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Menopause before the age of 40 years
Aubard Y.; Teissier M.-P.; Grandjean M.-H.; Le Meur Y.;
Baudet J.-H.
Y. Aubard, Service Gynecologie-Obstetrique I, CHRU Dupuytren,
87042 Limoges Cedex France
Journal de Gynecologie Obstetrique et Biologie de la
Reproduction (France), 1997, 26/3 231-237
Early menopause due to anexhaustion of the ovarian
follicles before the age of 40 years occurs in approximately
1% of women in this age range. Clinical signes of estrogen
deficiency with amenorrhea and sterility are usually confirmed
by hypergonadotrope hypogonadism at laboratory tests. The
syndrome is to be differentiated from gonadotrophine resistant
ovaries and rare gonadotrope adenomas. Ovary biopsy shows more
or less complete destruction of the follicles. There are many
causes of early menopause including abnormal number or
structure of chromosome X in 15-20 % of the cases. Certain
metabolic disorders and viral infections can also be
incrimined. Finally surgery, radiotherapy or chemotherapy can
be the cause of iatrogenic menopause. To determine prognosis,
the woman's follicular capacity must be estimated. Estrogen
therapy is currently the best choice to preserve chances for
ovulation and pregnancy. When there is no remaining follicular
capacity, ovum donation may be a solution. Finally, all
patients should be given hormone substitution therapy due to
the long-term risk of estrogen- progesterone deficiency.
Endometrial cancer and hormone replacement therapy:
Appropriate use of progestins to oppose endogenous and
exogenous estrogen
Sulak P.J.
Dr. P.J. Sulak, Scott and White Clinic, 2401 South 31st
Street, Temple, TX 76508 USA
Endocrinology and Metabolism Clinics of North America (USA),
1997, 26/2 (399-412)
Most instances of endometrial cancer are potentially
preventable. Unopposed endogenous estrogen stimulation of the
endometrium has been shown to be the predisposing risk factor
in most cases. Risk factors have been well-delineated, and it
is important to recognize and treat the progesterone-
deficient patient. Low-dose oral contraceptive pills in
healthy, nonsmoking, older reproductive-aged women are an
underutilized treatment modality. The many noncontraceptive
benefits of long-term oral contraceptive use until the
menopause should be explained to the patient, including the
prevention of ovarian and endometrial cancer, the maintenance
of bone density, and a reduction in the many surgical
procedures performed for menstrual disorders. Progestin
therapy in older reproductive-aged women and postmenopausal
women with unopposed estrogen production is mandatory to
prevent endometrial cancer. Knowledge and skill in simple
endometrial sampling techniques performed in patients with
known risk factors for endometrial cancer will often detect
premalignant lesions that are treatable with progestin therapy
or surgery.
Women's hearts are different
Reis S.E.; Holubkov R.; Zell K.A.
Dr. S.E. Reis, LHAS WPWHC, Division of Cardiology, University
of Pittsburgh Med. Center, Pittsburgh, PA USA
Current Problems in Obstetrics, Gynecology and Fertility
(USA), 1997, 20/3 (72-92)
Cardiovascular disease accounts for nearly 500,000 deaths
in American women each year, half of which may be attributed
to coronary heart disease (CHD). However, most women and many
primary care physicians are not aware that cardiovascular
disease is the leading cause of death of women in the United
States. This misperception may have contributed to the
relative exclusion of women from early cardiovascular clinical
trials; however, the results of these trials have been
routinely generalized to women. It is unclear whether
cardiovascular diagnostic and therapeutic strategies studied
in men may be applied to women, because gender discrepancies
may exist in the pathophysiology of cardiovascular symptoms,
accuracy of diagnostic testing, efficacies of therapies, and
outcomes after cardiac events. Atherosclerosis, the underlying
pathophysiologic abnormality in patients with CHD, may cause
'typical' angina by limiting coronary blood flow during
periods of increased myocardial oxygen demand (e.g., exertion
or emotional stress). The presentation of CHD differs between
men and women. The predominant initial manifestation of CHD in
women is angina, which occurs in 47% of women with CHD
compared with only 32% of men. The predominant presentation of
men with CHD is myocardial infarction (MI), which occurs in
46% of men compared with 32% of women. Although angina is the
predominant initial manifestation of CHD in women, 58% of
women versus 88% of men with 'typical' exertional angina have
angiographically defined coronary atherosclerosis. 'Atypical'
angina is associated with CHD in only 35% of women versus 67%
