Review: Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study
Treatments for infertility typically involve the administration of agents (such as gonadotrophin hormones or clomiphene citrate) that stimulate the ovaries to release eggs. A typical by-product of these treatments is altered levels of the hormones estrogen and progesterone. However, as both breast density and breast cancer risk are highly hormone-dependent, it is worth asking whether treatments for infertility have a bearing on these two factors. This is what Lundberg and her colleagues from Sweden’s Karolinska Institute set out to do. Their large cross-sectional study (totalling 43 313 women) compared women with no history of infertility to those with such a history. The latter were split into three groups—those receiving no treatment, those receiving controlled ovarian stimulation (COS; high doses of gonadotrophin hormones that typically result in superovulation) or women receiving other hormonal treatments (either low doses of gonadotrophins or clomiphene citrate, which both result in less intense ovulation induction). The women had their breast density measured by Volpara to explore any relationship between mammographic measures and fertility status.
It was revealed that women with impaired fertility had higher absolute volumes of dense tissue compared to those with no reported fertility problems. Furthermore, women receiving COS had higher dense volumes still relative to infertile women receiving no treatment or other types of hormonal treatment (an increase of approximately 3cm3). Although breast cancer risk was not directly evaluated in this study, a 3cm3 increase in dense tissue volume has corresponded to an approximate 2.5% increase in risk in previous studies from the Karolinska Institute. Furthermore, when comparing women receiving COS to untreated infertile women, the difference in dense tissue volume between the two groups increased with age.
It should be noted that a number of confounding factors (such as the cross-sectional design of the study) makes it hard to conclude whether the relationship between breast density and infertility (and its treatments) are causative or mere associations. Additionally, a simultaneous increase in absolute fat volume meant there was no overall change in percentage density in any of the women after adjustment for confounding factors (BMI, age at menarche, parity, etc.). Nevertheless, this is the first study to examine fertility status and breast density in a systematic and large-scale manner and it opens the door for further exploration of the effect of infertility on breast cancer risk. Furthermore, the automated objective measurements provided by Volpara are described as a particular strength of the study.