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Die einzigen in epidemiologischen Studien konsistent von Frauen angegebenen Korperempfindungen in den Wechseljahren sind Hitzewallungen und Schweisausbruche sowie Scheidentrockenheit. Eine ganze Reihe weiterer somatischer und psychischer Beschwerden werden von Frauen in der Lebensmitte angegeben, konnen aber aufgrund der Studienlage nicht als „typische“ Beschwerden in den Wechseljahren aufgefasst werden. Wunschen Frauen eine Behandlung vasomotorischer Beschwerden, stehen ihnen mit einer Ostrogentherapie bzw. einer Ostrogen-Gestagen-Kombinationstherapie effektive Behandlungsmoglichkeiten zur Verfugung. Uber die Varianz der Verlaufe und uber Spontanschwankungen von vasomotorischen Beschwerden gibt es wenig gesicherte Erkenntnisse.

Hintergrund Evidenzbasierte, allgemeinverstandliche Gesundheitsinformationen werden als essentiell zur Verminderung der Krankheitslast in der 2. Lebenshalfte angesehen. Wissenschaftliche Kenntnisse uber modifizierbare Risikofaktoren fur chronische Krankheiten wie Herz-Kreislauf- und Krebserkrankungen, die zahlenmasig am bedeutsamsten sind, sind verfugbar.

The menopausal transition is a natural phase of every womans life. Several symptoms emerging during the climacteric may be treated with estrogens. Hot flushes and symptoms of genital ageing may be relieved by estrogen therapy. Progestin therapy is indicated in all women with an intact uterus to avoid endometrial pathology. Given the present risk-benefit scenario, estrogen therapy is no longer a first-line choice to prevent osteoporosis. Counselling requires integration of recent knowledge provided by the first results of the Womens Health Initiative and other significant randomized, placebo-controlled, prospective clinical studies with clinically relevant outcomes, not the least unless good-quality data regarding other estrogens and progestins, apart from conjugated equine estrogens/medroxyprogesterone acetate are lacking. Women should be enabled to decide upon estrogen therapy after provision of extensive information by their physicians.

Das Management irregularer Blutungen unter sequentieller Ostrogen-Gestagen-Substitutionstherapie ist eines der haufigsten Probleme in der Behandlung postmenopausaler Frauen, die eine Hormonsubstitution durchfuhren. Zahlreiche Kombinationen von oralen und oder transdermalen Ostrogenen und Gestagenen sind in den letzten Jahren entwickelt worden, die in den entsprechenden klinischen Studien bei der grosen Mehrzahl der Patientinnen eine regelhafte Entzugsblutung bewirken. Alternativen stellen die sog. kombiniert kontinuierliche Substitution (fixe tagliche Dosis eines Ostrogens und eines Gestagens) und synthetische Gestagene wie Tibolon (androgene und schwach ostrogene Partialwirkungen) dar. Die Entwicklung von Formen der Hormonsubstitution, die eine langanhaltende und moglichst permanente Amenorrho herbeifuhren, bleibt dennoch eine derzeit ungeloste Aufgabe. Dieser Beitrag behandelt die Grundzuge in der hormonellen Behandlung bei postmenopausalen Blutungen ohne erkennbare uterine Ursache – die haufigste Situation – und bei Existenz von Myomen. Weiterhin werden ausgewahlte systemische Erkrankungen, die mit Einschrankung der Leber- oder Nierenfunktion einhergehen, sowie bestimmte Knochenstoffwechselerkrankungen in diesem Zusammenhang diskutiert. Auch selektive ...strogenrezeptormodulatoren (SERMs) wie Tamoxifen und Raloxifen konnen in unterschiedlichem Ausmas Blutungen verursachen; deren Bedeutung fur das klinische Management wird ebenfalls aufgezeigt.

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55–76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7–19% (30 mg) to 27– 36% (20 mg) showed moderate glandular proliferation. 20–33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68–70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Mullerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed.

