Endocrine roles of vitamin D in female reproduction: Mechanisms and clinical implications

Vitamin D a fat-soluble steroid hormone signals through Vitamin D Receptors (VDRs) located throughout the ovaries, uterus, placenta, hypothalamus, and pituitary gland, influencing immune regulation and female reproductive physiology. This review of studies from 2013-2025 found consistent associations between low vitamin D status and various disorders in women of childbearing age. In Premenstrual Syndrome (PMS), deficiency correlates with higher symptom severity, and evidence shows that supplementation significantly reduces total PMS scores, particularly improving mood-related domains. For uterine pathologies such as fibroids, endometriosis, and adenomyosis, low vitamin D status is linked to increased risk and severity. Repletion trials suggest antifibrotic and analgesic benefits, although larger, more rigorously designed studies are still needed for definitive clinical guidelines. In Polycystic Ovary Syndrome (PCOS), low vitamin D links to adverse metabolic and hormonal profiles. Multiple randomized controlled trials (RCTs) confirm that correcting deficiency improves insulin resistance, lowers total testosterone and free-androgen index, raises sex-hormone-binding globulin (SHBG), and helps regularize menstrual cycles. Targeted supplementation is recommended, especially for insulin-resistant or obese phenotypes. During pregnancy, maternal deficiency is associated with adverse outcomes including pre-eclampsia, gestational diabetes, and pre-term birth risk. However, intervention trials have yielded inconsistent preventive results, often complicated because rising Vitamin D-Binding Protein (VDBP) may mask true vitamin D status. In Assisted Reproduction like In Vitro Fertilization (IVF), correcting deficiency early during pre-conception or early folliculogenesis appears beneficial. This early dosing enhances oocyte quality, promotes granulosa cell proliferation, and modulates local transcriptomes toward anti-inflammatory pathways. In contrast, single high-dose boluses administered shortly before embryo transfer show limited impact on outcomes. The overall evidence is limited by heterogeneous study designs, variable dosing, and reliance on total serum levels rather than bioavailable vitamin D. Future research should prioritize large, multicenter RCTs utilizing standardized daily/weekly dosing, stratifying by genetic and phenotypic factors, and measuring bioavailable vitamin D to establish reliable effects on patient-centered outcomes.