[Lani]

...
It is well known that atrophic vaginitis in postmenopausal women can be worsened or
induced by the use of aromatase inhibitors for the treatment of breast cancer. In fact, these drugs
exert their benefits on breast cancer by decreasing E2 biosynthesis, thus increasing the frequency
and severity of menopausal symptoms [28; 29]. In a recent study where seven breast cancer
patients treated with aromatase inhibitors received Vagifem (estradiol tablet) at a daily dose of 25
!g for 2 weeks and then, thereafter, twice weekly, serum estradiol (E2) rose from a median of 3
pmol/l to 72 pmol/l, at 2 weeks (range 3 to 232) [30]. Serum E2 levels generally decreased
thereafter to values of 40 pmol/l or less although values of 137 and 219 pmol/l were found at
weeks 7-10. A patient who received Premarin cream had serum E2 levels of 83 pmol/l at 2 weeks.
It should be mentioned that blood sampling for E2 measurement was done at time of patient’s
visit, a timing not likely to correspond to the highest levels of serum E2 after Vagifem
administration. It is thus more than likely that the values reported in [30] underestimate, up to an
unknown extent, the true elevation of serum E2 after Vagifem administration. The authors
concluded that the use of Vagifem with aromatase inhibitors is contraindicated. These findings
obtained in breast cancer women treated with aromatase inhibitors raise a serious issue about the
use of any vaginal estrogen preparation in postmenopausal women.
In previous studies with Vagifem, maximal and mean 24 h serum E2 concentrations were
measured at 180 ± 99 pmol/l and 84 pmol/l for the 25 !g dose while values of 81 ± 62 pmol/l and
40 pmol/l, respectively, were found for the 10 !g dose [30]. Other vaginal estrogen tablets and
creams have led to high or even higher serum estrogen levels [31-33].