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Endocrine complications are a common late effect after childhood cancer. Our study assessed the prevalence and predictors of premature ovarian insufficiency (POI) and prospects of pregnancy in young female survivors. This nationwide study combined registry and survey data for female childhood cancer survivors aged 19 to 40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Of 1989 approached young women, 1333 (67%) participated by completing a survey. Median age at diagnosis 1981 to 2017 was 6 (range 0‐17) and at study 28 (19‐40) years. There were two indicators of POI, induced puberty reported in 5.3% and estrogen replacement therapy (ERT) in 9.3% at assessment. In separate logistic regression analyses (P <.001), induced puberty and ERT were significantly predicted by hematopoietic stem cell transplantation (HSCT), abdominal irradiation, central nervous system irradiation and chemotherapy. ERT was also associated with older age at diagnosis. Of the 626 women (48% of responders) who had tried to become pregnant, 25% had undergone fertility investigations and 72% reported having a biological child. Treatment with HSCT was associated with 5.4 times the odds of needing fertility investigations (P <.001). Having a biological child was associated with non‐HSCT treatment, but also with ever having had a partner and older age at the time of study (all P <.001). In conclusion, the majority of those female childhood cancer survivors who had tried to conceive were able to successfully give birth. However, a small identifiable group of female survivors are at risk of subfertility and early menopause. [ABSTRACT FROM AUTHOR]

Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy. • Aortic dissection in Turner syndrome is related to the size of the ascending aorta. • The current strategies for preventing aortic dissection are insufficient. • Aortic diameter cutoff of 3.3 cm is more reliable than the ASI cutoff of 2.5 cm/m2. • The risk of aortic dissection is low for absolute aortic diameter < 3.3 cm. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44–0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59–0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02–1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06–2.44) in older women, but no association was shown for all-cause mortality. Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear. [ABSTRACT FROM AUTHOR]

Objective: To investigate the use of menopausal hormone therapy (MHT) in premenopausal women after bilateral oophorectomy., Design: Retrospective register-based cohort study., Setting: Sweden., Population: Swedish women aged 35-44 years without malignancy who underwent bilateral oophorectomy in 2005-2020 were identified using The Swedish National Quality Register of Gynaecological Surgery (GynOp)., Methods: Data from GynOp were cross-linked with data on dispensed drugs extracted from the Swedish Prescribed Drug Register., Main Outcome Measures: Proportion of women dispensed MHT at least once within 1 year after surgery. Repeated treatment episodes were defined, and the proportion of 'person time' covered by dispensations was analysed., Results: In total, 1231 of all women (n = 1706) were dispensed MHT at some point after surgery, with 1177 women dispensed MHT within 1 year. This proportion increased from 64% in 2005 to 84% in 2019 (p < 0.001). In the total population, 4537 'treatment years' transpired, corresponding to 43% of the mean time covered. In women dispensed MHT within 1 year, the proportion of time covered was 63%., Conclusions: Only 69% of all women without malignancy of any kind who underwent bilateral oophorectomy were dispensed MHT within 1 year after surgery, and the duration of treatment was limited. It is important to study further the reasons behind the low dispensation rate in this group to increase adherence to current treatment guidelines, improve quality of life, and avoid increased morbidity and mortality., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: To describe the trends in the prevalence of use menopausal hormone therapy (MHT) in Sweden over the period 2000-2021 and to analyse the impact of different lengths of run-in on the calculated incident use., Study Design: Individual-level data on MHT dispensations for 2.5 million women aged 45-69 years for the period 2006-2021 were analysed. Aggregated sales volumes in defined daily dose (DDD) were available for the whole study period (2000-2021)., Main Outcome Measures: One-year prevalence and one-year incidence (18-month run-in) per 1000 women and DDD per 1000 women per day of MHT were the main outcome measures. The predictive values for incidence representing first-ever use of MHT were calculated for different run-in periods, which is a defined period without dispensations., Results: Both the DDD, from 2000, and the prevalence, from 2006, decreased by over 80 % in women aged 50-54 years, until 2010, when the use of MHT stabilised. The predictive value for incident users to be first-ever users was 88 % in women aged 50-54 years, with a run-in of 18 months, in 2021. The incidence was stable between 2007 and 2016. From 2017 the incidence increased, being most pronounced for women close to menopause., Conclusions: MHT use decreased significantly after the turn of the century, but has increased since 2017. A run-in period of 18 months was found suitable and reliable for defining incident users of MHT in the age intervals closest to menopause. Incidence seems to be a more sensitive measure than prevalence or DDD for the early detection of changes in trends in prescriptions of MHT., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Telomere length has been associated with longevity. As telomere length is partly determined by the human telomerase reverse transcriptase (hTERT), we investigated the association between an hTERT polymorphism located in its promoter region ((-) (1327)T/C) and longevity in two cohorts of older adults. Participants from the Kungsholmen project (KP; n = 1,205) and the Swedish National study of Aging and Care in Kungsholmen (SNAC-K; n = 2,764) were followed for an average period of 7.5 years. The main outcomes were hazard ratios (HR) of mortality and median age at death. In both cohorts, mortality was lower in female T/T carriers, aged 75+ years in KP (HR = 0.8, 95% CI: 0.5-0.9) and 78+ years in SNAC-K (HR = 0.6, 95% CI: 0.4-0.8) compared with female C/C carriers. T/T carriers died 1.8-3 years later than the C/C carriers. This effect was not present in men, neither in SNAC-K women aged 60-72 years. The association was not modified by presence of cancer, cardiovascular diseases, number of chronic diseases, or markers of inflammation, and did not interact with APOE genotype or estrogen replacement therapy. The gender-specific increased survival in T/T carriers can be due to a synergistic effect between genetic background and the life-long exposure to endogenous estrogen. [ABSTRACT FROM AUTHOR]