of men. Therefore the pathophysiology of chest pain is
gender-dependent. Indeed, women are more likely to have chest
pain caused by abnormal coronary vasomotor tone causing large
vessel spasm or inadequate vasodilatation of the coronary
microvasculature. Chest pain resulting from coronary
atherosclerosis is associated with an increased frequency of
adverse cardiac events. Although premenopausal women have a
low incidence of CHD, postmenopausal women are at increased
risk, suggesting that aggressive atherosclerotic risk factor
analysis and treatment is warranted. In addition to gender and
menopausal status, traditional atherosclerotic risk factors
include hypertension, diabetes, dyslipidemia, cigarette use,
and a family history of premature CHD. However, many of these
are not independent risk factors because of their associations
with gender. The magnitude of the effects of these risk
factors also differs between men and women. Because both
pathophysiologic mechanisms of chest pain and prevalences of
significant CHD are gender-related, it is to be expected that
the sensitivities and specificities of cardiovascular tests
differ by gender. Indeed, women have higher false-positive
rates and lower sensitivities of the treadmill exercise
electrocardiographic stress test. Similar findings have been
reported for Thallium-201 exercise stress tests. The low
specificity of noninvasive evaluations of chest pain in women
may contribute to a bias in the clinical evaluation of women.
Several studies have demonstrated that women with chest pain
or cardiovascular syndromes receive diagnoses and are treated
less aggressively than their male counterparts, as manifested
by a lower likelihood of referral for diagnostic coronary
angiography and percutaneous and surgical coronary
revascularization. The under use of invasive diagnostic and
therapeutic cardiovascular procedures in women may be related
to gender discrepancies in cardiac outcomes. For instance,
women who have a myocardial infarction are more likely than
men to die in-hospital or within 1 year and to have post-
myocardial infarction congestive heart failure and stroke.
After being referred for coronary angioplasty or bypass
surgery, women fare worse as manifested by increased
in-hospital mortality and less relief from angina. These
gender discrepancies are at least in part related to older
age, increased prevalences of comorbid diseases, and smaller
caliber coronary arteries in women. Women may reduce their CHD
risk by using postmenopausal hormone replacement therapy.
Meta-analyses of clinical studies suggest that postmenopausal
hormone replacement is associated with a 35% to 50% decrease
in cardiovascular risk. Favorable alteration of the lipid
profile accounts for less than half of estrogen's clinical
cardio-protective effect. Other proposed mechanisms include
direct inhibition of arterial intimal hyperplasia, inhibition
of low-density lipoprotein oxidation, and prevention of
abnormal coronary vasoconstriction. The latter mechanism
suggests that estrogen therapy may be effective in decreasing
symptoms of chest pain in postmenopausal women with coronary
vasospasm or microvascular angina.
Estrogen and the prevention and treatment of
osteoporosis
Battistini M.
Dr. M. Battistini, Department of Obstetrics/Gynecology, 5
Penn Tower, University of Pennsylvania, 33rd Street/Civic
Center Boulevard, Philadelphia, PA 19104 USA
Journal of Clinical Rheumatology (USA), 1997, 3/2 Suppl.
(S28-S33)
Osteoporosis is a systemic skeletal disease characterized
by decreased bone mass and impaired structural integrity of
remaining bone. Due to a decline in circulating estrogen, an
acceleration of bone loss occurs after the menopause.
Osteoclast activity is increased, leading to an imbalance of
bone resorption over formation, resulting in a net loss of
bone. Estrogen is an effective antiresorptive agent used in
both the prevention and treatment of osteoporosis. Estrogen
replacement effectively maintains bone mass and prevents
fractures. Replacement therapy is most effective when it is
initiated soon after the cessation of menses and is continued
long term. Historically, there is a low compliance rate with
long-term therapy in this country. The addition of a progestin
to estrogen replacement is necessary for endometrial
protection but negatively affects patient compliance. The
identification of other significant medical benefits, such as
the reduction of cardiovascular risk and possible amelioration
of Alzheimer's dementia, affirm the cost-effectiveness of
estrogen replacement and may increase its attractiveness to
patients. Clarification of breast cancer risk and improvement
of an individual's side effect profile through use of
different regimens, hormonal preparations, and routes of
administration may enhance compliance.
