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Randomized Controlled Trial
. 2025 Apr 2;17(7):1246.
doi: 10.3390/nu17071246.

Effects of Vitamin D3 Treatment on Polycystic Ovary Symptoms: A Prospective Double-Blind Two-Phase Randomized Controlled Clinical Trial

Béla E Tóth  1 , István Takács  2 , Zsuzsanna Valkusz  3 , Attila Jakab  4 , Zsanett Fülöp  1 , Kristóf Kádár  5 , Zsuzsanna Putz  2 , János Pál Kósa  2 , Péter Lakatos  2
Affiliations
Randomized Controlled Trial

Effects of Vitamin D3 Treatment on Polycystic Ovary Symptoms: A Prospective Double-Blind Two-Phase Randomized Controlled Clinical Trial

Béla E Tóth et al. Nutrients. .

Abstract

Background/objectives: Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders as well as ovulatory dysfunction. Vitamin D supplementation may improve ovarian dysfunction and follicular development by effecting gene expression. The aim of the present study was to investigate the effects of vitamin D supplementation in women with PCOS through a prospective, randomized, two-phase, parallel design, placebo-controlled trial.

Methods: We assessed the impact on ovarian morphology, cycle length, and ovulatory dysfunction. Transvaginal ultrasonography (TVUS) examinations and clinical laboratory assessments were conducted at the baseline, and again after 12 and 24 weeks. The participants received vitamin D (30,000 IU/week) or a placebo (without concurrent metformin use) for 12 weeks, supplemented with calcium, followed by an additional 12 weeks of vitamin D treatment.

Results: The treatment resulted in improvements in ovarian morphology and regularity of menstrual cycles in more than half of the patients. Additionally, vitamin D3 was associated with a significant increase in the ovulation rate. A statistically significant reduction in mean testosterone levels was observed in the subgroup of patients with an LH/FSH ratio greater than 2.

Conclusions: Our results suggest that vitamin D3 treatment could function as either a standalone or an adjunctive therapy in the management of PCOS.

Keywords: 25(OH)D; LH/FSH; PCOS; cycle length; ovarian morphology; ovulatory dysfunction; progesterone; testosterone; vitamin D3.

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Conflict of interest statement

B.E.T., I.T., Z.V. and L.P. have received consultancy fees and speaker fees from Pharma Patent Ltd. The authors A.J., Z.F., J.K., Z.P. and K.K. declare that they have no conflicts of interest. The founders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study flow chart and schedule of assessments.
Figure 2
Figure 2
Changes in cycle length (CL) in PCO patients by the end of the 12 weeks of treatment with vitamin D3 (Vit D) and calcium supplements. The horizontal axis presents the cycle length at baseline visit for each individual patient, and the spots represent the +/− change in CL from baseline in treatment group. Linear regression trendline with a negative slope is presented with dotted line.
Figure 3
Figure 3
Changes in cycle length (CL) in subgroups of patients with an average length of >28 days, >35 days, or >42 days at baseline as a result of treatment with vitamin D3 (Vit D) and calcium supplements. (Columns represent mean and ±SEM of baseline and at the end of 12 weeks of treatments; asterisks indicate statistical significances of * p < 0.05; ** < 0.01; and *** < 0.001).
Figure 4
Figure 4
The effect of vitamin D supplementation (360,000 IU) in PCOS (ITT population) in supplemented (VitD+) vs. depleted (VitD−) individual’s cycle length in patients with high androstenedione using the cut-off level of >12 nmol/L.
Figure 5
Figure 5
The frequency of ovulation is estimated by the proportion of elevated serum progesterone (>10 nmol/L) among PCOS patients before (Vit D3 depleted) and after (Vit D3 repleted) baseline and after a consequent 12 weeks of treatment with Vit D3 and calcium. The differences were statistically significant. Bars represent the proportion of individuals in a vitamin D-depleted (striped) or -repleted (filled) status.
Figure 6
Figure 6
Mean serum progesterone levels among PCOS patients by the end of the treatment with vitamin D3 (Vit D3) and calcium. Progesterone levels in patients with an LH/FSH ratio > 2 were significantly lower (* p = 0.036) at the baseline.. Columns represent mean ± SEM of serum progesterone for all patients and also the subgroups with LH/FSH ratio > 2 with marked effect and the LH/FSH ratio < 2 subgroup with no meaningful effect of treatment, respectively.
Figure 7
Figure 7
The frequency of ovulation by the stratification of high and normal androstenedione levels (cut-off 12 nmol/L). The rate of ovulation is estimated by reference to progesterone (≥10 nmol/L) in the group of Vit D3-depleted (striped bars) and Vit D3-repleted (filled bars) PCOS patients. The results suggest that higher androgen levels restrict the cycles with ovulation. Bars represent the proportion of individuals by reference to the estimated rate of ovulation.
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