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Study Question: Does the use of post-menopausal vaginal estradiol (VE) affect the mortality risk for coronary heart disease (CHD) and stroke.Summary Answer: The use of VE reduces the risk for cardiovascular mortality.What Is Known Already: A growing number of women use VE for post-menopausal genitourinary symptoms. Although this therapy is intended to have only local effects, estrogen is absorbed into the blood circulation and thus VE use may also have systemic effects.Study Design, Size, Duration: We studied a nationwide cohort in Finland 1994-2009 during which post-menopausal women (n = 195 756) initiated the use of VE (age [mean ± SD] 65.7 ± 10.9 years). Follow-up data gathered 1.4 million women-years and we assessed the mortality risk due to CHD (n= 9656) or stroke (n = 4294).Participants/materials, Setting, Methods: The mortality risk in VE users was compared with that in the age-matched background population (standardized mortality ratio; [SMR]; 95% confidence interval) and related to various durations of exposure to VE (1 to ≤3, >3 to ≤5, >5 to ≤10 and >10 years).Main Results and the Role Of Chance: The use of VE was accompanied by decreases in the risk for CHD and stroke death. The risk reduction for CHD death was highest for >3 to ≤5 years exposure (SMR 0.64; 0.57-0.70) and for stroke for >5 to ≤10 years exposure (SMR 0.64; 0.57-0.72). The risk reductions for both CHD and stroke mortality were detected in all age groups with the highest risk reduction being in women aged 50-59 years (SMR 0.43; 0.19-0.88 and SMR 0.21; 0.06-0.58, respectively).Limitations, Reasons For Caution: Our series lack a placebo arm and thus, may harbor a healthy woman bias. Moreover, data on clinical variables such as weight, smoking, blood pressure and family background were unobtainable for this study. Women using both VE and systemic hormone therapy (HT) were included in the comparator background population. This should not cause any significant error because the proportion of women using VE or other HT was modest (<10% in age-matched population) and because the use of systemic HT also reduces death risks in the same population. Our data cannot be directly applied for local regimens containing conjugated equine estrogens, because they are absorbed differently and may show effects that differ from those of estradiol.Wider Implications Of the Findings: In 1000 women using VE for up to 10 years, a maximum of 24 fewer CHD deaths and 18 fewer stroke deaths is likely to occur.Study Funding/competing Interests: This work was supported by unrestricted grants from the Päivikki and Sakari Sohlberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, Finska Läkaresällskapet, the Orion Farmos Research Foundation, the Paavo Nurmi Foundation and a special governmental grant for health sciences research. The funding sources had no role in the study design, data handling or manuscript preparation. EPID Research is a company that performs financially supported studies for several pharmaceutical companies. Dr Korhonen, Dr Hoti and MSc Vattulainen, employed by Epid Research, report financial activities from several other pharmaceutical companies outside the submitted work. Dr Mikkola has been a speaker and/or received consulting fees from Mylan and Novo Nordisk. Dr Tuomikoski has been a speaker and/or received consulting fees from Orion and Mylan. The remaining authors report no conflict of interest. [ABSTRACT FROM AUTHOR]

Data on the possible impact of postmenopausal hormone therapy (HT) on the incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore, we conducted a nationwide case-control study analyzing the association between the use of different HTs and PFTC. All women aged 50 years or older with an incident PFTC ( n = 360) during 1995-2007 were identified from the Finnish Cancer Registry. For each case of PFTC, ten age- and place of residence-matched controls were selected from the Finnish National Population Register, which also provided information on parity. Data on HT purchases were received from the Prescription Register, and data on hysterectomies and sterilizations from the National Care Register. Controls with a salpingectomy before the PFTC diagnosis of the respective case were excluded. The PFTC risk in relation to different HTs was estimated with a conditional logistic regression model, adjusted for parity, age at last delivery, hysterectomy and sterilization. The use for five years or more of estradiol combined with levonorgestrel-releasing-intrauterine system (odds ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not statistically significantly increased. The OR for the use of tibolone for one year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk of PFTC, particularly when a progestin component is intrauterine or systemic progestin is given in sequential manner. [ABSTRACT FROM AUTHOR]

Postmenopausal hormone therapy (HT) associates with an increased risk of ovarian cancer, but its' influence on tumor histology is not as well known. Therefore, we evaluated the effect of various types of HT on the risk of epithelial ovarian cancer by histological subtype. All Finnish women diagnosed with ovarian cancer ( n = 3,958) aged over 50 during 1995-2007 were identified from the Finnish Cancer Registry. For each case, three controls, matched for age and place of residence, were recruited from the Finnish National Population Register, which also provided data on parity and ages at deliveries. After exclusion of controls with oophorectomy, 11,325 controls remained. The prescription register provided HT use from age 50. Odds ratios (OR) for different HTs were estimated by conditional logistic regression: adjusted for parity, ages at deliveries and hysterectomy. Estradiol-only therapy use for 5 years or more associated with an increased risk (OR 1.45; 95% confidence interval 1.20-1.75) of a serous subtype, but with a decreased risk of mucinous subtype (0.35; 0.19-0.67). Use of sequential estradiol-progestin therapy (EPT) for 5 years or more associated with an increase in overall ovarian cancer risk (1.35; 1.20-1.63) and with an increase in the endometrioid subtype (1.88; 1.24-2.86) particularly. Continuous EPT, estradiol + levonorgestrel-releasing intrauterine system or tibolone had no effect on overall ovarian cancer risk. In conclusion, only sequential EPT use for 5 years or more associates with an increased risk of overall ovarian cancer. Furthermore, HT regimens differ significantly in their association with various histological types of ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Insufficient data exist on the effect of postmenopausal hormone therapy as the risk factor for uterine sarcomas. We therefore evaluated the association of estradiol–progestin therapy (EPT) with the risk of uterine sarcoma in nation-wide cohort study. Methods: All Finnish women (>50years of age) who had used EPT during the years 1994–2008 for at least 6months (n=243,857) were identified from the national Medical Reimbursement Registry. Their incidence of uterine stromal and leiomyosarcoma among the EPT users was compared to that in the background population with the aid of the Finnish Cancer Registry. Results: A total of 76 uterine sarcomas were encountered in the EPT cohort; 45 (59%) were leiomyosarcomas, 24 (32%) stromal sarcomas and 7 (9%) other sarcomas. The exposure to EPT for less than 5years did not associate with significant rises in the sarcoma risk but longer exposure was accompanied with significant risk elevations for all uterine sarcomas: the standardized incidence ratio (SIR) for 5–10years of use was 2.0, 95% confidence interval (CI) 1.4–2.9 and for ≥10years of use 3.0 (1.3–5.9): the SIRs were highest for leiomyosarcoma. The sequential and continuous uses of progestin were associated with similar increased SIRs for uterine sarcoma. Conclusions: The use of EPT for 5years or more is associated with an increased risk for uterine sarcomas. This turns to an absolute excess risk of 2–3 extra uterine sarcoma cases per 10,000 long-time EPT users followed for 10years. [Copyright &y& Elsevier]

The article reports on a study evaluating the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk among the 50 to 80 years women in Finland. A tendency toward an elevated risk both for exposure of <5 years was shown after the use of long-cycle EPT. The use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk while the use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer.

Abstract: Objective: Primary fallopian tube carcinoma (PFTC) is a rare malignancy and only sparse data exist on its possible association with postmenopausal hormone therapy (HT). We therefore studied this association in a nationwide cohort of Finnish HT users. Methods: All women>50years using systemic estradiol-only therapy (ET) (n=117,820 hysterectomized women) or estradiol–progestin therapy (EPT) (n=247,781 nonhysterectomized women) for ≥6months during 1994–2008 were identified from the national medical reimbursement register. The incidence of PFTC in HT users was compared to that in the comparable background population (standardized incidence ratio, SIR, with 95% confidence interval, CI). Results: A total of 160 cases of PFTC were encountered in users of ET (n=34) or EPT (n=126). The use of EPT≥5years was accompanied by an increased risk for PFTC (SIR 2.15; 95% CI 1.66–2.72). The SIR increased further to 3.36 (95% CI 2.02–5.24) when EPT use lasted ≥10years. The EPT-related risk for PFTC was restricted to the sequential EPT and it was not seen for continuous EPT. Two leading progestins in EPT, norethisterone acetate and medroxyprogesterone acetate, associated with comparable risk elevations. ET use was not associated with the risk for PFTC. Conclusions: The long-term, sequential use of EPT associates with an increased risk for PFTC. In absolute terms, 4 additional cases of PFTC would be detected in 10-year follow-up of 10,000 women who have used EPT for at least 5years. [Copyright &y& Elsevier]

Objectives: The role of postmenopausal hormone therapy (HT) in the incidence of acute coronary syndrome (ACS) has been studied extensively, but less is known of the impact of HT on the mortality risk due to an ACS.Study Design and Main Outcome Measures: We extracted from a population-based ACS register, FINAMI, 7258 postmenopausal women with the first ACS. These data were combined with HT use data from the National Drug Reimbursement Register; 625 patients (9%) had used various HT regimens. The death risks due to ACS before admission to hospital, 2-28, or 29-365days after the incident ACS were compared between HT users and non-users with logistic regression analyses.Results: In all follow-up time points, the ACS death risks in HT ever-users were smaller compared to non-users. Of women with HT ever use, 42% died within one year as compared with 52% of non-users (OR 0.62, p<0.001). Most deaths (84%) occurred within 28days after the ACS, and in this group 36% of women with ever use of HT (OR 0.73, p=0.002) and 30% of women with ≥5year HT use (OR 0.54, p<0.001) died as compared to 43% of the non-users. Age ≤60 or >60 years at the HT initiation was accompanied with similar reductions in ACS mortality risk.Conclusions: Postmenopausal HT use is accompanied with reduced mortality risk after primary ACS. [ABSTRACT FROM AUTHOR]