Cancer Risk After Exposure to Treatments for Ovulation Induction

Calderon‐Margalit, Ronit; Friedlander, Y; Yanetz, Rivka; Kleinhaus, Karine; Perrin, Mary; Manor, Orly; Harlap, Susan; Paltiel, Ora

doi:10.1093/aje/kwn318

Cited by 112 publications

(109 citation statements)

References 45 publications

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“…In contrast, some earlier case series and epidemiological studies (Whittemore et al, 1992;Rossing et al, 1994;Shushan et al, 1996) reported positive associations, with risk being particularly high in the subgroup of nulligravid women, whereas among those who took drugs but did achieve a pregnancy the risk was not significantly different from that among gravid women without a history of infertility. More recent cohort (Modan et al, 1998;Venn et al, 1999;Klip et al, 2002;Doyle et al, 2002;Brinton et al, 2004;Calderon-Margalit et al, 2008;Jensen et al, 2009) and case -control (Ness et al, 2003) studies, however, have failed to find any such association. The lack of clear trends with time since start of treatment would also argue against the hypothesis that ovulation stimulation induces growth of pre-existing latent tumours.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies have examined this question but three large cohort studies reported increases among women exposed to high doses or with longer follow-up (Modan et al, 1998;Althuis et al, 2005;Calderon-Margalit et al, 2008). Such a link would be biologically credible as clomiphene and tamoxifen are both selective estrogen-receptor modulators and tamoxifen use has been shown to be associated with an increased risk of cancer of the uterus (Swerdlow et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Some earlier studies (Whittemore et al, 1992;Rossing et al, 1994;Shushan et al, 1996) reported positive associations between ovarian stimulation and risk of ovarian cancer, but others did not confirm this. Raised risks have also been reported for cancers of the breast (Burkman et al, 2003;Orgéas et al, 2009), endometrium (Ron et al, 1987;Modan et al, 1998;Althuis et al, 2005;Calderon-Margalit et al, 2008), thyroid (La Vecchia et al, 1999) and malignant melanoma of the skin (Rossing et al, 1995;Calderon-Margalit et al, 2008), but again these findings were not replicated in other studies.…”

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confidence: 95%

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Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort

et al. 2009

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To assess long-term health effects of ovarian-stimulation drugs we followed-up for over 20 years a British cohort of 7355 women with ovulatory disorders, 43% of whom were prescribed ovarian-stimulation drugs, and identified a total of 274 deaths and 367 incident cancers. Relative to the general population, the cohort experienced lower mortality from most causes, including from all neoplasms combined, and lower incidence of cervical cancer, but higher incidence of cancers of the breast (relative risk: 1.13; 95% CI 0.97, 1.30) and corpus uteri (2.02; 1.37, 2.87). There were, however, no significant differences in the risk of cancers of the breast, corpus uteri, ovary, or of any other site, between women who had been prescribed ovarian-stimulation drugs and those who had not. Further analyses by type of drug and dose revealed a dose -response gradient in the risk of cancer of the corpus uteri (P for linear trend ¼ 0.03), with women given X2250 mg of clomiphene having a 2.6-fold (2.62; 0.94, 6.82) increase in risk relative to those who were not treated. These findings do not support strong associations between ovulation-stimulation drugs and cancer risks, but they indicate the need for continued monitoring to establish whether risks are elevated in certain subgroups of users. British Journal of Cancer (2009) Several case reports in the 1980s, linking assisted conception and ovarian cancer, raised concerns about the long-term health effects of infertility treatment (Fishel and Jackson, 1989). These reports prompted many investigations into potential associations between exposure to fertility treatments used to stimulate ovulation and cancer risks. Some earlier studies (Whittemore et al, 1992;Rossing et al, 1994;Shushan et al, 1996) A cause -effect relationship between infertility treatment and cancer risks would have important implications for assisted conception programmes, which have been expanding considerably in recent years. A total of 34 855 women had in vitro fertilisation treatment in the United Kingdom in 2006 corresponding to 44 275 cycles of treatment, a 6.8% increase in the number of patients relative to the previous year (HFEA, 2008). We investigated the long-term health effects of the use of ovarian-stimulation treatments, with particular attention to potential cancer risks, in a large British cohort of women investigated for ovulatory disorders who have been followed-up for over 20 years. MATERIALS AND METHODSStudy subjects were identified through two case series of women who attended reproductive endocrinology practices in London.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

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Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort

et al. 2009

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“…Then an increased amount of FSH stimulates development of follicles, ultimately resulting in ovulation (Randal and Templeton 1991;Martikainen et al 2006;Chaman and Asmatullah 2011). Some authors have reported that treatment with clomiphene is related with various malignancies including endometrial and ovarian cancers (Derman and Adashi 1994;Althuis et al 2005;Lerner-Geva et al 2006;Calderon-Margalit et al 2009;Jensen et al 2009). …”

Section: Clomiphenementioning

confidence: 99%

Genotoxicity of the some selective estrogen receptor modulators: a review

2014

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The objective of this article is to review genotoxicological profile of the major selective estrogen receptor modulators, including clomiphene, tamoxifen, toremifene, raloxifene. These drugs have been used for infertility treatment and breast cancer prevention in high risk-women. However, some studies reported that especially tamoxifen is a genotoxic agent and is related with endometrial cancer. Our review indicate that clomiphene and tamoxifen were found as genotoxic agent in majority of the tests. However published reports showed that toremifene is a weakly genotoxic agent. The genotoxic effects of raloxifene are still poorly known. Further genotoxicity studies should be conducted especially for raloxifene.

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“…I tabell 1 vises data og konklusjoner fra publikasjoner som omhandler risiko for brystkreft etter infertilitetsbehandling. Flere rapporter konkluderer med at det ikke er økt risiko for brystkreft etter infertilitetsbehandling (6)(7)(8)(9)(10)(11)(12)(13). I noen studier konkluderes det med en redusert risiko for brystkreft etter behandling for infertilitet (14,15).…”

Section: Risiko For Brystkreftunclassified