Readers React: Hormonal contraception and breast cancer

June 21, 2018

Readers respond to an editorial from Dr. Lockwood on hormonal contraception and breast cancer as well as an editorial on burnout and depression in medical students.

Dear Dr. Lockwood,

You missed the boat in your editorial on hormonal contraception and breast cancer. The greatest strength of the Danish study is the high number of participants, which yields high statistical precision. At the same time the larger the number of women in a study, the greater the impact of confounding variables.

The absence of complete information on important baseline confounders limits the conclusions from this database study. The Danish registries have incomplete information on family history, presence of inherited mutations, early menarche, breast feeding, body mass index, and smoking for most of the women, and complete lack of information on lifestyle choices such as alcohol use, physical activity, and age of women at first delivery; thus, adequate adjustment is impossible. The authors’ conclusion that risk increased with longer durations of use is especially vulnerable to the unknown impact of non-assessed confounders. To reach their conclusion, they relied on “a bias analysis” that assumed confounders not assessed were highly prevalent in the population and strongly associated with breast cancer risk. Attempting to parse out the effects of various treatments over many years without rigorous control for confounding renders their conclusion particularly weak.

The authors recognize that their numbers, if real, translate into a very low number of additional cases of breast cancers in users of hormonal contraception. When the statistical conclusions of analyses are in the risk range of 1 to 2, clinicians should be skeptical that there is real clinical meaning in the numbers. Add to this the uncertainty in this study regarding adjustments for the effect of all factors that influence breast cancer risk and there is no strong reason to change current practice or patient recommendations.

A well-recognized phenomenon is preferential prescribing. Clinicians tend to prescribe newer products or perhaps progestin-only products to patients with known risk factors. The impact of this phenomenon was not and probably could not be assessed in this study.

 Actually, the small increased risk in the Danish study confined to current/recent users supports the hypothesis that hormonal therapy may promote the growth of pre-existing breast cancers leading to early detection.1 The results indicate a rapid disappearance of excess risk after discontinuation of use among women who used hormonal contraception for short periods, exactly what you would expect if early detection is occurring with short-term use. The same effect is seen in the results with levonorgestrel-releasing intrauterine devices.

The above thoughts stimulate me to write to you and question your comment that the recent Danish data “advance in our understanding the relative and absolute risk of breast cancer conferred by hormonal contraception.” Furthermore, your advice to limit hormonal contraception in women after 35 is unwarranted. The cardiovascular risk after age 35 with low-dose products has been
demonstrated to be confined to women with recognized risk factors.

My best to you,
Leon Speroff, MD


In Reply:

Thanks, Leon. Your points are well taken, with a few caveats.

One, large sample sizes tend to minimize the impact of outliers and are generally considered more robust. Second, while the authors could not control for all the variables listed, there is no reason a priori why adverse factors would fall disproportionately amongst treated compared with untreated women. Finally, I agree that the preferential prescribing issue is, of course, a concern.

The bottom line is that any added absolute risk of breast cancer accruing hormonal contraception is small and the net health benefits, including avoiding pregnancy, are substantial. Leon, it is great to have you “back” writing for Contemporary OB/GYN with your usual lucid and thorough analysis. Best,

Charles J. Lockwood, MD, MHCM



1. Speroff L. Postmenopausal hormone therapy and the risk of breast cancer: a contrary thought. Menopause. 2008 Mar-Apr;15(2):393-400.

NEXT: Shining a light on burnout

Shining a light on burnout

Dear Dr. Lockwood:

I read with great interest your recent article Burnout and depression in medical students and mentors. Very well done.

I am a family physician, medical director at The North Carolina Physicians Health Program (, and an expert on professional job-related burnout. We are losing too many of our best and brightest because of burnout and the problems burnout can cause.

Thank you for shining your light on this important issue. If I can serve as a resource or assist your colleagues in any way, please feel free to contact me. I blog about burnout and just posted an article on the astoundingly high rate of alcohol use among female providers (409% higher than the general population).

Thank you again for your interest in this important topic.

Clark Gaither, MDRaleigh, NC