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Objective: Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration., Method: The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE ( n  = 13,974) and drug dispensations were received from national validated registers., Results: Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate., Discussion: The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect., Conclusion: PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

Objectives: To assess how women in Sweden with breast cancer (BC), endometrial cancer (EC), and/or pulmonary embolism (PE) were dispensed menopausal hormone therapy (HT)., Study Design: A retrospective study of Swedish women aged 40 years or more on 31 December 2005 (n = 2,863,643), followed through to December 2011. The study analysed three mandatory national healthcare registries: the Swedish Prescribed Drug Register, the National Inpatient Register and the Cancer Register. New users were defined as having a first dispensation after at least a 9-month break, and thus were possible to identify from April 2006. New users with at least one of the diagnoses BC, EC or PE before the first dispensation were classified as having a relative or absolute contraindication for HT., Main Outcome Measures: The relative risks of having HT dispensed after being diagnosed with BC, EC and/or PE., Results: In total, 171,714 women had at least one of the diagnoses BC, EC or PE. The relative risk of having hormone therapy dispensed (current and new users) after being diagnosed with any of the diagnoses was significantly lower (PE, IRR 0.11, 95% CI 0.10-0.12;/ BC, IRR 0.12, 95% CI 0.11-0.13; EC, IRR 0.43, CI 0.40-0.46) than for women without these diagnoses., Conclusions: One in about 250 women started treatment with HT after being diagnosed with BC, PE or EC. Swedish prescribers seem to be well aware of the recommendations for HT use in women with contraindications. A few women, however, are prescribed HT despite having BC, EC or PE, possibly after careful evaluation of the risks and benefits and giving informed consent. Women with a history of PE were prescribed transdermal HT to a larger extent than women in general, in line with results from observational studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Study Question: Are Swedish women age 40-44 years with assumed early menopause 'undertreated' by hormone therapy (HT)?, Summary Answer: Many women with probable early menopause discontinue their HT after a short period of time. Thus, they fail to complete the recommended replacement up to age 51-52 years, the average age of menopause., What Is Known Already: Spontaneous early menopause occurs in ∼5% of women age 40-45 years. Regardless of the cause, women who experience hormonal menopause due to bilateral oophorectomy before the median age of spontaneous menopause are at increased risk of cardiovascular disease, neurological disease, osteoporosis, psychiatric illness and even death., Study Design, Size, Duration: The study is descriptive, and epidemiological and was based on the use of national registers of dispensed drug prescriptions (HT) linking registers from the National Board of Health and Welfare and Statistics Sweden from 1 July 2005 until 31 December 2011., Participants/materials, Setting, Methods: The study population consisted of 310 404 women, 40-44 years old on 31 December 2005 who were followed from 1 July 2005 until 31 December 2011., Main Results and the Role of Chance: Only 0.9% of women 40-44 years old started HT during the study period. A majority of these women used HT <1 year., Limitations, Reasons for Caution: We do not know the indications that led to the prescription of HT but assume that early onset of menopause was the main reason. Because of the study design-making a retrospective study of registers-we can only speculate on the reasons for most of the women in this group discontinuing HT. Another limitation of this study is that we have a rather short observation time. However, we have up to now only been able to collect and combine the data since July 2005., Wider Implications of the Findings: As the occurrence of spontaneous early menopause in women age 40-45 is reported to be ∼5%, the fact that <1% of Swedish women age 40-44 are prescribed HT, and can be shown also to have had the medication dispensed at a pharmacy suggests an unexpectedly low treatment rate. Some women with early menopause may have used combined contraceptives as supplementation therapy, but in Sweden HT is the recommended treatment for early menopause so any such women are not following this recommendation. Women who experience early menopause are at increased risk for overall morbidity and mortality, and can expect to benefit from HT until they have reached at least the median age of spontaneous menopause. It is therefore important to individualize the information given these women and to convey new knowledge in this area to gynaecologists and physicians in general as well as the recommendation that women in this group continue HT at least until the average age for spontaneous menopause is reached., Study Funding/competing Interests: No competing interests exist., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The use of hormone therapy (HT) for hot flushes has changed dramatically over the past five decades. In this cross-sectional questionnaire study, the aim was to describe the use of HT and alternative treatments and to study the frequency of hot flushes. A further aim was to compare data from the present questionnaire with data from previous studies made in the same geographic area., Method: A questionnaire was sent to a random sample of 2000 women aged 47-56 years living in Östergötland County, Sweden. The results were compared with findings from previous studies regarding use of HT, alternative treatment and hot flushes, and the number of HT prescriptions dispensed during the corresponding time using data derived from the Swedish Prescribed Drug Registry., Results: The response rate was 66%. Six percent used HT, in line with prevalence data from the Swedish Prescribed Drug Registry. Alternative treatments were used by 10%. About 70% of postmenopausal women reported flushes and almost one-third of those with flushes stated that they would be positive to HT if therapy could be shown to be harmless, a view more often stated by women with severe complaints of hot flushes (67%)., Conclusion: The use of HT and alternative treatments is low and many women suffer from flushes that could be treated. Women considered their knowledge of the climacteric period and treatment options as insufficient. Individualized information should be given and women with significant climacteric complaints, without contraindications, should be given the opportunity to try HT.

