Progesterone Is Essential for Maintenance and Growth of Uterine Leiomyoma

Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Department of Obstetrics and Gynecology, 4th Floor, Suite 4-127, 303 East Superior Street, Chicago, Illinois 60611, USA.
Endocrinology (Impact Factor: 4.5). 04/2010; 151(6):2433-42. DOI: 10.1210/en.2009-1225
Source: PubMed


Uterine leiomyomata (ULs) represent the most common tumor in women and can cause abnormal uterine bleeding, large pelvic masses, and recurrent pregnancy loss. Although the dependency of UL growth on ovarian steroids is well established, the relative contributions of 17beta-estradiol and progesterone are yet to be clarified. Conventionally, estradiol has been considered the primary stimulus for UL growth, and studies with cell culture and animal models support this concept. In contrast, no research model has clearly demonstrated a requirement of progesterone in UL growth despite accumulating clinical evidence for the essential role of progesterone in this tumor. To elucidate the functions of ovarian steroids in UL, we established a xenograft model reflecting characteristics of these tumors by grafting human UL tissue beneath the renal capsule of immunodeficient mice. Leiomyoma xenografts increased in size in response to estradiol plus progesterone through cell proliferation and volume increase in cellular and extracellular components. The xenograft growth induced by estradiol plus progesterone was blocked by the antiprogestin RU486. Furthermore, the volume of established UL xenografts decreased significantly after progesterone withdrawal. Surprisingly, treatment with estradiol alone neither increased nor maintained the tumor size. Although not mitogenic by itself, estradiol induced expression of progesterone receptor and supported progesterone action on leiomyoma xenografts. Taken together, our findings define that volume maintenance and growth of human UL are progesterone dependent.

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    • "matched myometrium may be regulated by hormone levels. Hormones such as estrogen (E2) and progesterone (P4) are considered to be promoters of leiomyoma growth (Park et al., 2008; Ishikawa et al., 2010). We did not assess the hormonal status of the patients included in our study; however, the underlying mechanism should be explored in the future investigations. "
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    • "Even if involvement of progesterone and its receptor in etiopathogenesis of myomas remains unquestionable [42, 43], the range of their involvement has not yet been fully recognized. Ishikawa et al. [44] observed evident myoma growth upon treatment in common with estradiol and progesterone. Upon administration of estradiol only the volume of the tumour did not increase and the authors concluded that estradiol induced expression of progesterone receptors in myomas, promoting in this way the pathological effect of progesterone. "
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    • "Studies supporting a pregnancy-related growth of fibroids generally claimed a crucial role of sex steroids hormone [3], [7], [11], [12]. Estrogen has been considered to be the primary growth promoter of fibroids and there is also convincing evidence that the maintenance and growth of these lesions is progesterone dependent [12]. Noteworthy, selective progesterone-receptor modulators have been shown to effectively shrink fibroid size [13], [14]. "
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