Vorgestellt wird ein Fall einer interstitiellen Extrauteringraviditat (EUG) im intramuralen Anteil des linken Eileiters nach vorangegangener ipsilateralen Adnektomie. Die sonographische Diagnose wurde durch den Operationssitus bestatigt. The authors present a case of an interstitial extrauterine pregnancy in the intramural portion of the left oviduct after preceding ipsilateral adnectomy. Sonographic diagnosis was confirmed by the site at Operation.

We report the third case of a prenatal diagnosis of Larsen’s syndrome, which is the first report affecting both a 37-year-old primiparous caucasian woman and her fetus not considered to have Larsen’s syndrome until the finding of bilateral clubfeet was demonstrated on screening ultrasound at 23 weeks of gestation. History and physical examination of the pregnant woman revealed severe impairment in the mobility of hip, elbow and knee joints starting in early childhood. Additional findings were spatulate thumbs and a flat nasal bridge. The mother of the pregnant woman demonstrated similar joint symptoms. The differential diagnosis of Larsen’s syndrome was considered for the first time in both women. The patient wished to terminate her pregnancy, as the potential early onset of the same disorder was suggested by the finding of clubfeet. An intraamniotic instillation of ethacridinic acid was performed. On pathological examination including radiography of the male stillborn, various anomalies of the face, and upper and lower extremities were demonstrated compatible with Larsen’s syndrome.

We assessed the resistance index (RI) and pulsatility index (Pi), peak and average systolic velocities in uterine, arcuate and radial arteries, and endometrial thickness (ET) by transvaginal B mode and color Doppler sonography in patients on continuous combined hormonal replacement therapy (HRT) and controls. HRT consisted of 2 mg estradiol, 1 mg estriol and 1 mg norethisterone acetate daily (n = 33) compared to controls, who received none of these (n = 21). Age was 61 ± 6 and 59 ± 9 years (mean ± standard deviation) in the HRT and control groups, respectively. The duration of HRT was 5 ± 2 years, with a minimum of 1 year. We found that the uterine RI and, to a lesser extent, the uterine PI were significantly lower and the radial peak systolic velocities were significantly higher in the HRT group compared to controls. The highest uterine PI values were measured in controls with the shortest life-time exposure to endogenous estrogens, i.e. late menarcheal age or early menopause. The endometrial thickness of 2.8 ± 1.8 mm in the HRT group was not significantly different from that in the controls (4.2 ± 5.6 mm). In conclusion, the alteration in blood flow parameters demonstrated in this study would suggest that the long-term use of continuous oral estradio12 mg, estriol 1 mg and norethisterone acetate 1 mg daily is associated with a slight increase of flow in the uterine arteries compared to controls matched for (postmenopausal) age. Endometrial thickness does not increase with duration of use of continuous combined HRT. Copyright © 1997 International Society of Ultrasound in Obstetrics and Gynecology

The occurrence of uterine bleeding usually associated with hormonal replacement therapy is not acceptable for many women. Our objective was to review data on compliance and bleeding patterns in 70 postmenopausal women on oral replacement with estradiol 2 mg, estriol 1 mg, and norethisterone acetate 1 mg daily administered in a continuous combined fashion to avoid withdrawal bleeding. After 1 year, compliance was 97%, after 5 and 9 years 76% and 58%. The most common reason for discontinuation was spotting. Reproductive history, body weight and pretreatment estradiol and FSH concentrations were not different between the subgroups with bleeding — 19% — and without bleeding — 81%. The probability to maintain amenorrhoe on HRT did not increase with the length of the postmenopausal interval or weight. Endometrial histology revealed one case of a highly differentiated in situ adenocarcinoma of the endometrium. In the women with bleeding, induced serum estradiol levels were significantly higher and pretreatment SHBG-levels lower compared to the non-bleeders. Whether these findings may be significant for election of patients for continuous combined HRT remains to be determined. In conclusion, we demonstrate that adherence to this treatment regimen apparently provides a choice patients considering long-term HRT should be informed about. However, the lack of parameters to elect patients in conjunction with the problem of uterine bleeding does not permit the recommendation to regard continuous combined HRT as first line therapy for long-term HRT. Criteria need to be developed when to obtain an endometrial histology once uterine bleeding occurs, as the optimal surveillance of this mode of HRT is presently unknown.