Objectives: FM is a condition that preferentially affects women. Sex hormones, and in particular oestrogens, have been shown to affect pain processing and pain sensitivity, and oestrogen deficit has been considered a potentially promoting factor for FM. However, the effects of oestrogen treatment in patients suffering from FM have not been studied. Here, we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM., Methods: Twenty-nine post-menopausal women were randomized to either 8 weeks of treatment with transdermal 17β-oestradiol (50 µg/day) or placebo according to a double-blind protocol. A self-estimation of pain, a set of quantitative sensory tests measuring thresholds to temperature, thermal pain, cold pain and pressure pain, and a cold pressor test were performed on three occasions: before treatment, after 8 weeks of treatment and 20 weeks after cessation of treatment., Results: Hormonal replacement treatment significantly increased serum oestradiol levels as expected (P < 0.01). However, no differences in self-estimated pain were seen between treatment and placebo groups, nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points., Conclusion: Eight weeks of transdermal oestradiol treatment does not influence perceived pain, pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM., Trial Registration: ClinicalTrials.gov Registration; http://www.clinicaltrials.gov; NCT01087593.

Objective: The aim of this study was to investigate whether tapering down of combined estrogen plus progestogen therapy (EPT) reduced the recurrence of hot flashes and resumption of therapy compared with abrupt discontinuation. A secondary aim was to evaluate whether health-related quality of life (HRQoL) was affected after discontinuation of EPT and to investigate the possible factors predicting resumption of EPT., Methods: Eighty-one postmenopausal women undergoing EPT because of hot flashes were randomized to tapering down or abrupt discontinuation of EPT. Vasomotor symptoms were recorded in self-registered diaries, and resumption of hormone therapy (HT) was asked for at every follow-up. The Psychological General Well-being Index was used to assess HRQoL., Results: Neither the number nor the severity of hot flashes or HRQoL or frequency of resumption of HT differed between the two modes of discontinuation of EPT during up to 12 months of follow-up. About every other woman had resumed HT within 1 year. Women who resumed HT after 4 or 12 months reported more deteriorated HRQoL and more severe hot flashes after discontinuation of therapy than did women who did not resume HT., Conclusions: Women who initiate EPT because of hot flashes may experience recurrence of vasomotor symptoms and impaired HRQoL after discontinuation of EPT regardless of the discontinuation method used, abrupt or taper down. Because, in addition to severity of flashes, decreased well-being was the main predictor of the risk to resume HT, it seems important to also discuss quality of life in parallel with efforts to discontinue HT.

Objective: The purpose of this study was to investigate the extent of reappearance of vasomotor symptoms after cessation of postmenopausal hormone therapy (HT) in women who started HT because of hot flashes., Methods: A cross-sectional postal survey was conducted. A validated questionnaire was sent to all women 53 to 54 years old living in Linköping, Sweden (n = 1,733), including questions about menopause, HT, and vasomotor symptoms. Pearson's chi test and logistic regression were used for statistical analyses., Results: Response rate after one reminder was 77.3%. After omitting incomplete answers, 72.9% remained for analysis. In all women, 319 (25.3%) were current users of HT, 242 (19.2%) were previous users, and 702 (55.6%) were never-users. Of the 242 previous users, 165 (69%) women stated that they had vasomotor symptoms before starting HT. Vasomotor symptoms recurred after cessation of HT in 143 (87%) of these 165 women. We found no significant difference in symptom recurrence in comparisons of the three groups based on usage of HT for 0 to 1, 2 to 4, or 5 years or more., Conclusions: Most women who had vasomotor symptoms when they initiated HT reported recurrence of symptoms after cessation of HT (87%), although the flashes were usually reported to be less frequent and bothersome than they were before HT. Effective and safe treatment approaches for women with recurrence of vasomotor symptoms are needed.

