Hormone replacement therapy: one-year follow up of DNA damage

Although hormone replacement therapy (HRT) may offer considerable benefits for menopausal women, the potential cancer risk may limit its use. This work aimed at assessing whether HRT is able to induce DNA damage in postmenopausal women monitored by the micronucleus (MN) test, which provides a reliable biomarker of genotoxicity and cancer risk assessment. A group of 16 healthy women (non-smokers) in spontaneous menopause were given oral estradiol (2 mg oral micronized 17-beta estradiol daily) for 1 month, followed by a 30-day wash-out period and a transdermal treatment with 17-beta estradiol (1.5 mg gel daily) during 1 month. Oral intake of dihydrogesterone (10 mg/day for 12 days/month) was cyclically combined with oral or transdermal estradiol during the next 9 months. Venous blood samples were collected before the treatment, and after 1, 3, 6 and 12 months of therapy. Slides were scored blind and MN frequency was evaluated as number of micronuclei per 1000 binucleated cells. The baseline plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were simultaneously measured. The means of MN frequency were 18.2+/-1.6, 18.6+/-2.1, 14.8+/-1.5, 15.9+/-1.0 and 17.7+/-1.3 for samples collected before and at 1, 3, 6 and 12 months, respectively. The MN frequencies at every sampling time did not statistically differ from the basal values. In addition, no statistically significant associations between MN values and hormone levels of E2 and FSH were observed throughout the entire study. This study shows the absence of any significant increase of MN frequencies in women undergoing oral and/or transdermal HRT, sequentially monitored for up to 12 months of therapy.