La Edad Crítica de la Mujer
MATURITAS Vol. 24
July 1996
R Sobel:. MOODS: A menopause polemic. Maturitas
24: 3 (JUL 1996) :) 125-127
G Berg: The name game. Maturitas
24: 3 (JUL 1996) :129-130
Articles
UH Winkler: Hormone replacement therapy
and hemostasis: Principles of a complex interaction. Maturitas 24:
3 (JUL 1996): 131-145
- Postmenopausal women on hormone replacement therapy
(HRT) have been shown to be at reduced risk of arterial thrombotic disease.
The risk of venous thrombosis appears not to be increased in HRT users
in the absence of specific risk factors. However, while these data refer
predominantly to women using conjugated equine estrogens, it is less clear
whether the favourable impact on cardiovascular diseases may also be achieved
by other preparations. Dose, as well as route of application and, particularly,
the combination of steroids have been shown to affect both the clinical
and the metabolic profile. With regard to cardiovascular diseases, differential
effects on the hemostatic system are of particular interest. The principles
of the interaction of steroids with the hemostatic system are reviewed.
Also, the principal limitations of the assessment of the hemostatic system,
as well as its interpretation, with regard to cardiovascular diseases are
discussed. It is proposed to view the hemostatic system predominantly as
a monitor of endothelial function rather than as a mediator of potential
harmful effects on the cardiovascular system.
UH Winkler : Effects of androgens on haemostasis
.Maturitas 24: 3 (JUL 1996) : 147-155
- Androgen deficiency is associated with an increased
incidence of cardiovascular disease. There is evidence that thromboembolic
disease as well as myocardial infarction in hypogonadic males are mediated
by low baseline fibrinolytic activity. Hypogonadism in males is associated
with an enhancement of fibrinolytic inhibition via increased synthesis
of the plasminogen activator inhibitor PAI 1. On the other hand, stanozolol
and danazol reduce PAI 1 and are associated with increased fibrinolytic
activity. However, in male abusers of anabolic steroids the net effect
on the haemostatic system may change from anti- to prothrombotic; there
appears to be an individual threshold dose above which thrombogenic effects
on platelets and vasomotion may overcome the profibrinolytic effects on
PAI 1. There are numerous reports on weight-lifters dying of atherothrombotic
ischemic heart disease while abusing anabolic steroids. Androgens are known
to have profound effects on carbohydrate and lipid metabolism. In fact,
much of the individual inconsistency of the effects of androgens on fibrinolytic
and haemostatic activity appears to be based on the close interrelationship
of these metabolic systems. Androgens may have unfavourable effects on
the HDL/LDL cholesterol ratio, on triglyceride levels and on the insulin/insulin-like
growth factor 1 (IGF 1) system. Hypertriglyceridemia as well as insulin
resistance are both associated with low fibrinolytic activity and increased
PAI 1 levels. On the other hand, lipoprotein(a), a recently acknowledged
independent risk factor of CVD was shown to respond favourable to androgen
treatment, in men as well as in women. In women, agonistic as well as antagonistic
effects of estrogens and progestins need to be taken into account. In fact,
estradiol may modulate testosterone effects on haemostasis. Androgen medication
in premenopausal women, such as danazol, was found to reduce PAI 1 suggesting
an improvement of the fibrinolytic activity. Also, in hormone replacement
therapy (HRT) androgenic progestins for complex compounds with androgenic
effects are associated with a marked reduction of PAI 1 and an improvement
of fibrinolytic activity. Further improvement of fibrinolytic activity
may be associated with the marked decrease of lipoprotein (a) (Lp(a)) in
women on androgenic HRT. However, little is known on the interrelationship
of estrogens, 19-nortestosterone or progesterone derivatives and testosterone,
an interrelationship that may have substantial impact on the metabolic
and particularly haemostatic net effects of a preparation. In summary,
information on the effects of androgens on haemostasis is limited and may
be particularly incomplete due to the fact that interaction with other
sex steroids appears to be an important confounder. In any case, there
are numerous effects of synthetic androgens on the synthesis and release
of haemostatic factors, namely an increase of the inhibitors of coagulation
and a decrease of the inhibitor of the fibrinolytic system. However, the
use of androgens in patients with congenital deficiencies of these coagulation
factors or previous events of cardiovascular disease has yielded disappointing
results. On the other hand, particularly the reduction of fibrinolytic
inhibition (PAI 1) and Lp(a) were considered favourable effects of androgens
with regard to the risk of cardiovascular disease. Differences between
preparations with pronounced androgenic versus antiandrogenic effects and
the effect of combined preparations need to be studied in much more detail.
