Method: The epidemiological analysis utilizes cross-sectional data from the National Health and Nutrition Examination Survey 2001-2002 and 2003-2004. The cross sections include n=1,230 women aged 40-85 who received a clinical periodontal examination, responded to questions regarding hormone replacement therapy (HRT) and had a record of serum vitamin D levels. Attachment loss (AL) and number of teeth were regressed across HRT status (never vs. ever use) and Vitamin D status (<20 ng/ml vs ≥20 ng/ml) in multivariable linear regression models. For the mechanistic cell culture studies human THP-1 monocytes were cultured with or without LPS, estradiol, progesterone and/or 1,25-dihydroxyvitamin D3. RNA was extracted, purified and SYBR green qPCR was performed in respect to IL-6.
Result: Mean AL values were higher among participants not taking HRT compared to those taking. Similarly, participants taking HRT were missing 1 less tooth on average. HRT therapy was associated with greater reductions in mean AL and tooth loss among participant with vitamin D levels >= 20 ng/ml as compared to participants with vitamin D levels <20 ng/ml. The mechanistic cell data supported the epidemiological data as IL-6 gene expression was attenuated in monocytes treated with estradiol and progesterone and further attenuated when vitamin D was included.
Conclusion: : The maximal beneficial effect of female sex hormones in respect to periodontal disease is associated with subjects who also have high vitamin D levels. This effect is plausibly mediated via an anti-inflammatory transcriptional activity due to female sex hormones and vitamin D as demonstrated in human monocytes.