Quantitative CT of the axial skeleton (aQCT) may serve as an example of the evaluation and interpretation of bone densitometric data as it is the only state-of-the-art technique with valid longitudinal observations. The value of bone density measurements in interindividual cross sections refers to a grading derived from a representative reference population and provides an evaluation of fracture risk. The presence and rate of any bone loss can only be evaluated in an intraindividual longitudinal follow-up. Adequate follow-up for trabecular bone requires at least 3 to 5 years intervals to discriminate between different loss rates. Bone losses induced by steroid therapy or immobilisation may have faster kinetics apparent within months; bone density increase due to hormone substitution may be significant after one to two years. Morphological data allow critical evaluation of the quantitative measurements, eliminating false values and differentiating between rarefying and destructive osteopenia.

The diagnostic ranking of trabecular morphology for the evaluation of osteoporosis in quantitative CT (QCT) is presented. 5 patterns of cancellous bone correlating with trabecular density may be discerned. However, these patterns may indicate osteoporotic changes in particular cases only, by confluent rarefactions if the density is still within the normal range. There is neither a predictive value for the degree of spontaneous or therapy-induced bone loss, nor for therapy response. The trabecular appearances remain unchanged in short term even under strong quantitative changes and are therefore of no value for follow-up.

The menopausal transition is a natural phase of every womańs life. Several symptoms emerging during the climacteric may be treated with estrogens. Hot flushes and symptoms of genital ageing may be relieved by estrogen therapy. Progestin therapy is indicated in all women with an intact uterus to avoid endometrial pathology. Given the present risk-benefit scenario, estrogen therapy is no longer a first-line choice to prevent osteoporosis. Counselling requires integration of recent knowledge provided by the first results of the Womeńs Health Initiative and other significant randomized, placebo-controlled, prospective clinical studies with clinically relevant outcomes, not the least unless good-quality data regarding other estrogens and progestins, apart from conjugated equine estrogens/medroxyprogesterone acetate are lacking. Women should be enabled to decide upon estrogen therapy after provision of extensive information by their physicians.

The term ‘aneurysm of the vein of Galen’ encompasses a range of different midline arteriovenous fistula malformations. Prenatal real-time and Doppler sonography can contribute to the differential diagnosis of fetal cerebral cystic lesions of various origins, pineal and choroid tumors, and in tracerebral hematoma. Regardless of the type of treatment, perinatal morbidity and mortality are high, often due to cardiac failure. A case of spontaneous delivery at 36 weeks of gestation by a 30-year-old woman presenting with a fetal aneurysm of the vein of Galen is described. As the extrauterine cardiac function was normal and a steal phenomenon was not present, expectant management was justified. Five arterial embolizations within the following 4 years were performed as a means of treating the primary lesion. Our case illustrates the fact that elective spontaneous vaginal delivery followed by serial embolization is possible in cases of arteriovenous fistula malformation without signs of cardiac insufficiency. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology

That estrogen plays a role in the regulation of mood has been postulated since extracts of animal ovarian tissue were administered to oophorectomized women at the end of the last century to alleviate psychological symptoms thought to be related to the removal of the ovaries. The occurrence of depressive symptoms in the perimenopause is associated with a variety of factors. A previous history of either depression and/or premenstrual syndrome as well as cognitive factors explain most of the variance. There are no consistent findings of a correlation between any serum hormone level and severity or presence of mood symptoms. Neurobiological studies show, with regard to an antidepressant effect, promising effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic and GABAergic functions. Progestogens seem to oppose some of these effects. The role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials showed a modest effect on symptoms of depression. However, the predominantly poor methodological quality does not allow generalisation and recommendations. A "tonic" effect on well-being in non- or mild depressed women should not be regarded as true antidepressant effect. Results yielded in studies of surgically menopausal women may not be applicable to women with natural menopause. There is a great potential for exploring various types, doses, and routes of administration of both antidepressants and sex hormones. With regard to the domino theory, future studies should also focus on the mediation of treatment effects through alleviation of vasomotor symptoms or sleep quality.

