Use of Fertility Drugs and Risk of Ovarian Cancer: Results from a U.S.-based Case-control Study

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2012 Jun 19

PMID 22707710

Citations 20

Authors

Michelle L Kurta

Kirsten B Moysich

Joel L Weissfeld

Ada O Youk

Clareann H Bunker

Robert P Edwards

Francesmary Modugno

Roberta B Ness

Brenda Diergaarde

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies examining associations between use of fertility drugs and ovarian cancer risk have provided conflicting results. We used data from a large case-control study to determine whether fertility drug use significantly impacts ovarian cancer risk when taking into account parity, gravidity, and cause of infertility.

Methods: Data from the Hormones and Ovarian Cancer Prediction (HOPE) study were used (902 cases, 1,802 controls). Medical and reproductive histories were collected via in-person interviews. Logistic regression was used to calculate ORs and 95% confidence intervals (CI). Models were adjusted for age, race, education, age at menarche, parity, oral contraceptive use, breastfeeding, talc use, tubal ligation, and family history of breast/ovarian cancer.

Results: Ever use of fertility drugs was not significantly associated with ovarian cancer within the total HOPE population (OR, 0.93; 95% CI, 0.65-1.35) or among women who reported seeking medical attention for infertility (OR, 0.87; 95% CI, 0.54-1.40). We did observe a statistically significant increased risk of ovarian cancer for ever use of fertility drugs among women who, despite seeking medical attention for problems getting pregnant, remained nulligravid (OR, 3.13; 95% CI, 1.01-9.67).

Conclusions: These results provide further evidence that fertility drug use does not significantly contribute to ovarian cancer risk among the majority of women; however, women who despite infertility evaluation and fertility drug use remain nulligravid, may have an elevated risk for ovarian cancer.

Impact: Our results suggest that fertility drug use does not significantly contribute to overall risk of ovarian cancer when adjusting for known confounding factors.

Citing Articles

Infertility and risk of ovarian cancer: A systematic review and meta analysis.

Sambasivam I, Jennifer H, Chinnaiyan S J Family Med Prim Care. 2025; 14(1):15-21.

PMID: 39989588 PMC: 11845003. DOI: 10.4103/jfmpc.jfmpc_227_24.

Systematic review of the association between talc and female reproductive tract cancers.

Lynch H, Lauer D, Leleck O, Freid R, Collins J, Chen K Front Toxicol. 2023; 5:1157761.

PMID: 37608907 PMC: 10442069. DOI: 10.3389/ftox.2023.1157761.

Ovulation induction drug and ovarian cancer: an updated systematic review and meta-analysis.

Yu L, Sun J, Wang Q, Yu W, Wang A, Zhu S J Ovarian Res. 2023; 16(1):22.

PMID: 36694251 PMC: 9872323. DOI: 10.1186/s13048-022-01084-z.

Association of Combined Estrogen-Progestogen and Progestogen-Only Contraceptives with the Development of Cancer.

Williams W, Mitchell L, Carlson S, Raviele K Linacre Q. 2020; 85(4):412-452.

PMID: 32431377 PMC: 6322132. DOI: 10.1177/0024363918811637.

Association Between Breastfeeding and Ovarian Cancer Risk.

Babic A, Sasamoto N, Rosner B, Tworoger S, Jordan S, Risch H JAMA Oncol. 2020; 6(6):e200421.

PMID: 32239218 PMC: 7118668. DOI: 10.1001/jamaoncol.2020.0421.

References

Sanner K, Conner P, Bergfeldt K, Dickman P, Sundfeldt K, Bergh T . Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden. Fertil Steril. 2008; 91(4):1152-8. DOI: 10.1016/j.fertnstert.2008.01.073. View

. Aging and infertility in women: a committee opinion. Fertil Steril. 2002; 78(1):215-9. DOI: 10.1016/s0015-0282(02)03212-0. View

Ness R, Cramer D, Goodman M, Kjaer S, Mallin K, Mosgaard B . Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol. 2002; 155(3):217-24. DOI: 10.1093/aje/155.3.217. View

