Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors.
BACKGROUND
Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer.


METHODS
Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women.


RESULTS
Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women.


CONCLUSIONS
The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.
Kendall
A
A
Academic Department of Biochemistry, Royal Marsden Foundation NHS Trust, London, UK.
Dowsett
M
M
Folkerd
E
E
Smith
I
I
D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D000075202:Contraindications; D004333:Drug Administration Routes; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D014621:Vagina
D047072:Aromatase Inhibitors; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone