TOPLINE:

Transdermal hormone replacement therapy (HRT) in women with type 2 diabetes (T2D) was associated with a lower risk for ischemic heart disease, whereas oral HRT was linked to increased cardiovascular issues, including a twofold higher risk for pulmonary embolism and a 21% greater risk for ischemic heart disease.

METHODOLOGY:

• The proportion of postmenopausal women with T2D is rising, yet outcome data on HRT for midlife women with T2D are lacking.
• Researchers conducted an active-comparator retrospective cohort study using data from the TriNetX platform. Cohort 1 included women with and without T2D, all of whom were using transdermal HRT (n = 8316); cohort 2 included women with T2D who were either using or not using transdermal HRT (n = 8354); and cohort three included women with T2D who were using either transdermal or oral HRT (n = 8316).
• Overall, the mean age of all patients was 59 years, and 75% were White; propensity score matching was performed on the basis of age, ethnicity, and other factors.
• Participants were followed up for 5 years after initiation of HRT or a statin.
• Outcomes included pulmonary embolism, deep vein thrombosis, ischemic heart disease, ischemic stroke, and various cancers.

TAKEAWAY:

• Women with T2D using transdermal HRT had a reduced risk for ischemic heart disease compared with nonusers with T2D (hazard ratio [HR], 0.75; P < .001) ; no differences were observed in the risk for pulmonary embolism, deep vein thrombosis, stroke, or cancer.
• Among women treated with transdermal HRT, those with T2D had higher risk for deep vein thrombosis (HR 1.90; P = .002), ischemic heart disease (HR 1.77; P < .001), and stroke (HR 1.89; P < .001) compared to women without T2D.
• In women with T2D, oral HRT was linked to a doubled risk for pulmonary embolism (HR, 2.01; P < .001) and a 21% increased risk for ischemic heart disease (HR, 1.21; P = .004) compared with transdermal HRT, with no differences in the risk for other conditions.
• Rates of pulmonary embolism and cancers did not differ between HRT users with T2D and those without T2D.

IN PRACTICE:

“Up to five years of regulator approved doses of transdermal HRT appears safe in a large cohort of midlife women with T2D. Given increased risks with oral HRT, we propose that women with T2D should not be prescribed oral oestrogen therapy,” the authors wrote.

SOURCE: 

The study was led by Matthew Anson, Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool, UK. It was presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 held September 15-19, 2025 in Vienna, Austria.

LIMITATIONS: 

Owing to the retrospective design of the study, there may be a possibility of unmeasured confounding. Most participants were White women, which may affect the generalizability of the findings. The study did not match for the type of HRT, such as combined vs estrogen-only.

DISCLOSURES: 

Anson declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.