Menopause Live - IMS Updates

Date of release: 20 May, 2009

HRT and the new incidence of diabetes mellitus

The Kuopio Osteoporosis Risk Factor and Prevention Study is a prospective population-based cohort study. In a new publication [1], the effect of hormone replacement therapy (HRT) on the new incidence of diabetes mellitus was examined. Almost 8500 women in the early postmenopause were followed over a 5-year period. Almost one-third of the women were current users of HRT whilst around one-quarter had previously used HRT. The diagnosis of new diabetes was ascertained from the registry of specially refunded drugs which gives the right to full reimbursement for drugs used in chronic illnesses following a physician’s diagnosis. The incidence of diabetes was slightly reduced in past users of HRT (hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.57–1.16), further reduced in HRT users for < 2½ years’ duration (HR 0.53; 95% CI 0.24–1.15), and significantly reduced in HRT users for > 2½ years’ duration (HR 0.31; 95% CI 0.16–0.60). There were some baseline differences between HRT users and non-users. The HRT users were slightly younger, had lower body mass index, lower parity, lower prevalence of hypertension and greater prevalence of hysterectomy. However, the analyses were adjusted for these factors. The type and dose of HRT were not recorded, although this population is thought to reflect the use of oral 17β-estradiol, with or without a progestogen.


The findings are in keeping with previous studies, both observational and randomized, clinical trials, but the magnitude of the decrease, 69%, is much greater. The Nurses’ Health Study reported a 20% lower incidence of new-onset diabetes [2], whilst the Heart and Estrogen/progestin Replacement Study found a 35% reduction [3], the Women’s Health Initiative estrogen–progestogen arm found a 21% reduction [4], and the estrogen-alone arm a non-significant 12% reduction [5]. These studies reflect the use of conjugated equine estrogens in contrast to the oral 17β-estradiol presumed to be used in the Kuopio study. A very small observational study found that transdermal 17β-estradiol resulted in a 54% reduction in diabetes [6], which is surprising given the relative lack of effect of transdermal estradiol on glucose and insulin parameters [7]. Could there be a difference in the effects of different types of estrogen in preventing diabetes? Differences between conjugated equine estrogens and 17β-estradiol on glucose and insulin metabolism have been shown [7], but they may rather reflect dosage effects. It has become clear that yet another benefit of HRT may be in the prevention of maturity-onset diabetes in postmenopausal women.


John Stevenson
National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK


  1. Pentti K, Tuppurainen M, Honkanen R, et al. Hormone therapy protects from diabetes: the Kuopio Osteoporosis Risk Factor and Prevention Study. Eur J Endocrinol 2009; March 25 [Epub ahead of print].

  2. Manson JE, Rimm EB, Colditz GA, et al. A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus. Ann Epidemiol 1992;2:665-73.

  3. Kanaya AM, Herrington D, Vittinghoff E, et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2003;138:1-9.

  4. Margolis KL, Bonds DE, Rodabough RJ, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Womens Health Initiative hormone trial. Diabetologia 2004;47:1175-87.

  5. Bonds DE, Lasser N, Qi L, et al. The effect of conjugated equine oestrogen on diabetes incidence: the Womens Health Initiative randomised trial. Diabetologia 2006;49:459-68.

  6. Rossi R, Origliani G, Modena MG. Transdermal 17β-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women. Diabetes Care 2004;27:645-9.

  7. Stevenson JC. Hormone replacement therapy and carbohydrate metabolism. In Marsh MS, Compston JE, eds. Hormone Replacement Therapy and the Menopause. London: Dunitz, 2002:101-3.