Neoadjuvant progesterone therapy for primary breast
cancer: Rationale for a clinical trial
Jatoi I.
Dr. I. Jatoi, Department of Surgery, Attn: MCHE-SDG, Brooke
Army Medical Center, 3851 Roger Brooke Drive, San Antonio, TX
78234-6200 USA
Clinical Therapeutics (USA), 1997, 19/1 (56-61)
The hormonal milieu at the time of surgery may influence
mortality and disease-free survival in patients with primary
breast cancer. Indeed, there is evidence that circulating
unopposed estrogen is detrimental and that the presence of
circulating progesterone results in an improved disease-free
and overall survival rate. Thus patients who receive
neoadjuvant progesterone therapy may have a better outcome. A
randomized controlled trial in which women with primary breast
cancer receive either progesterone or placebo before surgery
is urgently needed to confirm this hypothesis.
Cardiovascular pathophysiology of ovarian
hormones
De Ziegler D.
Switzerland
Schweizerische Rundschau fur Medizin/Praxis (Switzerland),
1997, 86/5 (138-144)
Epidemiological data indicate that women are less likely to
suffer from coronary heart disease (CHD) than men of the same
age. This difference vanishes however after menopause
suggesting that it is the hormones produced by the ovaries
that are responsible for the relative cardioprotection that
women enjoy before menopause. In spite of the favorable impact
of oral estrogen treatments on the lipid profile it is
believed today that estrogens act mainly through direct
effects on vessels. Estrogens have vasodilative properties,
exert anti proliferative effects on the endothelium and after
the response of vessels to various stimuli (vaso-reactivity)
such as Acetylcholine (Ach). Direct assessment of large vessel
wall thickness or Intima Media Thickness (IMT) is considered
as the most predictive parameter of cardiovascular risk today
and may serve to single out women who must receive HRT for
cardiovascular reasons.
Hemostasis during hormone replacement therapy
Mammen E.F.
USA
Infertility and Reproductive Medicine Clinics of North
America (USA), 1997, 8/1 (35-48)
There is a major difference in the risk of cardiovascular
disease between men and women before the age of 50 years.
Women have less atherosclerosis until that age which may be
related to a more favorable lipid profile. Post menopause,
however, atherosclerosis develops rapidly, and a deteriorating
lipid profile has been found. Endogenous estrogen and
progesterone may exert a protective effect against
cardiovascular disease before menopause. In addition to
altered lipid profiles, postmenopausal women have changes in
the hemostasis system, generally characterized by increased
clotting factors, especially fibrinogen and factor VII. These
two procoagulants have been identified as independent risk
factors for arterial disease. Thechanges are not specific for
postmenopausal women only but rather are a reflection of
increasing age. Some anticoagulants, especially antithrombin,
also seem to increase with age. These changes in the clotting
system are balanced by an overall increase in fibrinolytic
activity, although some inhibitors of this system increase
with age, suggesting the potential for a hypofibrinolytic
state. The hemostatic alterations could be a reflection of the
increased development of atherosclerotic vessel disease.
Hormone replacement therapy leads to a more favorable lipid
profile in postmenopausal women, including reduced
lipoprotein(a) levels. Lipoprotein(a) is atherogenic and
thrombotic, probably by interfering with the fibrinolytic
system. During HRT, fibrinogen and factor VII levels are
reduced, whereas most other parameters remain unchanged. The
observed reduction in protein S levels is probably clinically
meaningless. In most studies, no increases in molecular
markers of in vivo hemostasis activation have been found,
suggesting that the clotting system is not activated by HRT.
The fibrinolytic system seems to be slightly activated, which
would counteract any increased clottability. All of these
changes are most likely involved in the protection of
postmenopausal women who undergo HRT from arterial
cardiovascular complications. There seems to be no increased
risk for venous thromboembolism with HRT. Exogenous
estrogen/progesterone supplementation in the form of HRT in
postmenopausal women seems to protect against risks for
cardiovascular disease. HRT alters lipid profiles in a more
favorable way and activates the fibrinolytic system without
adversely affecting the clotting system. There is no evidence
that HRT increases the risk for arterial or venous
thromboembolic events.