The profibrinolytic effects of androgens may be of particular interest
with regard to favourable effects of HRT on cardiovascular disease.
R Mezzopane, E Ricci, L Chatenoud, A Cisternino,
A Chiantera, F Parazzini: Attitudes and clinical practice of Italian
gynecologists towards prophylactic oophorectomy during hysterectomy for
benign conditions. Maturitas 24: 3 (JUL 1996) :157-159
- Objectives.
To evaluate the attitudes of Italian gynecologists towards prophylactic
oophorectomy in women who underwent hysterectomy for benign conditions.
Methods. A postal questionnaire was
sent to 490 physicians in charge in 42 obstetric and gynecologic centres
affiliated to the Association of Italian Obstetrics and Gynecologists.
Results. About 80% of gynecologists perform prophylactic oophorectomy
for women aged more than 50, but this percentage decreases to 50% for patients
aged 45-50. Most gynecologists avoid prophylactic oophorectomy in women
aged less than 40. Conclusions. This
study confirms the wide variability in attitudes of gynecologists towards
prophylactic oophorectomy in women aged 40-50 who undergo hysterectomy
for benign conditions.
JR Hilditch, J Lewis, A Peter, B Vanmaris,
A Ross, E Franssen, GH Guyatt, PG Norton, E Dunn. A menopause-specific
quality of life questionnaire: Development and psychometric properties.
Maturitas 24: 3 (JUL 1996) :161-175
- Objective:
To develop a condition-specific quality of life questionnaire for the menopause
with documented psychometric properties, based on women's experience. Methods:
Subjects: Women 2-7 years post-menopause with a uterus and not
currently on hormone replacement therapy. Questionnaire development: A
list of 106 menopause symptoms was reduced using the importance score method.
Replies to the item-reduction questionnaire from 88 women resulted in a
30-item questionnaire with four domains, vasomotor, physical, psychosocial
and sexual, and a global quality of life question. Psychometric
properties: A separate sample of 20 women was used to determine
face validity, and a panel of experts was used to confirm content validity.
Reliability, responsiveness and construct validity were determined within
the context of a randomized controlled trial. Construct validation involved
comparison with the Neugarten and Kraines' Somatic, Psychosomatic and Psychologic
subscales, the reported intensity of hot flushes, the General Well-Being
Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index,
and the Life Satisfaction Index. Results:
The face validity score was 4.7 out of a possible 5. Content validity was
confirmed. Test- retest reliability measures, using intraclass correlation
coefficients were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial,
sexual domains and the quality of life question. The intraclass correlation
coefficient for the vasomotor domain was 0.37 but there is evidence of
systematic change. Discriminative construct validity showed correlation
coefficients of 0.69 for the physical domain, 0.66 and 0.40 for the vasomotor
domain, 0.65 and -0.71 for the psychosocial domain, 0.48 and 0.38 for the
sexual domain, and 0.57 for the quality of life question. Evaluative construct
validity showed correlation coefficients of 0.60 for the physical domain,
0.28 for the vasomotor domain, 0.55 and -0.54 for the psychosocial domain,
0.54 and 0.32 for the sexual domain, and 0.12 for the quality of life question.
