4.3 | Clinical implications
Over a median 7.45 years of follow-up, women with UL had 21.4% higher risk for type 2 diabetes mellitus compared to women without UL in our study. Since the mean age of participants was 29.70 years, young women with UL are advised to pay attention to the prevention and monitoring of type 2 diabetes mellitus.
The pathophysiology of how UL affects the development of type 2 diabetes mellitus is unclear. The development of UL is known to be dependent on ovarian steroid hormones.4 Considering the hormonal changes in obese women or women with metabolic syndrome, it is likely that rather than UL itself, the uterus, endometrium, and ovaries might affect the development of type 2 diabetes mellitus.17-20 A retrospective population-based cohort study found that the risk of diabetes was higher in women with hysterectomy compared to that in those without hysterectomy (HR 1.37, 95%CI 1.23-1.52) and that diabetes risk was not increased in women with hysterectomy and oophorectomy (HR: 1.28, 95%CI 0.93-1.76).21 Interestingly, myomectomy seemed to attenuate the risk for type 2 diabetes mellitus in women with UL in our study. Compared to women without UL, women with UL who did not undergo myomectomy had a higher risk for type 2 diabetes (HR 1.328, 95%CI 1.143-1.542), but women with UL who underwent myomectomy did not. These findings suggest a possible effect of UL on the development of diabetes. UL has increased responsiveness and hypersensitivity to gonadal steroids through increased expression of steroid hormone receptors.21-24 Along with estrogen, which is considered a primary mitogenic factor for the uterus, progesterone and progesterone receptors are reported to play a key role in the development and growth of UL.23 In response to estrogen and progesterone, uterine fibroids can increase in size by cell proliferation, hypertrophy, and accumulation of extracellular matrix.24 Increased progesterone level is associated with reduced insulin sensitivity, which can lead to development of type 2 diabetes.25,26 An animal study showing improved glucose homeostasis in progesterone receptor knockout mice supports the adverse effect of progesterone on glucose tolerance and insulin release.27 A reasonable explanation for the reduction of type 2 diabetes risk associated with myomectomy may be the reduction of progesterone receptor expression through the mechanical removal of the UL.