By: Mitchell Rawson
Director’s Note: In this week’s blog, we see that Vitamin D’s potential role in reproductive health extends beyond its established importance in bone health. This research summary by Mitchell Rawson, DO, explores “Vitamin D, PCOS and androgens in men: a systematic review” by Trummer et al., which examines the relationship between vitamin D, polyendocrine metabolic ovarian syndrome (PMOS), and androgen levels in men. Promising findings point to vitamin D’s potential role in supporting metabolic and hormonal health and providing a foundation for further research to clarify who may benefit most from supplementation. Dr. Rawson, now a general surgery resident, completed the FACTS elective during his fourth year of medical school to deepen his understanding of natural family planning and help empower patients in their reproductive health decisions.
Introduction
Vitamin D deficiency is a significant public health concern due to its association with numerous adverse health outcomes, including insulin resistance, cardiovascular diseases, musculoskeletal diseases, infectious and autoimmune diseases, cancer, increased mortality, and decreased fertility. [1] The authors note that infertility, affecting about 15% of couples, has profound medical, psychosocial, and economic impacts. Polyendocrine metabolic ovarian syndrome (PMOS) is a leading cause of female infertility, and it’s linked to metabolic risks like type 2 diabetes, mellitus, and cardiovascular diseases due to common features like oligo- or anovulation, obesity, and insulin resistance. The introduction also underscores the role that male factors play in 30–40% of infertility cases, focusing on the interaction between the pituitary gland and testes and the importance of testosterone in male fertility and aging. It also highlights evidence that links low vitamin D and testosterone levels to adverse health effects. Given these considerations, the article sets the stage for a systematic review aimed at exploring the relationship between vitamin D, PMOS, and androgen metabolism in men.
“Vitamin D deficiency is a significant public health concern due to its association with numerous adverse health outcomes, including, insulin resistance, cardiovascular diseases … and decreased fertility.”
Methodology
Trummer et al. conducted a thorough systematic review by searching the PubMed database for relevant English-language publications from January 2012 to September 2017. Their search strategy was comprehensive and included a variety of key terms, including “vitamin D” in combination with “polycystic ovary syndrome,” “PCOS,” “testosterone,” and “hypogonadism.” To broaden their scope, they also included specific forms of vitamin D in the search criteria, such as “25-hydroxyvitamin D (25(OH)D),” “1,25-dihydroxyvitamin D,” and “calcitriol,” rather than focusing solely on the general term “vitamin D.” To strengthen the review, they supplemented the database search by examining references in the selected articles, thereby enhancing the depth and breadth of the investigation.
Results
Vitamin D and PCOS: Observational Studies
The observational studies on the relationship between vitamin D and PMOS present a nuanced picture, particularly regarding insulin resistance and glycemic control. Some findings indicate that lower levels of 25-hydroxyvitamin D (25(OH)D) are linked with higher insulin concentrations and insulin resistance, highlighting a potential beneficial role of vitamin D in managing these aspects of PMOS. Notably, one study demonstrated that 25(OH)D levels were significantly associated with insulin resistance in PMOS patients, independent of body fat percentage—a correlation not observed in non-PMOS individuals. However, this association was not consistent across all studies, with several reports failing to find a significant link between 25(OH)D levels and measures of insulin resistance or glycemic control in PMOS patients. Regarding the endocrine parameters of PMOS, the evidence is more uniform and does not show a significant correlation between vitamin D levels and key hormonal markers, such as total testosterone, free testosterone, and the free androgen index among others. This suggests that vitamin D’s role in addressing PMOS-related hormonal imbalances remains uncertain.
Vitamin D and PCOS: Interventional Studies
Recent studies on vitamin D supplementation in women with PMOS present mixed outcomes. Several randomized controlled trials (RCTs) have shown promising results, with vitamin D supplementation leading to significant improvements in metabolic, endocrine, and reproductive parameters in PMOS patients. For instance, daily doses of 4000 international units (IU) of cholecalciferol for 12 weeks resulted in significantly decreased fasting plasma glucose, serum insulin, and insulin resistance, as well as improvements in lipid profiles and inflammatory markers. Additionally, some studies found significant reductions in androgen concentrations—including total testosterone and dehydroepiandrosterone-sulfate (DHEA-S)—as well as improvements in fertility treatment outcomes, such as increased endometrial thickness, though they did not directly influence pregnancy rates. Conversely, other interventional studies found no significant effects of vitamin D supplementation on metabolic parameters or insulin sensitivity. These discrepancies may reflect differences in study design, including supplementation duration, dosing regimens, and participants’ baseline vitamin D status.
“Several randomized controlled trials (RCTs) have shown promising results, with vitamin D supplementation leading to significant improvements in metabolic, endocrine, and reproductive parameters in PMOS patients.”
The variability in outcomes across these studies suggests the need for further large-scale, well-designed RCTs to clarify the role of vitamin D supplementation in PCOS management, accounting for factors such as baseline vitamin D status, supplementation dosage, and treatment duration.
