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Biomedical subjects

G Samsioe

Publications and source records attributed to G Samsioe.

At least 37 records · Page 2Linked to original sources
PubMed1998

Urogenital aging--a hidden problem.

Urogenital problems in the elderly female population are experienced by one third of women from the age 50 years and onward. Symptoms from the lower urinary tract include incontinence, urethritis, and recurrent urinary tract infections. Atrophic changes within the bladder neck and urethra could be corrected by estrogen administration even at doses so low that endometrial proliferation is avoided. Hence such estrogens could be given without progestogen comedication. Control of micturition is a complex process of which estrogen deficiency is only one of several factors. The aging process with subsequent changes in membrane permeability, neuromuscular function, and collagen synthesis contributes to the local problems of control of micturition. In addition, the central control may also be affected by degenerative changes of the nervous system. Vaginal symptoms comprise dryness of vagina, dyspareunia, and recurrent vaginitis often followed by a foul odor and discharge. The microflora with lactobacilli and low pH as seen in fertile women is gradually replaced by a mixed germ flora including several of the pathogenic organisms common in urinary tract infections. Vaginal pH increases from around 4 to between 6 and 7. It is a puzzling fact that the urogenital tissues seem to be more "sensitive" to estrogens than other tissues. Conformational changes of the estrogen receptor(s) brought about by the local cytokine milieu is one possibility to explain the situation. The systemic absorption of low-dose estrogen preparations is dependent on the status of the vaginal mucosa. Absorption is high when the vaginal mucosa is atrophic and gradually decreases (but not to zero) as the vaginal mucosa matures under estrogen influence.

Aged↗
PubMed1998

Electrocardiogram pattern in hypercholesterolemic women: the influence of hormone replacement therapy.

OBJECTIVE: The aim of this study was to delineate electrocardiogram (ECG) patterns in postmenopausal women with hypercholesterolemia and to assess the possible influence of female sex hormones. STUDY DESIGN: A total of 72 postmenopausal women with moderately elevated total cholesterol levels constituted the case group, of which 48 came from a clinical trial and 24 from a cohort study. Some 236 women aged 50-59 years with normal levels of cholesterol were participants in the same cohort study in the local area. These 236 women had been subdivided into three groups: premenopausal, postmenopausal and postmenopausal with hormone replacement therapy (HRT). Of the 48 women in the clinical study group, 12 patients showed pathological ECG changes. Six of these patients were treated with HRT for 2 years (transdermal estradiol 50 micrograms/day and a daily dose of 5 mg medroxyprogesterone acetate, MPA) and the rest were non-users of HRT. RESULTS: In the women with hypercholesterolemia, 16 of 72 patients (22%) showed ischemic ECG changes, compared to nine of 88 (10%) with normal cholesterol levels (p = 0.04). We found no significant difference in the prevalence of ECG changes between postmenopausal women with and without HRT in the groups with normal levels of cholesterol. In the hormone treatment group, four of six patients showed an improvement in ECG pattern, in contrast to two of six non-users of HRT. CONCLUSIONS: This preliminary study revealed a higher prevalence of pathological ECG changes in postmenopausal women who had hypercholesterolemia than in normocholesterolemic women. These findings support the idea that hyperlipidemia contributes to the overall increase in cardiovascular disease, as this is also associated with ECG changes. Transdermal estradiol combined with MPA has a beneficial effect in reversing the process of atherosclerosis, as well as improving the ECG pattern. The prevalence of pathological ECG patterns was similar for HRT users and non-users. This outcome may be affected by several factors. Hence, further research is warranted.

Aged↗
PubMed1997

A study of European womens' experience of the problems of urogenital ageing and its management.

OBJECTIVES: A six country Pan-European study of aspects of urogenital ageing (UGA). METHODS: The study was carried out using a stratified random sample of 3000 women between the ages of 55 and 75 years. RESULTS: A total of 30% suffered from UGA symptoms, of whom 60% made efforts to alleviate their UGA problems, most commonly using HRT. There were some international differences regarding womens' perceptions of HRT, sexual relationships, prevalence and treatment of UGA problems and their attitudes to them across the six European States. CONCLUSIONS: Despite some international differences there was a generally similar experience of UGA problems across the six European populations studied, with a minority of women suffering significantly, however the distress of that subgroup highlighted the need for health professionals to appreciate the impact of UGA on those affected and to understand that many of these older women may be reticent in seeking help.

Aged↗
PubMed1997

Osteoporosis--an update.