Background: Prolonged survival in ovarian and endometrial cancer patients increases the importance of paying attention to quality of life. Hormone replacement therapy (HRT) after gynecologic cancer has been controversial. With this survey, we sought to describe Swedish gynecologists' and gynecologic oncologists' attitudes towards prescribing HRT to these cancer survivors and see if prescribing practice is consistent with the available evidence and national guidelines., Material and Methods: A web-based survey containing three hypothetical cases with a total of 15 questions was distributed to gynecologists and gynecologic oncologists in Sweden. Respondents were asked about their HRT prescription practices in endometrial/ovarian cancer patients with moderate to severe menopausal symptoms., Results: In total 262 gynecologists and 24 gynecologic oncologists answered the survey. In the low-risk endometrial cancer case a majority of the gynecologists (55%) and gynecologic oncologists (66.7%) would prescribe local estrogen. A total of 30% of the gynecologists would prescribe estrogen replacement therapy (ERT) in the high-risk endometrial cancer case compared to 58.3% of the gynecologic oncologists. The gynecologic oncologists felt more comfortable treating patients with endometrial cancer than did gynecologists, and the gynecologists were more likely to read the national guidelines. In the ovarian cancer case, 63.7% of the gynecologists would prescribe HRT compared to 92% of the gynecologic oncologists., Conclusion: Swedish gynecologic oncologists have a more favorable attitude towards HRT for endometrial/ovarian cancer patients and feel more comfortable treating their patients than do gynecologists. This study illustrates a need for education in these matters in order not to withhold HRT from women due to doctors' sometimes unjustified anxiety.

Objectives: Hot flushes and night sweats often cause discomfort and may negatively affect sleep and quality of life. Studies have shown that menopausal symptoms, like hot flushes, may persist for up to 20 years after the menopausal transition, but there are no published studies regarding the occurrence of hot flushes among women older than 80 years. The aim of this study is to determine the prevalence of hot flushes in 85-year-old women., Methods: All 85-year old women living in Linköping municipality in 2007 (n = 415) received a postal questionnaire. The majority, 74% (n = 307), answered the questionnaire and 47% (n = 194) agreed to visit the Department of Geriatric Medicine; during this visit questions regarding hot flushes and use of hormone therapy were asked., Results: About 16% (n = 29) of the women experienced hot flushes during the day and/or during the night and 6.5% (n = 12) of the women were currently using hormone therapy. Almost 10% (n = 17) of all responding women were very to moderately distressed by their hot flushes., Conclusion: Our results confirm and extend previous knowledge based on studies of younger postmenopausal women in showing that menopausal symptoms still occur in elderly women. We found that, while the prevalence of menopausal symptoms decreases with age, these symptoms are still experienced by some 85-year-old women.

