Yonsei Medical Journal Vol. 46, No. 4, pp. 471 - 479, 2005 Effect of Long-Term Hormone Therapy on Telomere Length in Postmenopausal Women Duk-Chul Lee,1 Jee-Aee Im,2 Jeong-Ho Kim,3 Hye-Ree Lee,1 and Jae-Yong Shim1 Departments of 1Family Medicine and 3Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea; 2Department of Laboratory Medicine, MizMedi Hospital, Seoul, Korea. Telomeres undergo attrition with each cell division, and telomere length is associated with age-related diseases and mortality in the elderly. Estrogen can influence the attrition of telomeres by diverse mechanisms. This is a retrospective case control study that investigated the influence of long-term hormone therapy (HT) on telomere length in postmenopausal women. We recruited 130 postmenopausal women from 55 to 69 years of age for this study, and divided them into two groups. The first group included 65 women who had been on estrogen and progesterone therapy for more than five years (HT group). The other group was composed of 65 women matched in age to the HT group who had never had HT (non- HT group). The relative ratios of telomere length of study subjects to a reference DNA from a healthy young female were measured using quantitative PCR. Plasma levels of lipid profiles, total antioxidant status (TAS), C-reactive proteins (CRP), fasting glucose levels, and estradiol levels were mea- sured. Age at menopause, vitamin use, and exercise, alcohol, and cigarette smoking histories were also assessed in a questionnaire. Mean duration (± SD) of HT was 8.4 ± 2.3 years. Prevalence of vitamin use and regular exercise were higher in the HT group than in the non-HT group (p<0.01). Relative telomere length ratios in the HT group were signifi- cantly greater than those in the non-HT group (p<0.01). HT was significantly correlated with the relative telomere length ratio in multivariate analysis when potential confounding variables were controlled for (p<0.05). In conclusion, telo- mere lengths were longer in postmenopausal women who had a history of long-term HT than in postmenopausal women without HT. Long-term HT in postmenopausal women may alleviate telomere attrition. Received October 5, 2004 Accepted April 12, 2005 This study was supported by Yonsei University research fund of 2003 Reprint address: requests to Dr. Jae-Yong Shim, Department of Family Medicine, Yongdong Severance Hospital, Yonsei University College of Medicine, P.O. Box 1217, Seoul 135-720, Korea. Tel: 82- 2-3497-3483, Fax 82-2-3463-3287, E-mail: faith@yumc.yonsei.ac.kr Key Words: Telomere, estrogen, menopause, hormone ther- apy, quantitative PCR INTRODUCTION Telomeres are repetitive structures of the se- quence of bases (TTAGGG) that appear at the ends of mammalian chromosomes,1 and which contribute to the stability and function of chromo- somes by preventing degradation and end-to-end fusion. Because of end replication problems, telo- meres undergo attrition in groups of 20-200 base pairs for each cell division until the critical telo- mere length is reached. When the critical length is reached, cells eventually enter into replicative senescence.2,3 In humans, the telomere appears to be a major component of cell senescence and aging.4 Alteration of telomere biology is shown in genetic disorders or syndromes of accelerated aging.5-7 Telomere length is also associated with cardiovascular aging in males,8,9 the severity of Alzheimer's disease,10 and the mortality of elderly people older than 60 years.11 The rate of telomere attrition is modified by gender12 and oxidative stress.13 At birth, telomere length is the same in both men and women,14 but by adulthood telomeres are longer in women than in men.8,9 This discrepancy between genders is probably caused by the effects of estrogen. It has been suggested that estrogen can protect telo- meres against reactive oxygen species (ROS) and induced DNA damage. Estrogen can also stimu- late telomerase directly or indirectly by stimu- lating nitric oxide production.15,16 Based upon these observations, it is hypothesized that estro- Yonsei Med J Vol. 46, No. 4, 2005