Androgens and the menopause; a study of
40-60-year-old women
Bancroft J.; Cawood E.H.H.
Dr. J. Bancroft, Kinsey Inst. for Research in Sex, Gender and
Reproduction, Indiana University, Bloomington, IN 47405-2501
USA
Clinical Endocrinology (United Kingdom), 1996, 45/5
(577-587)
Objective: The impact of the menopause on androgen
production is poorly understood. We have investigated the
impact of the menopause, as well as other factors such as age,
body mass index (BMI) and cigarette smoking, on ovarian and
adrenal androgen levels in women aged 40-60 years.
Design: Cross-sectional study of blood hormones sampled
weekly over one month in volunteer 40-60-year-old women.
Subjects: One hundred and forty-one women, aged between 40
and 60, recruited from community sources (non-clinical), not
using hormone replacement or steroidal contraceptives, and
with a current sexual partner. Fifty were categorized as
premenopausal (ovulating), 37 as perimenopausal and 54 as
post-menopausal.
Measurements: The following variables were assessed;
menopausal status (based on menstrual history and pattern and
plasma progesterone), age, BMI, smoking, oestradiol (E2),
oestrone (E1), LH, FSH, total testosterone (TT),
androstenedione (A), SHBG, free androgen index (FAI),
dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulphate
(DHEAS) and cortisol.
Results: Results are based on multiple regression analysis.
TT was positively related to A, BMI and LH. A was negatively
related to age and FSH, and positively to DHEA, DHEAS and
premenopausal status. SHBG was negatively related to BMI and
positively to E1 and non-smoking. DHEA and DHEAS were
negatively related to age and were higher in smokers. Both E1
and E2 were related to menopausal status and to FSH.
Surprisingly, E2 was negatively related to BMI.
Conclusions: A variety of factors influence androgen
production in this age group. Whereas it is difficult to
predict the effect of menopause on androgen levels, LH
stimulation of post-menopausal interstitial cells, modulated
by a variety of factors including nutrition, and smoking, are
likely to be relevant.
Cardiovascular effects of the ovarian
hormones
De Ziegler D.
Dr. D. De Ziegler, Dept. de Gynecologie Obstetrique, Hopital
de Nyon, Suisse et Columbia Research Labs., Paris France
Archives des Maladies du Coeur et des Vaisseaux (France),
1996, 89/Spec.Iss. 7 (9-16)
Women have fewer cardiovascular events before the menopause
than men of the same age but this difference disappears after
the menopause. This observation suggests that ovarian function
may be responsible for the cardiovascular protection. As oral
oestrogenic therapy improves the lipid profile, the
cardioprotective effect of ovarian function was rapidly
attributed to the oestrogens alone. However, it has been
recognised that oestrogens have direct effects on the vessels
which are probably more important than their effects on the
lipids. In all vascular territories studied, oestrogen therapy
to ovariectomised women led to different degrees of
vasodilatation. All points to the fact that this vasodilator
effect of endogenic and exogenic oestrogens is induced by
increased NO production by the endothelium. Even more
important, is that the oestrogens also modify the vascular
response to the action of vasoactive mediators; the hormonal
environment is said to affect the vascular reactivity. It has
been recognised that acetylcholine which causes
vasoconstriction in the absence of oestrogens, has, on the
contrary, a vasodilator effect in the presence of oestrogens.
Clinically, the effect of oestrogens on vascular reactivity is
expressed as a change in the reaction to effort observed in
women suffering from angina pectoris. In these women,
oestrogenisation increases effort capacity (duration of effort
to ST depression), a beneficial effect which is further
amplified by the prescription of a cyclic natural progesterone
administered non-orally, whereas, in the same conditions, one
of the most commonly used progestatives, medroxyprogesterone
acetate (MPA), appears to oppose the beneficial effects of
oestrogen therapy.
The effect of hormones on the lower urinary
tract
Gleeson C.; Cardozo L.
