| 1. |
- Andersson, K, et al.
(author)
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Intrauterine or oral administration of levonorgestrel in combination with estradiol to perimenopausal women--effects on lipid metabolism during 12 months of treatment
- 1996
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 41:5, s. 476-483
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Limited data concerning serum lipids and lipoproteins are available on the effect of HRT in perimenopausal women, who commonly have marked bleeding disturbances and may have severe climacteric symptoms. Almost all previously published data have utilized a simplified form of lipoprotein analysis, which includes an estimation and not a determination of LDL cholesterol. To delineate the role of locally administered progestogen, perimenopausal women were studied for a year. PATIENTS AND METHODS: 40 perimenopausal women with climacteric complaints. The continuous release of low-dose levonorgestrel from an intrauterine device was used as progestogen co-medication to estradiol in a new type of continuous combined hormone replacement therapy. Women were randomized to either cyclical treatment with 2 mg of oral estradiol valerate in combination with 250 micrograms of levonorgestrel for the last ten days (Cyclo Progynova) or continuously with 2 mg estradiol valerate orally in combination with a 20 micrograms per 24 hour levonorgestrel releasing intrauterine device. RESULTS: Reduced HDL cholesterol was initially recorded in both treatment arms and disappeared after 1 year of treatment. Triglycerides were reduced in the orally treated group, but not in the device group. No changes in LDL cholesterol were noted. CONCLUSIONS: The findings suggest that continuous combined HRT with intrauterine release of 20 micrograms levonorgestrel per 24 hours in perimenopausal women is neutral as far as lipid metabolism is concerned, since no alterations compared with pretreatment values could be noted after 12 months of treatment. Less marked lipid changes were obtained in perimenopausal women as compared with data on postmenopausal women. Differences in methodology may partly account for this.
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| 2. |
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| 3. |
- Lindoff, C, et al.
(author)
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Treatment with a GnRH analogue: effects on hemostatic risk factors for thrombo-embolic disease
- 1994
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 39:3, s. 133-139
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Journal article (peer-reviewed)abstract
- OBJECTIVE--Steroid hormones, especially estrogens, are known to affect hemostatic risk factors for thromboembolism, cardiovascular disease, and stroke. We examined these risk factors during depression of the serum estradiol concentration by a GnRH analogue. DESIGN--Patients were treated with a GnRH analogue, goserelin (Zoladex), 3.6 mg/inj monthly, for a period of 6 months. Blood samples were collected during and after treatment and in a control group. In ten patients a blood sample was also drawn before treatment. Measurements were made of serum estradiol, and the plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen, antithrombin III (AT III) and protein C activity, factor VII (FVII) antigen, and fibrinogen. SETTING--Outpatient clinics at the Departments of Obstetrics and Gynecology at two university hospitals in southern Sweden. PARTICIPANTS--Twenty-seven women with endometriosis were consecutively included. A control group comprised 20 women with normal menstrual cycles. MAIN OUTCOME MEASURES--The concentrations of the hemostatic components during depression of the serum estradiol concentrations, as compared to those during normal ovulatory cycles. RESULTS--Serum estradiol concentrations during treatment were comparable to those of postmenopausal women (mean, 23.2 pmol/L), and both AT III and protein C activity were significantly increased (P < .005 and P < .02, respectively). As compared to controls, plasma concentrations of PAI-1 and t-PA of patients were significantly higher both during and after treatment. In the subgroup also studied prior to treatment, there were no differences in hemostatic components, when comparing pretreatment and posttreatment values. CONCLUSIONS--Treatment with this type of GnRH analogue for 6 months is safe with regard to its effect on hemostatic risk factors. The similar responses of t-PA and its inhibitor, PAI-1, to alterations in estrogen levels as well as inflammatory reactivity presumably constitute a balance mechanism preserving fibrinolytic defenses.
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| 4. |
- Samsioe, Göran
(author)
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Cardioprotection by estrogens: implications of observational studies
- 1994
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 39:Suppl. 1, s. 20-27
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Samsioe, Göran
(author)
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Cardioprotection by estrogens: mechanisms of action--the lipids
- 1994
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 39:Suppl. 1, s. 43-49
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Journal article (peer-reviewed)abstract
- 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.
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| 6. |
- Samsioe, Göran, et al.