Jede postmenopausale Hormonsubstitution bedarf einer Indikation und deren gelegentlicher Uberprufung. Die regelmasige klinische Uberwachung ermoglicht die Wirkungen der Therapie zu uberprufen, Nebenwirkungen zu erkennen und Modifikationen der Behandlung vorzunehmen. Da heute auch im menschlichen Organismus nicht sezernierte ostrogene sowie synthetische Gestagene in der Hormonsubstitution eingesetzt werden, ware wohl die Bezeichnung Hormontherapie korrekter.

17 beta-estradiol, conjugated equine estrogens, esterified estrogens, and estriol constitute postmenopausal replacement therapy, all of which are in clinical use as oral preparations. Non-oral routes--matrix and reservoir patches, gel--were developed for estradiol, as was the intravaginal administration of estriol and estradiol. Daily doses of 1 mg estradiol(valerate) or 25 micrograms estradiol delivered via a patch or 0.5 mg gel or 0.3 mg conjugated equine estrogens are often sufficient to alleviate climacteric symptoms. Bone resorption may be effectively reduced and bone mineral density maintained by 1 mg estradiol or 25 micrograms transdermal estradiol. Maximal bone sparing dosages are 2 mg estradiol, 50 micrograms transdermal estradiol, 0.625 mg conjugated equine estrogens, and 1.25 mg estrone Estriol, predominantly used for the prevention and or treatment of urogenital symptoms, has no bone sparing effect at the doses in clinical use. Non-oral administration of estradiol may be superior in diabetic women and those with hypertriglyceridemia due to the different metabolism which does not mainly involve the hepatic first pass effect. Epidemiological data do not support any preference of oral versus non-oral routes of administration regarding side-effects such as venous thromboembolism. Progestogens--natural progesterone, derivatives structurally related to progesterone and testosterone, respectively--are necessary for endometrial protection. Sequential use of a progestogen for at least 10 days per month, preferably 12-14 days abolishes the increased incidence of endometrial hyperplasia which is likely to develop with unopposed use of estrogen. Observational studies do not suggest any superiority of a given progestogen regarding cardiovascular risk, prevention of osteoporosis, and cognitive function in postmenopausal women on estrogen replacement therapy. Tibolone, a derivative of norethindrone, is yet another option for replacement therapy. The recommended dose for treatment of climacteric symptoms and prevention of bone loss is 2.5 mg. Controlled clinical studies do not suggest that this compound is superior in achieving amenorrhea compared with continuous combined estrogen progestogen replacement therapy, as available data are inconsistent. In early postmenopause the sequential use of a progestogen in conjunction with an estrogen is the preferred treatment option. With advancing postmenopausal age either continuous combined replacement or tibolone may be choices in case withdrawal bleeding is no longer acceptable for women. However, there are no rigid age limit when to change treatments, the selection of which is largely influenced by the preference of the individual's acceptance of withdrawal bleeding.

Objective: We sought to compare vascular resistance and plasma lipids in postmenopausal women assigned to tibolone (a synthetic estrogen replacement steroid) therapy or continuous combined hormone replacement therapy. Study Design: Pulsatility and resistance indexes in pelvic arteries (color Doppler transvaginal ultrasonography) and lipids were monitored in this double-blind 1-year trial of 100 women randomized to either 2.5 mg tibolone or 2 mg 17β-estradiol plus 1 mg norethindrone acetate daily. Results: Both indexes of the arcuate arteries (uterine arteries) were significantly reduced beyond 3 and 6 months (12 months) from baseline, respectively, by the combined regimen compared with tibolone alone. Tibolone increased the resistance index of arcuate arteries but did not affect uterine arteries. There was no effect of either regimen on the internal iliac arteries. The medians of the percentage changes from baseline of high-density lipoprotein cholesterol (triglycerides) were significant between groups after 1 year, as follows: –17% (–16%) in the tibolone group and –4% (+15%) in the combined group, respectively. Both regimens similarly reduced total and low-density lipoprotein cholesterol and lipoprotein Lp(a). Conclusion: Hormone replacement therapy may induce different or opposite changes of both vascular resistance and lipids. It is unknown whether these findings may modify cardiovascular risk. (Am J Obstet Gynecol 2000;183:575-82.)

