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PubMed1977

[Coronary insufficiency in the female: possible effect of menopause].

A population of 239 women suffering from chronic coronary disease was divided into two groups according to whether or not they had sustained a myocardial infarction. For the 226 post-menopausal women, the type of menopause (natural or artificial) and their age at its onset were determined, together with the age of onset of the infarction or angina, and possible correlations with other risk factors in atherosclerosis. Whilst the average age at the time of artificial menopause was markedly less than that of natural menopause, the age of onset of coronary complications was comparable regardless of the type of menopause, this applying to both groups. Contrary to a classically accepted opinion, early menopause would not appear to favourise the premature development of atherosclerotic coronary problems, and, in addition, would not appear to affect other coronary "risk factors".

Adult↗

PubMed1978

Age at menarche and menopause of uterine cancer patients.

An investigation was undertaken of the ages at menarche and at menopause of cervical and endometrial cancer patients for the years 1950-55 and 1960-65. Analysis of the ages at menarche in relation to the year of birth did not show a difference between the uterine cancer groups, whereas the age at menopause did show such a difference. The menopause occurred later in the endometrial than in the cervical cancer group. There was an earlier mean age at menarche and a later mean age at menopause per decade. Therefore, the menopause seems a constitutional factor involved in the development of endometrial cancer and perhaps also cervical cancer.

Adolescent↗

PubMed1976

Hormonal profiles after the menopause.

The endocrinological changes of the climacteric have been defined by studying the concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), androstenedione, testosterone, oestrone, and oestradiol in 60 normal postmenopausal women of different menopausal ages. The women were studied in six groups, according to the number of years since their menopause. One year after the menopause androstenedione, oestrone, and oestradiol concentrations were reduced to about 20% of the values recorded during the early proliferative phase of the menstrual cycle. At the same time the mean concentration of FSH had risen by a factor of 13-4 and that of LH by a factor of 3-0. Concentrations of both gonadotrophins reached a peak of 18-4 and 3-4 times the proliferative phase value respectively after two to three years, and then gradually declined in the next three decades to values that were 40-50% of these maximal levels. Testosterone concentrations remained mostly in the normal range for premenopausal women but were depressed to 60% of these levels two to five years after the menopause, and the mean androstenedione levels showed a significant increase in the same group of women. The concentrations of both oestrone and oestradiol remained consistently low for 10 years after the menopause, but oestradiol concentrations inexplicably increased in the last two decades, with levels at the lower end of normal range for reproductive women in six patients.

Age Factors↗

PubMed1978

Menopause and coronary heart disease. The Framingham Study.

A rise in coronary heart disease incidence after menopause and a dramatic increase in the severity of the presenting diseases are noted in a cohort of 2873 Framingham women who were followed up for 24 years. No premenopausal woman developed a myocardial infarction or died of coronary heart disease. Such events were common in postmenopausal women. Even in women under 55, 40% of the postmenopausal coronary heart disease presented in these more serious forms, whether menopause was natural or surgical. The contrast was especially marked in the age group 40 to 44 years. In the age groups 45 to 49 and 50 to 54 years, incidence rates in menopausal and postmenopausal intervals were more than double those in premenopausal intervals, whether menopause was natural or surgical. In surgical menopause there was excess incidence whether the ovaries were removed or not. Postmenopausal women on hormones had a doubled risk of coronary heart disease.

Adult↗

PubMed1976

[The diagnosis of corpus carcinoma (Differentialdiagnostic importance of history- and clinical criteria in post-menopausal hemorrhage) (author's transl)].

Among 1554 patients with post-memopausal hemorrhage over 7 years one half were due to benign causes, the other in almost equal parts to carcinoma of the fundus or cervix. Ca of the fundus is more likely when post-menopausal bleeding occurs at a relatively old age, a late menopause and a long interval between menopause and post-menopausal bleeding. Nulliparae more often have Ca of the corpus than in the cervix or have benign changes. The trias known for the corpus Ca: adiposity, diabetes and hypertension is confirmed. An enlargement or softening of the uterus and myomatous changes also indicate Ca. Anatomical and clinical criteria permit not only a detailed assessment of post-menopausal bleeding but also a definition of cases at risk before bleeding occurs and give an indication for detailed investigations.

Age Factors↗

PubMed1979

Probability of menopause with increasing duration of amenorrhea in middle-aged women.

