• © 1999 by American Society of Clinical Oncology

Tamoxifen and Sexuality: Let's Listen to the Data Speak

To the Editor: Whether¹ or not² tamoxifen or another agent is adopted as a breast cancer prevention agent depends on an accurate assessment of the risk-to-benefit ratio. The article by Mortimer et al³ brings us a short-term, retrospective review of what effects tamoxifen has on the sexual functions of women with breast cancer who have been treated with the drug as well as what estrogenic effects tamoxifen has on the vaginal mucosa.

In the Introduction, the authors start out with a reasonable hypothesis. Specifically, they note that one theory was that tamoxifen might have an estrogen agonist effect on vaginal mucosa and thereby increase lubrication and improve sexual function. What was the effect of tamoxifen on the vaginal mucosa of patients? The authors state: “The women in whom estrogen effect was seen tended to be older. The median age for patients with estrogen effect was 54.5 years, compared with 49 years for patients without estrogen effect (P = .054).” Unfortunately, 54% of women responding to a questionnaire complained of pain, burning, or discomfort during sexual intercourse. Even worse, the presence of an estrogen effect was associated with negative reactions during intercourse (P = .02) and vaginal dryness or tightness (P = .046). The tamoxifen did have an estrogen effect on the mucosa of older patients, but they were not advantaged.

In their Summary, Mortimer et al3 report that “In our trial, we found an inverse correlation between the age and estrogen effect on the vagina, although this did not achieve statistical significance (P = .054).”

Assuming that the apparent contradiction is a typographical error, perhaps instead of concluding that their study “raises the possibility that tamoxifen may have estrogen agonist effects on the vagina of postmenopausal women and antagonist effects on younger women,” we should let the data speak. First, with 91% of either the 57 women completing the survey or the 41 patients in partnered relationships being postmenopausal, multiplication leads us to suspect that there are only four to five patients in the premenopausal group. There may well be insufficient data for meaningful subgroup analysis on the vaginal mucosa of premenopausal women who have taken tamoxifen.

The Introduction states that findings on vaginal smears were then correlated with symptoms of sexual dysfunction. As stated, the presence of an estrogen effect was significantly associated with negative reactions during sex and either vaginal dryness or tightness.

In their Discussion, the authors appropriately note the association of tamoxifen with dyspareunia suggested by the data. The authors might have concluded that in the postmenopausal group, although tamoxifen may have increased the karyopyknotic index, qualitatively at least, tamoxifen did not seem to improve vaginal lubrication, as manifested by the negative reactions during sex or either vaginal dryness or tightness. Apparently, the mucosal maturation index does not correlate with improved sexual function.