cholecalciferol and Uterine-Neoplasms

Uterine leiomyomas, or fibroids, are the most common benign tumor in reproductive aged women. Affected women may remain asymptomatic or may report symptoms related to abnormal uterine bleeding, infertility, or pelvic pain and pressure. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy). In those wishing to defer surgical management, non-hormonal therapies such as non-steroidal anti-inflammatory drugs and tranexamic acid have been shown to decrease menstrual blood loss. In patients with more symptomatic leiomyomas, hormonal therapies such as gonadotropin-releasing hormone agonists and selective progesterone receptor modulators are effective at reducing leiomyoma volume, uterine size, and menstrual blood loss. This manuscript will detail the available and emerging hormonal and non-hormonal treatments for symptomatic uterine leiomyomas.

Topics: Antifibrinolytic Agents; Aromatase Inhibitors; Cabergoline; Cholecalciferol; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptives, Oral, Synthetic; Danazol; Dopamine Agonists; Ergolines; Estrenes; Estrogen Antagonists; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Leiomyoma; Levonorgestrel; Mifepristone; Norpregnadienes; Oximes; Patient Care Planning; Selective Estrogen Receptor Modulators; Somatostatin; Tranexamic Acid; Uterine Neoplasms; Vitamins

To provide a detailed summary of current scientific knowledge on uterine fibroids (leiomyomas) in vitro and in in vivo animal models, as well as to postulate the potential role of vitamin D3 as an effective, inexpensive, safe, long-term treatment option for uterine fibroids.. PubMed search articles were used to identify the most relevant studies on uterine fibroids, as well as effects of vitamin D3 on uterine fibroid cells and fibroid tumor growth in in vivo animal models.. University research laboratory.. Not applicable.. None.. Despite numerous publications available on uterine fibroids, information about the role that vitamin D3 plays in the regulation of uterine fibroids is limited. Most of the recent vitamin D3-related studies on uterine fibroids were published from our group. Recent studies have demonstrated that vitamin D deficiency plays a significant role in the development of uterine fibroids. Our recent studies have demonstrated that vitamin D3 reduces leiomyoma cell proliferation in vitro and leiomyoma tumor growth in in vivo animal models. These results postulate the potential role of vitamin D3 for an effective, safe, nonsurgical medical treatment option for uterine fibroids.. This article reviews human and animal studies and uncovers new possibilities for understanding the vitamin D-based therapeutic option for an effective, safe, long-term treatment of uterine fibroids. On the basis of these results, a clinical trial with vitamin D3 or a hypocalcemic analog, paricalcitol, may be warranted for nonsurgical medical treatment of uterine fibroids.

Topics: Animals; Antineoplastic Agents; Black or African American; Cholecalciferol; Dietary Supplements; Ergocalciferols; Female; Humans; Leiomyoma; Risk Factors; Signal Transduction; Treatment Outcome; Uterine Neoplasms; Vitamin D; Vitamin D Deficiency

This is a preliminary report of the first cases of successful simultaneous use of ulipristal acetate (UPA) and vitamin D3 in uterine fibroid (UF) oral treatment in humans. We present two cases of 37- and 49-year-old females with clinically symptomatic UFs and vitamin D deficiency. Both patients were treated with a standard 3 months of UPA scheme (5 mg daily) with the additional use of vitamin D3 (7000 IU daily orally). In the 37-year-old female all the symptoms (pain, pressure, frequent urination) decreased, total tumor volume after the treatment changed by 47.8%. In the 49-year-old female most symptoms perished, total tumor volume was reduced by 63.3%. UPA and vitamin D share synergistic anti-fibroid properties. Further studies are necessary to show the exact effect of UPA and vitamin D as co-drugs.

Topics: Adult; Antineoplastic Agents, Hormonal; Cholecalciferol; Drug Synergism; Drug Therapy, Combination; Female; Humans; Leiomyomatosis; Middle Aged; Norpregnadienes; Treatment Outcome; Uterine Neoplasms

Somatic mutations in the Med12 gene are known to activate Wnt/β-catenin signaling in human uterine fibroids (UFs).. The objective of the study was to examine the role of vitamin D3 in the modulation of Wnt/β-catenin and mammalian target of rapamycin (mTOR) signaling in human UF cells.. Immortalized human UF cells (HuLM) and human primary UF (PUF) cells were treated with increasing concentrations of vitamin D3 and thereafter analyzed using Western blots and immunocytochemistry.. Wnt/β-catenin and mTOR signaling proteins in cultured HuLM and PUF cells were measured.. UF tumors with Med12 somatic mutations showed an up-regulation of Wnt4 and β-catenin as compared with adjacent myometrium. Vitamin D3 administration reduced the levels of Wnt4 and β-catenin in both HuLM and PUF cells. Vitamin D3 also reduced the expression/activation of mTOR signaling in both cell types. In contrast, vitamin D3 induced the expression of DNA damaged-induced transcription 4 (an inhibitor of mTOR) and tuberous sclerosis genes (TSC1/2) in a concentration-dependent manner in HuLM cells. Furthermore, we observed a concentration-dependent reduction of Wisp1 (Wnt induced signaling protein 1) and flap endonuclease 1 proteins in HuLM cells. Additionally, abrogation of vitamin D receptor expression (by silencing) in normal myometrial cells induces Wnt4/β-catenin as well as prompts a fibrotic process including an increase in cell proliferation and increased extracellular matrix production. Together these results suggest that vitamin D3 functions as an inhibitor of Wnt4/β-catenin and mTOR signaling pathways, which may play major roles in fibroid pathogenesis.. Vitamin D3 may have utility as a novel long-term therapeutic and/or preventive option for uterine fibroids.

Topics: beta Catenin; Cell Differentiation; Cell Proliferation; Cholecalciferol; Female; Humans; Leiomyoma; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Cells, Cultured; Uterine Neoplasms; Wnt Proteins