Shushan A, Paltiel O, Iscovich J, Elchalal U, Peretz T, Schenker J . Human menopausal gonadotropin and the risk of epithelial ovarian cancer. Fertil Steril. 1996; 65(1):13-8. View

Stephen E, Chandra A . Updated projections of infertility in the United States: 1995-2025. Fertil Steril. 1998; 70(1):30-4. DOI: 10.1016/s0015-0282(98)00103-4. View

Casagrande J, Louie E, Pike M, Roy S, Ross R, Henderson B . "Incessant ovulation" and ovarian cancer. Lancet. 1979; 2(8135):170-3. DOI: 10.1016/s0140-6736(79)91435-1. View

Chandra A, Martinez G, Mosher W, Abma J, Jones J . Fertility, family planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth. Vital Health Stat 23. 2006; (25):1-160. View

Cook L, Kamb M, Weiss N . Perineal powder exposure and the risk of ovarian cancer. Am J Epidemiol. 1997; 145(5):459-65. DOI: 10.1093/oxfordjournals.aje.a009128. View

Rossing M, Daling J, Weiss N, Moore D, Self S . Ovarian tumors in a cohort of infertile women. N Engl J Med. 1994; 331(12):771-6. DOI: 10.1056/NEJM199409223311204. View

10.

Jordan S, Green A, Nagle C, Olsen C, Whiteman D, Webb P . Beyond parity: association of ovarian cancer with length of gestation and offspring characteristics. Am J Epidemiol. 2009; 170(5):607-14. DOI: 10.1093/aje/kwp185. View

11.

Tung K, Wilkens L, Wu A, McDuffie K, Nomura A, Kolonel L . Effect of anovulation factors on pre- and postmenopausal ovarian cancer risk: revisiting the incessant ovulation hypothesis. Am J Epidemiol. 2005; 161(4):321-9. DOI: 10.1093/aje/kwi046. View

12.

Tsilidis K, Allen N, Key T, Dossus L, Lukanova A, Bakken K . Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer. 2011; 105(9):1436-42. PMC: 3241548. DOI: 10.1038/bjc.2011.371. View

13.

Brinton L, Lamb E, Moghissi K, Scoccia B, Althuis M, Mabie J . Ovarian cancer risk after the use of ovulation-stimulating drugs. Obstet Gynecol. 2004; 103(6):1194-203. DOI: 10.1097/01.AOG.0000128139.92313.74. View

14.

Whittemore A, Harris R, Itnyre J . Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol. 1992; 136(10):1184-203. DOI: 10.1093/oxfordjournals.aje.a116427. View

15.

Mosgaard B, Lidegaard O, Kjaer S, Schou G, Andersen A . Infertility, fertility drugs, and invasive ovarian cancer: a case-control study. Fertil Steril. 1997; 67(6):1005-12. DOI: 10.1016/s0015-0282(97)81431-8. View

16.

Siskind V, Green A, Bain C, Purdie D . Beyond ovulation: oral contraceptives and epithelial ovarian cancer. Epidemiology. 2000; 11(2):106-10. DOI: 10.1097/00001648-200003000-00005. View

17.

Kjaer S, Mellemkjaer L, Brinton L, Johansen C, Gridley G, Olsen J . Tubal sterilization and risk of ovarian, endometrial and cervical cancer. A Danish population-based follow-up study of more than 65 000 sterilized women. Int J Epidemiol. 2004; 33(3):596-602. DOI: 10.1093/ije/dyh046. View

18.

Titus-Ernstoff L, Perez K, Cramer D, Harlow B, Baron J, Greenberg E . Menstrual and reproductive factors in relation to ovarian cancer risk. Br J Cancer. 2001; 84(5):714-21. PMC: 2363792. DOI: 10.1054/bjoc.2000.1596. View

19.

Ness R, Grisso J, Cottreau C, Klapper J, Vergona R, WHEELER J . Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer. Epidemiology. 2000; 11(2):111-7. DOI: 10.1097/00001648-200003000-00006. View

20.

Harlow B, Cramer D, Bell D, Welch W . Perineal exposure to talc and ovarian cancer risk. Obstet Gynecol. 1992; 80(1):19-26. View