Background: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up., Methods: HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone., Results: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test)., Conclusion: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

Objective: To evaluate the effects of electro-acupuncture (EA) and hormone therapy (HT) on vasomotor symptoms in women with a history of breast cancer., Methods: Forty-five women were randomized to EA (n = 27) for 12 weeks or HT (n = 18) for 24 months. The number of and distress caused by hot flushes were registered daily before, during and up to 24 months after start of treatment., Results: In 19 women who completed 12 weeks of EA, the median number of hot flushes/24 h decreased from 9.6 (interquartile range (IQR) 6.6-9.9) at baseline to 4.3 (IQR 1.0-7.1) at 12 weeks of treatment (p < 0.001). At 12 months after start of treatment, 14 women with only the initial 12 weeks of EA had a median number of flushes/24 h of 4.9 (IQR 1.8-7.3), and at 24 months seven women with no other treatment than EA had 2.1 (IQR 1.6-2.8) flushes/24 h. Another five women had a decreased number of flushes after having additional EA. The 18 women with HT had a baseline median number of flushes/24 h of 6.6 (IQR 4.0-8.9), and 0.0 (IQR 0.0-1.6; p = 0.001) at 12 weeks., Conclusion: Electro-acupuncture is a possible treatment of vasomotor symptoms for women with breast cancer and should be further studied for this group of women.

Objectives: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy., Design: A randomised, double-blind, double-dummy, group comparative intervention trial., Setting: Multicentre study executed in 32 centres in 7 European countries., Sample: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years., Methods: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks., Main Outcome Measures: Prevalence of vaginal bleeding, hot flushes and adverse events., Results: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001)., Conclusion: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.

Objective: To investigate knowledge of hormone therapy (HT), reproductive physiology, and menopause in a population of 53- to 54-year-old women. Further aims were to determine whether the knowledge differed between users and nonusers of HT and between groups with different levels of education., Design: In 2003, all 53- and 54-year-old women (N = 1,733) in Linköping, Sweden, were sent a questionnaire containing questions about reproductive physiology related to menopause and HT. Answers from 73% of the women were analyzed., Results: Swedish women had limited knowledge of HT, reproductive physiology, and menopause irrespective of HT use or educational level. Most of the women knew that hot flashes are common around menopause and decreasing estrogen production causes the menopause. They knew little about the effects of progestagens and the effects of HT on fertility. Women with low educational level were more likely to answer the questions by stating that they were unsure than did women with high educational level. Ever-users of HT knew more than never-users about risks and benefits of HT in relation to breast cancer and osteoporosis, and ever-users thought that the risks of thrombosis and myocardial infarction were lower than did never-users., Conclusions: Women need improved knowledge of the risks and benefits of HT as well as education about the reproductive system around menopause. This would probably better support and empower women to manage an important period of their lives.

Background: It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making., Objective: The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition., Methods: Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden., Results: Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview., Conclusion: Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking.

Objectives: To assess changes in women's attitudes towards risk and benefits of, and use of hormone treatment in the menopausal transition (HT) before and after Heart and Estrogen/Progestin Replacement Study (HERS) and the oestrogen and progestin trial of Women's Health Initiative (WHI)., Methods: Postal questionnaires to all women 53 and 54 years of age in a Swedish community in 1999 (n=1.760) and 2003 (n=1.733). Data on sales of HT were collected from the database of the National Corporation of Swedish Pharmacies., Results: The fraction of women reporting current use of HT fell from 40.5 to 25.3% (p<0.001, chi2-test) both by fewer women starting and more women discontinuing treatment. This corresponded to a decrease in dispensation of HT in Linköping and nationwide for the same age group. The fraction of women who had tried complementary treatment for climacteric discomfort, increased from 9.6 to 18.1% for natural remedies (p<0.001, chi2-test). Women perceived HT as more risky and less beneficial in 2003 as compared with 1999 (both p<0.001, chi2-test). The most frequent source of information about HT during the last year before the 2003 questionnaire were newspaper or magazines (43.8%) and television or radio (31.7%)., Conclusions: The decreased use of HT in the community correlated with pronounced changes in the attitudes towards HT. Media were a more frequent source of information than health care personnel. This indicates that media reports about major clinical studies might have influenced the use of HT among women.

Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis., Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks., Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholesterol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year., Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.

Objective: To investigate how risks and benefits of hormone replacement therapy (HRT) are communicated to women in clinical practice. To evaluate the usefulness of a risk classification based on context framing, i.e. whether the risk is discussed for one or several alternative treatments, and/or in the same context as possible benefits., Design: Analysis of structure and content of transcribed consultations (n = 20) from first-time visits for discussion of climacteric discomfort and/or HRT with five physicians at three different out-patient clinics of gynecology., Results: All women received a prescription of HRT. An alternative to HRT was discussed in seven of the consultations. No decision aids were used. Risk discussion was dominated by the physicians giving information about long-time risk and benefits. The decision to prescribe was made either before the risk discussion was initiated, or before it was finished, in 8 of the 18 consultations where risk discussion was present. Risk classification according to context framing was performed and indicated use of different communication strategies by the physicians., Conclusions: The perspective of the physicians was mainly on prevention while the women were more focused on symptom alleviation. Each physician had a strategy of his/her own for the risk discussion. Thus, the major differences found between the consultations were between physicians, and not between the women. Risk discussion seemed to be aimed at motivating the woman to follow the physician's decision rather than to help her participate in the decision-making process.

Vasomotor symptoms with hot flushes and sweating are reported by about 75 percent of women around menopause. Hormone replacement therapy (HRT) is the treatment of choice but some women have medical contraindications or side effects. There is, therefore, a need of alternative therapies. Progestagens may decrease hot flushes, as will clonidin and selective serotonin reuptake inhibitors. Phytoestrogens, which exist in some dietary products and complementary and alternative medicines have estrogen-like effects and may decrease hot flushes, although there are contradictory scientific reports. Acupuncture, exercise and behavioral therapy may also decrease vasomotor symptoms. No alternative therapy is as effective as HRT.

Background: Some extragenital symptoms have been suggested to be associated with the menopause and thus to be affected by estrogen status. In such case extragenital symptoms may be more frequent in postmenopausal women without hormone replacement therapy (HRT) than in premenopausal women or women using HRT., Objective: To assess if the prevalence of a number of extragenital symptoms is higher in postmenopausal women without than with HRT, or in premenopausal women of the same age., Material and Methods: All women aged 53 and 54 years in the community of Linköping (n=1760) were sent a validated questionnaire about use of HRT, time since last menstruation and about different extragenital symptoms., Results: 1298 (73.8%) women answered the questionnaire and answers from 1180 (67%) women were possible to analyze. Postmenopausal women woke up significantly more often during night than premenopausal, and those without HRT often due to hot flushes and sweating. Women with HRT reported more muscular pain than the others. We found no other significant difference in prevalence of extragenital symptoms between the three groups of women., Conclusions: Sleeping disorders, arthralgia, xerophthalmia, xerostomia and dry skin are not more prevalent in 53 and 54 years old postmenopausal women without HRT than in women with HRT or in premenopausal women of the same age. It may still be that some of these symptoms are related to estrogen deficiency, but do not develop until some years after menopause. It may also be that women with the most severe symptoms decided to use HRT and thereby decreased symptoms to the same level as in non-users.

