Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study.

BACKGROUND: Ovarian cancer is one of the most lethal cancers and women with type 2 diabetes (T2D) have even poorer survival from it. We assessed the prognosis of ovarian cancer in women with type 2 diabetes treated with metformin, other forms of antidiabetic medication, or statins. METHODS: Study cohort consisted of women with T2D diagnosed with ovarian cancer in Finland 1998-2011. They were identified from a nationwide diabetes database (FinDM), being linked to several national registers. Patients were grouped according to their medication in the three years preceding ovarian cancer diagnosis. The Aalen-Johansen estimator was used to describe cumulative mortality from ovarian cancer and from other causes in different medication groups. Mortality rates were analysed by Cox models, and adjusted hazard ratios (HR) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of medication. Main outcome measures were death from ovarian cancer and death from other causes. RESULTS: During the accrual period 421 newly diagnosed ovarian cancers were identified in the FinDM database. No evidence was found for any differences in mortality from ovarian cancer or other causes between different antidiabetic medication groups. Pre-diagnostic use of statins was observed to be associated with decreased mortality from ovarian cancer compared with no such use (HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: Our findings are inconclusive as regards the association between metformin and ovarian cancer survival. However, some evidence was found for improved prognosis of ovarian cancer with pre-diagnostic statin use, requiring cautious interpretation, though.

Antidiabetic medication, statins and the risk of endometrioid endometrial cancer in patients with type 2 diabetes.

OBJECTIVE: To gain further evidence of an association between the incidence of endometrial cancer (EC) and the use of metformin, other antidiabetic medication (ADM) and statins in women with type 2 diabetes (T2D). METHODS: A retrospective cohort of 92,366 women with newly diagnosed T2D was obtained from a diabetes register (FinDM). 590 endometrioid ECs were observed during the follow-up time. Poisson regression was utilized to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of the endometrioid EC in relation to the use of metformin, other oral ADM, insulin and statins. Nested case-control analyses were performed, where up to 20 controls were matched for age and duration of DM for each EC case. The HRs were estimated by conditional logistic regression for never/ever and cumulative use of different forms of ADM and statins. RESULTS: In the case-control analyses the use of metformin (HR 1.24, 95% CI 1.02-1.51) and other oral ADM (HR 1.25, 95% CI 1.04-1.50) was associated with an increased incidence of endometrioid EC compared to no ADM use. No difference was observed between metformin users and those using other oral ADMs. The use of statins was inversely related to the incidence of endometrioid EC (HR 0.78, 95% CI 0.65-0.94). Results from the full cohort analysis supported this finding. CONCLUSIONS: In our study the use of metformin or other oral forms of ADM was not associated with a lowered risk of endometrioid EC in women with T2D. Instead statins were observed to be inversely associated with endometrioid EC in this population.

Incidence of cancer among grand multiparous women in Finland with special focus on non-gynaecological cancers: A population-based cohort study.

BACKGROUND: Many studies have previously revealed evidence of an association between grand multiparity (five or more deliveries) and gynaecological cancer. Oestrogen has an impact on cancer formation and the amount of circulating oestrogen is significantly higher during pregnancy. Also the lifestyle of grand multiparous women differs somewhat from the average population. Considering these factors it is plausible that also non-gynaecological cancers are associated with multiparity. The aim of our study was to determine cancer incidence among grand multiparous women, with special attention to non-gynaecological cancers. MATERIAL AND METHODS: All 102 541 women alive in 1974-2011 and having had at least five deliveries were identified in the Finnish Population Register and followed up for cancer incidence through the Finnish Cancer Registry to the end of 2011. Standardised incidence ratios (SIRs) were defined as ratios between observed and expected numbers of cases, the latter ones based on incidence in the entire Finnish female population. RESULTS: The overall incidence of non-gynaecological cancers was the same as in the reference population (SIR 0.98, 95% confidence interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26-1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was increased. There were significantly fewer cases than expected of urinary bladder cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94, 0.89-0.99) and all types of skin cancers. As a consequence of the decreased incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). CONCLUSION: The study demonstrated that grand multiparous women have a similar overall risk of non-gynaecological cancers as other women, despite significant differences in some specific forms of cancer.

Antidiabetic Medication, Statins and the Risk and Prognosis of Non-endometrioid Endometrial Cancer in Women with Type 2 Diabetes.

AIM: To determine the incidence and prognosis of non-endometrioid endometrial cancer (EC) in relation to the use of metformin, other antidiabetic medication (ADM) and statins in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In order to analyze the incidence and prognosis of non-endometrioid EC, two cohorts were obtained from a nationwide diabetes database (FinDM); 57 non-endometrioid ECs were observed in a cohort of 92,366 women with newly-diagnosed T2D during the follow-up (1996 to 2011) to assess the incidence, and a retrospective cohort of 105 women with T2D diagnosed with non-endometrioid EC (1998 to 2011) was used to estimate cumulative mortality from EC and other causes of death. Hazard ratios (HRs) with 95% confidence intervals (CIs) for EC incidence were estimated in the full-cohort analysis and in the nested case-control analysis, matched for age and duration of T2D. Cumulative mortality was estimated by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models regarding the pre-diagnostic use of different forms of ADM and statins. RESULTS: In the nested case-control analysis, the use of metformin was not associated with the risk of non-endometrioid EC (HR=1.09, 95% CI=0.59-2.00), whereas statin use was associated with a lower risk (HR=0.47, 95% CI=0.26-0.84). The results from the full-cohort analysis supported these findings. Mortality from non-endometrioid EC was not different between users of metformin and other types of oral ADM (HR=1.56, 95% CI=0.40-6.07) but was observed to be lower in statin users (HR=0.41, 95% CI=0.20-0.82). CONCLUSION: Our findings were inconclusive regarding the association of metformin with the risk and prognosis of non-endometrioid EC. However, statin use was associated with a lower incidence and mortality from this disease.