Department of Urogynaecology, King's Coll. Sch. of
Med./Dentistry, Denmark Hill, London SE5 8RX United
Kingdom
Archives of STD/HIV Research (USA), 1996, 10/3
(145-150)
Ageing may be responsible for a wide variety of urogenital
symptoms, influencing both the social and mental functioning
of elderly women. Some symptoms are related to the menopause,
and should therefore be treated with hormone replacement
therapy, however, others require further investigation and
alternative treatment. There have been few randomized
placebocontrolled trials which evaluate the efficacy of
estrogen therapy in the treatment of urinary incontinence,
leading to much debate over the type, dose and route of
administration if, indeed, estrogens are helpful at all. From
the evidence available, it would appear that stress
incontinence is unlikely to be cured by estrogen replacement
therapy alone although benefit may be obtained when used in
conjunction with an alpha-adrenergic agent such as
phenylpropanolamine. Estrogens alleviate irritative bladder
symptoms such as urgency, urge incontinence, frequency,
nocturia and dysuria. They may also be of benefit in
preventing recurrent urinary tract infections. Estrogen
supplementation ameliorates other climacteric symptoms such as
hot flashes, mood swings and leads to better sleep patterns.
This improves the quality of life of postmenopausal women,
making them better able to cope with other problems such as
lower urinary tract dysfunction, which may account for the
high subjective but low objective improvement rates seen. An
holistic approach needs to be taken to the prescription of
hormone replacement therapy of which urogenital problems play
a significant part.
Hormone substances and their efficacy in hormonal
replacement therapy
Fischl F.
Klinische Abt. Gynakologische, Endokrinologie,
Universitatsklinik Frauenheilkunde, Wahringer Gurtel 18-20,
A-1090 Wien Austria
Acta Chirurgica Austriaca (Austria), 1996, 28/5
(259-262)
Background: The most important steroid hormons produced in
the ovary are C 18 (Estradiol, Estron), C 21 (Progesteron) and
C 19 (Testosteron, Androstendion). These hormons play an
important role in the replacement therapy in menopausal women.
They are important substances in the metabolism of the
organism.
Methods: In A review the importance of estrogens, gestagen
and androgens in the hormonal replacement therapy is
summarized.
Results: The lack of estrogens is not only a risk for
osteoporosis, but also negative for the lipid metabolism,
which caused to high incidence of heart attacks and
cardiovascular diseases. Estrogens have a positive effect on
the central nervous system. A lack of these hormons influence
the cognitive efficiency of the brain in a negative way and is
one of the causes for early demenz in later years.
Conclusions: The replacement therapy with estrogens and
gestagens should neutralize the negative effects of the
missing endogenous estrogens and progesteron production.
The effects of various hormone replacement therapy
regimens on bone mineral density after 2 years of
treatment
Celikkanat H.; Moroy P.; Senoz S.; Cettindag I.; Gokmen
O.
Department Obstetrics Gynecology, Dr. Zekai Tahir Burak
Women's Hosp., Ankara Turkey
Marmara Medical Journal (Turkey), 1996, 9/4
(165-168)
Objective: The effects of various hormone replacement
therapies on bone mineral density after 2 years of treatment
were evaluated in this study.
Methods: A total of 138 patients treated with either
conjugated equine estrogen or transdermal 17-beta estradiol
alone or in combination with medroxyprogesterone acetate or
dydrogesterone had bone mineral density measurements of the
first four lumbar vertebrae by using a Dual X-ray Hologic 1000
quantitative digital radiography densitometer.
Results: After 2 years of treatment, a significant increase
in spinal bone mineral density was found in all groups. No
significant differences were found among 6 treatment
groups.
Conclusion: There were no differences between estrogen
replacement therapies and combined hormone replacement
therapies. Progesterone did not have any additional effect on
bone mineral density.
A randomized, double-blind, placebo-controlled,
crossover study on the effect of oral oestradiol on acute
menopausal symptoms
Chung T.K.H.; Yip S.K.; Lam P.; Chang A.M.Z.; Haines
C.J.