The purpose of this study was to analyze the midvertebral area of lumbar vertebrae in osteoporotic and nonosteoporotic female patients and to find out whether the midvertebral area may be used as an additional parameter in the diagnosis of osteoporosis. In 195 peri- and postmenopausal patients (average age 51.7 +/- 5.2 years) trabecular and cortical bone mineral density (BMD) were determined using quantitative CT (QCT) in L2-4. In addition, midvertebral cross-sectional area was measured in a standardized fashion on the CT sections and the height of the second lumbar vertebra was determined on the lateral digital radiographs. Body height and weight were obtained and vertebral fracture status was determined. According to WHO criteria 29 patients (average age 57.2 years) were considered osteoporotic, 93 osteopenic (average age 52.2 years) and 73 normal (average age 48.6 years). Body weight and size did not show significant differences between the individual groups. Average midvertebral area was 1278 +/- 173 mm2 in the osteoporotic patients, 1186 +/- 125 mm2 in the osteopenic patients and 1126 +/- 127 mm2 in the normals. A correlation of r = -0.39 (p0.05) was obtained between BMD and area. Thirty-six of 195 patients showed osteoporotic vertebral fractures. Midvertebral area in these patients was 1266 +/- 171 mm2 versus 1159 +/- 133 mm2 in the nonfractured females (p0.05). We therefore conclude that the lumbar midvertebral area is larger in osteoporotic and osteopenic patients compared with women with normal BMD. In contrast to biomechanical considerations midvertebral area seems not to be suited as an additional measure of bone strength in vivo.

Objective To evaluate endometrial thickness and the incidence of uterine bleeding in postmenopausal women using either tibolone 2.5 mg or continuous combined 2 mg estradiol and 1 mg norethisterone acetate (E+NETA) daily as hormone replacement therapy. Design We compared diary records of self-reported uterine bleeding and measurements of endometrial thickness, area, and volume by transvaginal sonography at baseline and after 1, 3, 6, and 12 months in a 1-year, prospective, randomized, double-blind, single-center trial of 100 postmenopausal women aged 46-69 years. Bleeding frequencies and endometrial thickness were assessed by Chi-square tests and analysis of covariance, respectively. Results Self-reported bleeding was significantly less in the tibolone group. Bleeding episodes were reported by 27.7% of women in the tibolone group and by 59.2% in the E+NETA group. The mean number of days with bleeding was 5.8 +/- 27.0 in the tibolone group and 35.6 +/- 58.6 in the E+NETA group. Six women in the tibolone group and seven in the E+NETA group discontinued the study; three in the E+NETA group because of bleeding. The mean endometrial thickness at baseline was 2.56 +/- 0.81 mm in the tibolone group and 2.58 +/- 1.04 mm in the E+NETA group. After 1 year, the corresponding figures were 3.32 +/- 1.58 mm and 3.07 +/- 1.68 mm. Thus, 86% of women in the tibolone group and 93% in the E+NETA group had an endometrial thickness of less than 5 mm. Conclusions Use of tibolone 2.5 mg daily for 1 year was associated with significantly less bleeding and spotting compared with daily continuous combined 2 mg estradiol and 1 mg norethisterone acetate in postmenopausal women in the presence of both minimal and nonprogressive increase of endometrial thickness associated with the two regimens.

The cessation of ovarian function after menopause is associated with a variety of symptoms from the urogenital tract in many postmenopausal women such as urinary incontinence, urgency, recurrent urinary tract infection, and dyspareunia (OLDENHAVE et al. 1993). The underlying condition is the development of local atrophy of the urethral and vaginal epithelium and their supportive tissues. The gradual increase of these symptoms is age-dependent. Thus, a substantial number of women at very old age are affected. One specific feature attached to this complex set of symptoms frequently referred to as urogenital aging is the influence of personal attitudes and cultural background towards hygiene and sexuality by both menopausal women and health care providers.

