title: Cancer Risk in Women Treated with Fertility Drugs According to Parity Status-A Registry-based Cohort Study.
abstract: Background:Long-term safety of assisted reproductive techniques (ART) is of interest as their use is increasing. Cancer risk is known to be affected by parity. This study examined the risk of cancer after fertility treatment, stratified by women's parity.Methods:Data were obtained from all women (n= 1,353,724) born in Norway between 1960 and 1996. Drug exposure data (2004-2014) were obtained from the Norwegian Prescription Database (drugs used in ART and clomiphene citrate). The Medical Birth Registry of Norway provided parity status. HRs were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer, and malignant melanoma.Results:In 12,354,392 person-years of follow-up, 20,128 women were diagnosed with cancer. All-site cancer risk was 1.14 [95% confidence interval (95% CI), 1.03-1.26] and 1.10 (95% CI, 0.98-1.23) after clomiphene citrate and ART exposure, respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR, 2.49; 95% CI, 1.30-4.78; and HR, 1.62; 95% CI, 0.78-3.35) versus parous women (HR, 1.37; 95% CI, 0.64-2.96; and HR, 0.87; 95% CI, 0.33-2.27). Elevated risk of endometrial cancers was observed for clomiphene citrate exposure in nulliparous women (HR, 4.49; 95% CI, 2.66-7.60 vs. HR, 1.52; 95% CI, 0.67-3.42). Risk was elevated for breast cancer in parous women exposed to clomiphene citrate (HR, 1.26; 95% CI, 1.03-1.54) for thyroid cancer and among nulliparous women after ART treatment (HR, 2.19; 95% CI, 1.08-4.44).Conclusions:Clomiphene citrate appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity.Impact:Continued monitoring of fertility treatments is warranted.Cancer Epidemiol Biomarkers Prev; 26(6); 953-62. ©2017 AACR.
authors.affiliation: Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway. martereigstad@gmail.com.|Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Marte Myhre
authors.initials: MM
authors.lastname: Reigstad
authors.affiliation: Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway.
authors.forename: Ritsa
authors.initials: R
authors.lastname: Storeng
authors.affiliation: Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Tor Åge
authors.initials: TÅ
authors.lastname: Myklebust
authors.affiliation: Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Nan Birgitte
authors.initials: NB
authors.lastname: Oldereid
authors.affiliation: Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Anne Katerine
authors.initials: AK
authors.lastname: Omland
authors.affiliation: Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Trude Eid
authors.initials: TE
authors.lastname: Robsahm
authors.affiliation: Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Louise Annette
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Norwegian National Advisory Unit on Women's Health, Oslo University Hospital, Oslo, Norway.
authors.forename: Siri
authors.initials: S
authors.lastname: Vangen
authors.affiliation: Department of Pharmacoepidemiology, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Furu
authors.affiliation: Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Inger Kristin
authors.initials: IK
authors.lastname: Larsen
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced*; D010298:Parity; D012042:Registries; D012307:Risk Factors
chemical_list: D005300:Fertility Agents, Female