Use of fertility drugs and risk of ovarian cancer: Danish Population Based Cohort Study

Danish Cancer Society, Institute of Cancer Epidemiology, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
BMJ (online) (Impact Factor: 17.45). 02/2009; 338(feb05 2):b249. DOI: 10.1097/01.ogx.0000349781.28386.c8
Source: PubMed


To examine the effects of fertility drugs on overall risk of ovarian cancer using data from a large cohort of infertile women.
Population based cohort study.
Danish hospitals and private fertility clinics.
54,362 women with infertility problems referred to all Danish fertility clinics during 1963-98. The median age at first evaluation of infertility was 30 years (range 16-55 years), and the median age at the end of follow-up was 47 (range 18-81) years. Included in the analysis were 156 women with invasive epithelial ovarian cancer (cases) and 1241 subcohort members identified in the cohort during follow-up in 2006.
Effect of four groups of fertility drugs (gonadotrophins, clomifene citrate, human chorionic gonadotrophin, and gonadotrophin releasing hormone) on overall risk of ovarian cancer after adjustment for potential confounding factors.
Analyses within cohort showed no overall increased risk of ovarian cancer after any use of gonadotrophins (rate ratio 0.83, 95% confidence interval 0.50 to 1.37), clomifene (1.14, 0.79 to 1.64), human chorionic gonadotrophin (0.89, 0.62 to 1.29), or gonadotrophin releasing hormone (0.80, 0.42 to 1.51). Furthermore, no associations were found between all four groups of fertility drugs and number of cycles of use, length of follow-up, or parity.
No convincing association was found between use of fertility drugs and risk of ovarian cancer.