Department of Obstetrics/Gynaecology, Prince of Wales
Hospital, Shatin, NT Hongkong
Maturitas (Ireland), 1996, 25/2 (115-123)
Acute menopausal symptoms occur less frequently in Asian
than in Caucasian women. Oestrogen replacement therapy has
been shown to be effective in controlling acute symptoms in
Caucasians, but the effect of oestrogens is not well
documented in Asian women. A randomized, double-blind,
placebo-controlled, crossover study of the effect of oral
oestradiol on the incidence of acute menopausal symptoms was
conducted in 83 Hong Kong Chinese women who had experienced a
surgical menopause. Although there was a significant increase
in the oestradiol concentration with treatment compared with
placebo (P < 0.001), there were no significant differences
in the reporting of symptoms between the treatment and placebo
groups. There is no obvious explanation for this apparent lack
of effect of oestrogen on acute menopausal symptoms in Chinese
women. Whilst it may be related to the generally low incidence
of symptoms or to a higher dietary intake of phytoestrogens in
Chinese women, further studies are necessary to explain these
findings.
The female brain hypoestrogenic continuum from the
premenstrual syndrome to menopause: A hypothesis and review of
supporting data
Arpels J.C.
California Pacific Medical Center, 3838 California Street,
San Francisco, CA 94118 USA
Journal of Reproductive Medicine for the Obstetrician and
Gynecologist (USA), 1996, 41/9 (633-639)
OBJECTIVE: To propose a theory to help unify the symptoms
of premenstrual syndrome (PMS), postpartum blues and
depression, the perimenopausal transition and menopause.
STUDY DESIGN: A review of supporting data is used to
explain the possible neuroendocrine mechanism upon which the
hypothesis is based.
CONCLUSION: The brain in women has been shown to be an
estrogen target organ. Common symptoms are shared by women
complaining of PMS, postpartum blues, the perimenopausal
transition and menopause: depression, sleep disturbance,
irritability, anxiety and panic, memory and cognitive
dysfunction and a decreased sense of well-being. The
antiestrogens progesterone, progestin and tamoxifen may also
elicit these same symptoms. It is proposed that whenever brain
estrogen levels fall below the minimum brain estrogen
requirement, for whatever reason and at whatever age, brain
center dysfunction may ensue.
Treatments for oestoporosis
Patri B.; Taurelle R.
Service de Gynecologie, Hopital Boucicaut, 78, Rue de la
Convention, 75730 Paris Cedex 15 France
Revue Francaise de Gynecologie et d'Obstetrique (France),
1996, 91/6 (329-334)
Preventive therapy for osteoporosis should theoretically be
recommended to women at cessation of menses and to elderly
individuals of either sex. However, therapeutic decisions
depend heavily on individual factors, primarily bone mass
assessed using absorptiometry or other means. Hormone
replacement therapy (HRT) with estrogen-progestogen
combinations is the most effective treatment for women at
menopause but is contraindicated in some patients; the results
of some studies that found a small increase in the breast
cancer risk in patients receiving HRT are open to criticism.
Fluoride therapy has generated considerable controversy but
can continue to be used according to reasonable rules.
Prophylactic calcitonin therapy is expensive and requires
treatment modalities that patients are reluctant to accept.
Supplemental calcium and vitamin D therapy is undeniably
effective, at least in very elderly subjects. Other treatments
are also discussed. Current views held by patients, and
perhaps by some physicians, regarding the value of preventive
treatment for osteoporosis need to be changed.
Variations in steroid hormone receptor content
throughout age and menopausal periods, and menstrual cycle in
breast cancer patients
Nikolic-Vukosavljevic D.; Vasiljevic N.; Brankovic-Magic M.;
Polic D.
Inst. Oncology/Radiology of Serbia, Dept.
Experimental/Clinicl Oncology, 11 000 Belgrade
Yugoslavia
Neoplasma (Slovak Republic), 1996, 43/3
(163-169)
Variations in steroid hormone receptor contents throughout
age and menopausal periods define three breast carcinoma
groups: younger premenopausal carcinomas (aged up to 45),
middle-aged carcinomas (pre-, peri- and postmenopausal aged
45-59) and older postmenopausal carcinomas (aged over 59).
