashi-ku, Fukuoka, Japan
Mech Ageing Dev 2002 Apr;123(8):1107-14
A 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. In subset analysis, strong positive correlation
of serum DHEA-S and estrone with BMD was observed in
postmenopausal women aged less than 69 years old. To study
a possible role of DHEA-S in preventing osteoporosis, we
characterized aromatase activity converting androgens to
estrogens in human osteoblasts, because postmenopausal
women maintain considerable levels of adrenal androgens.
Glucocorticoids at 10(-9) to 10(-7) M induced transiently
the expression of and the enzymatic activity of aromatase
cytochrome P450 (P450AROM) in primary cultured osteoblasts.
1,25-Dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) alone did not
induce the aromatase activity, but enhanced and maintained
the glucocorticoid-induced P450AROM gene expression.
Analysis of the activity of P450AROM gene 1b (I.4)
promoter, which is used dominantly in human osteoblasts,
indicated that the region from -888 bp to -500 bp, which
does not contain a typical vitamin D responsive element, is
responsible for the enhancing effect of 1,25-(OH)(2)D(3).
These results may suggest that adrenal androgen, DHEA, is
converted to estrone in osteoblast by P450AROM, which is
positively regulated by glucocorticoid and
1,25-(OH)(2)D(3), and is important in maintaining BMD in
the sixth to the seventh decade, after menopause.
Brassica vegetables and
breast cancer risk.
Terry, P., Wolk, A., Persson, I., Magnusson, C.
JAMA 2001 Jun 20; 285(23): 2975-7.
No abstract available.
Obesity type and
clustering of insulin resistance-associated cardiovascular
risk factors in middle-aged men and women.
Vanhala MJ, Pitkajarvi TK, Kumpusalo EA, Takala JK.
Pieksamaki District Health Centre, Naarajarvi Health
Station, Finland.
Int J Obes Relat Metab Disord 1998 Apr;22(4):369-74
OBJECTIVE: To examine different clusterings of the
insulin resistance-associated cardiovascular risk factors
with respect to different types of obesity. DESIGN: A
screening programme for obesity (body mass index; BMI>
or =30 kg/m2) and abdominal adiposity (waist-to-hip ratio;
WHR > or = 1.00 in men and > or = 0.88 in women).
SETTINGS: Pieksamaki District Health Centre and the
Community Health Centre of the City of Tampere,
Finland.
SUBJECTS: All volunteers were either aged 36, 41, 46 or
51 y (n=1148) and living in the town of Pieksamaki, with a
control population of 162 subjects in the City of
Tampere.
MAIN OUTCOME MEASURES: Different clusterings of: 1)
hypertension (a systolic blood pressure > or = 160 mmHg
and/or a diastolic blood pressure > or = 95 mmHg or
concurrent drug treatment for hypertension); 2)
hypertriglyceridaemia > or = 1.70 mmol/l; 3) a low level
of high-density-lipoprotein (HDL) cholesterol; < 1.00
mmol/l in men, < 1.20 mmol/l in women; 4) abnormal
glucose metabolism (impaired glucose tolerance or
non-insulin-dependent diabetes) and 5) hyperinsulinaemia
with a fasting plasma insulin > or = 13.0 mU/l.
RESULTS: The prevalence of a cluster consisting of
dyslipidaemia (hypertriglyceridaemia and/or low
HDL-cholesterol) and insulin resistance (abnormal glucose
metabolism and/or hyperinsulinaemia) was found to be 4% in
the control subjects, 18% in the abdominal adipose subjects
(WHR > or = 1.00 in men and > or = 0.88 in women with
a BMI < 30 kg/m2), 28% in the 'pure' obese subjects
(BMI> or = 30 kg/m2 with WHR < 1.00 in men and <
0.88 in women), and 46% in the central obese subjects
(subjects showing both 'pure' obesity and abdominal
adiposity). The prevalence rates of the other clusterings
of abnormalities varied similarly according to the type of
obesity.
CONCLUSION: Clusterings of insulin resistance-associated
abnormalities were related to the type of obesity in both
middle-aged men and middle-aged women.
Fiber, lipids, and
coronary heart disease. A statement for healthcare
professionals from the Nutrition Committee, American Heart
Association.
Van Horn, L.
Circulation 1997 Jun 17; 95(12): 2701-4.
No abstract available.
Epigenetic
downregulation of the retinoic acid receptor-beta2 gene in
breast cancer.
