Use of Fertility Drugs and Risk of Ovarian Cancer: Danish Population Based Cohort Study

Abstract

Objective To examine the effects of fertility drugs on overall risk of ovarian cancer using data from a large cohort of infertile women. Design Population based cohort study. Setting Danish hospitals and private fertility clinics. Participants 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. Main outcome measure 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. Results 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. Conclusion No convincing association was found between use of fertility drugs and risk of ovarian cancer.

Metformin is a reasonable first-line treatment option for non-obese women with infertility related to anovulatory polycystic ovary syndrome - A meta-analysis of randomised trials

“…What is becoming increasingly clear is that, contrary to the international consensus recommendation, 1,2 metformin is a very suitable alternative to clomiphene as a first‐line ovulation induction treatment for non‐obese women with anovulatory PCOS. In fact, metformin carries some potential advantages over clomiphene, including no known adverse endometrial effect (whilst endometrial thinning could reduce embryo receptivity for some women using clomiphene 19,20 ), no known increase in multiple pregnancy rate (unlike that associated with clomiphene) and thus no requirement for inconvenient and costly monitoring of ovulation induction cycles by serum oestradiol measurements with access to follicular ultrasound scanning (widely regarded as essential for clomiphene), and no concern over long‐term adverse effects on the ovaries (contrasting with the lingering concern over increased risk of ovarian cancer seen in some cohort studies of women using clomiphene, particularly serous ovarian cancer 21 and amongst those using long treatment courses 22 ).…”

Ovarian Stimulation: Is There a Long-Term Risk for Ovarian, Breast and Endometrial Cancer?

“…95%CI: 1.95-13.75). In a large cohort of over 54,000 infertile women, Jensen et al observed no excess risk for invasive ovarian cancer in any of the groups exposed to fertility drugs [39].…”

Fertility Drugs and the Risk of Breast and Gynecologic Cancers

“…These two studies prompted several other investigations, including cohort studies in Australia, 18,48 Israel, 14,16,49,50 the United States, 28,51 the Netherlands, 29 the United Kingdom, 52,53 Denmark, 54 and Sweden. [55][56][57] Most of these studies failed to provide confirmation of a link between fertility drug use and ovarian cancers.…”