Cause-specific mortality of grand multiparous women in Finland.

Knowledge is limited on mortality of grand multiparous women (> or =5 deliveries), whose hormonal, metabolic, and social conditions differ from the average. The authors studied overall and cause-specific mortality in 1974-2001 among 87,922 grand multiparous women including 3,678 grand grand multiparous women (> or =10 deliveries) in Finland. Standardized mortality ratios were defined as ratios of observed to expected numbers of deaths, both derived from national cause-of-death files. During follow-up, 18,870 grand multiparous women and 625 grand grand multiparous women died (standardized mortality ratios (SMRs) = 0.95 and 1.01, respectively). Decreased mortality among grand multiparous women was found for cancers of the breast (SMR = 0.64, 95% confidence interval (CI): 0.59, 0.69), corpus uteri (SMR = 0.68, 95% CI: 0.56, 0.80), ovary (SMR = 0.68, 95% CI: 0.60, 0.75), bladder (SMR = 0.59, 95% CI: 0.41, 0.82), and respiratory tract (SMR = 0.80, 95% CI: 0.72, 0.88). The only malignant tumor associated with elevated mortality was kidney cancer (SMR = 1.38, 95% CI: 1.21, 1.56). The standardized mortality ratio was also low for dementia (SMR = 0.78, 95% CI: 0.72, 0.84), respiratory diseases (SMR = 0.80, 95% CI: 0.75, 0.85), and accidents and violent causes (SMR = 0.79, 95% CI: 0.73, 0.84). Mortality from diabetes mellitus (SMR = 1.42, 95% CI: 1.29, 1.55) and ischemic heart disease (SMR = 1.10, 95% CI: 1.08, 1.13) was increased. According to this study, overall mortality among grand multiparous women is not elevated. Low mortality from cancers is offset by higher mortality from cardiovascular conditions and diabetes mellitus.

Incidence of ovarian cancer of grand multiparous women--a population-based study in Finland.

OBJECTIVES: Parity is known to induce protective effects on ovarian cancer. This study aimed to evaluate how far upon births the protection reaches, the effect of age at first birth, the interval between births in the whole population and the length of time from the first to the last birth and from the last birth to cancer among postmenopausal women. METHOD: The population-based cohort consisted of 87,929 grand multiparous (GM) women, i.e. women with at least 5 deliveries. Standardised incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases by the expected number based on the national incidence rates, both extracted from the population-based Finnish Cancer Registry. Conditional logistic regression for the case-control design nested in the GM cohort was used to estimate proportional hazards by different factors. RESULTS: The SIR for ovarian cancer among GM women was low (418 cases; SIR 0.64, 95% confidence interval 0.58-0.69). Further births over five did not give additional protection. The relative risk did not vary significantly by age at first birth or interval between the births in any histological subtype. CONCLUSION: The risk of ovarian cancer was low in all GM women no matter how many children and at which ages they had delivered or contracted cancer.

Grand multiparity and incidence of endometrial cancer: a population-based study in Finland.

The hormonal background of endometrial cancer is insufficiently characterised. We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery-free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. Data of the Population Register of Finland (86,978 GM-women) and the population-based Finnish Cancer Registry were combined. Standardised incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases by the expected number based on the national incidence rates. Multivariate relative risks (RRs) were estimated by Poisson regression analysis. The SIR for endometrial cancer among GM-women was low [419 cases; SIR=0.57, 95% confidence interval (CI) 0.52-0.63]. The RR of endometrial cancer was 0.58 (95% CI 0.34-0.97) among women giving their first birth at an age of more than 30 years compared to women with first birth before the age of 20. In ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8 births was 0.63 (95% CI 0.44-0.92) compared to those with 5 births, and those with a birth period of 20+ years had RR=0.57 (95% CI 0.34-0.96) compared to those with a period of <10 years, while prolonged average intensity between births showed only a small protective effect. The RR of endometrial cancer also correlated with the length of premenopausal delivery-free period (RR = 0.61, 95% CI 0.44-0.86) for women with a short (<10 years) period compared to women with a long (>15 years) period. Our findings, that a large number of births, old age at first birth, a long birth period and a short premenopausal delivery-free period reduced the risk of postmenopausal endometrial cancer of GM-women, emphasise the protective role of progesterone and the stimulatory role of estradiol in the hormonal background of this disease.