Problem: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies., Method of Study: We studied the in vivo effects of transdermal estrogens (50 microg 17 beta-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-gamma, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique., Results: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-gamma, IL-4 or IL-10 in relation to estrogen or placebo treatment., Conclusions: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

Objectives: To establish the prevalence of unsteadiness and rotatory vertigo in peri- and postmenopausal women, and whether balance disturbances are more common in women with vasomotor symptoms and without hormone replacement therapy (HRT)., Method: A validated questionnaire was sent to all 1523 women aged 54 or 55 years in Linköping, Sweden., Results: Daily or weekly unsteadiness was reported by 5%, and daily or weekly rotatory vertigo by 4% of all women. The frequency of vasomotor symptoms correlated with reported unsteadiness (rs = 0.23, p < 0.001). Fourteen per cent of women with daily vasomotor symptoms reported weekly or daily unsteadiness, compared with 3% of those without vasomotor symptoms (odds ratio (OR) 7.58, 95% confidence interval (CI) 3.72-15.45). The frequency of vasomotor symptoms correlated with rotatory vertigo (rs = 0.19, p < 0.001). Ten per cent of women with daily vasomotor symptoms reported weekly or daily rotatory vertigo, compared with 2% of women without vasomotor symptoms (OR 5.21, 95% CI 1.07-25.52). No correlation was seen between vasomotor symptoms and falls. Users of HRT had the same prevalence of balance disturbances as non-users., Conclusions: Women with frequent vasomotor symptoms seem to run a greater risk of unsteadiness and rotatory vertigo than do women without symptoms. This association may not be explained by means of a cross-sectional study, but there might exist a causal connection between vasomotor symptoms and balance disturbances.

Objective: To establish whether estrogen treatment affects well-being in postmenopausal women without current or previous vasomotor symptoms., Design: Forty postmenopausal women, aged 45-59 years, without current or previous vasomotor complaints, were included. They were randomized to masked treatment with either transdermal 17beta-estradiol 50 microg/24 h or to placebo. At baseline and after 12 and 14 weeks of treatment, the women completed a questionnaire which reflects well-being, the Psychological General Well-Being (PGWB) Index., Results: The women scored high on the PGWB Index, both at baseline and after 12 and 14 weeks of treatment. There was no significant difference in well-being according to PGWB Index between the groups treated with estrogen and placebo, neither at baseline, nor after therapy. Furthermore, there was no difference in change during therapy between the treatment groups., Conclusion: There is a gradual decline in estrogen during the climacteric, and it is controversial to which extent this affects women's mental health. The PGWB scores in this study were high before therapy, reflecting that these women without previous or current vasomotor complaints represented a selected sample. Neither short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone acetate during 2 weeks improved well-being in postmenopausal women without vasomotor symptoms who had high well-being at baseline.

Background: Most but not all women suffer from vasomotor symptoms around menopause. The exact mechanisms behind these symptoms are unknown, but the rate of decline in estrogen concentrations has been suggested to affect the risk of hot flushes., Objective: The objective was to assess whether vasomotor symptoms were induced in women without previous such symptoms, when the women were given combined estradiol and progestagen therapy for 3 months, whereafter therapy was abruptly withdrawn., Materials and Method: After randomization, 40 postmenopausal women without previous or current vasomotor symptoms were treated transdermally with either 50 micrograms/day 17 beta-estradiol or placebo during 14 weeks. During the 13th and 14th weeks, treatment was combined with oral medroxyprogesterone acetate 10 mg/day. Serum estradiol and follicle-stimulating hormone (FSH) concentrations were analysed before and after 12 weeks of therapy. Climacteric symptoms were assessed at the same intervals as well as 8 weeks after the end of therapy., Results: All women had low pretreatment levels of estradiol and high FSH concentrations. During estradiol therapy estradiol levels increased significantly, whereas FSH only decreased slightly. No woman developed vasomotor symptoms after withdrawal of therapy., Conclusion: Postmenopausal women without previous or current vasomotor symptoms did not develop such symptoms when estrogen replacement therapy was first instituted and then abruptly stopped. Probably other factors than the rate with which estrogen concentrations decrease determine whether or not a woman will develop vasomotor symptoms. Evidently, estrogens can be prescribed to a woman who has no vasomotor symptoms, without much risk of inducing such symptoms if she decides to abandon therapy, even after 3 months of treatment.

