Vitamin D is a steroid hormone produced mostly as a result of exposure to UV light and regulates the levels of calcium and phosphate in the blood (1). Except its role in bone health, studies have demonstrated its role in human reproduction, with 15% of subfertile couples having low vitamin D levels (2), as well in regulation of inflammation, having a potentially anti-inflammatory effect (3). On the other hand, endometriosis is known to have a negative impact on fertility, whilst chronic inflammation is believed to play a key role both in the initial presentation, as well as progress of endometriosis lesions (4). Indeed, the vitamin D receptor (VDR) has been found in endometriosis lesions (5). Based on the above, a possible correlation between insufficiency (or deficiency) of vitamin D and endometriosis is the focus of scientific research, as well as, whether supplementation of vitamin D levels may play a role in the prevention of endometriosis or, indeed, management of endometriosis-related symptoms.

Let us have a look, though, on what the relevant research has found on a possible correlation between vitamin D and endometriosis. As we will soon find out, results are often contradictory. Starting with a study by Somigliana et al. (6), women that underwent laparoscopy for endometriosis had higher levels of vitamin D compared to women operated for another gynaecological cause. However, another prospective study found women with endometriosis had significantly lower vitamin D levels compared to those without endometriosis (7). What is interesting in the latter study, is the correlation between vitamin D levels and, not only endometriosis, but also the symptom of endometriosis-related pelvic pain. This may be related to the role vitamin D plays in the regulation of chronic inflammation. In the study by Buggio et al. (8), no difference was identified between women with and without endometriosis. Actually, the authors investigated separately the correlation in women with deep endometriosis and those with ovarian endometrioma (chocolate cyst of the ovary), without again identifying any difference. Similar results were reported in the study by Agic et al. (9). No correlation was found between the severity of endometriosis and vitamin D levels (10-12). Systematic reviews have failed to prove a correlation between vitamin D and endometriosis (13,14), however, a recent meta-analysis found women with endometriosis to have lower vitamin D levels (15): In particular, 11 studies were included in the meta-analysis, with 8 finding a link between endometriosis and low vitamin D levels, 2 suggesting no link and only 1 suggesting that women with endometriosis have higher vitamin D levels.

What is the role of vitamin D in the prevention of endometriosis? A large study that investigated the link between dietary intake and endometriosis found that women with higher intake of dairy products and higher vitamin D levels had lower chances of suffering from endometriosis (16): The authors found that the chances of presenting with endometriosis were reduced by 18% in women consuming at least 3 servings of dairy products on a daily basis. However, it needs to be remembered that only a small proportion of vitamin D comes from dietary sources (1).

  As regards vitamin D and its role in the progress of existing endometriosis, data from laboratory studies were encouraging (17,18). Can vitamin D supplementation be used in the medical management of endometriosis and its symptoms? Unfortunately, again, the available scientific data cannot give a clear answer to this question. The combination of Cholecalciferol (D3) with other medical management options of endometriosis led to an improvement in endometriosis-related pain, according to 2 recent studies (19,20). However, this was not confirmed in further studies, that did not demonstrate any benefit of vitamin D supplementation in pain improvement (21,22).

Although this is not the primary aim of this article, we will briefly mention the data on the use of vitamin D in the non-invasive diagnosis of endometriosis. 2 relevant studies reported a higher vitamin-D-binding-protein (VDBP)-creatinine ratio in urine specimens of patients with endometriosis, compared to those without endometriosis (23,24). However, the sensitivity and specificity of this test in the diagnosis of endometriosis is low and, at present time, it is not used in the non-invasive diagnosis of endometriosis.

  In conclusion, a correlation between vitamin D and endometriosis appears to exist, particularly after the findings of the aforementioned, recent meta-analysis (15). However, one needs to acknowledge the presence of studies suggesting the opposite. This may be due to many factors, including methodological aspects of the relevant studies, affecting the final result. And if we accept that there exists a correlation between the vitamin D and endometriosis, the potential role of vitamin D supplementation in the prevention and management of symptoms of endometriosis is far from clear! Although such a role could be proven in the future, at present time, there are not enough published data to routinely suggest supplementation of vitamin D levels for those purposes. More data are required from future studies before we can give clear answers to those important questions.

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