Urogenital aging is given a low priority in the medical community and is an entity not well known to the general public. Many women are not aware of the possible disorders of the lower urinary tract and the vagina because of estrogen deficiency. These changes are perceived often as a normal part of the general aging process not associated with the possibility of medical attention, diagnosis, and treatment. Access to the information that certain urogenital dysfunctions, in particular incontinence, and vaginal discomfort respond to estrogen replacement therapy is not available for every woman. In addition, physicians and patients may hesitate to address these issues because of feelings of shame and embarrassment, feelings commonly encountered and specific for the complex of urogenital aging. Educational efforts and promotion of information with use of various media might help to improve knowledge and remove the taboo attached to urogenital aging in both health care providers and the general public. Thus a better understanding of urogenital aging would be achieved and the potential of estrogen replacement extended.

Intracranial tumours, often presenting with progressive hydrocephalus, are rare congenital diseases accounting for 0.5-1.5 per cent of all cases of brain tumours diagnosed during childhood. The differential diagnosis includes vascular malformations, infarctions, and haemorrhages. Sonographic signs suggestive of glioblastoma, teratoma, and astrocytoma do not establish the histological diagnosis, however. We report a case of an undifferentiated fetal glioma detected at 29 weeks' gestation. The diagnosis of an undifferentiated brain tumour was suspected by sonography because of the lack of normal brain structures in conjunction with a diffuse echogenic central lesion and an external hydrocephalus. Because of the very poor prognosis, we induced labour by intravaginal and intravenous administration of prostaglandin E2 and achieved the vaginal delivery of a stillborn child whose head circumference corresponded to 38 weeks of pregnancy. Histological and immunochemical features of this undifferentiated congenital glioma (glioblastoma) are presented.

We assessed the resistance index (RI) and pulsatility index (PI), peak and average systolic velocities in uterine, arcuate and radial arteries, and endometrial thickness (ET) by transvaginal B mode and color Doppler sonography in patients on continuous combined hormonal replacement therapy (HRT) and controls. HRT consisted of 2 mg estradiol, 1 mg estriol and 1 mg norethisterone acetate daily (n = 33) compared to controls, who received none of these (n = 21). Age was 61 +/- 6 and 59 +/- 9 years (mean +/- standard deviation) in the HRT and control groups, respectively. The duration of HRT was 5 +/- 2 years, with a minimum of 1 year. We found that the uterine RI and, to a lesser extent, the uterine PI were significantly lower and the radial peak systolic velocities were significantly higher in the HRT group compared to controls. The highest uterine PI values were measured in controls with the shortest life-time exposure to endogenous estrogens, i.e. late menarcheal age or early menopause. The endometrial thickness of 2.8 +/- 1.8 mm in the HRT group was not significantly different from that in the controls (4.2 +/- 5.6 mm). In conclusion, the alteration in blood flow parameters demonstrated in this study would suggest that the long-term use of continuous oral estradiol 2 mg, estriol 1 mg and norethisterone acetate 1 mg daily is associated with a slight increase of flow in the uterine arteries compared to controls matched for (postmenopausal) age. Endometrial thickness does not increase with duration of use of continuous combined HRT.

Objective : Estrogens are known to exhibit antioxidative effects. At present little information exists on the influence of co-administered progestins upon this effect. Therefore we investigated the influence of levonorgestrel, a potent antiestrogenic progestin, on the inhibition of the low-density lipoprotein (LDL) oxidation by 17β-estradiol or 17β-estradiol valerate in vitro and ex vivo. Methods : After isolation from blood, the in vitro oxidation of LDL was induced by copper ions and measured continuously by monitoring the formation of conjugated dienes. In 21 female ovariectomized White New Zealand rabbits the antioxidative action of 17β-estradiol alone or in combination with levonorgestrel after subcutaneous infusion for 3 days was determined using the copper-induced LDL-oxidation as an endpoint. Eleven postmenopausal women were exposed to sequential estrogen-progestin replacement therapy (day 1–21: 2 mg estradiol valerate/day, day 10–21: 0.15 mg levonorgestrel/day). Blood samples were collected at three times: on day 1, on day 10, on day 22 (after the combination phase). The lag time of ex vivo oxidation of LDL, the plasma estradiol and estrone levels were estimated. Results : In the chosen cell-free system, 17β-estradiol increased the lag time of the LDL-oxidation in a dose-dependent manner. Levonorgestrel showed neither pro-oxidative nor antioxidative effects when administered alone in different concentrations. Co-administration of different doses of levonorgestrel did not modify the antioxidative action of estrogen either. The two ex-vivo models confirmed these results. In rabbits the co-administered 19-nortestosterone derivative levonorgestrel did not impair or reverse the estradiol-dependent effect. In postmenopausal women the daily oral administration of levonorgestrel in conjunction with 17β-estradiol valerate did not diminish the antioxidative action of this estrogen given for the first 9 days. Conclusion : The antioxidative potential of estradiol and estradiol valerate is maintained in the presence of levonorgestrel.

