Objective: The aim of this study was to evaluate the possibility of preventing the metabolic health consequences of postmenopausal hypogonadism with the use of long-term hormone therapy (HT).

Methods: We used a monozygotic co-twin control design including 10 twin pairs (aged 56-62 y) discordant for HT (duration of HT, 2-10 y). In addition, 14 premenopausal women (aged 29-35 y) who did not use HT were studied to evaluate the differences in metabolic health between the premenopausal and postmenopausal states. Body composition was determined, and waist-to-hip ratio was used as an estimate for fat distribution. Serum sex steroids, sex hormone-binding globulin, and serum lipid and glucose profiles were analyzed. The serum levels of adiponectin, monocyte chemotactic protein-1, and leptin, as well as their local transcript levels in adipose tissue, skeletal muscle, and leukocytes, were measured.

Results: Long-term HT was associated with a healthier amount and distribution of body fat. No difference was seen in serum lipid concentrations between HT users and their nonusing identical twin sisters, but fasting serum glucose and glycated hemoglobin levels were 5% and 3% lower in HT users than in nonusers, respectively. Among the adipokines analyzed, the most notable finding was a 15% lower level of monocyte chemotactic protein-1 in HT users, particularly with respect to its suggested mediator role between obesity and insulin resistance.

Conclusions: Long-term HT is associated with healthier amount and distribution of body fat and better adipocytokine profile, with concomitant signs of improved insulin sensitivity.