Responsiveness scores ranged from 0.78 to 1.34. Conclusions:
The MENQOL (Menopause-Specific Quality of Life) questionnaire is
a self-administered instrument which functions well in differentiating
between women according to their quality of life and in measuring changes
in their quality of life.
R Hilditch, J Lewis, AH Ross, A Peter, B Vanmaris,
E Franssen, J Charles, P Norton, EV Dunn .A comparison of the effects
of oral conjugated equine estrogen and transdermal estradiol-17 beta combined
with an oral progestin on quality of life in postmenopausal women .Maturitas
24: 3 (JUL 1996) :177-184
- Objective:
To compare the effect of transdermal estradiol-17 beta and oral conjugated
equine estrogen when combined with an oral progestin on quality of life
in post-menopausal women. Design: Randomized
controlled double-blind trial. A randomization error lead to the exclusion
of six subjects but the soundness of the remaining randomization was confirmed.
Setting: Large urban community. Patients:
Women 2-7 years after menopause with a uterus and ovaries, and not currently
using hormone replacement therapy. Seventy-four women completed the trial.
Interventions: After baseline measures of quality of life, subjects were
randomly assigned to either continuous oral conjugated equine estrogen
0.625 mg daily or continuous transdermal estradiol-17 beta 50 meg twice
weekly, for four 4-week cycles. Medroxyprogesterone acetate 10 mg oral
tablets was administered to both groups for the last 12 days of each cycle.
Outcomes measured: Quality of life was determined using the Menopause-Specific
Quality of Life Questionnaire. Tolerability was determined by a specifically
designed list of adverse effects, Both measures were recorded at base-line
and in mid- cycle during the second, third and fourth cycles of treatment.
Results: There were no statistically
significant differences in any of the domains at baseline between the oral
and transdermal treatment groups. In the vasomotor domain, scores for the
oral and transdermal groups improved from baseline levels of 3.14 and 3.09,
respectively, to 1.32 and 1.23; physical domain scores improved from 2.45
and 2.73 to 2.04 and 1.78; psychosocial domain scores improved from 2.72
and 3.04 to 2.21 and 1.94; sexual domain scores improved from 2.32 and
2.16 to 1.64 and 1.30. There were no statistically significant group differences
or time/group interactions. Both forms of therapy were equally well tolerated.
Conclusions: Improvement in all domains, measured by the Menopause-Specific
Quality of Life Questionnaire, was observed in both the oral and transdermal
groups. In the absence of a placebo control group, the improvements observed
cannot be attributed solely to the therapy. Neither form of therapy offered
an advantage over the other in respect to improvement in quality of life.
H Benaryeh, I Gottlieb, S Ishshalom, A David,
H Szargel, D Laufer . Oral complaints related to menopause . Maturitas
24: 3 (JUL 1996) :185-189
- Objectives:
The purpose of the present study was to correlate oral and systemic symptoms
of menopause and the oral health and salivary composition and flow rate
in a group of women in menopause prior to hormone replacement therapy.
Methods: One-hundred fifty-four women
attending a menopause clinic were divided into two groups. Group A,58 women,
without any systemic disease or treatments, and Group B,96 women with diseases
and on various medications. They answered a questionnaire on their general
health and oral and systemic complaints related to menopause. Fifty-four
of the women agreed to have an oral examination and saliva analysis. Whole
resting and submandibular (SM-SL) stimulated saliva were analyzed. Results:
The oral discomfort complaint was found in 45% in Group A and in 60% in
Group B. 74% complained of climacteric symptoms in Group A and 63% in Group
B. The odds ratio (OR) between oral discomfort and climacterics complaints
of menopause was 8.03 in Group A and 4.08 in Group B. The salivary composition
and flow rates did not differ significantly between the groups of menopausal
women. However the salivary total protein and IgA concentrations were significantly
higher in comparison to healthy young controls. Conclusions:
The present study reports a high prevalence of oral discomfort in the women
attending a menopause clinic. A highly significant odds ratio between systemic
and oral complaints of menopause was found. The significantly altered salivary
composition in these women might point to sympathetic activation due to
psychological stress.
