Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors

• Published in: Annals of oncology Vol. 17; no. 4; pp. 584 - 587
• Main Authors: Kendall, A., Dowsett, M., Folkerd, E., Smith, I.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-04-2006; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: adjuvant; Antineoplastic agents; aromatase inhibitors; Aromatase Inhibitors - therapeutic use; Biological and medical sciences; breast cancer; Contraindications; Drug Administration Routes; Drug Interactions; Estradiol - administration & dosage; Female; Follicle Stimulating Hormone - blood; Gynecology. Andrology. Obstetrics; hormone replacement therapy; Humans; Luteinizing Hormone - blood; Mammary gland diseases; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Postmenopause; Prospective Studies; Tumors; Vagina; vaginal estrogen; hormone replacement therapy; breast cancer; aromatase inhibitors; adjuvant; vaginal estrogen; Human; Aromatase inhibitor; Estrogen; Breast cancer; Malignant tumor; Estradiol; Ovarian hormone; Mammary gland diseases; Postmenopause; Adult; Female; Adjuvant; Contraindication; Hormone replacement therapy; Sex steroid hormone; Woman
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdj127

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.
Patients and 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 ≤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.