Background: As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden)., Methods: The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study., Results: Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity., Conclusion: Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.

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.

Background: Evidence is mixed regarding how familial predisposition to breast cancer affects the relation between hormone replacement therapy and risk of postmenopausal breast cancer. We investigated whether the risk difference for invasive breast cancer attributable to estrogen plus progesterone replacement therapy is greater among women with a first-degree family history of the disease., Methods: This study is a longitudinal follow-up of 16,608 postmenopausal women aged 50-79 years who were enrolled between 1993 and 2002 in the Women's Health Initiative randomized trial of estrogen plus progesterone replacement therapy versus placebo., Results: Three hundred forty-nine cases of invasive breast cancer occurred during a mean follow-up period of 5.6 years. The invasive breast cancer risk difference attributable to the hormone therapy was 0.007 among women with first-degree family history and 0.005 among the others, resulting in a negligible interaction contrast (IC = 0.002; 95% confidence interval = -0.014 to 0.018). The interaction contrast restricted to estrogen-receptor-positive invasive breast cancers was also negligible (IC = -0.006; 95% CI = -0.021 to 0.008)., Conclusion: Family history and estrogen plus progesterone replacement therapy have independent and noninteracting effects on the risk of invasive breast cancer among participants in the Women's Health Initiative randomized trial.

Objective: To outline possible associations between urinary incontinence (UI) and serum levels of steroid hormones in middle-aged women., Design and Setting: Community-based observational study., Sample: All women aged 50-59 living in the Lund area by December 1995 were invited to a screening procedure. Sixty-four percent (n = 6,917) attended the screening that included physical and laboratory examinations and questionnaires., Methods: Serum levels of cortisol, testosterone, androstendione, SHBG (sex hormone-binding globulin), and estradiol were analyzed and the 2,221 (32%) women who reported urinary leakage causing a social or hygienic problem were compared to those who denied incontinence., Main Outcome Measure: Possible differences in serum levels of steroid hormones in continent and incontinent women., Results: There were no significant differences between continent and incontinent women regarding serum levels of cortisol, testosterone, androstendione, or testosterone + androstendione combined. Serum estradiol adjusted for body mass index, parity, smoking, and hysterectomy was significantly higher in incontinent women (87.1 +/- 138.4 pmol/l vs. 78.0 +/- 118.5 pmol/l, p = 0.005), whereas the ratio estradiol/SHBG was not. These differences persisted when the group of women not on hormonal treatment was analyzed., Conclusions: UI in middle-aged women seems related to higher serum estradiol levels. This corroborates with studies showing a higher incidence and/or prevalence of UI in women on hormone therapy. No association between UI and serum levels of cortisol, testosterone, or androstendione was found.

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.

Objective: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women., Design: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208)., Results: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group., Conclusion: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.

Objective: To assess the prevalence of hypertension and use of antihypertensive drug therapy in relation to menopausal status and to delineate perceived associations between androgens and blood pressure in perimenopausal women., Methods: A population-based sample of women aged 50-59 (n = 6893). Women were divided into three groups according to their hormonal status: premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy., Result: In the premenopausal, postmenopausal without hormone therapy, and postmenopausal with hormone therapy groups, the prevalence of high blood pressure (>/= 140 mmHg systolic or >/= 90 mmHg diastolic) was 43.9, 49.9 and 45.8%, respectively. In women with normal blood pressure, adjusting for age, body mass index and smoking, there were negative associations between serum testosterone and systolic blood pressure in the total sample (P < 0.01) and the postmenopausal without hormone therapy group (P < 0.05). In women using antihypertensive drug therapy with a blood pressure of at least 140/90 mmHg, positive associations were found between serum testosterone and systolic blood pressure in the total series (P < 0.05) and in the postmenopausal without hormone therapy group (P < 0.05)., Conclusion: Abnormal blood pressure is common in middle-aged women regardless of hormonal status. Our findings suggest that testosterone could have a dual influence on blood pressure in perimenopausal women.

Background: Different studies have presented conflicting results concerning the effect of menopause on lipid levels., Aims: To describe the serum lipid profile and the prevalence of hyperlipidemia in women aged 50-60 and the perceived relation to endogenous and exogenous hormones and age., Methods: Out of a total population of 10,766 women aged 50-59 years, 6908 (64%) participated in a health assessment program, including a lipid profile evaluation. The women were grouped according to hormonal status into pre-menopausal (PM), post-menopausal without hormone replacement therapy (PM0) (HRT) and post-menopausal with hormone replacement therapy (PMT). Age groups used were 50-54, 55-59 and >60 years., Results: Serum cholesterol and triglycerides increased significantly by age in PM0 (P < 0.0001) and triglycerides also in PMT (P < 0.0001). Serum high-density lipoprotein cholesterol (HDL) levels decreased significantly by age in PMT (P = 0.002) and low-density lipoprotein cholesterol (LDL) increased in PM0 (P < 0.0001) and PMT (P = 0.007). The co-prevalence of levels of cholesterol >7 and triglycerides >2 mmol/l decreased by age in PM, but increased by age in PM0 and PMT. The prevalence of high-risk lipid levels and the prevalence of coexisting additional two metabolic risk factors were higher in the PM0 compared to the PMT group. The prevalence of serum triglycerides >1.5 and serum cholesterol >5 mmol/l were increasing by age in each of the hormonal groups., Conclusions: These data suggest that loss of endogenous sex steroids contribute substantially to an increased atherogenic lipid profile. Hormone replacement therapy may partly reverse these differences.

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.

Background: There is widespread belief that obesity is associated with gastro-oesophageal reflux disease, but the scientific evidence is weak and contradictory. Our aim is to evaluate the relation between body mass and reflux oesophagitis., Methods: A population-based case-control study of endoscopically verified case subjects with reflux oesophagitis, and of randomly selected, control subjects matched for age, sex and area of residence. Subjects were classified within three body mass index (BMI) categories: BMI <25 (normal in the WHO classification), BMI 25-30 (overweight) and BMI >30 (obese). Odds ratios (OR) with 95% confidence intervals (CI) were the measures of association., Results: Of 179 matched case-control pairs included in the study, 71 pairs were female. In males, no association between overweight and/or obesity and the risk of reflux oesophagitis was found. In females, there was a strong association between increasing BMI and the risk of reflux oesophagitis, with an OR of 2.9 (95% CI: 1.1-7.6) in the BMI 25-30 group and 14.6 (95% CI: 2.6-80.9) in the BMI >30 group (P value for trend = 0.0007). The association between obesity and oesophagitis was further strengthened by the use of oestrogen replacement medication., Conclusions: The study discloses a strong and dose-dependent association between body mass and reflux oesophagitis in women as opposed to no association among men. This association might be caused by increased oestrogen activity in overweight and obese females.

Objective: To describe the prevalence and treatment of hot flushes in premenopausal and postmenopausal women from the 1960s to the 1990s., Design: This prospective study, based on a random sample of the total female population of 430,000 in Gothenburg, Sweden, was started in 1968, with follow-ups in 1974, 1980, and 1992. The participants were 1,462 women born in 1930, 1922, 1918, 1914, and 1908 (participation rate 90.1%) who were representative of women of the same age in the general population. For the purpose of analyzing secular trends, we included 122 participants who were 38 years old and 47 who were 50 years old in 1980-1981., Results: The prevalence of hot flushes increased from approximately 11% at 38 years to a maximal prevalence of approximately 60% at 52 to 54 years of age, then declined successively from approximately 30% at 60 years of age to approximately 15% at 66 years of age, and then to approximately 9% at 72 years of age. The predominant type of medication being prescribed changed during the observation period from sedatives/anticholinergic drugs in the 1960s to hormone replacement therapy in the 1980s. Hormone replacement therapy was considered to be an effective form of treatment for hot flushes by 70% to 87% of the women., Conclusions: Hot flushes were a common symptom, with a maximal prevalence of 64% at 54 years of age. Medical consultation and treatment did not increase in 50-year-old women from 1968-1969 to 1980-1981. Treatment changed and became more effective during the observation period.

