Women who are 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. “For these women, the link between HT and diabetes might fall on the benefit side of the equation.”
NAMs' newly revised position statement on hypertension is the group's first to review this evidence, Dr. Utian said. “In 2004 [when NAMS issued its last position paper], there were not enough data to address this issue.
Since then, a number of published studies have shown the same link between HT and a decreased incidence of diabetes.”
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—a significant difference).
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 (about 1,000 were excluded from the analysis because of a baseline diagnosis of diabetes).
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 patients in the active group was 6.2%, compared with 9.5% in patients in the placebo group—a significant risk reduction of 35%. The authors concluded that in this group, 30 was the number needed to treat to prevent 1 case of diabetes.
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.
In the meantime, patients who are at risk of diabetes should receive lifestyle counseling in addition to information about the hormone/diabetes link. “We need to focus on healthy living, diet, exercise, and moderation in alcohol.
“If patients would comply with those recommendations, they would be much more beneficial than any hormone therapy,” he noted.