Osteoporosis and subsequent fractures is a rapidly growing major health problem in many parts of the world. Even if prevalence and incidence are high in Europe, rate of increase is even higher in Asia. The majority of fractures occur in women underlining the importance of ovarian deficiency. Genetic factors and lifestyle greatly influence the incidence and prevalence both in men and women and the importance of estrogen deficiency at ages over 85, where a large number of fractures actually occur, may well be questioned. Among several risk factors the amount of bone mass remains crucial. Several techniques adequate in accuracy and precision exist to determine bone mass. The costs for these measurements are not negligible. Several pharmacologic regimens look promising for the prevention of osteoporosis and indeed for treatment of established osteoporosis. However, long-term data and clinical experience are warranted prior to establishing these pharmacological tools in the field of osteoporosis. For HRT and ERT such data are available. ERT and indeed HRT may halve the risk of osteoporotic fractures in women at least in current users. The effect at least on bone mass wears off after discontinuation of treatment but is never totally lost. In the interest of health care costs it is suggested that HRT could be started 15-20 years after the menopause and still provide protection for subsequent fractures.

Age Factors↗
PubMed1996

Effects of vaginally delivered estrogens.

INTRODUCTION: Atrophic condition in the vagina and lower parts of the urethral tract are common in elderly women. From population based surveys it has been estimated that 40% or more of women over 60 complain of insufficient control of micturation. In addition, lower urinary tract infections are common in this age group and recurrent cystitis is a scourge for many women (1, 2). Vaginal problems such as vaginal dryness, dyspareunia as well as infectious and non infectious disorders in the vagina may be even more common in elderly women (3) Vasomotor symptoms such as sweats and hot flushes commonly commence around the time of the menopause. In the majority of cases urogenital dysfunction does not become a problem until a decade later. Endogenous estrogens decline during the climacteric and the fall of estradiol levels from the time of onset of vasomotor symptoms until commencement of urogenital problems cannot be disregarded. In other words, it seems as if urogenital integrity can be maintained at lower estrogen levels than those required to resist vasomotor symptoms and conserve bone mass. Further evidence for this concept is achieved from numerous clinical studies in which various estrogens have been administered both orally and vaginally to elderly women with signs of urogenital atrophy which have resulted in amelioration. Such an alleviation of urogenital symptoms can be achieved without provoking endometrial growth.

Administration, Topical↗
PubMed1995

The menopause revisited.

The continuing growth of female life expectancy has resulted in a marked increase of women in years beyond the menopause. Women can nowadays expect to live one-third of their lives in a potential hormonal deficiency state. Women over 50 comprise 17% of the total population of any country in the modern western world. Any decision regarding their health issues will have a great impact on our limited health care resources. There is no doubt that estrogen replacement therapy effectively mitigates hot flushes and other vasomotor symptoms and more effectively so than other treatment modalities. Vasomotor symptoms affect more than half of the female population around the menopause with a mean duration of 2-3 years. When used to treat vasomotor symptoms hormone replacement therapy has repeatedly been shown to be cost effective. It is also well documented that hormone replacement therapy effectively prevents bone loss and osteoporotic fractures as well as heart disease. The majority of cases of both fractures and heart disease occur at ages over 75 and concern has been expressed if treatment from the menopausal age to the onset of fractures or heart disease is cost effective with regard to the perceived increase in risk of side effects, especially breast cancer. One important aspect in this scenario is the control system that we impose on women on HRT. Given our present preparations women are recommended an annual check-up. If the number of office procedures and visits to the clinic cannot be substantially reduced long-term therapy with HRT is not cost effective. An exception from this rule is the treatment of urogenital estrogen deficiency using low dose vaginal estrogens. Systemic concentrations of estrogens following such administration are negligible. Hence, low dose estrogen topical applications can be made an OTC preparation. As no control system is needed this therapy seems to be highly cost effective. The pharmaceutical industry is urged to produce better products so that side effects such as bleeding problems leading to a number of visits to the clinic and fear of cancer among women can be avoided. Recent data also imply that estrogen treatment may confer protection against Alzheimer's disease. Breast cancer is the remaining controversy even if recent data imply that estrogens could be given to women operated on for breast cancer without increasing the risk of a relapse.

Atrophy↗
PubMed1995

Is HRT indicated for the prevention of cardiovascular disease?

There is compelling evidence to suggest that estrogen administration to women of climacteric age reduces subsequent myocardial infarction by some 50%. Accumulating data also suggests estrogens confer substantial protection from stroke. Given this rationale, it is prudent to suggest to regulatory bodies that estrogen treatment would have this indication. Estrogens have other well-defined, and less well-defined, effects on various diseases; but observational studies suggest a decrease also in the overall mortality in estrogen users compared to nonusers. The critique of this concept is mainly that there is but one small clinical trial, and that observational data may be subject to confounders and biases. Questions have been raised whether the estrogen user comes from a preselected healthier population. Several of the observational studies are large enough to control for preexisting morbidity, including risk factors of cardiovascular disease. If anything, it would seem that women carrying risk factors inclusive of a sustained myocardial infarction are even better off (yielding a relative risk of 0.2) than those without risk factors. In order to protect the endometrium from malignant transformation and to ensure an acceptable bleeding pattern, a progestogen co-medication must be given with the estrogen. Observational data are based almost exclusively on estrogen-alone preparations, and concern has been expressed that progestogen addition may attenuate or even eliminate cardioprotection. Different estrogens at different doses, with different modes of administration, may also have an impact in this respect. The large variety of existing schedules for the administration of the progestogen adds to the difficulty in interpretation of the data with regard to cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Coagulation and anticoagulation effects of contraceptive steroids.