Age-related steroid hormone receptor contents within
premenopausal and postmenopausal carcinoma groups are
characterized by the important increase of both receptor
contents, while menopausal-related steroid hormone receptor
contents within middle-aged carcinoma group (aged 45-59) are
characterized by the important decrease of progesterone
receptor content and estrogen receptor functionality. No
variations in steroid hormone receptor contents throughout
menstrual cycle within the follicular and the luteal phases
were obtained. The important decrease of estrogen receptor
content in the mid-cycle phase versus the perimenstrual phase
was found. Variations in steroid hormone receptor contents
throughout age and menopausal periods, as well as throughout
menstrual cycle could not be associated with variations in the
blood steroid hormone concentrations. However, important
association between steroid hormone receptor contents and the
blood steroid hormone concentrations was found within the
luteal phase carcinoma group and within older postmenopausal
carcinoma group. It is interesting that within carcinoma group
with the highest concentration of progesterone, progesterone
receptor content increases with an increase of the ratio of
estradiol and progesterone blood concentrations, while within
carcinoma group with the lowest steroid hormone concentration
and the highest content of estrogen receptor content, estrogen
receptor content decreases with an increase of either the
blood estradiol concentration or the ratio of the blood
estradiol and progesterone blood concentrations.
Hormone therapy and Phytoestrogens
Lien LL; Lien EJ
Department of Pharmaceutical Sciences, USC School of
Pharmacy, Los Angeles 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 to elicit an oestrogenic
response in animals is compiled.
The menopause and hormone replacement therapy:
Lipids, lipoproteins, coagulation and fibrinolytic
factors
Tikkanen M.J.
Department of Medicine, Division of Cardiology, Helsinki
University Central Hospital, Hartmaninkatu 4, FIN-00290
Helsinki Finland
Maturitas (Ireland), 1996, 23/2 (209-216)
Objectives: To review the recent literature concerning the
effects of the menopause and hormone replacement therapy (HRT)
on the plasma lipoprotein and hemostatic system, as well as on
the interaction between these two coronary heart disease (CHD)
risk factor systems.
Methods: Collection of information from relevant scientific
journals, and by the use of Medline and Current Contents.
Results: The mainly beneficial effects of unopposed oral
estrogen replacement on the plasma lipoprotein pattern are
preserved to different degrees after addition of progestin to
the regimen. Nortestostorone-derived progestins tend to lower
HDL cholesterol levels more than progesterone derivatives. The
slight triglyceride-elevating effect of conjugated equine
estrogens was in a large study not significantly counteracted
by progesterone derivatives but can, according to other
studies, be reversed by nortestosterone-derived progestins, a
limited number of studies on transdermal administration of
estradiol has suggested that the effects on plasma
lipoproteins are smaller than during oral administration.
There is no convincing evidence that currently used HRT
regimens would significantly increase the risk of thrombosis.
Nevertheless, the finding in some studies that plasma
triglyceride elevations could in theory be associated with
impaired fibrinolysis and enhanced coagulation merit further
attention as some HRT regimens tend to increase plasma
triglyceride levels. From a theoretical point of view,
transdermal estrogen delivery would be preferable in women at
risk for thrombosis, as they have less pronounced effects on
liver functions, including production of hemostatic factors
and very-low-density lipoprotein triglycerides.
Conclusions: While the numerous existing HRT regimens
provide many alternative and useful possibilities, further
studies are needed concerning
(a) novel progestins with minimal HDL cholesterol lowering
effects,
(b) transdermal and other non-oral routes for HRT,
(c) possible antioxidative properties of estrogen and
(d) metabolic links between the lipoprotein and hemostatic
risk factor systems.
Prevention of cardiovascular disease by hormone
replacement therapy in the ostmenopause
Windler E.
Med. Klinik und Poliklinik, Universitats-Krankenhaus
Eppendorf, Martinistrasse 52, 20246 Hamburg Germany
Zentralblatt fur Gynakologie (Germany), 1996, 118/4
(188-197)
Cardiovascular disease is the most important cause of death
even among women. After menopause there is a steep increase in
risk factors like LDL-cholesterol and lipoprotein (a) as well
as the incidence of hypertension and diabetes mellitus. This
is followed by a rise especially in coronary artery disease.
