Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model

Fertil Steril. 2020 Jan;113(1):205-216.e4. doi: 10.1016/j.fertnstert.2019.09.018. Epub 2019 Nov 15.


Objective: To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis.

Design: Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model.

Setting: Hospital and university laboratories.

Patient(s)/animal(s): Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice.

Intervention(s): Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days.

Main outcome measure(s): Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computerized tomography and macroscopic examination), cell proliferation (immunohistochemistry and quantitative real-time polymerase chain reaction [qRT-PCR]), ECM (Western blot), transforming growth factor (TGF) β3 (qRT-PCR), and apoptosis (Westrn blot and TUNEL).

Result(s): Short-term treatment with vitamin D did not appear to alter leiomyoma size, based on in vivo monitoring and macroscopic examination. However, long-term high-dose treatment induced a significant reduction in leiomyoma size. Cell proliferation was not decreased in the short term, whereas 1 μg/kg/d vitamin D in the long term significantly reduced proliferation compared with control. Although collagen-I and plasminogen activator inhibitor 1 were not modified by short-term treatment, they were both significantly reduced by long-term high-dose vitamin D. Similarly, long-term high-dose vitamin D significantly reduced TGF-β3 expression. Finally, apoptosis significantly increased with both short- and long-term high-dose vitamin D treatment.

Conclusion(s): Long-term vitamin D acts as an antiproliferative, antifibrotic, and proapoptotic therapy that provides a safe, nonsurgical therapeutic option for reducing uterine leiomyoma size without side-effects.

Keywords: apoptosis; cell proliferation; extracellular matrix; uterine leiomyoma; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Drug Administration Schedule
  • Female
  • Humans
  • Leiomyoma / diagnostic imaging
  • Leiomyoma / drug therapy*
  • Leiomyoma / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Positron Emission Tomography Computed Tomography / methods
  • Treatment Outcome
  • Tumor Burden / drug effects*
  • Tumor Burden / physiology
  • Vitamin D / administration & dosage*
  • Xenograft Model Antitumor Assays / methods*


  • Vitamin D