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Available from: Susanne Kjaer, Oct 03, 2015
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    • "Jensen et al. [28] identified 156 ovarian cancer cases, through a linkage with the Danish Cancer Registry. The authors did not suggest an increased ovarian cancer risk associated with the use of gonadotropins (RR 0.83; 95% CI: 0.50-1.37), "
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    ABSTRACT: Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible association between the use of fertility treatments and the risk of ovarian cancer, through a scrupulous search of the literature published thus far in this field. Our principal objective was to give more conclusive answers on the question whether the use of fertility drug significantly increases ovarian cancer risk. Our analysis focused on the different types of drugs and different treatment schedules used. This study provides additional insights regarding the long-term relationships between fertility drugs and risk of ovarian cancer.
    Journal of Ovarian Research 05/2014; 7(1):51. DOI:10.1186/1757-2215-7-51 · 2.43 Impact Factor
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    • "Ovarian stimulation for IVF may increase the risk of ovarian malignancies, especially BOT (van Leeuwen et al., 2011). Other studies showed no significant increase in risk of ovarian malignancies after IVF treatment (Jensen et al., 2009; Yli-Kuha et al., 2012). It might be that specific causes of subfertility predispose for ovarian cancer and/or BOT. "
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    ABSTRACT: Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis. There is increasing evidence of an association between endometriosis and increased risk of ovarian cancer. However, most reports were based on self-reported diagnosis of endometriosis. We conducted a nationwide historic cohort study among women with subfertility problems between 1980 and 1995. For this analysis we selected all cohort members with endometriosis, and a comparison group of subfertile women (male factor or idiopathic) without endometriosis (total cohort of 8904 women). Median follow-up time was 15.2 for the entire study population. For this analysis we selected all cohort members with (n = 3657) and without (n = 5247) evidence of endometriosis. Seventy-eight per cent of diagnoses of endometriosis were confirmed by pathology report, and 22% was self-reported endometriosis (positive predictive value of 73%). We linked the cohort with the Dutch Pathology Database and the Netherlands Cancer Registry to assess the occurrence of ovarian cancer and BOT between January 1989 and June 2007. We observed a substantially increased risk of all ovarian malignancies combined in women with endometriosis when we based the definition of endometriosis on self-report, medical records information at subfertility treatment and/or the nationwide pathology database (hazard ratio (HR) 8.2; 95% confidence interval (CI) 3.1-21.6). The HR associated with endometriosis was 12.4 (95% CI 2.8-54.2) for ovarian cancer and 5.5 (95% CI 1.5-20.2) for BOT. When we excluded information from the pathology database, HRs were 3.0 (95% CI 1.5-6.1) for all ovarian tumours, 4.3 (95% CI 1.6-11.2) for ovarian cancer and 1.9 (95% CI 0.6-5.8) for BOT. Both ovarian and extra-ovarian endometriosis carried a significantly increased risk for ovarian cancer and BOT. We did not have information on oral contraceptive use and parity for 23.4 and 3.4%, of women in the analytic cohort, respectively. Furthermore, a limitation of our study, and also of other studies, is that the date of diagnosis of endometriosis is usually made long after the onset of the disease. Also, the number of cases in the cohort is small (n = 34), resulting in wide CIs. The fact that endometriosis was assessed before diagnosis of ovarian malignancy and the high degree of medical confirmation in our study likely contribute to the validity of our estimate of a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis. The risk of ovarian malignancies associated with endometriosis was much higher in analyses including information on endometriosis from the nationwide pathology database, implying that risk estimates from studies using self-reported information on endometriosis may be too low due to non-differential misclassification bias. None. None.
    Human Reproduction 09/2013; 125(12):S10–S11. DOI:10.1016/j.ygyno.2011.12.021 · 4.57 Impact Factor
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    • "Invasive ovarian cancer accounts for 6% of female cancer deaths in the USA (Jemal et al., 2008). Over the past decades, several studies reported a significant increase of ovarian cancer risk after FD use (Whittemore et al., 1992; Rossing et al., 1994; Brinton et al., 2005; Sanner et al., 2009; Källén et al., 2011), but others did not observe such an elevated risk (Franceschi et al., 1994; Bristow and Karlan, 1996; Mosgaard et al., 1997; Modan et al., 1998; Venn et al., 1999; Parazzini et al., 2001; Dor et al., 2002; Doyle et al., 2002; Ness et al., 2002; Rossing et al., 2004; Dos Santos Silva et al., 2009; Jensen et al., 2009), or reported non-significant risk increases for subgroups (Shushan et al., 1996; Ness et al., 2002; Brinton et al., 2004). Some studies noted an elevated risk of borderline ovarian tumours following the use of FDs (Harris et al., 1992; Rossing et al., 1994; Shushan et al., 1996; Parazzini et al., 1998; Ness et al., 2002; Sanner et al., 2009). "
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    ABSTRACT: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown. We identified a nationwide historic cohort of 19,146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997-1999, data on reproductive risk factors were obtained from 65% of women and data on subfertility (treatment) were obtained from the medical records. The incidence of ovarian malignancies (including borderline ovarian tumours) through 2007 was assessed through linkage with disease registries. The risk of ovarian malignancies in the IVF group was compared with risks in the general population and the subfertile comparison group. After a median follow-up of 14.7 years, the risk of borderline ovarian tumours was increased in the IVF group compared with the general population [standardized incidence ratio (SIR) = 1.76; 95% confidence interval (CI) = 1.16-2.56]. The overall SIR for invasive ovarian cancer was not significantly elevated, but increased with longer follow-up after first IVF (P = 0.02); the SIR was 3.54 (95% CI = 1.62-6.72) after 15 years. The risks of borderline ovarian tumours and of all ovarian malignancies combined in the IVF group were significantly increased compared with risks in the subfertile comparison group (hazard ratios = 4.23; 95% CI = 1.25-14.33 and 2.14; 95% CI = 1.07-4.25, respectively, adjusted for age, parity and subfertility cause). Ovarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. More large cohort studies are needed to confirm these findings and to examine the effect of IVF treatment characteristics.
    Human Reproduction 12/2011; 26(12):3456-65. DOI:10.1093/humrep/der322 · 4.57 Impact Factor
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