Therefore women too have to be included in prevention programs
for cardiovascular disease by normalizing risk factors. One
means is hormone replacement therapy. Estrogens lower
LDL-cholesterol by up to 20% and increase HDL-cholesterol up
to 30%. This effect remains even after addition of a suitable
progestin. Numerous large scale studies indicate that every
other cardiovascular death can be prohibited by the simple
measure of hormone replacement therapy. Because of the high
rate of cardiovascular disease low incidences of adverse
events cannot prevent the marked decrease in total
mortality.
Menopause and osteoporosis: The role of HRT
Carson D.S.
Medical University of South Carolina, Charleston, SC
USA
Journal of the American Pharmaceutical Association (USA),
1996, 36/4 (234-242)
Bone loss resulting from estrogen deficiency is the leading
cause of osteoporosis in postmenopausal women. Oral and
transdermal estrogen can prevent osteoporosis. For most women,
the benefits of hormone replacement therapy (HRT) outweigh any
risks that exist. The recurrence of vaginal bleeding is the
most common reason that women discontinue HRT.
Characterization of reproductive hormonal dynamics
in the perimenopause
Santoro N.; Brown J.R.; Adel T.; Skurnick J.H.
Dept. of Reproductive Endocrinology, New Jersey Medical
School, New Jersey Med./Dentistry Univ., 185 South Orange
Avenue, Newark, NJ 07103-2757 USA
Journal of Clinical Endocrinology and Metabolism (USA), 1996,
81/4 (1495-1501)
Medical therapy for women in the perimenopausal period is
controversial, in part due to varying degrees of ovarian
hormone secretion characteristic of this time of life. To
extend our understanding of the reproductive endocrine milieu
of perimenopausal women, we studied 6 cycling women, aged 47
yr and older, for 6 months with daily collections of first
morning voided urine. Five additional older reproductive aged
(43-47 yr old) women were studied with daily urine and serum
sampling for a single menstrual cycle; their urinary hormone
data were combined with the former group for menstrual cycle
comparisons. Urine was assayed for LH, FSH, estrone
conjugates, and pregnanediol glucuronide and normalized for
creatinine (Cr). Eleven midreproductive aged (19-38 yr old)
normally cycling women, 5 women with well defined premature
ovarian failure, and 5 women aged 54 yr and older who were at
least 1 yr postmenopausal were used for comparison.
Perimenopausal women had shorter follicular phases (11 plus or
minus 2 days vs. 14 plus or minus 1 days; P = 0.031) and,
hence, shorter menstrual cycles than midreproductive aged
controls. FSH excretion in perimenopausal women was greater
than that in younger women (range of means, 4-32 vs. 3-7 IU/g
Cr; P = 0.0005). LH secretion was overall greater than that in
younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2
IU/g Cr; P < 0.026). Overall mean estrone conjugate
excretion was greater in the perimenopausal women compared to
that in the younger women (76.9 ng/mg Cr (range, 13.1-135) vs.
40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023) and was similarly
elevated in both follicular and luteal phases. Luteal phase
pregnanediol excretion was diminished in the perimenopausal
women compared to that in younger normal subjects (range for
integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg
Cr/luteal phase; P = 0.015). Compared to postmenopausal women,
perimenopausal women had more overall estrone excretion
(2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower
mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P =
0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P =
0.041). Compared to women with premature menopause,
perimenopausal women again had lower FSH (range of means for
premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH
(range of means for premature menopause, 5.5-23.8 IU/g Cr; P =
0.0092), borderline higher mean estrone conjugates (range of
means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and
far longer periods of ovarian activity (one to two cycles in
prematurely menopausal women vs. three to six cycles in
perimenopausal women). We conclude that altered ovarian
function in the perimenopause can be observed as early as age
43 yr and include hyperestrogenism, hypergonadotropism, and
decreased luteal phase progesterone excretion. These hormonal
alterations may well be responsible for the increased
gynecological morbidity that characterizes this period of
life.
Effect of menopause and estrogen substitutional
therapy on magnesium metabolism
McNair P.; Christiansen C.; Transbol I.
Department of Clinical Chemistry, Glostrup Hospital,
University of Copenhagen, Glostrup Denmark
Miner. Electrolyte Metabol. (Switzerland), 1984, 10/2
(84-87)
No abstract.
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