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.