High endogenous sexual hormone levels and use of medium potency estrogens are associated with a reduced risk of hip fracture in postmenopausal women. However, it is not clear if low potency estrogens confer the same benefits as the more widely used forms of menopausal hormone replacement. We examined the association between postmenopausal use of low potency estrogens, mainly estriol, and hip fracture risk in a population-based, case-control study. Using data from mailed questionnaires and telephone interviews, we analyzed the association between low potency estrogen use and hip fracture risk among 1327 cases, 50-81 years of age, and 3262 randomly selected age-matched controls. Ever use of low potency estrogens was reported by 19% of the cases and 23% of controls. Compared to with never users of any hormone replacement therapy, ever users of low potency estrogens had a multivariate odds ratio (OR) for hip fracture of 0.96 (95% confidence interval [CI] 0.67-1.39). Current use was also not associated with a reduction in risk: OR 0.94 (95% CI 0.58-1.53), and longer duration of use was also not associated with a risk reduction. Even current use of the highest dose of oral estriol (2 mg/day) conferred no risk reduction (OR 1.01, 95% CI 0.61-1.67) compared with never use of hormone replacement therapy. After exclusion of ever users of medium potency estrogens from the analyses, we found a risk reduction of fracture among current vaginal low potency estrogen users (multivariate OR 0.67, 95% CI 0.49-0.92). In contrast to medium potency estrogens, low potency estrogens did not confer a substantial overall reduction in hip fracture risk.

Objective: To assess effects of cigarette smoking and alcohol consumption on the risk of endometrial cancer among postmenopausal women., Methods: We performed a nationwide population-based case-control study among postmenopausal women aged 50-74 years in Sweden, including 709 incident endometrial cancer cases and 3368 controls., Results: Compared to never smokers, recent/current smokers had a decreased risk of endometrial cancer (multivariate OR 0.61, 95% CI 0.47-0.80), but former smokers presented no substantial difference in risk (multivariate OR 0.90, 95% CI 0.72-1.14). We observed a decreased risk of endometrial cancer for postmenopausal smoking, but there was no clear impact on risk for premenopausal smoking. The inverse association of smoking with risk was not explained by differences in body mass index between smokers and nonsmokers. Alcohol consumption was not clearly associated with risk of endometrial cancer. The multivariate OR for women consuming up to 1.6 g of alcohol per day was 1.12 (95% CI 0.88-1.44), and 0.92 (95% CI 0.70-1.20) for women consuming more than 4 g per day (p for trend over categories = 0.44)., Conclusions: Current cigarette smoking reduces the risk of postmenopausal endometrial cancer, but the inverse association dissipates after smoking cessation. Premenopausal smoking might not affect risk of postmenopausal endometrial cancer. Alcohol consumption is not materially associated with risk.

Objective: To assess the acceptability, efficacy and endometrial safety of transdermal estradiol gel (Divigel/Sandrena) combined with monthly or quarterly oral progestogen (medroxyprogesterone acetate)., Methods: This 12-month, multicenter, open-label study was carried out at 12 study centers in Finland and Sweden. A total of 395 postmenopausal women received 1 mg estradiol in 1 g gel, daily, with oral medroxyprogesterone acetate 10 mg for the first 12 days every month (groups I and III) or every 3 months (group II). The main outcome measures were relief of climacteric symptoms, bleeding patterns and endometrial safety., Results: All regimens reduced the severity of hot flushes, sweating episodes and vaginal dryness. In groups I and III, approximately 80% and 70% of women, respectively, had regular monthly withdrawal bleeding (excepting the first cycle), with irregular bleeding in 8.3% and 5.3% of treatment months. In group II, approximately 94% of women had regular tri-monthly withdrawal bleeding, with irregular bleeding in 10.7% of the treatment months. Endometrial hyperplasia was observed in 0.3% of women. More than 87% of subjects completed the study, and 97% of these rated the gel as acceptable or convenient., Conclusions: Both the 1- and 3-month regimens were equally effective in controlling climacteric symptoms and protecting against endometrial hyperstimulation. The bleeding patterns were comparable between groups and were similar to those reported for oral estrogens. Estradiol gel was highly acceptable to the majority of women.

Background: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain., Method: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded., Findings: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30., Interpretation: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.

Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men.