Objective: The objective was to assess whether menopausal women with vasomotor symptoms had a lower stress-coping than menopausal women without symptoms and if stress-coping changed when vasomotor symptoms had been effectively treated with estrogens. The objective was also to assess whether menopausal women, effectively treated for vasomotor symptoms, had a higher neuroticism score than women without such symptoms., Methods: Two groups of physically and mentally healthy postmenopausal women were recruited from the outpatient clinic at the Department of Obstetrics and Gynaecology, University Hospital of Linköping, Sweden. Sixteen women with vasomotor symptoms (target group) were treated with oral 17 beta-estradiol, 2 mg/day during 3 months. A comparison group was formed comprising 17 women without vasomotor symptoms. The Kupperman Index was used to cover menopausal characteristics in all women at baseline as well as at the second visit after 3 months. Stress-coping was measured by means of the Stress Coping Inventory, which is an instrument developed to measure of the individual's appraisal of having adaptive resources for handling stressful situations. At the second visit all women were also asked to complete the Eysenck Personality Inventory., Results: Women in the target group had a significantly lower stress-coping than women in the comparison group at baseline as well as after 3 months. Stress-coping did not change after estrogen therapy, although the vasomotor symptoms had virtually disappeared. Women in the target group successfully treated for vasomotor symptoms, had a significantly higher neuroticism score compared to the comparison group., Conclusions: Differences in behaviour patterns and personality are probably two reasons why some women report or seek advice due to vasomotor symptoms and some women do not. Stress-coping in women with moderate to severe vasomotor symptoms is unaffected by estrogens.

Objective: To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability., Design: Double-blind, randomised controlled trial., Setting: Twenty-nine sites in Denmark, nine in Norway and six in Sweden., Participants: Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy., Interventions: Daily treatment with tibolone 2.5 mg (n = 218) or 17beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) (n = 219)., Main Outcome Measures: Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks., Results: Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E2/NETA (P < 0.0001), mainly during the first six treatment cycles., Conclusions: Both tibolone and E2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.

Study Design: Cross-sectional study with two age cohorts., Objective: To assess whether women receiving hormone replacement therapy after menopause have a higher prevalence of back problems than women who do not receive such treatment., Background: Back pain is a common medical problem throughout life and especially during pregnancy. Hormonal factors have been proposed as a possible contributor., Patients and Methods: A validated postal questionnaire was sent in early 1995 to all 1324 women of 55 years and 56 years of age residing in Linköping, Sweden. This questionnaire included questions about current hormone replacement treatment, previous and current back problems, medical care for back problems, parity, exercise and smoking habits, and occupation., Results: The questionnaire was returned by 84.7% of the women. There was a significant, albeit weak, positive association between current use of hormone replacement treatment and low back pain. Previous back problems during pregnancy was a strong risk factor for current back pain, whereas neither current smoking nor regular physical exercise was a risk factor according to multiple logistic regression analysis. The interaction of smoking and an occupation involving heavy lifting significantly affected back pain., Conclusions: Women receiving hormone replacement treatment had a slightly, but significantly, higher prevalence of current back pain than nonusers (48% vs. 42%, respectively, P < 0.05), which could not be explained by differences in occupation, smoking habits, or current physical activity. Although the association between hormone replacement therapy and back problems is weak and probably of minor clinical importance, it is speculated that hormonal effects on joints and ligaments may be involved.

To chart current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population, in relation to previous oral contraceptive (OC) usage, all 1,323 55-56-year-old women living in Linköping in 1995 were sent a questionnaire concerning health status and climacteric symptoms, and previous and/or current use of HRT, OCs and alternative remedies. Current HRT was more common among previous OC users than among those who had never used OCs (41.4 vs. 23.1 percent). As compared with non-HRT users, HRT users were characterised by greater physical activity but less strenuous occupations, and a higher prevalence of hysterectomy. Of the series as a whole, 35 per cent were currently on HRT, half of them having been so for at least two years, and only 5 per cent had abandoned HRT after trying it for some time. Alternative remedies were used by 5 per cent of the women as therapy for climacteric complaints, but about four times as many women had tried such therapy and abandoned it. The sole characteristic feature of alternative remedy usage was that it was less common among hysterectomised women. Of women treated for breast cancer, none used HRT and few used alternative remedies. Thus, in this postmenopausal population, the prevalence of HRT was high, as was the level of compliance. Previous OC usage was probably a determinant of current attitudes toward HRT.