The empirical percent probability that natural menopause has occurred after first presentation of amenorrhea of various durations in women greater than or equal to 45 years of age has been calculated using data from a cohort of subjects who prospectively recorded menstrual flow and related gynecologic events. The probability that menopause has occurred increases with the amenorrheal interval (duration), and for a given interval, the probability increases with age. After 180 days of amenorrhea, 45% to 72% of subjects were menopausal; after 360 days, 90%. These data may offer assistance in advising patients on the probability of menopause and the continuance of contraceptive practices, and in considering whether late genital bleeding after amenorrhea represents a physiologic or pathologic process.

Age Factors↗

PubMed2026

Menopausal timing and senescent-immune coupling in age-related lobular involution of the human breast: a longitudinal cohort study.

BACKGROUND: Incomplete postmenopausal breast involution leaves persistent epithelial-rich lobules and elevated breast density in about 40% of women and is associated with higher breast cancer risk, but why remodelling stalls remains unclear. METHODS: We studied a longitudinal cohort of 81 women with paired benign breast biopsies (baseline age 45-55 years; follow-up 2-10 years), all with baseline NanoString transcriptomics and two-timepoint digital morphometry, and with multiplex immunofluorescence in spatial-imaging subsets (baseline n = 14-16 depending on panel; follow-up n = 14). A separate postmenopausal endpoint cohort (12 women: eight noninvoluted, four completely involuted), profiled by genome-wide expression array and multiplex immunofluorescence, defined the persistent-lobule phenotype. FINDINGS: Noninvoluted postmenopausal tissue retained a proliferation-competent, tumour-associated epithelial state and showed immune accumulation at lobular boundaries with reduced access to p16+ (senescence-associated) epithelial foci. The same SASP and innate immune programmes that predicted slower involution across the menopausal transition predicted faster involution after menopause. Follow-up boundary CD45→p16 engagement was directionally consistent with this reversal in Pre→Post and Post→Post women. Spatial imaging resolved this reversal into a perimenopausal stall architecture and a postmenopausal clearance-associated architecture marked by direct CD16+ innate-effector engagement of p16+ epithelium; macrophage targeting provided convergent support (two-sided exact permutation interaction p = 0.0077). INTERPRETATION: Menopausal timing conditions whether senescent-immune programmes couple to productive clearance or to spatially uncoupled surveillance and persistent risk-associated tissue. Biomarker interpretation should therefore be anchored to menopausal timing. FUNDING: Casey DeSantis Cancer Fund and US National Cancer Institute.

Humans↗

PubMed1976

Exogenous estrogens and breast cancer in women with natural menopause.

Age, age at menopause, and calendar year at menopause were controlled as factors related to estrogen use. Data on 90 breast cancer patients and 83 conrols--all of whom had a natural menopause--showed no relationship between breast cancer and estrogen usage after the start of menopause symptoms.

Age Factors↗

PubMed1978

Sex hormone concentrations in post-menopausal women.

Plasma sex hormone concentrations (testosterone, (T), androstenedione (A), oestrone (E1) and oestradiol (E2) were measured in forty post-menopausal women more than 4 years post-normal menopause. Correlations between these and age, years post-menopause (YPM), degree of obesity and fat mass respectively were studied. T and A, as well as E1 and E2 were positively correlated (P less than 0.01), but no statistically significant correlation between A and E1 was observed. Sex hormone concentrations in this group of postmenopausal women (greater than 4YPM) did not show any variation as a function of age, with the possible exception of E2 which showed a tendency to decrease in the late post-menopause. E1 and to a lesser extent E2 as well as the E1/A ratio were significantly corelated with degree of obesity or fat mass, suggesting a possible role of fat tissue in the aromatization of androgens. Neither the T/A nor the E2/E1 ratios were correlated with fat mass, suggesting that the reduction of 17 oxo-group does not occur in fat tissue. The E1/A ratio was significantly higher than the reported conversion rate of A in E1. This might suggest the existence of an additional precursor of plasma E1.

Age Factors↗

PubMed1979

The vaginal flora after natural or surgical menopause.