Adult obesity has been associated with an increased risk of post-menopausal breast cancer, but it is unclear whether this relationship reflects a causal role of obesity during childhood and adolescence, of weight gain during adult life or of adult obesity per se. In a population-based case-control study in all of Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with invasive breast cancer, and 3,454 (82% of all selected) controls of similar age. Mailed questionnaires and telephone interviews were used to collect detailed information on anthropometric measures. Odds ratios were estimated through multiple logistic regression. Women with the leanest somatotype at age 7 had about a 3-fold higher risk of breast cancer than the most obese (P for trend 0.0009). A suggested protective effect of a high body mass at age 18 and a detrimental influence of body mass 1 year prior to data collection largely reflected the effect of weight gain after age 18, a strong predictor of breast cancer risk. Among women at least 20 years post menopause, those who had gained 30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval 1.20-3.48) of breast cancer compared with those who had maintained their weight unchanged. The effect of weight gain was unequivocal among non-users but not among users of hormone replacement therapy. Our findings have important implications, suggesting weight preservation as a means for prevention of post-menopausal breast cancer as well as a causal role of childhood body build in breast cancer etiology.

The aims of this investigation were to assess the prevalence of burning mouth symptoms (BM) in a representative population of Swedish middle-aged and elderly women (n=1017) and its relation to general and oral health status. BM was reported by 4.6% (n=47), and 85% of the BM subjects had experienced BM for more than 6 months. A stepwise multiple logistic regression with BM/non-BM as dependent variable showed that 7 covariates were found to be predictive of BM. These variables were medication with antihypertensives, sedatives and female sex hormones. Moreover, headache, tinnitus, dry mouth, and reduced chewing ability were included in the final model.

Very recently we have seen the advent of new approaches to the investigation, treatment and prevention of osteoporosis. Pending the results of large prospective studies, a Swedish panel of experts has attempted to appraise currently available scientific knowledge of osteoporosis and make recommendations. A summary of this appraisal includes advice on bone densitometry, and on the treatment and management of patients with suspected or verified osteoporosis. It is suggested that individually tailored physical activity should be a fundamental feature of prevention and treatment, and that women in the 50-70-year-old age group, and perhaps older women as well, should have a daily calcium intake of 1200 mg. Vitamin D supplementation is recommended for the elderly under institutional care who spend no time outdoors. Oestrogen replacement therapy should be considered as prophylaxis in women at greater risk-e.g., due to manifest heredity, early menopause, low body weight, heavy smoking, or low bone mass, and in patients at risk of secondary osteoporosis.

In a population-based cohort study, 1280 women, aged 61, were interviewed regarding their genitourinary and other postmenopausal symptoms by means of an anonymous questionnaire. The group selected was to constitute all women of 61 years of age living in Uppsala county, Sweden. The response rate was 84%. All were postmenopausal women. Seventy-three percent of the women answering admitted some degree of urinary incontinence and 33% more severe degree. Forty-nine percent reported some degree of stress incontinence, 25% a more severe degree. Thirty-one percent experienced urge incontinence, 14% severely. A minority (4%), had had more than two urinary infections during the last year. The majority (67%) had changed urinating habits, going to the toilet at night and a minority complained of increased frequency of micturation (8%). Of the participating women, 59% were still sexually active, 43% had trouble with vaginal dryness and 10% with vaginal burning. Vasomotor problems such as hot flushes (30%), daily (33%) and nightly sweating (36%) were all common troubles. Forty-seven percent of the women had asked for medical help for estrogen deficiency problems, 82% were satisfied with the help they had received. Thirty-four percent were on estrogen therapy, 16% had systemic therapy 18% low dose estrogen treatment.

Objective: To study the relationship between sleep and nocturnal micturition in women 40-64 years old., Methods: A questionnaire study was carried out in 3669 (6000 invited) randomly selected women in the County of Jämtland in Sweden. Questions were asked about the general state of health, nocturnal micturition, sleep, menstruation and menopausal symptoms, and also about visits to doctors and the use of sleeping pills and hormone preparations., Results: The subjective evaluation of the general state of health and of a feeling of contentedness and of confidence in the future worsened with increasing numbers of nocturnal voiding episodes. Sleep was more strongly correlated to the number of nocturnal voiding episodes (R2 = 0.099; P < 0.0001) than to age (R2 = 0.021; P < 0.0001) or the menopause (R2 = 0.017; P < 0.0001). Daytime sleepiness was three times more common among women with three or more nocturnal voiding episodes than among those with no nocturnal micturition. Women who voided three or more times in the night consulted a doctor twice as frequently as those without nocturnal micturition and were treated with drugs 2.5 times as often. The corresponding figures for sick-listing were 75 and 15 days per year, respectively., Conclusion: Frequent nocturnal micturition is common in 40-64-year-old women and impair sleep with subsequent decrease in daytime performance and general well-being.