Objectives: to compare the effects of tibolone 2.5 mg (Livial) with those of 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (Kliogest) on sexual life., Methods: in a 48 week, double blind, multicenter study, 437 postmenopausal women were randomised to treatment with either tibolone or 17 beta-estradiol 2 mg plus norethisterone acetate. Treatment groups were compared with respect to different aspects of sexual life with a questionnaire covering sexual experience and responsiveness during the last 30 days., Results: a total of 315 subjects completed 48 weeks treatment. In the E2/NETA group an improvement after 48 weeks compared to baseline was observed in five out of seven items assessing sexual life. In the tibolone group an improvement regarding all seven items assessing sexual life was seen. When tibolone was compared to E2/NETA significantly higher scores were found for the items assessing 'frequency', 'satisfaction' and 'enjoyment'., Conclusions: this study indicate that tibolone and E2/NETA -which both have an androgenic profile-affect several aspects of sexual life positively. The difference with respect to satisfaction with sexual enjoyment and frequency could be of clinical importance.

Objective: To establish whether hormone replacement therapy affects postural balance in postmenopausal women., Methods: Nineteen healthy postmenopausal women with vasomotor symptoms were included. Median age was 54 years, median time since menopause was 3 years. They underwent dynamic posturography before and after 4 and 12 weeks of transdermal estrogen treatment (17 beta-estradiol 50 micrograms/day) as well as after 2 additional weeks of combined estrogen-progestagen treatment. The dynamic posturography method quantifies the amplitude, frequency, and pattern of body sway and tests the visual, vestibular, and somatosensory systems, which together maintain balance. The two most difficult tests either cancel visual and distort somatosensory inputs or give distorted information from both the visual and somatosensory systems., Results: Hormone replacement therapy increased static balance performance assessed by dynamic posturography. A highly significant improvement was seen in the two most difficult tests between the pretreatment test and the test performed after 4 weeks of estrogen therapy (P < .01, P < .001, respectively). This improvement was sustained after 12 weeks and also during the 14th week, with the women on combined estrogen-progestagen treatment., Conclusion: Estrogen treatment increased balance performance measured by dynamic posturography, indicating that the beneficial effects from estrogens on postmenopausal fracture risk may include central nervous system effects on balance. Two weeks' addition of gestagen to the treatment regimen did not counteract the estrogen effects.

Objectives: To assess the current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population and to relate HRT use to previous use of oral contraceptives., Material and Methods: All 1323 women living in Linköping of 55 or 56 years old during 1995 were sent a questionnaire asking for data with relation to health and climacteric symptoms as well as to previous and current use of HRT, oral contraceptives and alternative remedies., Results: Current use of HRT was more common among women who previously used oral contraceptives (41.3%) than among women who had never used oral contraceptives (23.1%). HRT users were also more often physically active, had undergone hysterectomy and had lighter occupation than non-users. Of all women 35% were current users of HRT, half of them for at least 2 years, whereas only 5% had tried HRT and abandoned therapy. Alternative remedies were used by 5% of the women as therapy for climacteric complaints, and about four times as many women had tried such therapy but abandoned it. The only characteristic about use of alternative medicines was that they were used less often by women who had been hysterectomized. No women treated for breast cancer used HRT and only few of them used alternative remedies., Conclusions: The prevalence of HRT use, as well as compliance, was high. Previous use of oral contraceptives probably affected the attitude towards using HRT.

Objectives: Unopposed estrogen therapy may induce endometrial hyperplasia. To protect the endometrium, estrogen replacement therapy should be combined with a progestin in menopausal women with an intact uterus. The aim of this open non-comparative study was to evaluate the effects on bleeding control and endometrium of 'spacing-out' the 14-day progestin therapy to every second month during transdermal combined hormonal replacement therapy., Methods: Sixty-eight healthy women, previously treated with sequential combined transdermal hormonal replacement therapy every month for 3 years, were treated for the following 2 years in cycles with 6 weeks of transdermal estradiol 50 micrograms/daily (Estraderm, Ciba-Geigy), followed by 2 weeks of combined norethisterone acetate 0.25 mg/day and 50 micrograms estradiol per day., Results: Annual endometrial biopsies diagnosed hyperplasia in one woman during the second year whereas most biopsies showed a secretory endometrium. Vaginal ultrasound showed no correlation to either bleeding-pattern or histopathological diagnosis. Most women had a regular bleeding-pattern., Conclusions: Transdermal progestin every second month might be an alternative to regular monthly sequential hormonal replacement therapy.