Epidemiologic data support the notion that first-generation high-dose oral contraceptives (containing > 80 micrograms of estrogen) increased the incidence of thromboembolic events. The quantitative interpretation of these data is difficult because results were often confounded by life-style factors and inadequate diagnostic procedures. With the introduction of modern low-dose combination oral contraceptives, the incidence of thromboembolic events decreased markedly. Although all combined oral contraceptives induce statistically significant changes in hemostatic factors, these changes are generally within normal ranges, and their clinical significance is questionable. Overall, increased activity in hemostatic mechanisms appears to remain in balance. Progestin-only formulations seem to affect hemostatic parameters to a much lesser degree, and their use has not led to an increased risk of thrombosis. Interindividual variations in pharmacokinetics and pharmacodynamics of contraceptive steroids are great and could tentatively explain why certain persons may be at an increased risk of thrombosis. Although most studies have looked at steady-state conditions during contraceptive steroid intake, it would seem prudent to investigate further the hemostatic system during a non-steady-state condition, such as that occurring during the first few days of the pill-free interval.

Blood Coagulation↗
PubMed1994

The endometrium: effects of estrogen and estrogen-progestogen replacement therapy.

A large bulk of data link the use of unopposed estrogens to an increased risk of endometrial cancer. Cancers associated with estrogen use are often well differentiated and carry a good prognosis. Concomitant use of progestogens either cyclically or continuously substantially reduces the risk of promoting endometrial cancer. The development of endometrial cancers as a result of prolonged estrogen medication often occurs via hyperplasia (and atypical hyperplasia). The reason for this increase is not known in detail, but estrogens are believed to be promoter substances by increasing miotic activity and possibly also by down-regulating the defense system against abnormal cell clones. Estrogen receptor activity seems to be dependent on the degree of phosphorylation. Receptor interaction with the specific sites upstream of "regulatory genes" may regulate a variety of steps in gene expression from transcription and mRNA half-life to protein processing, permitting a rapid regulation of the nuclear protooncogenes. This may also explain why serum placental protein reflects endometrial status during hormone replacement therapy. Both 17 beta-estradiol and medroxyprogesterone acetate are capable of modulating DNA synthesis in the endometrial glandular epithelium. The endothelin receptor type A seems to be stimulated during the proliferative phase, whereas an increase in the endothelin B type receptor has been noted in secretory and menstrual phases. Furthermore, low doses of oral norethisterone and levonorgestrel induce morphological changes inclusive of breaks in the endothelial lining of veins with and without hemostatic plugs. Endometrial fibrinolytic enzymes seem to be modulated by estrogens and progestogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrial Neoplasms↗
PubMed1994

Cardioprotection by estrogens: implications of observational studies.

Women younger than 50 have a lower age-specific incidence of CVD than men. With advancing age this difference gradually disappears. These well-established facts provide the rationale for numerous primary and a few secondary intervention studies with ERT. With increasing sophistication and longer observation periods, both case-control and cohort studies agree on a cardioprotective effect by estrogens. A meta-analysis suggests that estrogens halve the risk of myocardial infarction (MI). As observational studies do not control exposure, confounders and biases may be present. Even when considering the most pessimistic scenario, however, the clinical significance for preventing MI by ERT would still be substantial; albeit insufficient data from a clinical trial agree on a markedly reduced risk for MI. Some of the primary prevention trials are large enough to permit analysis of subgroups. In women carrying risk factors for CVD, the cardioprotective effect appears to be augmented. Such risk factors comprise smoking, hypertension, and perturbed serum lipids. In women who have already had MI, the relative risk may be as low as 0.2 for those treated with ERT. While there are compelling epidemiologic data to suggest cardioprotection by ERT, the epidemiology on combined therapy and CVD is scanty. However, there is no epidemiological evidence to suggest a reduced cardioprotection by progestogen co-medication, but further data are urgently needed in support of this notion.

Bias↗
PubMed1994

Cardioprotection by estrogens: mechanisms of action--the lipids.

