Diabetes Risk Lower in Women on Hormones

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.