Objective: To investigate the relationship between reproductive history and body composition., Design: Prospective population study in Sweden., Subjects: 1462 randomly selected women representing five separate age cohorts (38, 46, 50, 54 and 60 at the 1968-1969 baseline examination) have been followed longitudinally., Measurements: Relative weight, fat distribution, and fat cellularity were related to menarche, parity, lactation, menopause and oestrogen medication., Results: Age of menarche did not show any association with subsequent fat distribution, nor did length of lactation time. On the other hand parity was positively associated to total as well as central obesity, and lactation time was positively associated to abdominal fat cell diameter. Premenopausal women showed higher mean body weight and hip circumference than postmenopausal women of the same age. Change from pre- to postmenopausal status was associated with increase of waist circumference as well as reduction of hip circumference, resulting in an increased waist-hip ratio (WHR). Oestrogen replacement suggested some postponement of this increase., Conclusion: Parity and menopause are the reproductive factors most associated with gradual changes in body fat distribution. Oestrogen medication seems to play an additional role in diminishing waist circumference increase and could thus contribute to decreased cardiovascular morbidity in women.

We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.

A questionnaire study was carried out in 6000 randomly selected women in the County of Jämtland in Sweden. The response rate was 61.2%. Questions were asked about general health, height and body weight, sleep, menstruation and menopausal complaints. There were also questions about visits to doctors and the use of sleeping pills and hormone preparations. A deterioration of the night's sleep after the age of 60 years was associated especially with a low body mass index (BMI). In the subgroup with a BMI below 20 (kg m-2), frequent awakenings were reported 4 times more often in women 60-64 years old than in those aged 40-44 years. No such difference was found with a BMI > or = 30. In the age group 60-64 years twice as many women with BMI > or = 30 as women with BMI < 20 slept without waking up at night. BMI was similar in women with and without oestrogen therapy before the menopause. After the menopause the BMI in these two groups was 25.0 +/- 3.1 (mean +/- S.D.) and 25.6 +/- 3.8, respectively (P < 0.05). Oestrogen-treated women had fewer sleep disorders than other women of the same age. Of the premenopausal women, 3.4% used sleeping pills, compared with 8.0% after the menopause. Before the menopause the use of sleeping pills was not related to BMI, but after the menopause this use was twice as common among women with BMI < 20 kg m-2 than among those with BMI > or = 30kg m-2.

Study Objective: To examine who may benefit from estrogen replacement therapy from a quality of life (QoL) perspective, taking both disease-specific and general aspects at baseline into account., Design: A double-blind multi-center randomized placebo-controlled prospective study. The subjects were randomized to receive either transdermal estradiol or placebo for 12 weeks. QoL measures were disease-specific and generic., Location: University hospital, teaching hospital and private practice., Material: Post-menopausal volunteering Swedish women (n = 223) with mild to severe climacteric symptoms, as clinically evaluated by the Kupperman's Index., Results: All QoL assessments showed highly significant improvement in the estradiol group in comparison with the placebo group. The women receiving placebo treatment also improved, but their improvement reached a peak at six weeks of treatment and then declined. In the estradiol group the improvement continued throughout the 12 weeks. After 12 weeks of treatment the change in the placebo-treated group was smaller on the disease-specific scales than on the generic scales and the Kupperman's Index. A high correlation was seen between the baseline score for a certain QoL assessment and the change in this score during treatment. The most striking result was that the mean change in QoL for the two groups was statistically significant for almost any pre-treatment QoL status., Conclusions: Women with slightly, moderately or severely diminished QoL status would benefit from estrogen treatment during the climacteric period. A similar tendency was seen in women with mild symptoms at baseline.