Widschwendter M, Berger J, Muller HM, Zeimet AG, Marth
C. Department of Obstetrics and Gynecology, University of
Innsbruck, Austria. martin.widschwendter@uklibk.ac.at
J Mammary Gland Biol Neoplasia 2001 Apr;6(2):193-201
A growing body of evidence supports the hypothesis that
the retinoic acid receptor beta2 (RAR-beta2) gene is a
tumor suppressor gene which induces apoptosis and that the
chemopreventive and therapeutic effects of retinoids are
due to induction of RAR-beta2. During breast cancer
progression, RAR-beta2 is reduced or even lost. It is known
from studies of other tumor-suppressor genes that
methylation of the 5'-region is the cause of loss of
expression. Several groups demonstrated that this is also
true for the RAR-beta2 in breast cancer by treating breast
cancer cell lines with a demethylating agent and examining
expression of the RAR-beta2 gene in response to a challenge
with retinoic acid. Studies using sodium bisulfite genomic
sequencing as well as methylation specific PCR showed that
a number of breast cancer cell lines as well as breast
cancer tissue showed signs of methylation. The RAR-beta2
gene was unmethylated in non-neoplastic breast tissue as
well as in other normal tissues. A combination of retinoic
acid with demethylating agents as well as with histone
deacetylase inhibitors acts synergistically to inhibit
growth. This review presents data that suggest that
treatment of cancer patients with demethylating agents
followed by retinoic acid may offer a new therapeutic
modality. Both the time of commencement of chemoprevention
and the choice of substances that are able either to
prevent de novo methylation or to reverse
methylation-caused gene silencing may be important
considerations.
Dose-ranging study of
indole-3-carbinol for breast cancer
prevention.
Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J,
Osborne MP. Strang Cancer Prevention Center, New York, New
York 10021, USA.
J Cell Biochem Suppl 1997;28-29:111-6
Sixty women at increased risk for breast cancer were
enrolled in a placebo-controlled, double-blind dose-ranging
chemoprevention study of indole-3-carbinol (I3C).
Fifty-seven of these women with a mean age of 47 years
(range 22-74) completed the study. Each woman took a
placebo capsule or an I3C capsule daily for a total of 4
weeks; none of the women experienced any significant
toxicity effects. The urinary estrogen metabolite ratio of
2-hydroxyestrone to 16 alpha-hydroxyestrone, as determined
by an ELISA assay, served as the surrogate endpoint
biomarker (SEB). Perturbation in the levels of SEB from
baseline was comparable among women in the control (C)
group and the 50, 100, and 200 mg low-dose (LD) group.
Similarly, it was comparable among women in the 300 and 400
mg high-dose (HD) group. Regression analysis showed that
peak relative change of SEB for women in the HD group was
significantly greater than that for women in the C and LD
groups by an amount that was inversely related to baseline
ratio; the difference at the median baseline ratio was 0.48
with 95% confidence interval (0.30, 0.67). No other
factors, such as age and menopausal status, were found to
be significant in the regression analysis. The results in
this study suggest that I3C at a minimum effective dose
schedule of 300 mg per day is a promising chemopreventive
agent for breast cancer prevention. A larger study to
validate these results and to identify an optimal effective
dose schedule of I3C for long-term breast cancer
chemoprevention will be necessary.
Inhibition of
trans-retinoic acid-resistant human breast cancer cell
growth by retinoid X receptor-selective
retinoids.
Wu Q, Dawson MI, Zheng Y, Hobbs PD, Agadir A, Jong L, Li
Y, Liu R, Lin B, Zhang XK. The Burnham Institute, La Jolla
Cancer Research Center, California 92037, USA.
Mol Cell Biol 1997 Nov;17(11):6598-608
All-trans-retinoic acid (trans-RA) and other retinoids
exert anticancer effects through two types of retinoid
receptors, the RA receptors (RARs) and retinoid X receptors
(RXRs). Previous studies demonstrated that the
growth-inhibitory effects of trans-RA and related retinoids
are impaired in certain estrogen-independent breast cancer
cell lines due to their lower levels of RAR alpha and
RARbeta. In this study, we evaluated several synthetic
retinoids for their ability to induce growth inhibition and
apoptosis in both trans-RA-sensitive and trans-RA-resistant
breast cancer cell lines. Our results demonstrate that
RXR-selective retinoids, particularly in combination with
RAR-selective retinoids, could significantly induce RARbeta
and inhibit the growth and induce the apoptosis of
trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells
but had low activity against trans-RA-sensitive ZR-75-1
cells that express high levels of RAR alpha. Using gel
retardation and transient transfection assays, we found
that the effects of RXR-selective retinoids on MDA-MB-231
cells were most likely mediated by RXR-nur77 heterodimers
that bound to the RA response element in the RARbeta
promoter and activated the RARbeta promoter in response to
RXR-selective retinoids. In contrast, growth inhibition by
RAR-selective retinoids in trans-RA-sensitive, RAR
alpha-expressing cells most probably occurred through
RXR-RAR alpha heterodimers that also bound to and activated
the RARbeta promoter. In MDA-MB-231 clones stably
expressing RAR alpha, both RARbeta induction and growth
inhibition by RXR-selective retinoids were suppressed,
while the effects of RAR-selective retinoids were enhanced.