F Parazzini, A Tavani, E Ricci, C Lavecchia
. Menstrual and reproductive factors and hip fractures in post menopausal
women . Maturitas 24: 3 (JUL 1996) : 191-196
- Objectives: We analyzed the relationship between
menstrual and reproductive history and risk of hip fractures in post-menopausal
women using data from an Italian case-control study. Methods: Cases were
206 post-menopausal women admitted for fractures of the hip/proximal femur
to a network of teaching and general hospitals in Milan, Italy. The comparison
group consisted of 590 post-menopausal women admitted to the same network
of hospitals for acute, non-neoplastic, non-hormone-related conditions,
other than traumatic or orthopedic disorders. Odds ratios (OR) of hip fracture
were derived from unconditional multiple logistic regression. Results:
No relation emerged between risk of hip fractures and age at menarche,
lifelong menstrual cycle pattern and age at menopause. In comparison with
women with age at menopause greater than or equal to 53 years, the multivariate
OR of hip fractures were 1.2, 1.1, 1.2 and 0.5 in women with menopause
at 50-52, 45-49, 40-44 and before 40 years (X(1)(2) trend 0.21). In comparison
with nulliparae, the estimated age-adjusted OR was 0.6 (95% confidence
interval, CI, 0.4-0.9) for parous women, but the multivariate estimate
was not significant (OR 0.8, 95% CI 0.6-1.3) and the multivariate trend
in risk with number of births was not significant either. No relation emerged
between hip fractures and age at first and last birth, and history of abortions.
Conclusions: This study found no relevant influence of menstrual and reproductive
factors on the risk of hip fractures in post-menopausal women. However,
this is not in contrast with the observation of a short-term effect of
menopause and, more in general, female hormone levels on osteoporosis and
hence on hip fractures. ISBN/ISSN 0378-5122 Publisher Elsevier Sci Ireland
Ltd, Customer Relations Manager, Bay 15, Shannon Industrial, Estate Co,
Clare, Ireland
C Falconer, G Ekmanordeberg, U Ulmsten, G Westergrenthorsson,
K Barchan, A Malmstrom. Changes in paraurethral connective tissue at
menopause are counteracted by estrogen. Maturitas 24: 3 (JUL
1996): 197-204
- Objective:
To study whether the transition to menopause is accompanied by changes
in the paraurethral connective tissue and if these changes are modified
by estrogen replacement therapy. Study design:
Biopsies were obtained from the paraurethral tissue from 34 women; 12 menstruating,
14 postmenopausal without estrogen treatment, and 8 with estrogen treatment.
Collagen concentration and collagen extractability by pepsin digestion
were measured. Proteoglycan composition and concentration were analysed
using Alcian blue. The mRNA levels for collagen I and III, the small proteoglycans
(PGS) decorin and biglycan, and the large proteoglycan versican, were estimated.
Results: The paraurethral biopsies
consisted of fibrous connective tissue, with collagen fibers as dominating
structure. Several proteoglycans were identified; versican, heparansulphate
proteoglycans, biglycan and decorin. The small proteoglycan decorin represented
85% of all proteoglycans. The collagen concentration was almost doubled
in postmenopausal biopsies compared to premenopausal. The collagen fibril
organization was also changed with higher cross-linking after menopause
whereas the amount and the composition of the proteoglycans were unchanged.
The proteoglycan/collagen ratio was significantly decreased. Estrogen replacement
therapy resulted in decreased collagen concentration, decreased cross-linking
of the collagen and reversal of the PGS/collagen ratio to almost premenopausal
level. The therapy resulted in increased levels of mRNA for collagen I
and III which suggests that the changes are due to an increased turnover.
Conclusion: The decrease in estrogen
levels at menopause results in a connective tissue with different qualities
after menopause. Estrogen replacement therapy tends to restore the metabolism
of the genitourinary connective tissue to premenopausal conditions.
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