We wanted to provide details on the psychometric documentation of the Swedish version of the Women's Health Questionnaire (WHQ), a patient based measure of postmenopausal complaints. The results of two clinical trials in Sweden in which the WHQ had been used as one out of several measurement tools were used to document the reliability, the validity and the responsiveness to change of the WHQ. More than 350 women suffering from postmenopausal complaints were included in the two trials. A factor analysis, using the baseline values of all women in each study, showed that the Swedish version of the WHQ was very close to the English original. The internal consistency reliability was excellent. The clinical validity was confirmed by a significant correlation between change in E2 levels and change in the WHQ during estrogen therapy. A high construct validity was established by the agreement between the WHQ and other quality of life scales. For use in clinical trials the WHQ was sensitive to treatment-induced changes, and added important information to the clinical effect variables.

Background: The protective effect of postmenopausal estrogen replacement therapy on coronary heart disease has been shown in several studies. However, the effect on stroke is more controversial, and data on estrogen-progestin combinations are sparse., Methods: A total of 23,088 women living in the Uppsala (Sweden) Health Care Region were identified from pharmacy records as having been prescribed noncontraceptive estrogens during 1977 through 1980. They were followed up from 1977 to 1983 for admissions to the hospital because of a first stroke (International Classification of Diseases, Eighth Revision, codes 430 through 438 and 344). The mean observation time was 5.8 years. The expected number was based on person-years in the cohort and incidence rates in the population of the region., Results: Overall, 361 cases of first stroke were observed in the cohort, as compared with 403.2 expected (relative risk [RR], 0.90; 95% confidence limits, 0.81, 0.99). The RR for acute stroke (International Classification of Diseases, Eighth Revision, codes 431 through 436) was 0.85 (0.75, 0.97). In women younger than 60 years at entry who were prescribed estradiol compounds (1 to 2 mg) or conjugated equine estrogens (0.625 to 1.25 mg), the risk of any stroke was reduced by almost 30% (RR, 0.72; 0.58, 0.88) and the risk of acute stroke was reduced by 40% (RR, 0.61; 0.46, 0.79). Women prescribed a combined estradiol-levonorgestrel brand also had a lowered risk of stroke (RR, 0.61; 0.40, 0.88). Weak compounds (mainly estriol) showed no stroke-protective effect, nor was there any relationship between hormone replacement and risk of subarachnoid hemorrhage., Conclusion: Hormone replacement therapy with potent estrogens alone or cyclically combined with progestins can, particularly when started shortly after menopause, reduce the risk of stroke.

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.

Intrauterine administration of progestogens from an IUD was introduced more than 15 years ago in order to improve the contraceptive efficacy and to reduce side-effects. A device releasing 20 micrograms levonorgestrel daily (Levonova) with a life span of at least 5 years is now available and has been subjected to an extensive study including 1821 women followed during 5 years. The safety and efficacy were evaluated in comparison to Cu-T IUDs. The pregnancy rate (Pearl index) was 0.09. During the first two cycles after insertion intermenstrual bleeding was common, otherwise the frequency of side-effects was low. The results seem to justify the conclusion that intrauterine administration of progestogens represents a further development of IUDs and hormonal contraception. Furthermore, these devices have proven to be effective in treatment of heavy menstrual blood losses. In many menorrhagic women, use of these IUDs can replace more invasive surgical methods such as hysterectomy or endometrial resection. Intrauterine administration of progestogens is also effective in opposing the proliferative effect of oestrogen on the endometrium in women on hormonal replacement therapy.

Survival was studied in a population-based cohort of over 23,000 women who were prescribed hormone replacement therapy. Complete follow-up through 1986 revealed a total of 1472 deaths, which was somewhat lower than expected; the relative survival being 101.1% (95% CL, 100.8, 101.3) after 5 years and 102.4% (95% CL, 101.9, 102.8) after 10 years. The relative survival increased with increasing age at entry into the cohort, being 98.2% (95% CL, 96.6, 99.8) in the 40-44 and 105.2% (95% CL, 101.4, 109.1) in the 65-69 year age group after 10 years. Neither the type of compound (potent vs non-potent estrogens), nor the year of entry into the cohort seemed to affect survival, whereas survival advantage generally increased with years of follow-up. Multivariate analysis showed that age at time of first prescription was the only determinant that significantly affected the death risk. This pattern could be explained by confounding due to selection of healthy subjects receiving hormone replacement therapy and/or by the specific choice of estrogen compounds (and progestogens), related to age. It is concluded that hormone replacement therapy is associated with a survival which is similar to or--notably at ages above 50-60 years--slightly higher than that in the general population.