Tamoxifen in prevention/management of gynecomastia and related, antiandrogen-induced side effects


According to a new, systematic review of data from four independently conducted clinical trials, tamoxifen may be the most effective agent for the management of breast events induced by treatment with non-steroidal antiandrogens (e.g., bicalutamide) in men with prostate cancer.

This review by Kunath et al. in BMC Medicine is currently available in abstract form or as a provisional PDF of the typescript. Brief commentary on the paper is also available on the HealthDay web site.

Data on the potential of the anti-estrogenic agent tamoxifen (a drug widely used in the management of breast cancer) in the prevention and management of gynecomastia and breast pain associated with the use of non-steroidal antiandrogens like bicalutamide (Casodex) and flutamide (Eulexin) has been evolving over the past few years. Historically, it was recommended that men being treated with long-term use of non-steroidal antiandrogens receive prophylactic low-dose radiation therapy to the chest to prevent such problems.

It does need to be noted, up front, that the long-term use of anti-estrogens in men with prostate cancer may be problematic, and that further research will be needed if long-term use of tamoxifen to prevent or manage gynecomastia and breast pain is to become standard practice in men with prostate cancer on long-term antiandrogen therapy.

Kunath et al. report that they were able to identify four, relatively small, randomized, multi-center trials in which tamoxifen was compared to other forms of therapy:

  • A three-arm trial, in which tamoxifen at 20 mg/day (in 37 men) was compared to the aromatase inhibitor anastrozole at 1 mg/day (in 36 men) or a placebo (in 40 men)
  • A six-arm trial, in which tamoxifen at 20 mg/day (in 35 men) was compared to a placebo (in 60 men)
  • A three-arm trial, in which tamoxifen at 10 mg/day (in 50 men) was compared to radiotherapy (in 50 men) or no additional treatment (in 51 men)
  • A three-arm trial, in which tamoxifen at 20 ng/day (in 35 men) was compared to anastrozole at 1 mg/day (in 36 men) or a placebo (in 36 men)

The reviewers report that:

  • Tamoxifen reduced the risk of gynecomastia (relative risk [RR] = 0.10) and breast pain (RR = 0.06) at 6 months compared to untreated controls.
  • Tamoxifen reduced the risk of gynecomastia (RR = 0.22) and breast pain (RR = 0.25) when compared to anastrozole after a median of 12 months.
  • In one study, tamoxifen reduced the risk of of gynecomastia (RR = 0.24) and breast pain (RR = 0.20) at 6 months compared with radiotherapy.
  • Radiotherapy increased the risk of suffering from nipple erythema (redness of the skin due to congestion of the capillaries) and skin irritation.
  • There were no significant differences between types of therapy (including placebo or non-therapy) for any other adverse events.

The authors conclude that:

  • The optimal dose of tamoxifen for prevention/management of risk for gynecomastia and breast pain still needs to be determined.
  • Larger, well-designed, randomized trials, with longer follow-up, are still appropriate.
  • The impact of tamoxifen therapy on long-term adverse events, prostate cancer progression, and patient survival remains unclear.

However, it also appears that tamoxifen has significant potential benefits in the prevention of gynecomastia and breast pain as compared to other forms of therapy — if such long-term use does not present safety problems.

7 Responses

  1. This is very promising information for the chemical treatment of gynecomastia. Thank you for such a thorough conveyance of the study.

    As many cosmetic surgeons know, prostate medications are one of the leading causes of gynecomastia in men who receive this treatment.

    It’s difficult to understand just how traumatic it can be for a man to not only have to worry about treating and surviving the cancer, but to add gynecomastia to it all can sometimes feel like the straw that broke the camel’s back. Thank you for sharing this positive information. It gives patients hope.

  2. What about the extra side effects from tamoxifen? Many women taking tamoxifen report various side effects mainly related to hormonal imbalance. Tamoxifen forms carcinogenic metabolites in the liver which may lead to liver cancer when used long term.

  3. Despite the fact that several papers have now pitched the case for using tamoxifen to block gynecomastia from various ADT protocols, what is of concern to me is that they all seem to either ignore or understate the problematic side effects of tamoxifen itself and the normal roles of estradiol in males.

    Any prostate cancer patient who is thinking of going on tamoxifen might want to read the following papers and make sure that their prescribing MDs are aware of this literature.

    Wassersug RJ, Oliffe JL. The social context for psychological distress from iatrogenic gynecomastia with suggestions for its management. J Sex Med. 2009; 6:989-1000.

    Wibowo E, et al. Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy. J Urol. 2011; 185:17-23.

    Wibowo E, et al. Estradiol treatment modulates spontaneous sleep and sleep recovery after sleep deprivation in castrated male rats. Behav Brain Res. 2012; 226:456-464.

  4. Dear Gerry:

    I assume that your concerns are exactly why the authors (as reported) think that further study is necessary. This was a review of studies of relatively short-term use of tamoxifen, and the potential risks of longer-term use most certainly do exist.

  5. Richard:

    Please see my response to Gerry Potter above.

  6. I took a pro hormone and developed a slight case of gynecomastia. I have been off supplements now for almost 9 months and there is still a little left. Would it be worth while to try tamoxifen before discussing surgery?

  7. Justin,

    Have you read the literature on the side effects of tamoxifen in women? In the absence of any new data, it would be reasonable to assume that males get the same side effects. Given some concern about the impact of the drug on cognitive function, I would be cautious about taking tamoxifen to avoid gynecomastia.

    Of course, there are guys who are happy to give up some of their brains to avoid having breasts. I suspect that guys who reason that way may not have that much cognitive function in the first place.

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