Epidemiological data strongly suggest a substantial improvement of quality of life for post-menopausal women using hormonal replacement therapy (HRT). Nevertheless, reluctance of women to choose HRT is high. Various attempts to develop regimens with substantially better acceptance are being investigated. Sequential and continuous combined regimens, oral and transdermal routes of administration are available; however, no regimen nor any mode of administration has proven superior with regard to patients' compliance. Research on the specific problems of compliance in HRT has not yet offered solutions to the medical community about optimal conditions concerning long-term hormonal therapy. Unless metabolic profiles of the various modes of treatment are defined in long-term trials, general recommendations are difficult to justify. As long as the occurrence of uterine bleeding is associated with any concept of HRT in non-hysterectomized women, adherence has been reported to be very low. Persisting endometrial atrophy has not been achieved by any type of HRT. New regimens not stimulating endometrial growth are essential, since women in most cultures do not accept uterine bleeding after cessation of ovarian function. Educational programs should be developed to inform women about the physiology of menopause in general and the rationale of HRT. The occurrence of uterine bleeding due to the present types of HRT needs to be specifically addressed. Risk-benefit assessments are to be explained to patients to reach an informed decision on HRT, and fears of women about actual or alleged negative metabolic impacts of HRT need to be discussed.

OBJECTIVE: We assessed compliance, relief of climacteric symptoms, and impact on lumbar bone mineral density in two groups of 140 patients treated with a sequential estrogen-progestogen or a continuous combined replacement therapy in comparison with controls. STUDY DESIGN: Patients were randomized to 2 mg of estradiol valerate daily and 5 mg of medroxyprogesterone acetate daily for 12 days per month sequentially to induce withdrawal bleeding (group A) or 2 mg of estradiol, 1 mg of estriol, and 1 mg of norethisterone acetate daily continuously to maintain amenorrhea (group B) or a control group (group C). RESULTS: Compliance was 93% after 1 year and 73% after 2 years in group B and 66% and 49% in group A after 1 and 2 years, respectively. Improvement of climacteric symptoms was similar in groups A and B. Uterine bleeding in 24% of patients in group A and 3% in group B was the most frequent reason for discontinuation of drug intake. Only continuous combined therapy (group B) increased bone mineral density after 1 and 2 years compared with baseline: -13% and 17% ( p = 0.01). In groups A and C no significant changes in bone mineral density were recorded. Compliance was unrelated to the age of menopause. CONCLUSION: Continuous combined therapy is superior to sequential estrogen progestogen replacement in compliance and prevention of bone loss but not with regard to relief of climacteric symptoms.

At least one of four women will suffer from osteoporosis with fractures of vertebrae, forearm or hip. Maintenance of bone mass is a crucial argument for long-term estrogen replacement for prophylaxis of osteoporosis. 2 mg estradiol or 0.625 mg conjugated estrogens orally or 50 to 100 micrograms estradiol percutaneously are equally sufficient for prevention of osteoporosis. The additional use of a progestogen in women with intact uterus may support the antiresorptive effects of estrogens. Improvement of patients' compliance-administered today by only 25% of postmenopausal women in Germany through sufficient information upon estrogen replacement therapy provided by the medical community is a rewarding task for physicians and scientists engaged in the field of menopause and prevention of osteoporosis.