A study was made of the cervical and upper vaginal flora in menopausal women, in an attempt to determine whether such women are predisposed to infections when undergoing gynecologic operations. The series comprised 72 women (age range, 44-80 years) classified as follows: a) 35 with a natural menopause, b) 18 with a surgical menopause induced by abdominal panhysterectomy, and c) 19 postmenopausal women after vaginal hysterectomy performed for genital prolapse. The vaginal flora of these menopausal women consisted predominantly of Gram-positive bacteria which, together with the Gram-negative bacteria, conformed to the normal pattern of microorganisms in the vagina. Such bacteria also are found in women of child-bearing age, but occasionally they can be pathogenic. Despite the inherent biohormonal changes of the memopause, expressed especially by the low estrogen level, 26.4 percent of the cultures in our study were sterile, even after major vaginal operations. Thus, the pattern of the vaginal flora, even though occasionally pathogen, should not be a contraindication to gynecologic surgical procedures in postmenopausal women. Even when vaginal cultures show the presence of these bacteria, it does not seem necessary to use prophylactic antibiotic and hormonal therapy routinely. Rather, it should be given selectively, depending upon the local state of the tissues and upon the postoperative course.

Adult↗

PubMed1976

The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.

Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.

Adolescent↗

PubMed1976

Difference between effects of conjugated estrogen on neurotics and non-neurotics of climacteric women complaining of menopausal symptoms and its clinical application for their screening.

In order to screen the neurotics and non-neurotics of climacteric women with menopausal symptoms, conjugated estrogen was injected intravenously and the reactions were compared. Menopausal symptoms were represented by Kupperman's menopausal index. After estrogen injection the non-neurotics showed a decrease of the index, i.e., alleviation of the symptoms, while the neurotics showed no change of the index. Taking advantage of this difference, a discriminant function between neurotics and non-neurotics was calculated using, as variables, Kupperman's menopasual indices determined before and after administration of the conjugated estrogen. The calculative screening obtained from this discriminant function yielded consistency with clinical diagnosis in about 94% of the neurotics and about 87% of the non-neurotics, suggesting that this test is of value in the screening of neurotics and non-neurotics in the climacteric women with menopausal symptoms.

Adult↗

PubMed1977

Acute effects of intravenous infusion of conjugated estrogen on serum levels of LH and FSH in post-menopausal and castrated women.

In order to quantify the changes of feed-back effect of estrogen on the release of pituitary gonadotropin which is regulated by the hypothalamic-pituitary-ovarian system, the responses of LH and FSH to the intravenous infusion of 20 mg of conjugated estrogen were studied in 49 post-menopausal and 20 castrated women. In the group of women within 1 year after menopause, serum LH levels were elevated following the infusion of the conjugated estrogen. The responses of serum LH and FSH levels were different between post-menopausal and castrated women. The data indicated that the difference between the two groups was probably due to the difference of secrection patterns of the gonadotropins in post-menopausal and castrated women.

Adult↗

PubMed1977

Oestrogens and menopausal and postmenopausal women.

The majority of women experience a variety of symptoms at the time of the menopause, but these are frequently regarded as being unworthy of management by their doctors. Recent reports of a possible association between exogenous oestrogens and endometrial carcinoma have increased professional reluctance to prescribe oestrogens for menopausal symptoms. This report describes the initial 50 patients who have attended a special clinic established to manage symptomatic menopausal women; common complaints included hot flushes, lack of energy, altered temperament, dyspareunia and headache. Oestrogen therapy was effective in the alleviation of symptoms and the practical aspects of oestrogen use are discussed. It is recommended that with due recognition of its potential complications, oestrogen therapy should be made available to symptomatic menopausal women, and that it requires further study in regard to its place in the long-term prophylaxis of osteoporosis.

Climacteric↗

PubMed1975

[Menopause: apropos of some psychological and psychiatric aspects].

Menopause, begining of woman's involutional period, may (or must) be systematically treated by estrogens, preventing most of immediate or later menopausel complications and limitating effects of aging. This use of estrogens (which causes many controversies and resistances) has also probably a positive neuropsychic effect. The author reminds classical psychopathological explanations supporting mental troubles of this period which are usually considered as reaction to a crisis, instead properly psychiatric diseases are included in involutional pathology. A short review of psychiatric litterature indicates that psychiatrists refuse any specificity to menopausal psychic troubles. He points out also "the phobia of menopause", the increasing fear of old age in a "youth culture", in spite of progress of woman emancipation, social liberation following biological liberation (birth control, decrease of child mortality, etc). The reports of Jaszmann and Van Keep and Kellerhars are summarized. They show the main role of sociological, economical and familial factors in appearance, intensity and duration of climacteric troubles and progressive degradation with aging of: personnal integration, intellectual and cultural integration, and human relation-ships, and mental sanity. These reports seem to indicate that menopause is only a critical period of the slow process of aging and decadence. But systematic estrogen treatment and improvement of femine social condition should change drasticelly these troubles and this decadence.