Together, our results demonstrate that activation of RXR
can inhibit the growth of trans-RA-resistant MDA-MB-231
breast cancer cells and suggest that low cellular RAR alpha
may regulate the signaling switch from RAR-mediated to
RXR-mediated growth inhibition in breast cancer cells.
Risks and benefits of
estrogen plus progestin in healthy postmenopausal women:
principal results From the Women's Health Initiative
randomized controlled trial.
Writing Group for the Women's Health Initiative
Investigators Rossouw JE, Anderson GL, Prentice RL, LaCroix
AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA,
Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group
for the Women's Health Initiative Investigators. Division
of Women's Health Initiative, National Heart, Lung, and
Blood Institute, 6705 Rockledge Dr, One Rockledge Ctr,
Suite 300, Bethesda, MD 20817, USA.rossouw@nih.gov
JAMA. 2002 Jul 17;288(3):321-33.
CONTEXT: Despite decades of accumulated observational
evidence, the balance of risks and benefits for hormone use
in healthy postmenopausal women remains uncertain.
OBJECTIVE: To assess the major health benefits and risks of
the most commonly used combined hormone preparation in the
United States. DESIGN: Estrogen plus progestin component of
the Women's Health Initiative, a randomized controlled
primary prevention trial (planned duration, 8.5 years) in
which 16608 postmenopausal women aged 50-79 years with an
intact uterus at baseline were recruited by 40 US clinical
centers in 1993-1998. INTERVENTIONS: Participants received
conjugated equine estrogens, 0.625 mg/d, plus
medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n =
8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The
primary outcome was coronary heart disease (CHD) (nonfatal
myocardial infarction and CHD death), with invasive breast
cancer as the primary adverse outcome. A global index
summarizing the balance of risks and benefits included the
2 primary outcomes plus stroke, pulmonary embolism (PE),
endometrial cancer, colorectal cancer, hip fracture, and
death due to other causes. RESULTS: On May 31, 2002, after
a mean of 5.2 years of follow-up, the data and safety
monitoring board recommended stopping the trial of estrogen
plus progestin vs placebo because the test statistic for
invasive breast cancer exceeded the stopping boundary for
this adverse effect and the global index statistic
supported risks exceeding benefits. This report includes
data on the major clinical outcomes through April 30, 2002.
Estimated hazard ratios (HRs) (nominal 95% confidence
intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63)
with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290
cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13
(1.39-3.25) with 101 cases; colorectal cancer, 0.63
(0.43-0.92) with 112 cases; endometrial cancer, 0.83
(0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98)
with 106 cases; and death due to other causes, 0.92
(0.74-1.14) with 331 cases. Corresponding HRs (nominal 95%
CIs) for composite outcomes were 1.22 (1.09-1.36) for total
cardiovascular disease (arterial and venous disease), 1.03
(0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined
fractures, 0.98 (0.82-1.18) for total mortality, and 1.15
(1.03-1.28) for the global index. Absolute excess risks per
10 000 person-years attributable to estrogen plus progestin
were 7 more CHD events, 8 more strokes, 8 more PEs, and 8
more invasive breast cancers, while absolute risk
reductions per 10 000 person-years were 6 fewer colorectal
cancers and 5 fewer hip fractures. The absolute excess risk
of events included in the global index was 19 per 10 000
person-years. CONCLUSIONS: Overall health risks exceeded
benefits from use of combined estrogen plus progestin for
an average 5.2-year follow-up among healthy postmenopausal
US women. All-cause mortality was not affected during the
trial. The risk-benefit profile found in this trial is not
consistent with the requirements for a viable intervention
for primary prevention of chronic diseases, and the results
indicate that this regimen should not be initiated or
continued for primary prevention of CHD.
Role of retinoid
receptors in the prevention and treatment of breast
cancer.
Yang LM, Tin-U C, Wu K, Brown P. Department of Medicine,
The University of Texas Health Science Center at San
Antonio, 78284, USA.
J Mammary Gland Biol Neoplasia 1999 Oct;4(4):377-88
Retinoids are vitamin A-related compounds that have been
found to prevent cancer in animals and humans. In this
review, we discuss the role of retinoids and their
receptors in the treatment and prevention of breast cancer.