Vitamin D and Testosterone in Men: Observational Studies
Observational studies generally indicate a significant independent association between vitamin D levels and circulating androgen levels or hypogonadism in men. Key findings show positive correlations of 25-hydroxyvitamin D (25(OH)D) with total testosterone (TT) and in some cases free testosterone (FT) levels across various populations. However, results are mixed with some studies finding no significant association after adjusting for factors such as BMI and other demographic and lifestyle variables. Notably, vitamin D deficiency is consistently linked with higher odds of hypogonadism and altered androgen levels, suggesting vitamin D’s role in male hormonal health.
Vitamin D and Testosterone in Men: Interventional Studies
Interventional studies and randomized controlled trials (RCTs) on the effects of vitamin D supplementation on androgen levels in men have shown inconsistent outcomes. One study reported significant increases in total testosterone (TT) levels and improved erectile dysfunction scores following vitamin D supplementation in middle-aged men with vitamin D insufficiency. However, other studies, including those focusing on men with conditions like Klinefelter syndrome or hypogonadism, found no significant impact of vitamin D supplementation on TT levels. A notable RCT observed increased TT levels after one year of vitamin D supplementation in men undergoing weight reduction, but this was an isolated finding. The effect of vitamin D on TT levels was not the primary outcome of the study. Contradictory results from subsequent RCTs, which included healthy men with relatively high baseline TT levels, suggest vitamin D’s effect on androgen levels may depend on factors like the baseline vitamin D status, testosterone levels, and specific characteristics of the study population. Further research is recommended to clarify the potential benefits of vitamin D supplementation on androgen levels, particularly in different cohorts such as hypogonadal men or those with severe vitamin D deficiency.
Discussion
In “Vitamin D, PCOS, and Androgens in Men: A Systematic Review” by Trummer et al., the authors meticulously analyze the intricate connections between vitamin D levels, polyendocrine metabolic ovarian syndrome (PMOS), and androgen levels in men. This review is pivotal for women and men’s health, fertility awareness, and family planning and offers insights into how vitamin D might influence metabolic, endocrine, and reproductive aspects of PMOS—a condition that significantly affects fertility and women’s health in general.
The observational studies highlighted in the review suggest a beneficial role of vitamin D in managing insulin resistance in PMOS, an important consideration given the condition’s link with metabolic syndrome and diabetes. However, the relationship between vitamin D and hormonal imbalances in PMOS remains uncertain, underlining a gap in our understanding of vitamin D’s full potential in treating PMOS-related fertility issues.
For men, observational studies suggest a significant association between vitamin D levels and androgen levels, with deficiency linked to higher odds of hypogonadism. Interventional studies, however, show inconsistent results on the impact of vitamin D supplementation on androgen levels, suggesting that effects may vary based on individual factors like baseline vitamin D and testosterone levels.
“For men, observational studies suggest a significant association between vitamin D levels and androgen levels, with deficiency linked to higher odds of hypogonadism.”
The review’s strength lies in its comprehensive analysis of both observational and interventional studies, which provides a broad perspective on the existing literature. However, the inherent limitations of research reviews, such as the reliance on the methodology and reporting quality of included studies, may impact the conclusiveness of findings. Another limitation is variability in study designs, vitamin D supplementation dosages, and baseline characteristics of study populations—which complicates direct comparisons and limits the ability to draw definitive conclusions.
This review offers valuable insights into the potential of vitamin D as a modifiable factor in managing PMOS and its complications. However, the research also raises several questions regarding the optimal levels of vitamin D supplementation needed to achieve therapeutic effects in PMOS patients and in men with low androgen levels or hypogonadism.
The call for future research is clear. Large-scale, well-designed randomized controlled trials (RCTs) are urgently needed to address these gaps. Studies that delineate the effects of vitamin D supplementation on fertility and metabolic outcomes in women with PMOS and on androgen levels in men are needed. Such studies should aim to standardize vitamin D dosing, account for baseline vitamin D status, and consider the heterogeneity within PMOS populations. Additionally, exploring the impact of vitamin D on male fertility and androgen levels further would fill a significant void in the current literature.
Ultimately, this review emphasizes the potential of vitamin D in enhancing fertility awareness and management and offers a promising avenue for improving reproductive health outcomes. However, until more robust evidence is available, any general recommendations for vitamin D supplementation in the context of PMOS and male androgen levels remain premature.
REFERENCES
[1] Trummer C, Pilz S, Schwetz V, Obermayer-Pietsch B, Lerchbaum E. Vitamin D, PCOS and androgens in men: a systematic review. Endocr Connect. 2018 Mar;7(3):R95-R113. doi: 10.1530/EC-18-0009. Epub 2018 Feb 15. PMID: 29449314; PMCID: PMC5854850.
ABOUT THE AUTHOR
Mitchell Rawson, DO is a general surgery resident at the University of South Dakota Sanford School of Medicine. He attended medical school at Kansas City University in Kansas City, MO, while pursuing an MBA in Healthcare Management at the Helzberg School of Management at Rockhurst University. Mitchell completed his undergraduate education at Marquette University, where he majored in Biomedical Engineering with a focus in Biomechanics. Mitchell is set to complete his residency in General Surgery at the University of Minnesota and is extremely interested in Minimally Invasive Surgical Techniques. Mitchell enrolled in the FACTS elective to gain a better understanding of natural family planning methods and manners in which to share these methods with future patients so they can feel more empowered over their health and reproductive decisions.
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