All women (n = 2465) living in the community of Linköping, Sweden, aged 55, 57, 59 and 65 years were studied in a cross-sectional trial concerning the prevalence of vasomotor symptoms, hormonal replacement therapy (HRT) and sexual activities. After one reminder, answers were received from 1867 (76%) women. In all, 51% of the women reported vasomotor symptoms. Ten percent of the women used HRT at the time of the survey. Another 10% of the women had previously used oral HRT but had abandoned treatment. One third of these women reported no vasomotor symptoms when they abandoned treatment. One fifth ceased treatment after recommendation from their physician and another fifth because of 'fear' of hormonal treatment. Sixty-two percent of the women reported sexual activity. The most common reasons for not having a regular sex-life were lack of partner or lack of desire.

To evaluate the effect of transdermal sequential treatment with estradiol and estradiol/norethisterone acetate on lipoprotein metabolism, 25 postmenopausal women received treatment for 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day and 2 weeks a combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Blood samples for lipoprotein analyses were drawn before treatment and in estrogen and combined phases in cycles 3 and 12. Plasma total cholesterol, low (LDL) and high (HDL) density lipoprotein were all significantly reduced in both estrogen and combined phases. Eighteen of the women continued the treatment for 36 cycles. In this group the HDL-cholesterol had returned to baseline values in combined phase in cycle 24. Plasma cholesterol and LDL-cholesterol values remained significantly reduced throughout the whole study compared to the pre-trial values. The present study by transdermal sequential hormonal treatment results in a lipid and lipoprotein pattern with reduced total cholesterol and LDL cholesterol in postmenopausal women.

The efficacy of transdermal norethisterone acetate in sequence with transdermal estradiol has been investigated in a multicenter study of 136 post-menopausal women to determine the incidence of endometrial hyperplasia, the effects on the vaginal cytology and the control of bleeding. Treatment consisted of 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day followed by 2 weeks of a new combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Endometrial histology was assessed by two pathologists. Of the 136 pre-treatment biopsies 89% provided no material, an inadequate sample or an inactive (atrophic or non-secretory) endometrium. Of the post-treatment biopsies from 110 women who completed the study: 65% showed secretory, 3% proliferative and 24% inadequate material or inactive endometrium. Hyperplasia was found in two biopsies (2%); in one of these focal atypical hyperplasia was agreed by both pathologists, in another a hyperplastic endometrial polyp was diagnosed by one pathologist. The bleeding was regular in 80% of the 1195 cycles and irregular in 11%. No bleeding occurred in 9% of the cycles. Vaginal cytology showed a significant shift towards increased maturation during treatment.

The long-term effect on aspects of quality of life (QoL) of treatment with transdermal oestrogen for 2 weeks followed by transdermal oestrogen/progestogen norethisterone acetate/oestradiol TTS 0.25/0.05 mg/day for the next 2 weeks was investigated in postmenopausal women within the framework of a 1-year seven-centre trial. Of the 136 women who were included (mean age 53 +/- 4.8 years), 110 completed the study. Aspects of QoL that are of relevance in the perimenopause and postmenopause were evaluated using the Psychological General Well-Being (PGWB) index, the Women's Health Questionnaire (WHQ) and the Sleep Dysfunction Scale before and after 3 and 9 months of therapy in the oestrogen phase. Climacteric complaints were also assessed by means of the Kupperman Index. Improved well-being, i.e. less anxiety and depression, increased vitality and better self-control (P less than 0.0001) were observed, as well as reduced sleep disturbance (P less than 0.0001). The WHQ showed decreased vasomotor and somatic symptoms, and improved sex life, emotions and cognitive function (P less than 0.0001). Improvement was the same at 3 and 9 months. According to the Kupperman Index, climacteric symptoms were alleviated (P less than 0.0001). Relief of vasomotor symptoms was correlated with improvement in the WHQ (r = 0.82), the PGWB index (r = 0.58, P less than 0.0001) and sleep (r = 0.51, P less than 0.0001). Because of the absence of a placebo control group, the results must be regarded with caution until confirmed in a placebo-controlled trial.