Adult↗

PubMed1975

[The influence of menopause on prognosis of breast cancer (author's transl)].

Between 1949 and 1968, 1369 female patients received primary treatment for breast cancer in the Robert-Rössle-Clinic of the Central Institute for Cancer Research of the Academy of Sciences of the GDR. Using a sequential procedure based on decision theory, the influence of menopause on prognosis of breast cancer was investigated in clinical stage I--III. The following rank order of negative prognostic signs was found in the 365 patients of 46-55 years age (5-year survival rate in braquets): skin involved beyond breast (0%); inflammatory type of cancer (0%); fixation of chest wall (0%); radiation treatment only (10%); tumor diameter in surgical specimen 5 cm and more (26%); tumor diameter 10+ cm by clinical examination (31%); skin ulceration (0%); axillary lymph nodes considered to contain growth (40%); menopause (59.7%). 85% of menstrating patients without these adverse prognostic signs survived for more than 5 years. Taking into consideration other observations, it is suggested that breast cancer before menopause is mostly oestrogen-dependent. When the ovary ceases to produce oestrogens in the next future, the cancer looses hormonal stimuli necessary for growth. This interpretation is in agreement with the observations that younger menstruating women show a definitely worse prognosis (5-year survival rate 55,8%). In controlled clinical trials, patients before and after menopause should be randomized separately.

Breast Neoplasms↗

PubMed2026

Early-adulthood body mass index, mammographic density and post-menopausal breast cancer risk: a mediation analysis.

BACKGROUND: To explore potential mechanistic pathways and inform prevention strategies, this study examined whether mammographic density (MD) mediates the inverse association between higher early-adulthood body mass index (BMI) and lower post-menopausal breast cancer risk. METHODS: We analysed data from 33,816 post-menopausal women in the UK PROCAS cohort, with self-reported BMI at age 20. MD was measured using full-field digital mammography and assessed using the visual analogue scale (VAS) percentage density and Volpara®-derived fibroglandular volume (FGV). Counterfactual mediation modelling estimated natural direct and indirect effects. RESULTS: Over a median follow-up of 10.44 years, there were 1261 new post-menopausal breast cancers. Higher VAS and FGV were associated with increased breast cancer risk. BMI at age 20 was associated with lower VAS density and reduced breast cancer risk [Hazard Ratio per 5 kg/m²: 0.849 (0.771-0.938)]. The calculated proportion mediated by VAS density was 59.9% (32.6-150), after accounting for intermediate confounding by BMI in later adulthood. FGV was positively associated with higher BMI at cohort entry but not at age 20. CONCLUSIONS: Lower VAS density may partially explain the inverse association between early-adulthood BMI and post-menopausal breast cancer risk. The link between FGV and breast cancer risk may represent a different biological pathway.

Journal Article↗

PubMed2026

Differential Effectiveness of Adjuvant Endocrine Therapy According to Menopausal Status, Body Mass Index, and Molecular Subtype in Hormone Receptor-Positive Breast Cancer.

The effectiveness of adjuvant endocrine therapy for hormone receptor-positive (HR+) breast cancer (BC) varies according to menopausal status, body mass index (BMI), and tumor biology. We evaluated the association between selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and BC-specific mortality according to menopausal status, BMI, and molecular subtype in a nationwide Korean cohort. We analyzed data from 31,030 patients with HR+ BC who were registered in the Korean Breast Cancer Society Registry, diagnosed between 2000 and 2008, and followed through 2013. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BC-specific mortality after adjusting for demographic and clinical factors. Of the 31,030 patients, 19,634 received SERM therapy, and 3,354 received AI therapy. SERM use was associated with lower BC-specific mortality in premenopausal women (HR, 0.75; 95% CI, 0.63-0.91), whereas AI therapy was more strongly associated with lower BC-specific mortality among postmenopausal women (HR, 0.76; 95% CI, 0.61-0.94). Lower BC-specific mortality was observed among patients with a BMI ≥ 23 kg/m² who received SERM (HR, 0.84; 95% CI, 0.72-0.98) or AI therapy (HR, 0.78; 95% CI, 0.62-0.99). The strongest association with lower BC-specific mortality was observed in postmenopausal women with luminal B tumors (HR, 0.59; 95% CI, 0.42-0.83). The association between adjuvant endocrine therapy and BC-specific mortality differed according to menopausal status, BMI, and molecular subtype. These findings suggest that menopausal status, BMI, and molecular subtype are important considerations when evaluating endocrine treatment strategies.

Aromatase Inhibitors↗