The retinoid receptors are expressed in normal and
malignant breast cells, and are critical for normal
development. In breast cells, when bound by retinoid
hormones, these proteins regulate proliferation, apoptosis,
and differentiation. The mechanism by which retinoids
inhibit breast cell growth has not been completely
elucidated, however, retinoids have been shown to affect
multiple signal transduction pathways, including IGF-,
TGFbeta-, and AP-1-dependent pathways. Retinoids have also
been shown to suppress the growth and prevent the
development of breast cancer in animals. These agents
suppress tumorigenesis in carcinogen-treated rats and in
transgenic mice, and inhibit the growth of transplanted
breast tumors. These promising preclinical results have
provided the rationale to test retinoids in clinical trials
for the treatment and prevention of breast cancer. Several
retinoids, including all trans retinoic acid and 9-cis
retinoic acid, have been shown to have modest activity in
the treatment of breast cancer, and these agents are now in
clinical trials in combination with cytotoxic agents and
anti-estrogens. Another retinoid, 4-HPR, is currently being
tested in a human cancer prevention trial. Preliminary
results suggest that 4-HPR may suppress breast cancer
development in premenopausal women. Future clinical trials
will focus on testing new synthetic retinoids that have
reduced toxicity and enhanced therapeutic and preventive
efficacy.
[Anti-mutagenicity
activity of dehydroepiandrosterone] [Article in
Chinese]
Yang S, Fu Z, Wang F, Cao Y, Han R. Institute of Materia
Medica, Chinese Academy of Medical Sciences, Peking Union
Medical College, Beijing 100050, China.
Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):137-140
OBJECTIVE: The chemopreventive activity and mechanism of
dehydroepiandrosterone (DHEA) were studied. METHODS: Model
of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced
breast carcinoma in Sprague-Dawley rats, uitra-violet
(UV)-induced DNA damage and Salmonella mutation assay were
used. RESULTS: In DMBA-induced rat mammary tumor model, the
rats were orally given daily DHEA for 2 weeks before DMBA
and continued for 10 weeks after DMBA administration. The
results showed significant inhibition of tumor development
by DHEA. The incidence of mammary carcinoma also decreased
significantly on daily dose of oral 25 mg/kg DHEA with the
mean tumor volume per rat also remarkably reduced by 92%.
Moreover, 25 mg/kg DHEA treatment could significantly
increase the carcinoma latency for about 3.5 weeks as
compared with the control. Using polymerase chain reaction
(PCR) assay, in vitro 10(-9) mol/L DHEA showed significant
inhibitory effect on UV-induced DNA damage by 90%. In Ames
test, DHEA was found to decrease DMBA and benzo (alpha)
pyrene-induced TA98 and TA100 His(+) revertants markedly
and the number of Salmonella clones were significantly
reduced by 53.2% and 73.0% on dose of 5 &mgr;g
DHEA/plate. It was also shown that in vitro 10(-7) mol/L
DHEA could also effectively inhibit the G-6-PDH activity,
which might play an important role in its chemoprophylaxis
activities. CONCLUSION: The results strongly prove that
DHEA is a potent cancer chemoprophylaxis agent, which
exhibits inhibitory potential on mutation and chemical
carcinogen in vivo and in vitro.
Replacement of DHEA in
aging men and women. Potential remedial
effects.
Yen SS, Morales AJ, Khorram O. Department of
Reproductive Medicine, University of California, San Diego,
La Jolla 92093, USA.
Ann N Y Acad Sci 1995 Dec 29;774:128-42
DHEA in appropriate replacement doses appears to have
remedial effects with respect to its ability to induce an
anabolic growth factor, increase muscle strength and lean
body mass, activate immune function, and enhance quality of
life in aging men and women, with no significant adverse
effects. Further studies are needed to confirm and extend
our current results, particularly the gender
differences.
Hormonal abnormalities
in obesity.
Zumoff B. Department of Medicine, Beth Israel Medical
Center, New York, NY.
Acta Med Scand Suppl 1988;723:153-60
We have found a number of interesting hormonal
abnormalities in obese men and women: 1) Obese women have
normal levels of estrone, total estradiol, and total
testosterone, but as a consequence of their subnormal
levels of SHBG, their levels of free estradiol and free
testosterone are significantly elevated. 2) Massive weight
loss in obese women (to still elevated weight) results in
normalization of the previously elevated free estradiol and
free testosterone. 3) Obese women have normal plasma DHEA
levels, but a significant, age-invariant decrease of the
plasma DHEA/T ratio, which could be due to increased tissue
activity of 3 beta-hydroxysteroid dehydrogenase. 4) Massive
weight loss produces an age-dependent effect on DHEA levels
in obese women: the levels increase to supranormal values
in women around age 20, with diminishing increases at
higher premenopausal ages and no increase at all at
perimenopausal age. 5) Obese men have elevated levels of
estrone and both free and total estradiol, and subnormal
levels of free and total testosterone and of FSH; all these
abnormalities are proportional to the degree of obesity.
They also have relatively subnormal LH levels, i.e. normal
in the face of hypotestosteronemia. The combination of
these findings represents a state of mild hypogonadotropic
hypogonadism (HHG), which we believe to be induced by the
hyperestrogenemia. 6) Normalizati |