Tamoxifen in men: a review of adverse events
Wibowo E, Pollock PA, Hollis N, Wassersug RJ
Andrology. 2016 Sep;4(5):776-88. doi: 10.1111/andr.12197. Epub 2016 May 6
Background
Most male breast cancer is hormone dependent, via estrogen (ER/PR positive i.e. estrogen receptor, progesterone receptor positive). This is, on the whole, good news as it means the cancer cells are dependent (at least initially) on a signal coming from estrogen via its receptor for survival. Cut that off, and the cells mostly die, or at least become dormant. This is why for many men with breast cancer hormone therapy is the most effective part of their treatment plan.
That means we get Tamoxifen, as there is no data in support of other types of hormone therapy (actually there is little data either way as I have discussed in another post). That Tamoxifen has side effects is widely known, especially for women, because larger studies have been done for them on this subject. For men there is less evidence available, and Wibowo and colleagues have done a great service in pulling together what there is to survey the situation of Tamoxifen complications for men.
Findings
Wibowo and colleagues searched the literature for trials on Tamoxifen, and found 14 randomized clinical trials (the most valuable kind of trial design) on men receiving Tamoxifen though none of these were on men with breast cancer (they were for prostate cancer, infertility and gynecomastia). They also found 39 non-randomized clinical trials (a lower level of evidence), 11 of which were on men with breast cancer.
Overall there are relatively speaking few adverse effects, and it is relatively rare that men stop taking their Tamoxifen because of them (I say relatively as compared to, for example most chemo). Focusing on the data for men with breast cancer, the authors find that the most common type of adverse effect was psychiatric (~30%), including decreased libido, anxiety and sleep disorders. Cardiac and vascular disorders were rarer (~10%), but were more often serious health threats.
Over the entire study the discontinuation rate was small – around 5%. Interestingly for men with breast cancer it was higher at 10%.
Comment
The news is good – an effective therapy is mostly well tolerated and leads to few adverse effects that result in discontinuation.
My main concern, though, is how well the studies surveyed here for male breast cancer represent the experience of the now thousands of men on this drug. The higher discontinuation rate may well relate to the longer duration of treatment for men with breast cancer, which is typically 5 or even 10 years now. The trials for the other conditions had treatment durations of a few months to 3 years. Perhaps men faced with a significantly longer duration are less willing to endure? I think that what is necessary is a long-term, large population study on Tamoxifen adherence in men with breast cancer, such as are being undertaken for women.
The authors also report biochemical changes from some of the trials they report for disease other than male breast cancer. Very interestingly there is no consensus on the impact of Tamoxifen on E2 (estradiol) levels with trials reporting increases, decreases and no change. Similarly testosterone levels were sometimes seen to go up, and in other cases not to change or more rarely to decrease. The basis for this is unclear – there are likely feedback mechanisms in play, and reduction in ER signaling may cause such changes, but it is clearly not a simple relationship.
Häggström M, Richfield D (2014). “Diagram of the pathways of human steroidogenesis”. Wikiversity Journal of Medicine 1 (1). DOI:10.15347/wjm/2014.005. ISSN 20018762. – Self-made using bkchem and inkscape
Another aspect of estrogen biology the authors discuss is the findings of ER functions in different brain regions that have been made over the past 10 or 15 years. These allow for the hypothesis that the psychiatric effects seen with Tamoxifen are due to direct effects on brain function rather than downstream of changes in systemic hormone levels. This of course requires more study, but raises the hope that perhaps in the future the brain could be spared from the hormone therapy, reducing the side effects that men (and women) suffer.
Entering a World of Pink 
Thanks Oliver. Very interesting read.
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Dr. Bolger,
You and I have some shared experiences. I am 50 and an anesthesiologist at Johns Hopkins. In May, 2012 I was diagnosed with breast cancer. A mastectomy, 6 months of chemo and a bunch of tamoxifen later, I am right as rain.
A friend sent me a story about you. I am very pleased you are working to promote awareness of the need to study breast cancer treatment in men.
I have had only one unnerving experience with insurance since all of this started. Every year, I have been denied tamoxifen by my insurance company because it is a “woman’s drug”. They actually say that. Because I am tenacious, I always get it covered eventually. It would be a humiliating experience if I were not so (overly) self confident. I could imagine that some men would be discouraged and simply stop taking the drug.
I am not a social media guy so I am not very connected. If you hear other men describing treatment like this, maybe it’s a big problem. Obviously the drug is important for us.
Thank you very much for the comment – really appreciate the connection and shared experience. What you describe about your insurance company is something I have heard from a few others. It sounds like the impact of a template which restricts tamoxifen to women (even though many men get it also for conditions other than breast cancer). It reminds me of the same template issue when doctors create breast cancer clinical trials, and click the box “women” and not the box “men” for the same reason. We have to keep talking about it for it to change and I appreciate your making this comment.
Another take, not male focused, but relevant, I think: http://blogs.cancer.org/expertvoices/2015/10/27/does-hormone-therapy-for-breast-cancer-affect-the-brain/. I was diagnosed two weeks ago, had mastectomy last Friday, and expect to discuss hormone therapy pros and cons at appointment next week.
I’m also a male breast cancer survivor on Tamoxifen. I’m 4 years out of treatment and having trouble with the side effects of Tamoxifen. I’m also being treated for CLL. I haven’t found a support group and need one. Maine lacks that. Any pointers would be greatly appreciated.
I too am a male breast cancer survivor. I was misdiagnosed and carried the tumor for over a year and a half before getting the correct diagnosis of stage 3 estrogen related bc. Had mastectomy chemo and radiation with Tamoxifen therapy. I’m 4 years out. I’ve been having trouble with the side effects of Tamoxifen, as I’m also being treated for CLL. I haven’t found a support group here in Maine, and I need one. Any pointers would be greatly appreciated. Thanks
Dear Frank – are you on twitter? If so, searching for #malebreastcancer will connect you with many members of the MBC community. Best wishes, Oliver