Mar 27, 2023

Jan Friberg M.D., Ph.D.

Uterine fibroids are present in almost ¾ of all American women at the age of 50. Myomectomy has been the standard treatment for patients with symptomatic fibroids who desire children. However, surgery is not without risk and a need for blood transfusions and treatment of wound infections may be necessary in 10 – 15% of all procedures. New medical treatment to shrink fibroids have recently been introduced in the U.S. Foremost among them is the use of orally active gonaldotropin – releasing hormone antagonists elagolix (Orilissa ® 150 mg once daily) and relugolix (Myfembree® 40 mg daily). The use of add back estrogen and progesterone to the treatment has drastically reduced unpleasant side effects such as hot flashes and vaginal dryness. The new treatments effectively reduces fibroid size and fibroid associated symptoms and control the often accompanying heavy menstrual periods.

                Uterine fibroids are caused by many factors and are stimulated by estrogen and progesterone as well as growth factors and cytokines. The result is the accumulation of extracellular matrix with collagen, fibronectin, and proteoglycans in smooth muscle cells which causes fibrosis. Other risk factors for fibroid development are genetic and epigenetic factors, age, race, ethnicity, family history, elevated body mass index and environmental exposure to toxins.

                D-Vitamin deficiency has been identified as an important risk factor for development of fibroids. Vitamin D deficiency is considered with serum D vitamin levels of less than <20 ng/ml (50 nmol/L), levels between 20 – 30 ng/ml are judged to be borderline and >30 ng/ml considered normal. Low levels of serum vitamin D are associated with increased sizes of fibroids in different ethnic groups. African American women not only have higher rates of fibroids but also are more likely to be vitamin-D deficient.

                Vitamin D is important for optimal function of many organ systems in the human body. Dietary consumption of fatty fish, eggs, fortified milk and cod liver oil add vitamin D to the body, but the most important source of vitamin D is its conversions from precursors in the skin through the action of sunshine. The chemical target tissues for vitamin D are bone, kidney, intestine, brain, skin and liver but reproductive tissues such as uterus, testis, ovaries, prostate, placenta, and mammary glands have plenty of vitamin D receptors so an appropriate supply of vitamin D is necessary for proper function of both the female and male genital organs. Vitamin D also has the capacity to decrease the incidence of certain illnesses such as colon, prostate, and breast cancer.

Several studies have reported the beneficial effect of vitamin D on uterine fibroids. Vitamin D inhibits cell proliferation and induces cell death (apoptosis) and reduces the function of pro-fibrotic factors such as fibromodulin, biglycan and versican. Long term treatment (many months) have shown that fibroid tumors in women decrease in size because of a reduction of the extracellular matrix and up-regulation of apoptosis through the action of transforming growth factor β responsive genes that act on Wnt/β-catenin and mTOR signaling pathways.

Poor outcome in IVF cycles for patients with abnormally low vitamin D levels initiated a debate in 2010 which is still ongoing. Several groups showed low IVF pregnancy rate in vitamin D deficient patients while other studies disagreed and still no final conclusion has been agreed upon. Many different techniques can be utilized to measure vitamin D and no standardized approach has been agreed on. Measurements can be free 25 (OH) vitamin D and/or 25 (OH) vitamin D bound to its binding proteins. Genetic differences in the binding proteins can influence levels and high estrogen levels created in IVF treatment increase the production of binding proteins from the liver. Vitamin D levels decrease during storage of blood specimens which is a common approach in clinical studies and this affects the results. Until more data are available the best thing appears to be to test the regular total 25(OH) vitamin levels in infertility patients and treat patients with levels less than 30 ng/ml.