(author)
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Ethical issues in obstetrics
- 1996
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 41:3, s. 284-287
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Journal article (peer-reviewed)abstract
- Ethical issues in modern obstetrics commonly relate to a conflict between the rights and possibilities of the fetus versus those of the mother. After delivery, when the fetus by definition is a child, all legal rights are granted to this new individual. Whether any rights should be given or offered to the fetus is dependent on the prevailing situation. General rules are difficult to give due to the rapid evolution of clinical medicine-too firm rules given today could well be an obstacle in the near future. All cultures have well-established opinions regarding issues related to pregnancy and childbirth. Cultural and religious dogmas are often in conflict with modern medical technology and financial issues. In several modern societies, state laws regulate legal abortion and other aspects of termination of pregnancy. Current laws often determine not only decisions but also the minds of doctors, as well as of patients. Advanced medical technology has yielded a possibility of selective feticide. Again our experience with this new technique is limited, and several issues of ethical importance may arise from the use of such techniques. The indications for a selective feticide are dependent upon the benefits and risks of the procedure itself, and also on the selection process of what fetus should be aborted. Clearly, no definitive rules could be given at this stage of development. The advice given to the woman by her doctor is of critical importance for the outcome of the given pregnancy, be it selective feticide or legal abortion. However, the prevailing social welfare system and the support a woman could be given by her society are also factors. Should she give birth to a child with an inborn error of metabolism, or some other chronic illness? Drug abuse, including alcohol and, indeed, also tobacco, constitutes a special problem. In Sweden, drug-addicted pregnant women are hospitalized during their last trimester. This policy results in a drug-free last trimester and a reduction of afflicted newborns. Should a similar approach also be enforced when dealing with abuse of alcohol and tobacco during pregnancy? The improvement of in vitro fertilization techniques has introduced a novel concept, the surrogate mother. In some countries, this is forbidden by law, in others, it is an accepted medical practice, but several medico-legal as well as ethical issues warrant further clarification. What are the legal rights of the surrogate mother? Should there be an age limit for surrogate mothers? Who is responsible for problems in the pregnancy itself? In cases of male infertility, ethical issues may arise. Should the child have a legal right to learn the name of the biological father? Should there be a limit for the use of donor sperm in respect to number of fertility attempts, as well as potential female patients who may use the same sperm donor?
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| 7. |
- Samsioe, Göran
(author)
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Hormone replacement therapy: aspects of bleeding problems and compliance
- 1996
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 41:1, s. 11-15
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Journal article (peer-reviewed)abstract
- Mitigation of vasomotor symptoms and urogenital problems, along with reductions in osteoporosis and cardiovascular disease, provides the rationale for using hormone replacement therapy (HRT), and the duration of use. However, user surveys have indicated poor compliance with HRT, and that means user time may be less than 12 months, a period unlikely to influence metabolic disorders. The main reasons for discontinuing HRT are unacceptable bleeding pattern and fear of cancer. There is solid evidence that HRT does not increase gynecological, gastrointestinal, or other adenocarcinomas. In fact, the only remaining controversy relates to breast cancer. Since the media often underscore and strengthen "old wives' tales" about the menopause and HRT, access to correct, unbiased information is the key to combating the misconceptions about HRT. Information also helps women understand the nature of menstrual-like bleeding, and thus contributes to compliance. Unfortunately, existing formulations do not control the bleeding pattern in every women. Our understanding of spotting and breakthrough bleeding is still poor. Older data, which suggested routine endometrial histology to find the cause and select treatment of vaginal bleeds, have been contradicted, rendering endometrial biopsy less useful in decision making; endometrial ultrasonography seems to be of more value for endometrial surveillance in HRT. Recent advances in understanding the nature and function of growth factors in uterine tissues help to unravel an array of events of importance for explaining the bleeding sometimes encountered during continuous combined therapy. The pharmaceutical industry should be challenged to work closely with scientists and regulating agencies. Doing so will help to advance our knowledge and therapeutic modalities, which will help us to combat the chief cause of poor compliance to, and discontinuation of, a very important potential contributor to maintaining quality of life of elderly women.
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| 8. |
- Samsioe, Göran
(author)
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Medical and surgical strategies for treating urogynecological disorders
- 1996
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In: International Journal of Fertility and Menopausal Studies. - 1069-3130. ; 41:2, s. 136-141
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Journal article (peer-reviewed)abstract
- Symptoms and signs of the urogenital estrogen deficiency syndrome occur relatively late in a women's life when endogenous estrogen levels are well below those required to stimulate endometrial growth. At age 60 and above symptoms are common and progress with advancing age. The first and most common complaint is vaginal dryness, but symptoms of lost control of micturition as well as urge incontinence are also frequent. Recurrent infections of the lower urinary tract are common, as well as dyspareunia and a sensation of burning and itching. One third of women above age 60 suffer from urogenital estrogen deficiency syndromes, a figure that rises to two thirds at the age of 75. With a rapid growth of the elderly female population, these symptoms are an increasing burden to the individual as well as to any given health care system. Several clinical trials have repeatedly demonstrated the efficacy in alleviating these symptoms of low daily estrogen doses as exemplified by 8 micrograms/day of vaginally administered estradiol. For reasons not completely understood, the urogenital tissues respond to this low estrogen level but the endometrium does not. Hence, estrogen therapy aiming at mitigating urogenital deficiency symptoms could be given without a progestogen. No side effects have been described for vaginal preparations, and neither absolute nor relative contraindications exist. No protection is offered against cardiovascular disease or osteoporosis, though. In 1991, vaginal low-dose estrogens were declared OTC preparations in Sweden. The costs for the society for this program can be limited to the costs of medication only, for medical monitoring is not compulsory. The clinical efficiency is remarkable, and urogenital symptoms are almost abolished in elderly women receiving this type of treatment, which is practically devoid of side effects.
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