Potential Mental Health Advantages Found for Transdermal Versus Oral Hormone Therapy

Postmenopausal women on transdermal HT experienced lower incidence of anxiety and depression compared with those receiving oral HT

By Elana Gotkine HealthDay Reporter

TUESDAY, Oct. 28, 2025 (HealthDay News) — For postmenopausal women, transdermal hormone therapy (HT) is associated with a lower incidence of anxiety and depression compared with oral HT, according to a study presented at the annual meeting of the Menopause Society, held from Oct. 21 to 25 in Orlando, Florida.

Liying Wei, from the Drexel University College of Medicine in Philadelphia, and colleagues compared the incidence of obesity, cardiovascular disease, anxiety, depression, and Alzheimer disease among postmenopausal women receiving oral versus transdermal HT in a retrospective study conducted using the TriNetX database. Postmenopausal women aged 46 to 60 years who were prescribed oral or transdermal estrogen for HT were identified and categorized into two cohorts: Cohort 1 included women prescribed HT defined as oral estrogen, and cohort 2 included women prescribed transdermal estrogen-only HT. After propensity score-matching, 3,844 postmenopausal women were included in each cohort.

The researchers found that women taking transdermal HT experienced a lower incidence of anxiety (7.2 versus 9.1 percent) and depression (3.3 versus 5.1 percent) compared with those receiving oral HT. The hazard ratio for depression was increased significantly over time in association with oral HT (hazard ratio, 1.30), while there was no significant difference in the hazard ratio for anxiety. The treatment groups did not differ significantly in terms of risks for obesity, cardiovascular disease, or Alzheimer disease.

“While our findings suggest that transdermal estrogen may offer potential mental health advantages compared with oral formulations, these results should not be generalized to the broader postmenopausal population,” coauthor Xuezhi (Daniel) Jiang, M.D., Ph.D., also from the Drexel University College of Medicine, said in a statement.