Pathogenesis

Pathogenesis of Uterine Leiomyomas

Key Points


  • Leiomyomas are benign tumors originating from myometrial smooth muscle, composed of smooth muscle cells and fibrous tissue.
  • Genetic and molecular mechanisms behind leiomyoma formation and growth are not fully understood. However, chromosomal rearrangements, deletions, trisomy, and somatic mutations have been identified in their development.
  • Leiomyomas are hormonally responsive and dependent on ovarian steroid hormones, estradiol, and progesterone, with progesterone directly related to their growth.
  • Leiomyoma cells express higher levels of estrogen and progesterone receptors compared to normal myometrial cells.
  • Growth factors such as EGF, PDGF, IGF, TGF-β, VEGF, and FGF are involved in leiomyoma development and proliferation.
  • Leiomyomas are classified by the International Federation of Obstetrics and Gynecology (FIGO) based on their relationship to the uterine serosa and/or endometrium.
  • The FIGO classification includes subgroups based on the percentage of leiomyoma diameter within the myometrium, involvement of the endometrium or serosa, and other characteristics.
  • Pregnancy can impact leiomyomas, and their growth may be influenced by hormonal changes during pregnancy.
  • Post-menopausally, with the decline in ovarian hormone production, leiomyomas tend to regress.
  • Medications that impact gonadal suppression, such as hormone therapies or GnRH analogs, can be used to manage leiomyomas.


Interim Text


1. Genetic Origins

 a. Leiomyomas originate from myometrial smooth muscle cells.

 b. Genetic mechanisms underlying leiomyoma formation and growth are not fully understood.

 c. Chromosomal rearrangements, deletions, and somatic mutations have been implicated.

 d. MED12 gene mutations are found in a significant percentage of leiomyomas.


2. Hormonal Responsiveness

 a. Leiomyomas are hormonally responsive to estrogen and progesterone.

 b. Leiomyoma cells express higher levels of estrogen and progesterone receptors compared to normal myometrial cells.

 c. Aromatase production allows for endogenous estrogen production within leiomyomas.

 d. Progesterone directly promotes the growth of leiomyomas.


3. Growth Factors

 a. Various growth factors contribute to the development and proliferation of leiomyomas.

 b. Growth factors involved include EGF, PDGF, IGF, heparin-binding EGF, TGF-β, TGF-α, VEGF, basic FGF, and acidic FGF.

 c. These factors interact with each other and are differentially regulated by sex steroids.


4. Impact on Endometrial Receptivity and Local Hemostasis

 a. Increased TGF-Beta 3 production and BMP-2 related impacts affect expressions related to endometrial receptivity.

 b. Pathways influenced by leiomyomas can impact local hemostasis within the uterus.


5. Growth Rates and Classification

 a. Growth rates of leiomyomas can vary greatly among individuals.

 b. Approximately one-third of leiomyomas display growth rates of over 20% per year, while a minority may shrink.

 c. Leiomyomas are classified using the FIGO system based on their relationship to the uterine serosa and/or endometrium.


6. Impact of Gonadal Steroids

 a. Estrogens and progesterone play a significant role in leiomyoma growth and development.

 b. Leiomyomas exhibit increased growth during the luteal phase and in response to progestational agents.


7. Pregnancy and Post-Menopausal Impacts

 a. Pregnancy can influence leiomyoma growth due to hormonal changes. During pregnancy, some leiomyomas may decrease in size or become undetectable with ultrasound.

 b. Post-menopausally, with the decline in ovarian hormone production, leiomyomas tend to regress.


8. Medications Impacting Gonadal Suppression

 a. Medications such as hormone therapies or GnRH analogs can be used to manage leiomyomas by suppressing gonadal activity.


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