Combined estrogen plus progestin for menopausal symptoms not linked to type 2 diabetes risk

Key takeaways :

• Use of compounded HT and estrogen alone for menopause symptoms were associated with increased risk for type 2 diabetes.
• Combined estrogen plus progestin from the manufacturer was not linked to diabetes risk.

Risk for type 2 diabetes with use of menopausal hormone therapy varied by type of HT, according to a retrospective cohort study of women in South Korea published in Menopause.

“The types of menopausal hormone therapy currently being prescribed are different from [those used in] existing studies. The risk of diabetes should not limit the prescribing of currently used drugs based on studies with different menopausal hormone therapies,” Jin-Sung Yuk, MD, PhD, from the department of obstetrics and gynecology at Inje University Sanggye Paik Hospital in Seoul, South Korea, and colleagues wrote. “In addition, research is needed to determine whether tibolone, which is prescribed as the mainstay of

menopausal hormone therapy outside of the U.S., actually causes diabetes. Therefore, we used a nationwide population-based health-insurance and health-checkup database for a cohort study.”

This retrospective cohort study utilized national health insurance data and cancer screening data from 2002 to 2019 in South Korea. Researchers identified 330,771 women older than 40 years who used at least one HT for menopausal symptoms for at least 6 months between 2003 and 2011. These women were then group by type of HT: tibolone (n = 164,728), combined estrogen plus progestin by the manufacturer (n = 113,294), oral estrogen (n = 45,458), combined estrogen plus progestin compounded by the physician (n = 5,593) and transdermal estrogen (n = 1,698). In addition, researchers identified 798,550 postmenopausal women who had never been prescribed menopausal HT from 2002 to 2019 as the control group.

The primary outcome was type 2 diabetes incidence between women in the menopausal HT group and the control group.

The median duration of prescribed menopausal HT was 23 months. Researchers observed a type 2 diabetes diagnosis among 16.6% of women in the tibolone (Organon) group, 12.1% in the manufacturer’s combined estrogen plus progestin group, 16.6% in the oral estrogen group, 15.4% in the compounded combined estrogen plus progestin group, 17% in the transdermal estrogen group and 15.2% in the control group.

Factors including low socioeconomic status (HR = 1.441; 95% CI, 1.402-1.481), rural area (HR = 1.036; 95% CI, 1.024-1.047), high Charlson comorbidity index of two or more (HR = 1.264; 95% CI, 1.247-1.282), high parity of three or more (HR = 1.217; 95% CI, 1.187-1.247), age of 55 years or older (HR = 1.263; 95% CI, 1.229-1.298), current smoking (HR = 1.437; 95% CI, 1.4-1.476) and time from menopause to of 10 years or more (HR = 1.287; 95% CI, 1.26-1.314) were associated with increased risk for type 2 diabetes.

When adjusted for variable factors, manufacturer’s combined estrogen plus progestin was not associated with increased risk for type 2 diabetes. Risk for type 2 diabetes increased with use of tibolone (HR, 1.235; 95% CI, 1.217-1.252), oral estrogen (HR, 1.155; 95% CI,

1.127-1.183), compounded combined estrogen plus progestin (HR, 1.085; 95% CI, 1.012-1.163) and transdermal estrogen (HR, 1.178; 95% CI, 1.046-1.327) were all associated with increased type 2 diabetes incidence. Only tibolone was associated with increased type 2 diabetes risk among women older than years.

“This study showed that tibolone, oral estrogen, combined estrogen plus progestin [compounded] by the physician, and transdermal estrogen increased the incidence of type 2 diabetes,” the researchers wrote. “In contrast, combined estrogen plus progestin by the manufacturer did not increase the risk of type 2 diabetes.”