Reductions of total and LDL-cholesterol and, to a lesser extent, increase in HDL are known to decrease cardiovascular disease (CVD) incidence. All oral estrogens are known to induce such changes in a dose-dependent manner at doses commonly used in ERT, somewhat more markedly for estradiol than for conjugated equine estrogens (CEE). Low-dose estriol used for urogenital discomfort is void of lipid effect. Transdermal estradiol induces similar reductions in the important LDL fraction, whereas HDL is less affected. Modified, especially oxidized, LDL is particularly atherogenic. Accumulating evidence suggests estrogen inhibits LDL oxidation in a process not counteracted by progestins. Elevated triglycerides are considered an important risk factor in women aged about 50. Oral estradiol and, especially, conjugated estrogens augment serum triglycerides, whereas estrogens with non-oral delivery systems rather reduce triglyceride concentrations. The clinical significance of pharmacologically induced changes in triglycerides remains to be clarified. Estrogen-induced changes in the serum lipid profile, however, account for no more than a third of the cardioprotective effect. Lipoprotein (a), another important indicator of CVD risk, is probably also reduced by the action of estrogens. Neither lipoprotein (a) nor oxidized LDL is measured by the routine serum lipid profile. At this time it is impossible to deduce the quantitative importance of changes in these two variables with respect to cardioprotection by estrogens.

Animals↗
PubMed1993

Transdermally administered oestradiol combined with oral medroxyprogesterone acetate: the effects on lipoprotein metabolism in postmenopausal women.

OBJECTIVE: To investigate the effects of two doses of transdermally applied oestradiol on lipid and lipoprotein metabolism in climacteric women. DESIGN: A randomised double blind cross-over comparison. SETTING: Departments of Obstetrics and Gynaecology, Ostra and Sahlgren's Hospital, Göteborg and Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Fifty-two women with climacteric symptoms were treated with oestradiol transdermally applied (50 micrograms and 100 micrograms/24 h). A daily dose of 5 mg oral medroxyprogesterone acetate was added 14 days each treatment cycle of four weeks. INTERVENTIONS: Blood samples were drawn after an overnight fast before and after four and eight months of treatment. MAIN OUTCOME MEASURES: Assays for serum triglycerides and cholesterol as well as low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol including the subfractions HDL2 and HDL3 were performed. RESULTS: Significant decrements were found in triglycerides and serum and LDL cholesterol during treatment with both doses. A modest rise in HDL2 cholesterol was observed after treatment with the 100 micrograms/24 h dose. CONCLUSIONS: The serum lipid and lipoprotein profile encountered in these women was similar to that reported with oral formulations except for a decrease in triglycerides. The metabolic differences between the two doses of transdermal oestradiol is probably of minor clinical significance in normal postmenopausal women.

Administration, Cutaneous↗
PubMed1993

Hormone replacement therapy and cardiovascular disease.

Cardiovascular disease is the chief cause of death among women in industrialized countries. Even breast cancer deaths, at 100/100,000 annually, are only 20% those from cardiovascular disease. However, the research effort in the area of cardiovascular disease among postmenopausal women is far smaller than those for osteoporosis or cancer. In postmenopausal women, the risk of cardiovascular disease rises dramatically, and among the elderly exceeds that of males. Although there is overwhelming evidence that HRT reduces the incidence, many physicians assume that it may cause hypertension and thrombosis, perhaps under the mistaken impression that HRT has the same side effects as the first generation of steroid contraceptives. A number of studies have demonstrated that cardiovascular mortality of postmenopausal women on HRT decreases by approximately one-half. The main epidemiologic evidence for this is a series of case-control and prospective (cohort) studies. Some 20 studies over the last 15 years could be briefly summarized by saying that approximately one third found cardiovascular risk among HRT users to be reduced by > 50% compared with non-users; one third found risk reductions < 50%; and one third found increased risks. HRT appears to affect a large number of risk factors associated with cardiovascular disease; but many formerly thought to be of significance have little clinical relevance, whereas some factors, such as peripheral vascular resistance and certain prostanoids, are apparently much benefited. The benefits of HRT for lipid factors (HDL-cholesterol, LDL-cholesterol, etc.) are well known, but recent evidence indicates that changes in these lipids account for only 20-25% of the cardiovascular benefits of HRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗
PubMed1992

Introduction to steroids in the menopause.

Menopausal symptoms and signs associated with the reduction of ovarian function include an increased incidence of cardiovascular disease and loss of bone mass as well as less serious but more uncomfortable symptoms such as vasomotor flushes and atrophy of the vaginal wall. Although unopposed estrogen effectively reverses these and other menopausal symptoms, it is well established that without the addition of progestin there is an unacceptably high risk of developing hyperplasia or cancer of the endometrium. Depending on the type and dose of progestin added, however, this addition may reverse estrogen's beneficial cardiovascular effects and produce unwanted side effects. Lower doses and newer progestins, such as norgestimate, gestodene, and desogestrel, have demonstrated a decreased potential to reverse the positive cardiovascular effects of estrogen while still eradicating persisting or de novo endometrial hyperplasia.

Endometrial Hyperplasia↗